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In clinical practice&#44; the modulation of the immunosuppressive regimen is common in order to avoid the long-term adverse effects&#46; The calcineurin inhibitors &#40;CNI&#41; withdrawal or conversion to mTOR-inhibitor is currently performed to reduce nephrotoxicity or risk of malignancy&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">4&#44;5</span></a> These changes in immunosuppression are risk of development of new HLA-Abs and consequently ABMR&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">6&#44;7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The steroids withdrawal is also desirable to avoid their adverse effects on long-term treatment&#44; but its relationship with the development of new HLA-Abs is not yet well established&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">One of the most important adverse effects of steroids is increased cardiovascular risk&#46; 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there are potent immunosuppressants in maintenance therapy &#40;Tacrolimus and Mycophenolic mofetil-MMF&#41; and the steroids withdrawal seems plausible&#44; at least in those patients with low immunological risk&#46; Steroids withdrawal has risk of acute rejection and higher slope of glomerular filtration rate &#40;GFR&#41; loss in the long term&#46; We hypothesize that steroids elimination can contribute to production of donor specific antibodies &#40;DSA&#41;&#46; So&#44; the aim of our study is to assess the relationship between steroid withdrawal and development of HLA-Abs after renal transplantation&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Material and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Patients</span><p id="par0030" class="elsevierStylePara elsevierViewall">We studied 652 kidney transplant recipients&#44; performed in University Hospital Marqu&#233;s de Valdecilla&#44; Santander &#40;Spain&#41; from January 1998 to December 2011 who met the following criteria&#58; graft survival of at least two years and maintenance of immunosuppression with tacrolimus and MMF during the first two years after transplantation&#46; We excluded of the study&#58; combined transplants&#59; retransplants which lost the first transplant for rejection&#59; panel reactive of antibodies &#40;PRA&#41; pretransplant &#62;20&#37; by complement-dependent cytotoxicity &#40;CDC&#41;&#44; acute antibody-mediated rejection &#40;ABMR&#41; during the 7 months after transplantation&#46; Finally&#44; 182 kidney transplant recipients fulfilled the inclusion criteria and were included in the study&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The patient data were obtained from the prospectively maintained database of renal transplant patients at our centre&#46; The demographic&#44; immunologic and clinical parameters are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; Patients were classified into two groups according to steroid withdrawal&#58; Group-I&#58; removal of steroids at 7 months posttransplant &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>130&#41; and Group-II&#58; steroids maintenance during the first two years after transplantation &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>52&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">Both groups were comparable in terms of gender&#44; time on dialysis&#44; retransplants&#44; cold ischaemia time&#44; HLA mismatches&#44; pretransplant sensitization &#40;tested by CDC&#41;&#44; induction therapy with thymoglobulin or basiliximab&#44; and acute rejection during the 7 months after transplantation&#46; The Group II patients were significantly younger and predominate transplants before 2003&#44; as the only statistically significant differences&#46; The mean study follow-up was two years after transplantation&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Steroid withdrawal protocol</span><p id="par0045" class="elsevierStylePara elsevierViewall">In 2003&#44; we started a protocol with steroid withdrawal up to 7 months after kidney transplantation in patients treated with tacrolimus and MMF&#44; and excluding those patients with high immunological risk &#40;acute ABMR&#59; acute cellular rejection with a degree<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>Ib of the Banff classification in the 7 months after transplantation&#44; pretransplant PRA<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>20&#37; or rejection with graft loss in prior transplants&#41;&#46; However&#44; even before 2003&#44; in some patients&#44; steroids were withdrawn at 7 months with the same criteria&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">An earlier withdrawal was not performed at our centre because we do not use induction thymoglobuline routinely&#44; and decided to make a slow pattern of steroids that ended at 7 months&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The prednisone dose reduction consisted in gradually decreasing the dose until the complete withdrawal up to 7 months after transplantation&#58; 15<span class="elsevierStyleHsp" style=""></span>mg&#47;d at 15 days&#59; 10<span class="elsevierStyleHsp" style=""></span>mg&#47;d a day at one month&#59; 7&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;d at two months&#59; 5<span class="elsevierStyleHsp" style=""></span>mg&#47;d at three months&#59; 5<span class="elsevierStyleHsp" style=""></span>mg&#47;d and 2&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;d alternating at four months&#59; 2&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;d at five months&#59; 2&#46;5<span class="elsevierStyleHsp" style=""></span>mg every other day at six months until complete withdrawal at seven months&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Serum samples selection and sera analysis</span><p id="par0060" class="elsevierStylePara elsevierViewall">Serum samples of all transplanted patients were routinely collected and stored at &#8722;80<span class="elsevierStyleHsp" style=""></span>&#176;C&#46; Frozen serum samples were selected to investigate the presence of HLA-Abs&#46; For every patient&#44; two samples were selected&#44; one immediately before transplantation and another one two years after transplantation&#46; The sera were analyzed by LABScreen&#174;Mixed &#40;One Lambda Inc&#46;&#44; Canoga Park&#44; CA&#44; USA&#41; for screening antibodies and LABScreen&#174;Single antiHLA Antigen &#40;One Lambda&#41; class-I and&#47;or class-II if were positive in the screening&#46; A total of 372 serum samples were analyzed&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">A mean fluorescence intensity &#40;MFI&#41; value greater than 1500 was considered positive for a particular HLA specificity&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Statistical methods</span><p id="par0070" class="elsevierStylePara elsevierViewall">Quantitative variables were compared using the <span class="elsevierStyleItalic">t</span>-Student&#39;s test&#46; The percentages were obtained with the chi-square test&#46; Differences were considered significant when <span class="elsevierStyleItalic">p</span>-value was below 0&#46;05&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results</span><p id="par0075" class="elsevierStylePara elsevierViewall">Twenty-two patients &#40;16&#46;92&#37;&#41; in group I and eleven patients &#40;21&#46;15&#37;&#41;&#44; in Group II &#40;pNS&#41; presented serum HLA-Abs at two years after transplantation &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">When pretransplant sera were analyzed by Luminex a total of fifteen patients &#40;11&#46;53&#37;&#41; in steroid withdrawal group&#44; and six patients &#40;11&#46;53&#37;&#41; in the group of steroid maintenance presented HLA-Abs prior kidney transplantation&#44; despite the exclusion criteria of PRA<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>20&#37; by CDC&#46; Of these patients&#44; ten developed new specificities after two years &#40;66&#46;66&#37;&#41; from the group I&#44; versus four patients &#40;53&#46;02&#37;&#41; from the group II &#40;<span class="elsevierStyleItalic">p</span> 0&#46;058&#41;&#44; with a similar percentage of DSA &#40;33&#46;33&#37; in group I vs 36&#46;36&#37; in group II&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">Within the patients without HLA-Abs before kidney transplantation &#40;group I-<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>115&#59; group II-<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>45&#41;&#44; seven patients in steroid withdrawal group &#40;6&#46;08&#37;&#41; developed de novo HLA-Abs&#44; four of them being DSA &#40;3&#46;47&#37;&#41; whereas four patients in the group II &#40;7&#46;69&#37;&#41; developed de novo HLA-Abs and two of them were DSA &#40;3&#46;84&#37;&#41;&#59; pNS &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46; Therefore&#44; in the subgroup without preformed antibodies&#44; there are not differences in the development of antibodies in both groups &#40;6&#46;08&#37; vs 7&#46;69&#37;&#44; pNS&#41;&#44; although steroid withdrawal &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">Only two patients &#40;1&#46;5&#37;&#41; in group I had acute cellular rejection after steroid withdrawal&#44; with grades Ia and Ib of Banff classification&#46; The last one had already pretransplant HLA-Abs&#44; and developing a DSA &#40;DQ4&#41; at two years&#46; The other did not develop HLA-Abs&#46; None of recipients in both groups had ABMR during the study period&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">In terms of graft survival&#44; no statistically significant differences in both groups &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41; are appreciated&#44; however those patients with HLA-Abs at two years after transplantation have worse survival &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a> and <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>&#41;&#46; The influence of HLA Abs is confirmed in graft survival&#44; after multivariate analysis &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001 and HR 2&#46;758&#44; 95&#37; CI 1597&#8211;4764&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0025"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discussion</span><p id="par0100" class="elsevierStylePara elsevierViewall">The minimization of immunosuppression could increase the risk of HLA-Abs development as previously demonstrated in CNI conversion to imTOR&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">6&#44;7</span></a> Steroids withdrawal are not been studied in relation to the development of DSA in organ transplantation&#46; The huge advantages of steroids elimination in relation to metabolic and cardiovascular adverse events may not be sufficient if a significant immunological risk is demonstrated&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">There is only one study that analyzes the production of HLA-Abs in kidney transplants in adults&#44; after early steroid withdrawal &#40;7 days post-transplant&#41;&#46; They concluded that steroid withdrawal at 7 days posttransplant was not at higher risk for developing HLA antibodies&#44; but all patients have received induction with thymoglobuline&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">12</span></a> Our study is the first to assess the relationship between intermediate steroid withdrawal and the detection of serum HLA-Abs in renal transplants with standard immunosuppression &#40;tacrolimus and MMF&#41;&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Our data suggest that steroid withdrawal up to 7 months after transplantation does not imply a higher risk of HLA-Abs development in patients with low immunological risk&#44; and&#44; more specifically&#44; in patients who do not have HLA-Abs before transplantation&#46; On the contrary&#44; in patients with preformed HLA-Abs&#44; the frequency of new HLA-Abs after steroid withdrawal increased &#40;66&#46;66&#37;&#41; as compared with non-withdrawal group &#40;53&#46;02&#37;&#59; <span class="elsevierStyleItalic">p</span> 0&#46;058&#41;&#46; Although there is no statistically significant difference&#44; a higher tendency is observed in the group of steroid withdrawal&#44; but further study is needed to confirm this point&#46; This is in agreement with previous results from our group in kidney recipients converted from CNI therapy to mTORi therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">7</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">The primary goal of the study was to observe the development of HLA-Abs after steroid withdrawal&#44; not to assess the effect on rejection or graft survival&#46; However&#44; we have analyzed graft survival&#44; detecting worse survival in those with anti-HLA antibodies&#46; We have found no differences between the Group I and II&#46; In the study period&#44; only two patients in group I &#40;1&#46;5&#37;&#41; had a acute cellular rejection after steroid withdrawal&#46; There are well-designed studies addressing this point&#46; In a meta-analysis&#44; Knight et al&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">13</span></a> observed that the acute rejection rate was slightly higher in the group of steroid withdrawal&#44; but most of it of low-grade &#40;class I-Banff classification&#41;&#46; This group also showed a tendency to increase the rate of graft loss censored death&#46; This trend disappears when all graft losses are included&#44; including death with a functioning graft&#46; Such data probably reflect the benefit on patient survival by removing the steroids to reduce cardiovascular risk&#46; The studies included in the meta-analysis presented different moments of withdrawal&#44; from the first day after transplantation up to 24 months after transplantation&#46; In contrast&#44; Opelz et al&#46;&#44; <a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">14</span></a> in a prospective study following 7 years after transplantation&#44; compared a group with steroid withdrawal not earlier than 6 months after transplantation &#40;1100 patients&#41;&#44; and a control group with steroids maintenance &#40;3045 patients&#41;&#46; They observed benefits in the group that had undergone steroid withdrawal in terms of graft survival&#44; patient survival&#44; graft survival censoring death&#44; and improvement in cardiovascular risk factors&#46; They detected no difference in the rate of acute rejection or dysfunction renal in both groups&#44; unlike other studies &#40;with fewer patients&#41; in which the steroid withdrawal was earlier and more acute rejection rate&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Currently&#44; there is no universal steroid withdrawal protocol&#46; In accordance with the study of Opelz et al&#46;&#44; it seems safe enough to remove steroids after 6&#8211;7 months of transplantation&#44; as we followed in our protocol&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">The present study has a number of limitations&#46; First of all&#44; it is an observational study&#46; Although the steroid withdrawal protocol at 7 months after transplantation in patients with low immunological risk was established in 2003&#44; it was not universally applied to all patients&#46; Nonetheless&#44; between 1998 and 2003&#44; some patients had a steroid withdrawal at 7 months at our centre&#46; This has allowed us to have a time-matched group in steroids maintenance&#46; The withdrawal protocol was followed by patients without acute rejection &#8805; Ib of Banff classification&#44; however a small percentage of patients &#40;5&#46;3&#37;&#41; with such rejection grades were removed from steroids at 7 months&#44; only one of them developed DSA&#44; but he had preformed antibodies&#44; and the remaining patients did not develop antibodies&#46; In the group with steroids maintenance&#44; the frequency of patients with acute cellular rejection &#8805; Ib was higher &#40;11&#46;5&#37;&#41;&#44; and this is one reason why steroids were kept&#46; None of these patients developed antibodies at two years&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">We also observed that patients from the steroids withdrawal group were older&#46; It is another limitation of a retrospective study difficult to avoid since patients were follow-up by different nephrologist and some of them decided not to withdraw steroids in younger patients because of the risk of an immunological event and good cardiovascular profile&#46; In older patients&#44; who already had impaired fasting glucose&#44; worse control of blood pressure&#44; dyslipidemia&#44; osteoporosis&#44; etc&#46;&#44; the decision of steroids withdrawal was easier to take&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">It can be argued that transplants were performed predominantly before 2003 in the group II&#46; We have included all transplant patients who met the rigorous inclusion criteria &#40;especially the maintenance tacrolimus and MMF during the two years of study&#41; of our centre from 1998 to 2011&#46; The protocol steroid withdrawal began in our hospital in 2003&#44; however&#44; it was not applied universally to all patients&#44; for several reasons&#58; acute cellular rejection &#8805; IB before 7 months and the presence of several physicians in kidney transplant consultation &#40;refer to the discussion in the previous paragraph&#41;&#46; As this group was not broad enough for a non-steroid withdrawal&#44; we extended the study until 1998&#46; During that period&#44; there were patients who had been withdrawn from steroids before 7 months of treatment&#46; This allowed us to have a group of maintenance steroids comparable in time&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Another limitation is the limited sample size&#44; which does not allow reach statistically significant differences&#46; Larger studies with more statistical power are needed to confirm the results&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">The inclusion criteria based on the PRA by CDC is another limitation&#46; We detected an increased sensitization level of patients pretransplant by using a more sensitive diagnostic method &#40;Luminex&#41;&#44; with a slight tendency towards a higher percentage in group II&#46; We decided not to discard them from the analysis&#44; and to study the effect in these subgroups&#44; although again there were significant differences&#46; When we remove these highly sensitized patients from the study&#44; we observed that the rate of development of HLA-Abs was similar in both groups&#44; making this an important finding from our study&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">In conclusion&#44; steroids withdrawal can be carried out safely in terms of HLA-Abs production in those recipients without pretransplant antibodies and under treatment with tacrolimus and MMF&#46; The use of new and more sensitive methods to measure HLA-Abs makes possible to better select patients as candidates for steroids withdrawal&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Authors</span><p id="par0155" class="elsevierStylePara elsevierViewall">The authors have participated in the design&#44; conduct or analysis and interpretation of work results&#46; They have reviewed its content and approved the final form of the work&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflicts of interest</span><p id="par0160" class="elsevierStylePara elsevierViewall">The authors declare that they have no potential conflicts of interest related to the contents of this article&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Funding</span><p id="par0165" class="elsevierStylePara elsevierViewall">This work was partially supported by grants of Fondo de Investigaciones Sanitarias-ISCIII &#40;PI1100990 and RD16&#47;0009&#47;0027&#41; and Fundaci&#243;n Marqu&#233;s de Valdecilla-IFIMAV &#40;API 11&#47;24&#41;&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Steroid withdrawal in renal transplantation is desirable to avoid their adverse effects&#46; However&#44; by decreasing the immunosuppression&#44; could lead to an increased risk for the development of HLA-Abs&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objective</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Evaluate the relationship between steroid withdrawal and development of HLA-Abs in renal transplantation&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">We analyzed sera by Luminex from 182 kidney transplants performed from 1998 to 2011&#44; before and two years after transplantation&#46; All the patients had a pretransplant PRA &#40;panel reactive of antibodies&#41; &#60;20&#37; by complement-dependent cytotoxicity &#40;CDC&#41; and maintenance immunosuppression with tacrolimus and mycophenolate mofetil &#40;MMF&#41;&#46; We compared a group of steroid withdrawal at 7 months &#40;group-I&#59; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>130&#41; and another control with non-withdrawal &#40;group-II&#59; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>52&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">22 patients &#40;16&#46;9&#37;&#41; in group-I and 11 patients in group-II &#40;21&#46;1&#37;&#41; had HLA-Abs after two years &#40;pNS&#41;&#46; Despite excluding patients with PRA &#62;20&#37;&#44; we detected HLA-Abs pretransplant by Luminex in 11&#46;5&#37; of patients in both groups&#44; of which&#44; 66&#46;6&#37;&#44; versus 53&#37; &#40;<span class="elsevierStyleItalic">p</span> 0&#46;058&#41;&#44; developed new specificities&#44; with a similar percentage of donor specific antibodies &#40;DSA&#41; in both groups &#40;33&#46;33&#37; vs 36&#46;36&#37;&#41;&#44; pNS&#46; In the subgroup without pretransplant HLA-Abs &#40;group-I&#59; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>115&#44; group-II&#59; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>45&#41;&#44; 6&#46;08&#37; developed de novo HLA-Abs&#44; being DSA 3&#46;4&#37; &#40;Group-I&#41; versus 7&#46;69&#37; in group II with 3&#46;84&#37; DSA &#40;pNS&#41;&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Steroid withdrawal at 7 months of renal transplantation does not entail a higher risk in terms of HLA-Abs development in patients without pretransplant HLA-Abs and treatment with tacrolimus and MMF&#44; although larger studies are needed to confirm these findings&#46;</p></span>"
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introducci&#243;n</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">La retirada de esteroides en el trasplante renal es deseable por sus efectos adversos&#44; sin embargo&#44; al disminuir la inmunosupresi&#243;n podr&#237;a conllevar un riesgo superior para el desarrollo de Ac-anti-HLA&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivo</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Evaluar la relaci&#243;n entre la retirada de esteroides y el desarrollo de Ac-anti-HLA en el trasplante renal&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se evaluaron los sueros por Luminex de 182 trasplantados renales desde 1998 a 2011&#44; antes y a los 2 a&#241;os del trasplante&#46; Todos ten&#237;an un panel reactivo frente a anticuerpos &#40;PRA&#41;<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>20&#37; pretrasplante por citotoxicidad dependiente de complemento y mantuvieron la inmunosupresi&#243;n con tacrolim&#250;s y micofenolato mofetilo &#40;MMF&#41;&#46; Comparamos un grupo de retirada de esteroides a los 7 meses &#40;grupo <span class="elsevierStyleSmallCaps">i</span>&#59; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>130&#41; y otro de no retirada &#40;grupo <span class="elsevierStyleSmallCaps">ii</span>&#59; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>52&#41;&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">22 pacientes &#40;16&#44;9&#37;&#41; en el grupo <span class="elsevierStyleSmallCaps">i</span> y 11 pacientes en el grupo <span class="elsevierStyleSmallCaps">ii</span> &#40;21&#44;1&#37;&#41; presentaban Ac-anti-HLA a los 2 a&#241;os &#40;pNS&#41;&#46; A pesar de excluir a los pacientes con PRA<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>20&#37;&#44; detectamos Ac-anti-HLA pretrasplante por Luminex en el 11&#44;5&#37; de los pacientes en ambos grupos&#44; de los cuale&#44; desarrollaron nuevas especificidades el 66&#44;6&#37; del grupo <span class="elsevierStyleSmallCaps">i</span> y el 53&#37; en el grupo <span class="elsevierStyleSmallCaps">ii</span> &#40;p 0&#44;058&#41;&#44; con un similar porcentaje de anticuerpos donante espec&#237;ficos &#40;DSA&#41; &#40;33&#44;3&#37; vs&#46; 36&#44;36&#37;&#41;&#44; pNS&#46; En el subgrupo sin Ac-anti-HLA pretrasplante &#40;grupo <span class="elsevierStyleSmallCaps">i</span>&#59; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>115&#59; grupo <span class="elsevierStyleSmallCaps">ii</span>&#59; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>45&#41;&#44; el 6&#44;08&#37; desarrollaron Ac-anti-HLA de novo&#44; siendo DSA el 3&#44;4&#37; &#40;grupo-I&#41; vs&#46; 7&#44;69&#37; con DSA en el 3&#44;84&#37; &#40;grupo-II&#41;&#44; pNS&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">La retirada de esteroides a los 7 meses del trasplante renal no conlleva un riesgo superior en t&#233;rminos de desarrollo de Ac-anti-HLA en aquellos pacientes sin anticuerpos pretrasplante y en tratamiento con tacrolim&#250;s y MMF&#44; aunque se requieren estudios m&#225;s amplios para confirmar estos hallazgos&#46;</p></span>"
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          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Comparison of graft survival in both groups&#46; Group I&#58; steroids withdrawal&#44; Group II&#58; steroids maintenance&#46; Log rank&#58; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;432&#46;</p>"
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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Comparison of graft survival between patients who had HLA-Abs at two years of transplantation &#40;Group B&#41; who did not have HLA-abs at two years&#46; Log Rank&#58; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Group I &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>130&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Group II<br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>52&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age &#40;years<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">53&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">45&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;0&#46;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gender &#40;&#37; male&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">70&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">73&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dyalisis time &#40;months&#58; median&#44; range&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13&#46;17<br>&#40;9&#46;3&#8211;26&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17&#46;16<br>&#40;9&#46;6&#8211;28&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HLA mismatches<br>4&#8211;6 &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">65&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">54&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PRA pre-Tx &#40;&#60;10&#37;&#47;&#8805;10&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">128&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">56&#47;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Retrasplant&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">28 &#40;21&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13 &#40;25&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cold ischaemia time &#40;hours<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Transplantion before 2003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4 &#40;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">32 &#40;61&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;0&#46;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Induction with thymoglobulin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Induction with basiliximab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30 &#40;23&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7 &#40;13&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Donor type &#40;deceased&#47;living&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">125&#47;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">51&#47;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Acute rejection<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>7 months after transplantation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15 &#40;11&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8 &#40;15&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Acute cellular rejection<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>Ib &#40;&#60;7 months&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7 &#40;5&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6 &#40;11&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Acute rejection &#62;7 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 &#40;1&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Acute cellular rejection<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>Ib &#40;&#62;7 months&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Acute antibody-mediated rejection<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>24 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Case&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Class-I specificities<br>pre-Tx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Class-I specificities at two years after Tx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Class-II specificities pre-Tx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Class-II specificities at two years after Tx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">DSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">MFI<br>DSA post-Tx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head  " colspan="7" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Group I</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NNDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DSA &#40;DR7&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DR7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4080&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NNDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DSA &#40;DR52&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>NNDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DR52&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9836&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NNDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DSA &#40;DQ4&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>NNDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DQ4 &#40;associated to DR8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4887&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DSA &#40;DR51&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>NNDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DR51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8270&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DSA &#40;DR7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DR7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3518&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DSA &#40;B44&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">B44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3782&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA<br>Cw6&#44; Cw15<br>Cw17&#44; Cw18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DSA &#40;DR53&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a><br>DR53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2724&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DSA &#40;DR15&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>NNDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DR15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&#44;989&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DSA &#40;DR53&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>NNDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DR 53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4080&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA<br>Cw1&#44; Cw2<br>Cw4&#44; Cw5<br>Cw6&#44; Cw7<br>Cw8&#44; Cw9<br>Cw10&#44; Cw12<br>Cw14&#44; Cw15<br>Cw16&#44; Cw17<br>Cw18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NNDSA<br>Cw15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NNDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cw 15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DP14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NNDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NNDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1476018.png"
              ]
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            1 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " colspan="7" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Group II</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DSA &#40;DR53&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>NNDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DR53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&#44;371&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DSA &#40;DR8&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>NNDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DR8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2368&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DSA &#40;A2&#44; A29&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">A2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3567&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">A29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2497&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DSA &#40;DR4&#41; <span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>NNDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DR4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4613&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NNDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA<br>DP1&#44; DP20&#44; DP23&#44; DPA1&#42;02&#58;01<br>DPA1&#42;04&#58;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DP13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cw4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                0 => "xTab1476016.png"
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          "notaPie" => array:2 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">NA&#58; not available due to lack of C-locus typing&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">NA&#58; not available due to lack of DP-locus typing&#46;</p>"
            ]
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        "descripcion" => array:1 [
          "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">List of specificities HLA-Abs detected pretransplant and posttransplant&#46; DSA with the MFI value&#46;</p>"
        ]
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        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Table "
            "rol" => "short"
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          "leyenda" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">NN&#58; not new specificities&#59; NDSA&#58; not donor specific antibodies&#59; DSA&#58; donor specific antibodies&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Group I<br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>130&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Group II<br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>52&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HLA Abs pre-Tx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15 &#40;11&#46;53&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6 &#40;11&#46;53&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">NN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5 &#40;33&#46;33&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;33&#46;33&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5 &#40;33&#46;33&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;16&#46;66&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">DSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5 &#40;33&#46;33&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3 &#40;36&#46;36&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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      "titulo" => "References"
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Original article
Intermediate steroid withdrawal after renal transplantation and anti-HLA antibodies (HLA-Abs) development
Retirada intermedia de esteroides después del trasplante renal y desarrollo de anticuerpos anti-HLA (Ac-antiHLA)
Elena Monfáa,
Autor para correspondencia
elenamonfa@gmail.com

Corresponding author.
, David San Segundob,d, Juan Carlos Ruiz San Millána, Judith Sanabriac, Zoila Albinesa, Emilio Rodrigoa, Iñigo Romónd, Esther Asensiob,d, Manuel Ariasa, Marcos López-Hoyosb,d
a Nephrology Department, Hospital Universitario Marqués de Valdecilla-IDIVAL, Santander, Spain
b Immunology Department, Hospital Universitario Marqués de Valdecilla-IDIVAL, Santander, Spain
c Pharmacology Department, Hospital Universitario Marqués de Valdecilla-IDIVAL, Santander, Spain
d Histocompatibility Testing Laboratory, Hospital Universitario Marqués de Valdecilla, Santander, Spain
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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Comparison of graft survival between patients who had HLA-Abs at two years of transplantation &#40;Group B&#41; who did not have HLA-abs at two years&#46; Log Rank&#58; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The detection of antibodies against the HLA system &#40;HLA-Abs&#41; in transplantation has been linked to the development of acute and chronic antibody mediated rejection &#40;ABMR&#41;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a> in clinical and subclinical forms of presentation&#44; and remains as a major cause of graft losses&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">2</span></a> Monitoring HLA-Abs has become a routine practice in the clinical follow up of renal transplant recipients<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">3</span></a> that helps to indicate a graft biopsy and early treatment&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The development of de novo HLA-Abs is usually associated with modifications in the immunosuppressive treatment&#46; In clinical practice&#44; the modulation of the immunosuppressive regimen is common in order to avoid the long-term adverse effects&#46; The calcineurin inhibitors &#40;CNI&#41; withdrawal or conversion to mTOR-inhibitor is currently performed to reduce nephrotoxicity or risk of malignancy&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">4&#44;5</span></a> These changes in immunosuppression are risk of development of new HLA-Abs and consequently ABMR&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">6&#44;7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The steroids withdrawal is also desirable to avoid their adverse effects on long-term treatment&#44; but its relationship with the development of new HLA-Abs is not yet well established&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">One of the most important adverse effects of steroids is increased cardiovascular risk&#46; The steroid maintenance has been linked to the onset of diabetes mellitus&#44; dyslipidemia&#44; hypertension and obesity&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">8&#44;9</span></a> In a study involving 68&#44;781 patients who received prednisone versus 82&#44;200 patients who did not&#44; it was observed that the patients who received doses of prednisone &#8805;7&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;day had a relative risk of 2&#46;5 for cardiovascular events&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">10</span></a> In addition&#44; the rate of death with a functioning graft is high &#40;40&#37;&#41; being cardiovascular events the most frequent cause&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">11</span></a> Therefore&#44; the maintenance of steroids could be a modifiable cause of death with a functioning graft&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Currently&#44; there are potent immunosuppressants in maintenance therapy &#40;Tacrolimus and Mycophenolic mofetil-MMF&#41; and the steroids withdrawal seems plausible&#44; at least in those patients with low immunological risk&#46; Steroids withdrawal has risk of acute rejection and higher slope of glomerular filtration rate &#40;GFR&#41; loss in the long term&#46; We hypothesize that steroids elimination can contribute to production of donor specific antibodies &#40;DSA&#41;&#46; So&#44; the aim of our study is to assess the relationship between steroid withdrawal and development of HLA-Abs after renal transplantation&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Material and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Patients</span><p id="par0030" class="elsevierStylePara elsevierViewall">We studied 652 kidney transplant recipients&#44; performed in University Hospital Marqu&#233;s de Valdecilla&#44; Santander &#40;Spain&#41; from January 1998 to December 2011 who met the following criteria&#58; graft survival of at least two years and maintenance of immunosuppression with tacrolimus and MMF during the first two years after transplantation&#46; We excluded of the study&#58; combined transplants&#59; retransplants which lost the first transplant for rejection&#59; panel reactive of antibodies &#40;PRA&#41; pretransplant &#62;20&#37; by complement-dependent cytotoxicity &#40;CDC&#41;&#44; acute antibody-mediated rejection &#40;ABMR&#41; during the 7 months after transplantation&#46; Finally&#44; 182 kidney transplant recipients fulfilled the inclusion criteria and were included in the study&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The patient data were obtained from the prospectively maintained database of renal transplant patients at our centre&#46; The demographic&#44; immunologic and clinical parameters are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; Patients were classified into two groups according to steroid withdrawal&#58; Group-I&#58; removal of steroids at 7 months posttransplant &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>130&#41; and Group-II&#58; steroids maintenance during the first two years after transplantation &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>52&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">Both groups were comparable in terms of gender&#44; time on dialysis&#44; retransplants&#44; cold ischaemia time&#44; HLA mismatches&#44; pretransplant sensitization &#40;tested by CDC&#41;&#44; induction therapy with thymoglobulin or basiliximab&#44; and acute rejection during the 7 months after transplantation&#46; The Group II patients were significantly younger and predominate transplants before 2003&#44; as the only statistically significant differences&#46; The mean study follow-up was two years after transplantation&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Steroid withdrawal protocol</span><p id="par0045" class="elsevierStylePara elsevierViewall">In 2003&#44; we started a protocol with steroid withdrawal up to 7 months after kidney transplantation in patients treated with tacrolimus and MMF&#44; and excluding those patients with high immunological risk &#40;acute ABMR&#59; acute cellular rejection with a degree<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>Ib of the Banff classification in the 7 months after transplantation&#44; pretransplant PRA<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>20&#37; or rejection with graft loss in prior transplants&#41;&#46; However&#44; even before 2003&#44; in some patients&#44; steroids were withdrawn at 7 months with the same criteria&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">An earlier withdrawal was not performed at our centre because we do not use induction thymoglobuline routinely&#44; and decided to make a slow pattern of steroids that ended at 7 months&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The prednisone dose reduction consisted in gradually decreasing the dose until the complete withdrawal up to 7 months after transplantation&#58; 15<span class="elsevierStyleHsp" style=""></span>mg&#47;d at 15 days&#59; 10<span class="elsevierStyleHsp" style=""></span>mg&#47;d a day at one month&#59; 7&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;d at two months&#59; 5<span class="elsevierStyleHsp" style=""></span>mg&#47;d at three months&#59; 5<span class="elsevierStyleHsp" style=""></span>mg&#47;d and 2&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;d alternating at four months&#59; 2&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;d at five months&#59; 2&#46;5<span class="elsevierStyleHsp" style=""></span>mg every other day at six months until complete withdrawal at seven months&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Serum samples selection and sera analysis</span><p id="par0060" class="elsevierStylePara elsevierViewall">Serum samples of all transplanted patients were routinely collected and stored at &#8722;80<span class="elsevierStyleHsp" style=""></span>&#176;C&#46; Frozen serum samples were selected to investigate the presence of HLA-Abs&#46; For every patient&#44; two samples were selected&#44; one immediately before transplantation and another one two years after transplantation&#46; The sera were analyzed by LABScreen&#174;Mixed &#40;One Lambda Inc&#46;&#44; Canoga Park&#44; CA&#44; USA&#41; for screening antibodies and LABScreen&#174;Single antiHLA Antigen &#40;One Lambda&#41; class-I and&#47;or class-II if were positive in the screening&#46; A total of 372 serum samples were analyzed&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">A mean fluorescence intensity &#40;MFI&#41; value greater than 1500 was considered positive for a particular HLA specificity&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Statistical methods</span><p id="par0070" class="elsevierStylePara elsevierViewall">Quantitative variables were compared using the <span class="elsevierStyleItalic">t</span>-Student&#39;s test&#46; The percentages were obtained with the chi-square test&#46; Differences were considered significant when <span class="elsevierStyleItalic">p</span>-value was below 0&#46;05&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results</span><p id="par0075" class="elsevierStylePara elsevierViewall">Twenty-two patients &#40;16&#46;92&#37;&#41; in group I and eleven patients &#40;21&#46;15&#37;&#41;&#44; in Group II &#40;pNS&#41; presented serum HLA-Abs at two years after transplantation &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">When pretransplant sera were analyzed by Luminex a total of fifteen patients &#40;11&#46;53&#37;&#41; in steroid withdrawal group&#44; and six patients &#40;11&#46;53&#37;&#41; in the group of steroid maintenance presented HLA-Abs prior kidney transplantation&#44; despite the exclusion criteria of PRA<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>20&#37; by CDC&#46; Of these patients&#44; ten developed new specificities after two years &#40;66&#46;66&#37;&#41; from the group I&#44; versus four patients &#40;53&#46;02&#37;&#41; from the group II &#40;<span class="elsevierStyleItalic">p</span> 0&#46;058&#41;&#44; with a similar percentage of DSA &#40;33&#46;33&#37; in group I vs 36&#46;36&#37; in group II&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">Within the patients without HLA-Abs before kidney transplantation &#40;group I-<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>115&#59; group II-<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>45&#41;&#44; seven patients in steroid withdrawal group &#40;6&#46;08&#37;&#41; developed de novo HLA-Abs&#44; four of them being DSA &#40;3&#46;47&#37;&#41; whereas four patients in the group II &#40;7&#46;69&#37;&#41; developed de novo HLA-Abs and two of them were DSA &#40;3&#46;84&#37;&#41;&#59; pNS &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46; Therefore&#44; in the subgroup without preformed antibodies&#44; there are not differences in the development of antibodies in both groups &#40;6&#46;08&#37; vs 7&#46;69&#37;&#44; pNS&#41;&#44; although steroid withdrawal &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">Only two patients &#40;1&#46;5&#37;&#41; in group I had acute cellular rejection after steroid withdrawal&#44; with grades Ia and Ib of Banff classification&#46; The last one had already pretransplant HLA-Abs&#44; and developing a DSA &#40;DQ4&#41; at two years&#46; The other did not develop HLA-Abs&#46; None of recipients in both groups had ABMR during the study period&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">In terms of graft survival&#44; no statistically significant differences in both groups &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41; are appreciated&#44; however those patients with HLA-Abs at two years after transplantation have worse survival &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a> and <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>&#41;&#46; The influence of HLA Abs is confirmed in graft survival&#44; after multivariate analysis &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001 and HR 2&#46;758&#44; 95&#37; CI 1597&#8211;4764&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0025"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discussion</span><p id="par0100" class="elsevierStylePara elsevierViewall">The minimization of immunosuppression could increase the risk of HLA-Abs development as previously demonstrated in CNI conversion to imTOR&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">6&#44;7</span></a> Steroids withdrawal are not been studied in relation to the development of DSA in organ transplantation&#46; The huge advantages of steroids elimination in relation to metabolic and cardiovascular adverse events may not be sufficient if a significant immunological risk is demonstrated&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">There is only one study that analyzes the production of HLA-Abs in kidney transplants in adults&#44; after early steroid withdrawal &#40;7 days post-transplant&#41;&#46; They concluded that steroid withdrawal at 7 days posttransplant was not at higher risk for developing HLA antibodies&#44; but all patients have received induction with thymoglobuline&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">12</span></a> Our study is the first to assess the relationship between intermediate steroid withdrawal and the detection of serum HLA-Abs in renal transplants with standard immunosuppression &#40;tacrolimus and MMF&#41;&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Our data suggest that steroid withdrawal up to 7 months after transplantation does not imply a higher risk of HLA-Abs development in patients with low immunological risk&#44; and&#44; more specifically&#44; in patients who do not have HLA-Abs before transplantation&#46; On the contrary&#44; in patients with preformed HLA-Abs&#44; the frequency of new HLA-Abs after steroid withdrawal increased &#40;66&#46;66&#37;&#41; as compared with non-withdrawal group &#40;53&#46;02&#37;&#59; <span class="elsevierStyleItalic">p</span> 0&#46;058&#41;&#46; Although there is no statistically significant difference&#44; a higher tendency is observed in the group of steroid withdrawal&#44; but further study is needed to confirm this point&#46; This is in agreement with previous results from our group in kidney recipients converted from CNI therapy to mTORi therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">7</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">The primary goal of the study was to observe the development of HLA-Abs after steroid withdrawal&#44; not to assess the effect on rejection or graft survival&#46; However&#44; we have analyzed graft survival&#44; detecting worse survival in those with anti-HLA antibodies&#46; We have found no differences between the Group I and II&#46; In the study period&#44; only two patients in group I &#40;1&#46;5&#37;&#41; had a acute cellular rejection after steroid withdrawal&#46; There are well-designed studies addressing this point&#46; In a meta-analysis&#44; Knight et al&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">13</span></a> observed that the acute rejection rate was slightly higher in the group of steroid withdrawal&#44; but most of it of low-grade &#40;class I-Banff classification&#41;&#46; This group also showed a tendency to increase the rate of graft loss censored death&#46; This trend disappears when all graft losses are included&#44; including death with a functioning graft&#46; Such data probably reflect the benefit on patient survival by removing the steroids to reduce cardiovascular risk&#46; The studies included in the meta-analysis presented different moments of withdrawal&#44; from the first day after transplantation up to 24 months after transplantation&#46; In contrast&#44; Opelz et al&#46;&#44; <a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">14</span></a> in a prospective study following 7 years after transplantation&#44; compared a group with steroid withdrawal not earlier than 6 months after transplantation &#40;1100 patients&#41;&#44; and a control group with steroids maintenance &#40;3045 patients&#41;&#46; They observed benefits in the group that had undergone steroid withdrawal in terms of graft survival&#44; patient survival&#44; graft survival censoring death&#44; and improvement in cardiovascular risk factors&#46; They detected no difference in the rate of acute rejection or dysfunction renal in both groups&#44; unlike other studies &#40;with fewer patients&#41; in which the steroid withdrawal was earlier and more acute rejection rate&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Currently&#44; there is no universal steroid withdrawal protocol&#46; In accordance with the study of Opelz et al&#46;&#44; it seems safe enough to remove steroids after 6&#8211;7 months of transplantation&#44; as we followed in our protocol&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">The present study has a number of limitations&#46; First of all&#44; it is an observational study&#46; Although the steroid withdrawal protocol at 7 months after transplantation in patients with low immunological risk was established in 2003&#44; it was not universally applied to all patients&#46; Nonetheless&#44; between 1998 and 2003&#44; some patients had a steroid withdrawal at 7 months at our centre&#46; This has allowed us to have a time-matched group in steroids maintenance&#46; The withdrawal protocol was followed by patients without acute rejection &#8805; Ib of Banff classification&#44; however a small percentage of patients &#40;5&#46;3&#37;&#41; with such rejection grades were removed from steroids at 7 months&#44; only one of them developed DSA&#44; but he had preformed antibodies&#44; and the remaining patients did not develop antibodies&#46; In the group with steroids maintenance&#44; the frequency of patients with acute cellular rejection &#8805; Ib was higher &#40;11&#46;5&#37;&#41;&#44; and this is one reason why steroids were kept&#46; None of these patients developed antibodies at two years&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">We also observed that patients from the steroids withdrawal group were older&#46; It is another limitation of a retrospective study difficult to avoid since patients were follow-up by different nephrologist and some of them decided not to withdraw steroids in younger patients because of the risk of an immunological event and good cardiovascular profile&#46; In older patients&#44; who already had impaired fasting glucose&#44; worse control of blood pressure&#44; dyslipidemia&#44; osteoporosis&#44; etc&#46;&#44; the decision of steroids withdrawal was easier to take&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">It can be argued that transplants were performed predominantly before 2003 in the group II&#46; We have included all transplant patients who met the rigorous inclusion criteria &#40;especially the maintenance tacrolimus and MMF during the two years of study&#41; of our centre from 1998 to 2011&#46; The protocol steroid withdrawal began in our hospital in 2003&#44; however&#44; it was not applied universally to all patients&#44; for several reasons&#58; acute cellular rejection &#8805; IB before 7 months and the presence of several physicians in kidney transplant consultation &#40;refer to the discussion in the previous paragraph&#41;&#46; As this group was not broad enough for a non-steroid withdrawal&#44; we extended the study until 1998&#46; During that period&#44; there were patients who had been withdrawn from steroids before 7 months of treatment&#46; This allowed us to have a group of maintenance steroids comparable in time&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Another limitation is the limited sample size&#44; which does not allow reach statistically significant differences&#46; Larger studies with more statistical power are needed to confirm the results&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">The inclusion criteria based on the PRA by CDC is another limitation&#46; We detected an increased sensitization level of patients pretransplant by using a more sensitive diagnostic method &#40;Luminex&#41;&#44; with a slight tendency towards a higher percentage in group II&#46; We decided not to discard them from the analysis&#44; and to study the effect in these subgroups&#44; although again there were significant differences&#46; When we remove these highly sensitized patients from the study&#44; we observed that the rate of development of HLA-Abs was similar in both groups&#44; making this an important finding from our study&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">In conclusion&#44; steroids withdrawal can be carried out safely in terms of HLA-Abs production in those recipients without pretransplant antibodies and under treatment with tacrolimus and MMF&#46; The use of new and more sensitive methods to measure HLA-Abs makes possible to better select patients as candidates for steroids withdrawal&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Authors</span><p id="par0155" class="elsevierStylePara elsevierViewall">The authors have participated in the design&#44; conduct or analysis and interpretation of work results&#46; They have reviewed its content and approved the final form of the work&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflicts of interest</span><p id="par0160" class="elsevierStylePara elsevierViewall">The authors declare that they have no potential conflicts of interest related to the contents of this article&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Funding</span><p id="par0165" class="elsevierStylePara elsevierViewall">This work was partially supported by grants of Fondo de Investigaciones Sanitarias-ISCIII &#40;PI1100990 and RD16&#47;0009&#47;0027&#41; and Fundaci&#243;n Marqu&#233;s de Valdecilla-IFIMAV &#40;API 11&#47;24&#41;&#46;</p></span></span>"
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        1 => array:2 [
          "identificador" => "xpalclavsec862999"
          "titulo" => "Keywords"
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          "identificador" => "xres874607"
          "titulo" => "Resumen"
          "secciones" => array:5 [
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              "titulo" => "Introducci&#243;n"
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              "titulo" => "Objetivo"
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              "titulo" => "M&#233;todos"
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              "identificador" => "abst0045"
              "titulo" => "Resultados"
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              "identificador" => "abst0050"
              "titulo" => "Conclusiones"
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        3 => array:2 [
          "identificador" => "xpalclavsec862998"
          "titulo" => "Palabras clave"
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        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
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          "identificador" => "sec0010"
          "titulo" => "Material and methods"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Patients"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Steroid withdrawal protocol"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Serum samples selection and sera analysis"
            ]
            3 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Statistical methods"
            ]
          ]
        ]
        6 => array:2 [
          "identificador" => "sec0035"
          "titulo" => "Results"
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        7 => array:2 [
          "identificador" => "sec0040"
          "titulo" => "Discussion"
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          "titulo" => "Authors"
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          "identificador" => "sec0050"
          "titulo" => "Conflicts of interest"
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          "identificador" => "sec0055"
          "titulo" => "Funding"
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        11 => array:1 [
          "titulo" => "References"
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    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2016-07-17"
    "fechaAceptado" => "2017-02-13"
    "PalabrasClave" => array:2 [
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        0 => array:4 [
          "clase" => "keyword"
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          "palabras" => array:5 [
            0 => "Kidney transplantation"
            1 => "Immunosuppression"
            2 => "Withdrawal"
            3 => "Steroids"
            4 => "Anti-HLA-antibodies"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec862998"
          "palabras" => array:5 [
            0 => "Trasplante renal"
            1 => "Inmunosupresi&#243;n"
            2 => "Retirada"
            3 => "Corticoides"
            4 => "Anticuerpos anti-HLA"
          ]
        ]
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    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Steroid withdrawal in renal transplantation is desirable to avoid their adverse effects&#46; However&#44; by decreasing the immunosuppression&#44; could lead to an increased risk for the development of HLA-Abs&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objective</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Evaluate the relationship between steroid withdrawal and development of HLA-Abs in renal transplantation&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">We analyzed sera by Luminex from 182 kidney transplants performed from 1998 to 2011&#44; before and two years after transplantation&#46; All the patients had a pretransplant PRA &#40;panel reactive of antibodies&#41; &#60;20&#37; by complement-dependent cytotoxicity &#40;CDC&#41; and maintenance immunosuppression with tacrolimus and mycophenolate mofetil &#40;MMF&#41;&#46; We compared a group of steroid withdrawal at 7 months &#40;group-I&#59; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>130&#41; and another control with non-withdrawal &#40;group-II&#59; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>52&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">22 patients &#40;16&#46;9&#37;&#41; in group-I and 11 patients in group-II &#40;21&#46;1&#37;&#41; had HLA-Abs after two years &#40;pNS&#41;&#46; Despite excluding patients with PRA &#62;20&#37;&#44; we detected HLA-Abs pretransplant by Luminex in 11&#46;5&#37; of patients in both groups&#44; of which&#44; 66&#46;6&#37;&#44; versus 53&#37; &#40;<span class="elsevierStyleItalic">p</span> 0&#46;058&#41;&#44; developed new specificities&#44; with a similar percentage of donor specific antibodies &#40;DSA&#41; in both groups &#40;33&#46;33&#37; vs 36&#46;36&#37;&#41;&#44; pNS&#46; In the subgroup without pretransplant HLA-Abs &#40;group-I&#59; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>115&#44; group-II&#59; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>45&#41;&#44; 6&#46;08&#37; developed de novo HLA-Abs&#44; being DSA 3&#46;4&#37; &#40;Group-I&#41; versus 7&#46;69&#37; in group II with 3&#46;84&#37; DSA &#40;pNS&#41;&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Steroid withdrawal at 7 months of renal transplantation does not entail a higher risk in terms of HLA-Abs development in patients without pretransplant HLA-Abs and treatment with tacrolimus and MMF&#44; although larger studies are needed to confirm these findings&#46;</p></span>"
        "secciones" => array:5 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Objective"
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          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Methods"
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            "identificador" => "abst0020"
            "titulo" => "Results"
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            "identificador" => "abst0025"
            "titulo" => "Conclusions"
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      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introducci&#243;n</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">La retirada de esteroides en el trasplante renal es deseable por sus efectos adversos&#44; sin embargo&#44; al disminuir la inmunosupresi&#243;n podr&#237;a conllevar un riesgo superior para el desarrollo de Ac-anti-HLA&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivo</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Evaluar la relaci&#243;n entre la retirada de esteroides y el desarrollo de Ac-anti-HLA en el trasplante renal&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se evaluaron los sueros por Luminex de 182 trasplantados renales desde 1998 a 2011&#44; antes y a los 2 a&#241;os del trasplante&#46; Todos ten&#237;an un panel reactivo frente a anticuerpos &#40;PRA&#41;<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>20&#37; pretrasplante por citotoxicidad dependiente de complemento y mantuvieron la inmunosupresi&#243;n con tacrolim&#250;s y micofenolato mofetilo &#40;MMF&#41;&#46; Comparamos un grupo de retirada de esteroides a los 7 meses &#40;grupo <span class="elsevierStyleSmallCaps">i</span>&#59; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>130&#41; y otro de no retirada &#40;grupo <span class="elsevierStyleSmallCaps">ii</span>&#59; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>52&#41;&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">22 pacientes &#40;16&#44;9&#37;&#41; en el grupo <span class="elsevierStyleSmallCaps">i</span> y 11 pacientes en el grupo <span class="elsevierStyleSmallCaps">ii</span> &#40;21&#44;1&#37;&#41; presentaban Ac-anti-HLA a los 2 a&#241;os &#40;pNS&#41;&#46; A pesar de excluir a los pacientes con PRA<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>20&#37;&#44; detectamos Ac-anti-HLA pretrasplante por Luminex en el 11&#44;5&#37; de los pacientes en ambos grupos&#44; de los cuale&#44; desarrollaron nuevas especificidades el 66&#44;6&#37; del grupo <span class="elsevierStyleSmallCaps">i</span> y el 53&#37; en el grupo <span class="elsevierStyleSmallCaps">ii</span> &#40;p 0&#44;058&#41;&#44; con un similar porcentaje de anticuerpos donante espec&#237;ficos &#40;DSA&#41; &#40;33&#44;3&#37; vs&#46; 36&#44;36&#37;&#41;&#44; pNS&#46; En el subgrupo sin Ac-anti-HLA pretrasplante &#40;grupo <span class="elsevierStyleSmallCaps">i</span>&#59; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>115&#59; grupo <span class="elsevierStyleSmallCaps">ii</span>&#59; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>45&#41;&#44; el 6&#44;08&#37; desarrollaron Ac-anti-HLA de novo&#44; siendo DSA el 3&#44;4&#37; &#40;grupo-I&#41; vs&#46; 7&#44;69&#37; con DSA en el 3&#44;84&#37; &#40;grupo-II&#41;&#44; pNS&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">La retirada de esteroides a los 7 meses del trasplante renal no conlleva un riesgo superior en t&#233;rminos de desarrollo de Ac-anti-HLA en aquellos pacientes sin anticuerpos pretrasplante y en tratamiento con tacrolim&#250;s y MMF&#44; aunque se requieren estudios m&#225;s amplios para confirmar estos hallazgos&#46;</p></span>"
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            "titulo" => "Objetivo"
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            "identificador" => "abst0040"
            "titulo" => "M&#233;todos"
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            "titulo" => "Resultados"
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            "titulo" => "Conclusiones"
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Study design and description of patients with pretransplant HLA-Abs and development HLA-Abs at 2 years after kidney transplantation&#46; PRA&#44; panel reactive antibodies&#59; CDC complement-dependent citotoxicity&#59; Tx&#44; transplantation&#59; ABMR&#44; antibody-mediated rejection&#46;</p>"
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          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Comparison of graft survival in both groups&#46; Group I&#58; steroids withdrawal&#44; Group II&#58; steroids maintenance&#46; Log rank&#58; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;432&#46;</p>"
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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Comparison of graft survival between patients who had HLA-Abs at two years of transplantation &#40;Group B&#41; who did not have HLA-abs at two years&#46; Log Rank&#58; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#46;</p>"
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                  <table border="0" frame="\n
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                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Group I &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>130&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Group II<br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>52&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age &#40;years<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">53&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">45&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;6&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gender &#40;&#37; male&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">73&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dyalisis time &#40;months&#58; median&#44; range&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HLA mismatches<br>4&#8211;6 &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">54&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13 &#40;25&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cold ischaemia time &#40;hours<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;6&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Transplantion before 2003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4 &#40;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">32 &#40;61&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;0&#46;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Induction with thymoglobulin&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Induction with basiliximab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30 &#40;23&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7 &#40;13&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Donor type &#40;deceased&#47;living&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">125&#47;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">51&#47;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Acute rejection<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>7 months after transplantation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15 &#40;11&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8 &#40;15&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Acute cellular rejection<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>Ib &#40;&#60;7 months&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7 &#40;5&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6 &#40;11&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Acute rejection &#62;7 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 &#40;1&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Acute cellular rejection<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>Ib &#40;&#62;7 months&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Acute antibody-mediated rejection<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>24 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Demographic&#44; immunologic and clinical parameters of the patients included in the study &#40;Group I&#58; steroid withdrawal&#59; Group II&#58; non steroid withdrawal&#41;&#46;</p>"
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        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
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          "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">DSA&#58; donor specific antibodies&#59; NDSA&#58; not donor specific antibodies&#59; NNDSA&#58; new not donor specific antibodies&#59; NN&#58; not new specificities&#59; MFI&#58; mean fluorescence intensity&#59; Tx&#58; transplantation&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Case&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Class-I specificities<br>pre-Tx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Class-I specificities at two years after Tx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Class-II specificities pre-Tx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Class-II specificities at two years after Tx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">DSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">MFI<br>DSA post-Tx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head  " colspan="7" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Group I</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NNDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DSA &#40;DR7&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DR7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4080&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NNDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DSA &#40;DR52&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>NNDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DR52&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9836&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NNDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DSA &#40;DQ4&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>NNDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DQ4 &#40;associated to DR8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4887&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DSA &#40;DR51&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>NNDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DR51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8270&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DSA &#40;DR7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DR7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3518&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DSA &#40;B44&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">B44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3782&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA<br>Cw6&#44; Cw15<br>Cw17&#44; Cw18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DSA &#40;DR53&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a><br>DR53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2724&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DSA &#40;DR15&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>NNDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DR15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&#44;989&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DSA &#40;DR53&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>NNDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DR 53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4080&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA<br>Cw1&#44; Cw2<br>Cw4&#44; Cw5<br>Cw6&#44; Cw7<br>Cw8&#44; Cw9<br>Cw10&#44; Cw12<br>Cw14&#44; Cw15<br>Cw16&#44; Cw17<br>Cw18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NNDSA<br>Cw15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NNDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cw 15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DP14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NNDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NNDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1476018.png"
              ]
            ]
            1 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " colspan="7" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Group II</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DSA &#40;DR53&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>NNDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DR53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&#44;371&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DSA &#40;DR8&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>NNDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DR8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2368&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DSA &#40;A2&#44; A29&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">A2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3567&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">A29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2497&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DSA &#40;DR4&#41; <span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>NNDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DR4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4613&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NNDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA<br>DP1&#44; DP20&#44; DP23&#44; DPA1&#42;02&#58;01<br>DPA1&#42;04&#58;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">DP13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NDSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cw4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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        "descripcion" => array:1 [
          "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">List of specificities HLA-Abs detected pretransplant and posttransplant&#46; DSA with the MFI value&#46;</p>"
        ]
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      5 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
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          "leyenda" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">NN&#58; not new specificities&#59; NDSA&#58; not donor specific antibodies&#59; DSA&#58; donor specific antibodies&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Group I<br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>130&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6 &#40;11&#46;53&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;33&#46;33&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;16&#46;66&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3 &#40;36&#46;36&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Patients with HLA-Abs pretransplant&#44; and differentiation according to the specificities observed after two years of transplantation&#46;</p>"
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4 &#40;7&#46;69&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;3&#46;84&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">DSA de novo&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;3&#46;84&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Graft survival&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">130&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">86&#46;9&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">68&#46;6&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">86&#46;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">60&#46;7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HLA-Abs positive at two years&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HLA-Abs negative at two years&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">Graft survival according to steroids withdrawal&#47;maintenance and presence of HLA-Abs at two years after transplantation&#46;</p>"
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    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:15 [
            0 => array:3 [
              "identificador" => "bib0080"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:3 [
                  "comentario" => "http&#58;&#47;&#47;www&#46;ncbi&#46;nlm&#46;nih&#46;gov&#47;pubmed&#47;20613523"
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical relevance of circulating donor-specific HLA antibodies"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "F&#46;H&#46; Claas"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/MOT.0b013e32833b9c38"
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Opin Organ Transplant"
                        "fecha" => "2010"
                        "volumen" => "15"
                        "paginaInicial" => "462"
                        "paginaFinal" => "466"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20613523"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0085"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:3 [
                  "comentario" => "http&#58;&#47;&#47;www&#46;ncbi&#46;nlm&#46;nih&#46;gov&#47;pubmed&#47;22081892"
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Understanding the causes of kidney transplant failure&#58; the dominant role of antibody mediated rejection and nonadherence"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:5 [
                            0 => "J&#46; Sellares"
                            1 => "D&#46;G&#46; de Freitas"
                            2 => "M&#46; Mengel"
                            3 => "J&#46; Reeve"
                            4 => "E&#46; Einecke"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1600-6143.2011.03840.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Transplant"
                        "fecha" => "2012"
                        "volumen" => "12"
                        "paginaInicial" => "388"
                        "paginaFinal" => "399"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22081892"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:3 [
                  "comentario" => "http&#58;&#47;&#47;www&#46;ncbi&#46;nlm&#46;nih&#46;gov&#47;pubmed&#47;15280674"
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Consensus opinion from the antibody working group on the diagnosis&#44; reporting&#44; and risk assesment for antibody mediated rejection and desensitization protocols"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:5 [
                            0 => "R&#46;A&#46; Montgomery"
                            1 => "M&#46;A&#46; Hardy"
                            2 => "S&#46;C&#46; Jordan"
                            3 => "L&#46;C&#46; Racusen"
                            4 => "L&#46;E&#46; Ratner"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Transplantation"
                        "fecha" => "2004"
                        "volumen" => "78"
                        "paginaInicial" => "181"
                        "paginaFinal" => "185"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15280674"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0095"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:3 [
                  "comentario" => "http&#58;&#47;&#47;www&#46;ncbi&#46;nlm&#46;nih&#46;gov&#47;pubmed&#47;15548969"
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Early cyclosporine a withdrawal in kidney-transplant recipients receiving sirolimus prevents progression of chronic pathologic allograft lesions"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "J&#46;C&#46; Ruiz"
                            1 => "J&#46;M&#46; Campistol"
                            2 => "J&#46;M&#46; Grinyo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Transplantation"
                        "fecha" => "2004"
                        "volumen" => "78"
                        "paginaInicial" => "1312"
                        "paginaFinal" => "1318"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15548969"
                            "web" => "Medline"
                          ]
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            4 => array:3 [
              "identificador" => "bib0100"
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                0 => array:3 [
                  "comentario" => "http&#58;&#47;&#47;www&#46;ncbi&#46;nlm&#46;nih&#46;gov&#47;pubmed&#47;21792049"
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lower malignancy rates in renal allograft recipients converted to sirolimus-based&#44; calcineurin inhibitor-free immunotherapy&#58; 24-month results from the CONVERT trial"
                      "autores" => array:1 [
                        0 => array:2 [
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