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    "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">INTRODUCTION</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">One of the great challenges in kidney transplant management is acute rejection &#40;AR&#41; but with the new immunosuppression regimen&#44; the frequency of AR has decreased in recent decades&#44; and we have observed a significant long-term improvement in graft and patient survival&#46;<span class="elsevierStyleSup">1&#44;2 </span>In Mexico&#44; graft and patient survival is comparable to that reported in other countries&#46;<span class="elsevierStyleSup">3&#44;4 </span>However&#44; there is still a considerable loss of renal grafts due to patient death with a functional graft &#40;up to 40&#37;&#41;&#44;<span class="elsevierStyleSup">5 </span>in which cardiovascular disease is the main cause of mortality&#46; Unfortunately&#44; corticosteroids &#40;as the basis for post-transplant immunosuppression&#41; have been directly associated as one of the major cardiovascular risk factors&#46;<span class="elsevierStyleSup">6&#44;7</span></p><p class="elsevierStylePara">The prevalence of diabetes mellitus&#44; obesity and metabolic syndrome in the general population is increasing&#44;<span class="elsevierStyleSup">8&#44;9 </span>and the risk of developing them after transplantation with the use of corticosteroids could be higher&#44; thus leading to an increase in morbidity and mortality&#46; In fact&#44; the use of these drugs is associated with <span class="elsevierStyleItalic">de novo</span> diabetes after renal transplantation&#46;<span class="elsevierStyleSup">10 </span>A strategy aimed at reducing these comorbidities is avoiding the use of&#44; or the withdrawal of corticosteroids &#40;whether it be late or early&#41;&#44; after transplantation&#44; whenever the risk of AR and graft survival are not compromised&#59; however&#44; the results in this regard have been controversial&#46;<span class="elsevierStyleSup">11-13</span></p><p class="elsevierStylePara">Our population and probably some others are at greater risk of developing diabetes mellitus and other complications after renal transplantation&#44; and as such&#44; strategies for avoiding or reducing risk factors in this type of patient are necessary&#46; Therefore&#44; the objective of this study was to compare the effect of early steroid withdrawal &#40;ESW&#41; on the estimated glomerular filtration rate &#40;eGFR&#41;&#44; graft survival&#44; frequency of AR and the metabolic profile in a renal transplantation cohort &#40;ESW-C&#41; treated with tacrolimus &#40;TAC&#41; and mycophenolate mofetil &#40;MMF&#41;&#44; in comparison with a control group &#40;C-C&#41; treated with the internationally recommended triple immunosuppression regimen &#40;TAC&#44; MMF and PDN&#41;&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">MATERIAL AND METHOD</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">A retrospective cohort study was carried out on 32 renal graft recipients at the CMNO&#44; IMSS Specialist Hospital in whom corticosteroid treatment was withdrawn&#46; These patients received transplantations between December 2005 and July 2009&#44; and were followed up until July 2010&#46; During the study period&#44; a total of 989 renal transplantations were performed &#40;48 deceased donor&#41;&#44; mostly from related living donors&#46; Most patients selected received transplants from living donors &#40;58&#47;60&#41; and all had a low immunological risk &#40;panel reactive antibody against HLA classes I and II &#60;30&#37;&#41;&#46; The ESW is an intervention that is very infrequently performed in our hospital and the decision to withdraw corticosteroids was taken by the nephrologist in accordance with the patient&#8217;s characteristics and their experience&#46; We included all of the patients for whom corticosteroids were withdrawn during this period &#40;ESW-C&#41;&#59; the C-C consisted of recipients who had the same transplantation time&#44; immunosuppression regime and immunological risk&#46; Patients with a history of using corticosteroids before transplantation&#44; diabetes mellitus&#44; delayed renal graft function &#40;those requiring renal replacement therapy immediately after transplantation&#41; and multiple organ transplantation were excluded&#46;</p><p class="elsevierStylePara">All patients received our hospital&#8217;s standard induction immunosuppression regimen based on&#58; 0&#46;18mg&#47;kg&#47;day TAC &#40;divided into two doses&#41;&#44; 2g&#47;day MMF &#40;divided into two doses&#41;&#44; 500mg intravenous methylprednisolone &#40;MPD&#41; &#40;peri-operatively&#41; and 20mg of basiliximab peri-operatively and four days after transplantation&#46; Oral maintenance therapy was performed with 2g&#47;day MMF and 0&#46;15mg&#47;kg&#47;day TAC&#44; with an adjustment in accordance with serum levels &#40;9-15ng&#47;ml in the first 30 days and 8-10ng&#47;ml during follow-up&#41;&#46;</p><p class="elsevierStylePara">The ESW was carried out as follows&#58; one day before and during transplantation &#40;peri-operatively&#41;&#44; patients received 500mg&#47;day MPD&#44; followed by 250&#44; 125&#44; 60 and 30g&#47;day in days 1&#44; 2&#44; 3 and 4&#44; respectively&#46; The total withdrawal of steroids was carried out five days after transplantation&#46; The C-C received maintenance immunosuppression with prednisone&#44; in accordance with international recommendations&#44; combined with TAC and MMF&#46;</p><p class="elsevierStylePara">The following clinical and biochemical variables were obtained from medical registries in the post-transplantation phase&#58; age&#44; sex&#44; family history of diabetes mellitus&#44; personal history of pregnancy &#40;females&#41;&#44; cause of kidney disease&#44; type of and time on renal replacement therapy&#44; weight&#44; height&#44; blood pressure&#44; glucose&#44; total cholesterol&#44; total cholesterol linked to high-density lipoproteins &#40;HDL&#41; and cholesterol linked to low-density lipoproteins &#40;LDL&#41;&#44; triglycerides&#44; HLA&#44; risk of infection by the cytomegalovirus &#40;CMV&#41;&#44; time of ischaemia and use of antihypertensive drugs and&#47;or statins&#46;</p><p class="elsevierStylePara">All assessments were carried out after 3&#44; 6 and 12 months&#44; and subsequently&#44; each year in the post-transplantation period&#44; and information was collected&#44; such as&#58; time of transplantation&#44; immunosuppressant maintenance dose&#44; episodes of AR&#44; type and dose of anti-rejection therapy &#40;MPD or polyclonal antibodies&#41;&#44; medication &#40;antihypertensive drugs&#44; statins&#44; hypoglycaemic agents&#41;&#46; Risk of CMV infection was classified in accordance with the serological result of the ELISA for CMV &#40;IgG&#41;&#58; high risk&#58; positive donor&#47;negative recipient&#59; intermediate risk&#58; positive donor&#47;positive recipient&#59; low risk&#58; negative donor&#47;negative recipient&#46;<span class="elsevierStyleSup">14&#44;15</span></p><p class="elsevierStylePara">eGFR was calculated using the formula MDRD-4<span class="elsevierStyleSup">16</span> &#40;MDRD &#91;ml&#47;min&#47;1&#46;73m<span class="elsevierStyleSup">2</span>&#93; &#61; 186x &#91;creatinine&#47;88&#46;4&#93;<span class="elsevierStyleSup">-1&#44;154</span> x age<span class="elsevierStyleSup">-0&#44;203</span> x 0&#46;742 if the patient was female&#41;&#46; The results of protocol biopsies were recorded &#40;which have been carried out for ten years in our hospital as a matter of course&#44; 3&#44; 6 and 12 months after transplantation&#41;&#59; furthermore&#44; we recorded indicated biopsy results &#40;whether due to renal dysfunction or proteinuria&#41; and all the biopsies were assessed by the same nephrologist using the Banff histopathological classification&#46;<span class="elsevierStyleSup">17 </span>The study was assessed and approved by the Local Research and Ethics Committee&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">&#160;</span></span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Statistical analysis</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Data are displayed as mean &#177; standard deviation or numbers and percentages&#46; The Student&#8217;s t-test and &#967;<span class="elsevierStyleSup">2</span> tests were used for comparisons between groups&#46; Graft survival was assessed by Kaplan-Meier and the comparisons were carried out using the Log-rank test&#46; The Cox proportional hazards model was used to assess the influence of steroid withdrawal at the start of AR&#46; The statistical analyses were carried out using the SPSS&#228; version 17 software &#40;SPSS&#44; Inc&#46;&#44; Chicago&#44; IL&#41;&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">RESULTS</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The transplantation demographic characteristics are displayed in Table 1&#46; We did not find differences between the groups in terms of the age or gender of the donor and recipient&#44; the type of donor&#44; a history of diabetes&#44; the risk of CMV&#44; the date and type of dialysis or compatibility of the HLA&#46; Two grafts were transplanted from deceased donors in the ESW-C and the rest of the grafts came from living donors&#46; Warm ischaemia was shorter in the ESW-C&#44; while the C-C had a longer follow-up period&#46;</p><p class="elsevierStylePara">The clinical and biochemical comparisons at the start of the study and at follow-up are displayed in Table 2&#46; At the start of the study&#44; ESW-C patients had significantly lower blood pressure&#44; lower total cholesterol and triglycerides and higher HDL concentrations than the controls&#44; although&#44; the percentage of patients who used antihypertensive drugs and statins was not significantly different&#46; At the end of follow-up&#44; patients in the C-C had higher blood pressure&#44; glucose&#44; triglycerides&#44; total cholesterol and LDL and a higher percentage of statin use than those of the ESW-C&#46; At the end of follow-up&#44; only one patient developed PTDM and this patient was in the C-C&#46;</p><p class="elsevierStylePara">Curiously&#44; the percentage of patients who used antihypertensive drugs decreased significantly in the ESW-C from 66&#37; to 13&#37; at the end of the study&#44; which was significantly lower than the percentage of use in the C-C&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">&#160;</span></span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Graft function and acute rejection</span></p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">&#160;</span></span></p><p class="elsevierStylePara">Graft survival &#40;defined as a loss of &#8805;30&#37; of GFR&#41; is displayed in Figure 1A&#46; ESW-C patients had significantly better renal function than the controls &#40;<span class="elsevierStyleItalic">p</span>&#61;<span class="elsevierStyleItalic">&#46;</span>04&#41;&#46; When we compared renal function &#40;measured by serum creatinine or eGFR&#41;&#44; there were no differences between the cohorts in the baseline assessment&#59; however&#44; at the end of follow-up&#44; ESW-C patients had better graft function &#40;Figure 1B and Table 3&#41;&#46; With regard to the histopathological results &#40;&#35; biopsies indicated for each cohort&#41;&#44; there were 9 cases &#40;15&#37;&#41; of AR in the first 3 months and 9 cases &#40;30&#37;&#41; at the end of follow-up &#40;Table 4&#41;&#46; The accumulated incidence of AR was significantly lower &#40;<span class="elsevierStyleItalic">P</span>&#61;<span class="elsevierStyleItalic">&#46;</span>04&#41; in the ESW-C &#40;19&#37;&#41; than in the C-C &#40;43&#37;&#41;&#46; The Cox proportional hazards model was used to assess potential predictors of AR&#44; such as independent variables included in the immunosuppression regimen &#40;ESW 1&#44; control 0&#41;&#44; HLA&#44; age&#44; sex and serum cholesterol&#46; However&#44; none of these variables were significant independent predictors of AR &#40;c<span class="elsevierStyleSup">2 </span>model 2&#46;63&#44; <span class="elsevierStyleItalic">P&#61;</span>&#46;76&#41;&#46;</p><p class="elsevierStylePara">Table 4 displays the histopathological results of the renal biopsies&#46; Nine episodes of AR were found in the protocol biopsies carried out within the first 3 months after transplantation&#59; of the patients in the ESW-C&#44; 3 had borderline AR and 2 had Banff IA AR&#44; while the controls had 2 Banff IA AR&#44; 1 Banff IIA AR and 1 acute humoral rejection&#46; In the biopsies carried out after between 9 and 12 months &#40;whether by protocol or indicated&#41;&#44; of the patients in the ESW-C&#44; 1 had Banff IA AR&#44; while of those in the C-C&#44; 5 had borderline AR and 3 had Banff IA AR&#46; The latter findings were significantly different between cohorts &#40;<span class="elsevierStyleItalic">P</span>&#61;&#46;006&#41;&#46; Three C-C patients had chronic vascular disease of the graft in the biopsies conducted after 1 year of follow-up&#46; Moreover&#44; toxicity due to TAC was found in 23 patients &#40;36 events of toxicity&#41;&#58; 14 patients &#40;61&#37;&#41; of the ESW-C and 9 patients &#40;39&#37;&#41; of the C-C &#40;<span class="elsevierStyleItalic">P</span>&#61;&#46;21&#41;&#46; Of these&#44; 10 patients &#40;4 of the ESW-C&#47;6 of the C-C&#41; were changed to sirolimus and the GFR was not different between these two groups <span class="elsevierStyleBold">&#40;72&#46;31&#177;22&#46;80&#44; 74&#46;37&#177;19&#46;75&#44; <span class="elsevierStyleItalic">p</span>&#61;&#46;82&#41;</span>&#44; and none had AR&#46;</p><p class="elsevierStylePara">Despite the higher frequency of toxicity by TAC &#40;confirmed by biopsy&#41; in the ESW-C&#44; levels of the drug in blood were not significantly different between the cohorts and they were within the therapeutic range in all cases &#40;Table 3&#41;&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Corticosteroids are currently used in most renal transplantation centres around the world&#46; However&#44; there is a growing tendency to avoid their use due to their side effects and the negative impact on graft and patient survival&#44; even at low doses&#46;<span class="elsevierStyleSup">18-20 </span>Results of various studies in which steroids have been withdrawn have been controversial&#44; probably due to the heterogeneity of the different immunosuppression protocol used&#44; based on cyclosporine&#44; TAC&#44; azathioprine&#44; MMF&#44; rapamycin or everolimus&#44;<span class="elsevierStyleSup">12&#44;21 </span>with or without antibodies &#40;monoclonal or polyclonal&#41;&#46;<span class="elsevierStyleSup">13&#44;22-24 </span>In the Latin American population&#44; there are no data available for this intervention&#44; especially with homogeneous immunosuppression regimens based on TAC and MMF&#46; Nowadays&#44; there is a documented higher risk in the development of obesity and diabetes in various populations&#44;<span class="elsevierStyleSup">8&#44;9 </span>which could be exacerbated after renal transplantation &#40;and corticosteroids could be a major risk factor&#41;&#46; In our setting&#44; a higher risk of <span class="elsevierStyleItalic">de novo</span> diabetes after transplantation was associated with corticosteroid use&#59;<span class="elsevierStyleSup">10 </span>medical interventions such as ESW may be beneficial in transplant recipients&#46; Obviously&#44; this intervention must not increase the risk of AR or decrease renal function&#46; Initially&#44; only patients with a low immunological risk and who ideally use potent immunosuppressive drugs would be candidates for steroid withdrawal&#46;</p><p class="elsevierStylePara">We included patients who met these requirements and our results were similar to those of other studies carried out in similar conditions&#46;<span class="elsevierStyleSup">25 </span>One of the main concerns with the withdrawal of corticosteroids was the greater risk of AR&#46; The results of some studies that have reported a high rate<span class="elsevierStyleSup">13 </span>of AR are questionable&#44; since a significant number of them did not perform renal biopsies &#40;gold standard&#41; or even reported the methodology for diagnosing AR&#44; which could explain the results of a higher AR rate&#46; In this study&#44; AR was documented with protocol or indicated biopsies&#44; and as such&#44; both subclinical and clinical rejections were identified&#46; Our results with ESW did not predict the development of AR or the incidence of AR during the first year and this was consistent with that reported by other hospitals&#46;<span class="elsevierStyleSup">26 </span>Most late episodes of AR were documented in biopsies carried out due to an increase in serum creatinine and were more common in C-C &#40;29&#37;&#41; than in ESW-C &#40;3&#37;&#41;&#46; A possible explanation for this result is that the ESW-C had higher toxicity due to TAC documented histopathologically than the C-C&#44; in spite of patients in the ESW-C receiving lower doses of TAC &#40;data not displayed&#41;&#46; From a pharmacological point of view&#44; corticosteroids are cytochrome P450 inducer stimulants &#40;isoenzyme CYA4&#41; responsible for the biotransformation of TAC&#44; and in ESW&#44; this favours greater bioavailability of TAC&#44; which may explain why patients with ESW had greater toxicity due to TAC and a lower rate of AR&#46;<span class="elsevierStyleSup">27&#44;28 </span>In the C-C&#44; the eGFR was lower in comparison with that of the ESW-C&#44; which could be explained by the higher rate of AR observed in this group during follow-up&#46; The withdrawal of steroids could potentially improve the haemodynamic and metabolic profile&#46; Gonz&#225;lez-Molina et al&#46;<span class="elsevierStyleSup">29</span> retrospectively assessed 923 kidney recipients &#40;deceased donor&#41; with steroid withdrawal and found lower blood pressure&#44; total cholesterol and triglycerides&#46; In this study&#44; both groups had an appropriate control of blood pressure and serum lipids&#59; however&#44; ESW-C achieved this control with the use of a lower dose and frequency of drugs and these results were consistent with other studies&#46;<span class="elsevierStyleSup">13 </span>These results have encouraged us to continue this intervention in our population through clinical trials to test these findings&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">CONCLUSION</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">In patients with a low immunological risk&#44; with an immunosuppression regimen based on TAC and MMF&#44; ESW does not change graft survival&#44; renal function or the rate of AR in this cohort&#46; Toxicity due to TAC &#40;confirmed by biopsy&#41; tends to be more common in ESW-C than in the controls and the reason for this merits further research&#46; ESW-C patients had a lower requirement for antihypertensive drugs and hypolipidaemic agents in comparison with the C-C&#44; which suggests a better metabolic profile&#46; Our findings require further clinical trials in homogenous populations in order to avoid controversy with this type of intervention&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Conflicts of interest</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The authors declare that they have no conflicts of interest related to the contents of this article&#46;</p><p class="elsevierStylePara"><a href="grande&#47;12028&#95;16025&#95;56435&#95;en&#95;t110&#46;12028&#95;i&#46;jpg" class="elsevierStyleCrossRefs"><img src="12028_16025_56435_en_t110.12028_i.jpg" alt="Demographic and transplantation characteristics&#46;"></img></a></p><p class="elsevierStylePara">Table 1&#46; Demographic and transplantation characteristics&#46;</p><p class="elsevierStylePara"><a href="grande&#47;12028&#95;16025&#95;56436&#95;en&#95;t210&#46;12028&#95;i2&#46;jpg" class="elsevierStyleCrossRefs"><img src="12028_16025_56436_en_t210.12028_i2.jpg" alt="Clinical and biochemical comparisons between the cohorts at the start and end of follow-up&#46;"></img></a></p><p class="elsevierStylePara">Table 2&#46; Clinical and biochemical comparisons between the cohorts at the start and end of follow-up&#46;</p><p class="elsevierStylePara"><a href="grande&#47;12028&#95;16025&#95;56437&#95;en&#95;t3&#95;10&#46;12028&#95;i4&#46;jpg" class="elsevierStyleCrossRefs"><img src="12028_16025_56437_en_t3_10.12028_i4.jpg" alt="Comparison of renal function between cohorts at the start and end of follow-up&#46;"></img></a></p><p class="elsevierStylePara">Table 3&#46; Comparison of renal function between cohorts at the start and end of follow-up&#46;</p><p class="elsevierStylePara"><a href="grande&#47;12028&#95;16025&#95;56438&#95;en&#95;t4&#95;10&#46;12028&#95;i4&#46;jpg" class="elsevierStyleCrossRefs"><img src="12028_16025_56438_en_t4_10.12028_i4.jpg" alt="Histopathological findings in renal biopsies carried out after 3 or &#38;"></img></a></p><p class="elsevierStylePara">Table 4&#46; Histopathological findings in renal biopsies carried out after 3 or &#38;</p><p class="elsevierStylePara"><a href="grande&#47;12028&#95;16025&#95;56439&#95;en&#95;f1&#95;10&#46;12028&#95;i3&#46;jpg" class="elsevierStyleCrossRefs"><img src="12028_16025_56439_en_f1_10.12028_i3.jpg" alt="Comparison of survival in accordance with the study cohort&#46; B&#46; Comparison of renal function in each cohort&#46;"></img></a></p><p class="elsevierStylePara">Figure 1&#46; Comparison of survival in accordance with the study cohort&#46; B&#46; Comparison of renal function in each cohort&#46;</p>"
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        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Antecedentes&#58; </span>No hay suficiente evidencia sobre la frecuencia de rechazo agudo y la funci&#243;n del injerto en los pacientes con retiro temprano de esteroides &#40;RTE&#41;&#46; El objetivo del presente estudio es comparar el efecto del RTE sobre la tasa de filtrado glomerular &#40;TFG&#41;&#44; la supervivencia&#47;rechazo del injerto en receptores de una cohorte de tratados con tacrolimus&#47;mofetil micofenolato&#44; comparada con un grupo control&#46; <span class="elsevierStyleBold">Material y m&#233;todos&#58;</span> Cohorte retrospectiva en 60 receptores de bajo riesgo inmunol&#243;gico entre diciembre de 2005 y julio de 2010&#46; Cohorte del estudio &#40;C-RTE&#59; N&#160;&#61;&#160;32&#41;&#44; el RTE se hizo el 5&#186; d&#237;a mientras recib&#237;an tacrolimus&#47;mofetil micofenolato&#46; La cohorte control &#40;C-C&#44; N &#61; 28&#41; recibi&#243; prednisona&#47;tacrolimus&#47;mofetil micofenolato&#46; Las variables cl&#237;nicas&#44; bioqu&#237;micas e histol&#243;gicas fueron evaluadas al inicio del estudio&#44; y a los 3&#44; 6 y 12 meses de seguimiento&#46; Se utiliz&#243; Kaplan-Meier y el modelo de riesgos proporcionales de Cox para evaluar la supervivencia&#46; Las comparaciones entre cohortes fueron hechas por la <span class="elsevierStyleItalic">t</span> de Student y <span class="elsevierStyleItalic">c<span class="elsevierStyleSup">2</span></span>&#46; <span class="elsevierStyleBold">Resultados</span><span class="elsevierStyleBold">&#58;</span> Durante el seguimiento&#44; la C-C muestra presi&#243;n sangu&#237;nea significativamente mayor tanto sist&#243;lica &#40;125&#160;&#177;&#160;10 frente a 114&#160;&#177;&#160;8&#41; como diast&#243;lica &#40;81&#160;&#177;&#160;8 frente a 72&#160;&#177;&#160;7&#41;&#44; glucosa s&#233;rica &#40;96&#160;&#177;&#160;13 frente a 86&#160;&#177;&#160;10&#41;&#44; triglic&#233;ridos &#40;177&#160;&#177;&#160;61 frente a 129&#160;&#177;&#160;34&#41;&#44; colesterol total &#40;183&#160;&#177;&#160;43 frente a 148&#160;&#177;&#160;34&#41; y colesterol LDL &#40;100&#160;&#177;&#160;22 frente a 87&#160;&#177;&#160;25&#41;&#46; La C-C present&#243; una mayor proporci&#243;n de uso de antihipertensivos &#40;57 frente a 13&#160;&#37;&#41; y de estatinas &#40;27 frente a 9&#160;&#37;&#41;&#46; La TFGe fue mejor en la C-RTE que en la C-C &#40;85&#44;4&#160;&#177;&#160;20&#44;6 frente a 70&#44;6&#160;&#177;&#160;17&#44;0&#44; <span class="elsevierStyleBold">p</span>&#160;<span class="elsevierStyleBold">&#61;</span>&#160;<span class="elsevierStyleBold">0&#44;004</span>&#41;&#46; La frecuencia de rechazo agudo fue menor en la C-RTE&#46; <span class="elsevierStyleBold">Conclusiones</span><span class="elsevierStyleBold">&#58;</span> La supervivencia del injerto&#44; la TFG&#44; la tasa de rechazo agudo y el perfil metab&#243;lico fueron mejores en la C-RTE que en la C-C&#46;</p>"
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        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Background&#58;</span> Acute rejection and graft function have not been completely clarified in early-steroid-withdrawal &#40;ESW&#41; patients&#46; The objective of this study was to compare the effect of early steroid withdrawal on GFR&#44; graft survival&#47;rejection in recipients in a cohort treated with tacrolimus&#47;mycophenolate mofetil compared to a control cohort&#46; <span class="elsevierStyleBold">Material and method&#58;</span> Retrospective cohort&#44; in 60 low immunological risk recipients between December 2005 and July 2010&#46; Study cohort &#40;ESW-C N&#61;32&#41;&#44; steroid withdrawal was carried out after 5 days&#44; while they were receiving tacrolimus&#47;mycophenolate mofetil&#46; The control cohort &#40;C-C&#44; N&#61;28&#41; received prednisone&#47;tacrolimus&#47;mycophenolate mofetil&#46; Clinical&#44; biochemical and histological variables were assessed at baseline and after 3&#44; 6&#44; and 12 months of follow-up&#46; Kaplan-Meier and the Cox proportional hazards model were used to assess survival&#46; Comparisons between cohorts were carried out by the Student&#8217;s t and <span class="elsevierStyleItalic">c<span class="elsevierStyleSup">2</span></span> tests&#46; <span class="elsevierStyleBold">Results&#58;</span> At follow-up&#44; C-C displayed significantly higher systolic &#40;125&#177;10 <span class="elsevierStyleItalic">vs&#46;</span> 114&#177;8&#41; and diastolic &#40;81&#177;8 <span class="elsevierStyleItalic">vs&#46;</span> 72&#177;7&#41; blood pressure&#44; serum glucose &#40;96&#177;13 vs&#46; 86&#177;10&#41;&#44; triglycerides &#40;177&#177;61 <span class="elsevierStyleItalic">vs&#46;</span> 129&#177;34&#41;&#44; total &#40;183&#177;43 <span class="elsevierStyleItalic">vs&#46;</span><span class="elsevierStyleItalic"> </span>148&#177;34&#41; and LDL-cholesterol &#40;100&#177;22 <span class="elsevierStyleItalic">vs&#46;</span> 87&#177;25&#41;&#46; C-C had a higher proportion of antihypertensive &#40;57 <span class="elsevierStyleItalic">vs&#46;</span> 13&#37;&#41;&#44; and statins &#40;27 <span class="elsevierStyleItalic">vs&#46;</span> 9&#37;&#41; use&#46; eGFR was better in ESW-C than in C-C &#40;85&#46;4&#177;20&#46;6 <span class="elsevierStyleItalic">vs&#46;</span> 70&#46;6&#177;17&#46;0&#44; <span class="elsevierStyleBold"><span class="elsevierStyleItalic">p</span></span><span class="elsevierStyleBold">&#61;&#46;004</span>&#41;&#46; AR frequency was lower in ESW-C&#46; <span class="elsevierStyleBold">Conclusions&#58;</span><span class="elsevierStyleItalic"><span class="elsevierStyleBold"> </span></span>Graft survival&#44; GFR&#44; AR rate and metabolic profile were better in the ESW-C than in C-C&#46;</p>"
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            20 => array:3 [
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                  "referenciaCompleta" => "Montagnino G, Sandrini S, Casciani C, Schena FP, Carmellini M, Civati G, et al. A randomized trial of steroid avoidance in renal transplant patients treated with everolimus and cyclosporine. Transplant Proc 2005;37:788-90. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15848532" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
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                  ]
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            21 => array:3 [
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                  "referenciaCompleta" => "ter Meulen CG, van Riemsdijk I, Hené RJ, Christiaans MH, Borm GF, van Gelder T, et al. Steroid-withdrawal at 3 days after renal transplantation with anti-IL-2 receptor alpha therapy: a prospective, randomized, multicenter study. Am J Transplant 2004;4:803-10. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15084178" target="_blank">[Pubmed]</a>"
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                  "referenciaCompleta" => "Woodle ES, Vincenti F, Lorber MI, Gritsch HA, Hricik D, Washburn K, et al. A multicenter pilot study of early (4-day) steroid cessation in renal transplant recipients under simulect, tacrolimus and sirolimus. Am J Transplant 2005;5:157-66. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15636625" target="_blank">[Pubmed]</a>"
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Early steroid withdrawal in a renal transplant cohort treated with tacrolimus, mycophenolate mofetil and basiliximab
Retiro temprano de esteroides en una cohorte de trasplante renal tratada con tacrolimus, mofetil micofenolato y basiliximab
, Unidad de Investigación Médica en Enfermedades Renalesb, Jorge Andrade-Sierrac, Enrique Rojas-Camposd, Ernesto Cardona-Muñoze, Luis A. Evangelista-Carrillof, Abel Puentes-Camachof, Orlando Lugo-Lópezf, Benjamín Gómezf, Carlos Valdespinof, Ignacio Cerrillosf, Miguel Medina-Pérezf, Basilio Jalomof, Juan J. Nievesf, Mario Sandovalf, Francisco Ramos-Solanof, Francisco Monteón-Ramosf, Alfonso M. Cueto-Manzanod
b Unidad de Investigación en Enfermedades Renales, UMAE, Hospital de Especialidades, Guadalajara, Jalisco, México,
c Unidad de Investigación en Enfermedades Renales. Departamento de Nefrología y Unidad de Trasplante del Hospital de Especialidades, CMNO, IMSS. Departa, México.,
d Unidad de Investigación en Enfermedades Renales,
e Departamento de Fisiología. Centro Universitario de Ciencias de la Salud. Universidad de Guadalajara. Guadalajara, Jalisco. México,
f Departamento de Nefrología y Unidad de Trasplante del Hospital de Especialidades, CMNO, IMSS,
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    "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">INTRODUCTION</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">One of the great challenges in kidney transplant management is acute rejection &#40;AR&#41; but with the new immunosuppression regimen&#44; the frequency of AR has decreased in recent decades&#44; and we have observed a significant long-term improvement in graft and patient survival&#46;<span class="elsevierStyleSup">1&#44;2 </span>In Mexico&#44; graft and patient survival is comparable to that reported in other countries&#46;<span class="elsevierStyleSup">3&#44;4 </span>However&#44; there is still a considerable loss of renal grafts due to patient death with a functional graft &#40;up to 40&#37;&#41;&#44;<span class="elsevierStyleSup">5 </span>in which cardiovascular disease is the main cause of mortality&#46; Unfortunately&#44; corticosteroids &#40;as the basis for post-transplant immunosuppression&#41; have been directly associated as one of the major cardiovascular risk factors&#46;<span class="elsevierStyleSup">6&#44;7</span></p><p class="elsevierStylePara">The prevalence of diabetes mellitus&#44; obesity and metabolic syndrome in the general population is increasing&#44;<span class="elsevierStyleSup">8&#44;9 </span>and the risk of developing them after transplantation with the use of corticosteroids could be higher&#44; thus leading to an increase in morbidity and mortality&#46; In fact&#44; the use of these drugs is associated with <span class="elsevierStyleItalic">de novo</span> diabetes after renal transplantation&#46;<span class="elsevierStyleSup">10 </span>A strategy aimed at reducing these comorbidities is avoiding the use of&#44; or the withdrawal of corticosteroids &#40;whether it be late or early&#41;&#44; after transplantation&#44; whenever the risk of AR and graft survival are not compromised&#59; however&#44; the results in this regard have been controversial&#46;<span class="elsevierStyleSup">11-13</span></p><p class="elsevierStylePara">Our population and probably some others are at greater risk of developing diabetes mellitus and other complications after renal transplantation&#44; and as such&#44; strategies for avoiding or reducing risk factors in this type of patient are necessary&#46; Therefore&#44; the objective of this study was to compare the effect of early steroid withdrawal &#40;ESW&#41; on the estimated glomerular filtration rate &#40;eGFR&#41;&#44; graft survival&#44; frequency of AR and the metabolic profile in a renal transplantation cohort &#40;ESW-C&#41; treated with tacrolimus &#40;TAC&#41; and mycophenolate mofetil &#40;MMF&#41;&#44; in comparison with a control group &#40;C-C&#41; treated with the internationally recommended triple immunosuppression regimen &#40;TAC&#44; MMF and PDN&#41;&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">MATERIAL AND METHOD</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">A retrospective cohort study was carried out on 32 renal graft recipients at the CMNO&#44; IMSS Specialist Hospital in whom corticosteroid treatment was withdrawn&#46; These patients received transplantations between December 2005 and July 2009&#44; and were followed up until July 2010&#46; During the study period&#44; a total of 989 renal transplantations were performed &#40;48 deceased donor&#41;&#44; mostly from related living donors&#46; Most patients selected received transplants from living donors &#40;58&#47;60&#41; and all had a low immunological risk &#40;panel reactive antibody against HLA classes I and II &#60;30&#37;&#41;&#46; The ESW is an intervention that is very infrequently performed in our hospital and the decision to withdraw corticosteroids was taken by the nephrologist in accordance with the patient&#8217;s characteristics and their experience&#46; We included all of the patients for whom corticosteroids were withdrawn during this period &#40;ESW-C&#41;&#59; the C-C consisted of recipients who had the same transplantation time&#44; immunosuppression regime and immunological risk&#46; Patients with a history of using corticosteroids before transplantation&#44; diabetes mellitus&#44; delayed renal graft function &#40;those requiring renal replacement therapy immediately after transplantation&#41; and multiple organ transplantation were excluded&#46;</p><p class="elsevierStylePara">All patients received our hospital&#8217;s standard induction immunosuppression regimen based on&#58; 0&#46;18mg&#47;kg&#47;day TAC &#40;divided into two doses&#41;&#44; 2g&#47;day MMF &#40;divided into two doses&#41;&#44; 500mg intravenous methylprednisolone &#40;MPD&#41; &#40;peri-operatively&#41; and 20mg of basiliximab peri-operatively and four days after transplantation&#46; Oral maintenance therapy was performed with 2g&#47;day MMF and 0&#46;15mg&#47;kg&#47;day TAC&#44; with an adjustment in accordance with serum levels &#40;9-15ng&#47;ml in the first 30 days and 8-10ng&#47;ml during follow-up&#41;&#46;</p><p class="elsevierStylePara">The ESW was carried out as follows&#58; one day before and during transplantation &#40;peri-operatively&#41;&#44; patients received 500mg&#47;day MPD&#44; followed by 250&#44; 125&#44; 60 and 30g&#47;day in days 1&#44; 2&#44; 3 and 4&#44; respectively&#46; The total withdrawal of steroids was carried out five days after transplantation&#46; The C-C received maintenance immunosuppression with prednisone&#44; in accordance with international recommendations&#44; combined with TAC and MMF&#46;</p><p class="elsevierStylePara">The following clinical and biochemical variables were obtained from medical registries in the post-transplantation phase&#58; age&#44; sex&#44; family history of diabetes mellitus&#44; personal history of pregnancy &#40;females&#41;&#44; cause of kidney disease&#44; type of and time on renal replacement therapy&#44; weight&#44; height&#44; blood pressure&#44; glucose&#44; total cholesterol&#44; total cholesterol linked to high-density lipoproteins &#40;HDL&#41; and cholesterol linked to low-density lipoproteins &#40;LDL&#41;&#44; triglycerides&#44; HLA&#44; risk of infection by the cytomegalovirus &#40;CMV&#41;&#44; time of ischaemia and use of antihypertensive drugs and&#47;or statins&#46;</p><p class="elsevierStylePara">All assessments were carried out after 3&#44; 6 and 12 months&#44; and subsequently&#44; each year in the post-transplantation period&#44; and information was collected&#44; such as&#58; time of transplantation&#44; immunosuppressant maintenance dose&#44; episodes of AR&#44; type and dose of anti-rejection therapy &#40;MPD or polyclonal antibodies&#41;&#44; medication &#40;antihypertensive drugs&#44; statins&#44; hypoglycaemic agents&#41;&#46; Risk of CMV infection was classified in accordance with the serological result of the ELISA for CMV &#40;IgG&#41;&#58; high risk&#58; positive donor&#47;negative recipient&#59; intermediate risk&#58; positive donor&#47;positive recipient&#59; low risk&#58; negative donor&#47;negative recipient&#46;<span class="elsevierStyleSup">14&#44;15</span></p><p class="elsevierStylePara">eGFR was calculated using the formula MDRD-4<span class="elsevierStyleSup">16</span> &#40;MDRD &#91;ml&#47;min&#47;1&#46;73m<span class="elsevierStyleSup">2</span>&#93; &#61; 186x &#91;creatinine&#47;88&#46;4&#93;<span class="elsevierStyleSup">-1&#44;154</span> x age<span class="elsevierStyleSup">-0&#44;203</span> x 0&#46;742 if the patient was female&#41;&#46; The results of protocol biopsies were recorded &#40;which have been carried out for ten years in our hospital as a matter of course&#44; 3&#44; 6 and 12 months after transplantation&#41;&#59; furthermore&#44; we recorded indicated biopsy results &#40;whether due to renal dysfunction or proteinuria&#41; and all the biopsies were assessed by the same nephrologist using the Banff histopathological classification&#46;<span class="elsevierStyleSup">17 </span>The study was assessed and approved by the Local Research and Ethics Committee&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">&#160;</span></span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Statistical analysis</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Data are displayed as mean &#177; standard deviation or numbers and percentages&#46; The Student&#8217;s t-test and &#967;<span class="elsevierStyleSup">2</span> tests were used for comparisons between groups&#46; Graft survival was assessed by Kaplan-Meier and the comparisons were carried out using the Log-rank test&#46; The Cox proportional hazards model was used to assess the influence of steroid withdrawal at the start of AR&#46; The statistical analyses were carried out using the SPSS&#228; version 17 software &#40;SPSS&#44; Inc&#46;&#44; Chicago&#44; IL&#41;&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">RESULTS</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The transplantation demographic characteristics are displayed in Table 1&#46; We did not find differences between the groups in terms of the age or gender of the donor and recipient&#44; the type of donor&#44; a history of diabetes&#44; the risk of CMV&#44; the date and type of dialysis or compatibility of the HLA&#46; Two grafts were transplanted from deceased donors in the ESW-C and the rest of the grafts came from living donors&#46; Warm ischaemia was shorter in the ESW-C&#44; while the C-C had a longer follow-up period&#46;</p><p class="elsevierStylePara">The clinical and biochemical comparisons at the start of the study and at follow-up are displayed in Table 2&#46; At the start of the study&#44; ESW-C patients had significantly lower blood pressure&#44; lower total cholesterol and triglycerides and higher HDL concentrations than the controls&#44; although&#44; the percentage of patients who used antihypertensive drugs and statins was not significantly different&#46; At the end of follow-up&#44; patients in the C-C had higher blood pressure&#44; glucose&#44; triglycerides&#44; total cholesterol and LDL and a higher percentage of statin use than those of the ESW-C&#46; At the end of follow-up&#44; only one patient developed PTDM and this patient was in the C-C&#46;</p><p class="elsevierStylePara">Curiously&#44; the percentage of patients who used antihypertensive drugs decreased significantly in the ESW-C from 66&#37; to 13&#37; at the end of the study&#44; which was significantly lower than the percentage of use in the C-C&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">&#160;</span></span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Graft function and acute rejection</span></p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">&#160;</span></span></p><p class="elsevierStylePara">Graft survival &#40;defined as a loss of &#8805;30&#37; of GFR&#41; is displayed in Figure 1A&#46; ESW-C patients had significantly better renal function than the controls &#40;<span class="elsevierStyleItalic">p</span>&#61;<span class="elsevierStyleItalic">&#46;</span>04&#41;&#46; When we compared renal function &#40;measured by serum creatinine or eGFR&#41;&#44; there were no differences between the cohorts in the baseline assessment&#59; however&#44; at the end of follow-up&#44; ESW-C patients had better graft function &#40;Figure 1B and Table 3&#41;&#46; With regard to the histopathological results &#40;&#35; biopsies indicated for each cohort&#41;&#44; there were 9 cases &#40;15&#37;&#41; of AR in the first 3 months and 9 cases &#40;30&#37;&#41; at the end of follow-up &#40;Table 4&#41;&#46; The accumulated incidence of AR was significantly lower &#40;<span class="elsevierStyleItalic">P</span>&#61;<span class="elsevierStyleItalic">&#46;</span>04&#41; in the ESW-C &#40;19&#37;&#41; than in the C-C &#40;43&#37;&#41;&#46; The Cox proportional hazards model was used to assess potential predictors of AR&#44; such as independent variables included in the immunosuppression regimen &#40;ESW 1&#44; control 0&#41;&#44; HLA&#44; age&#44; sex and serum cholesterol&#46; However&#44; none of these variables were significant independent predictors of AR &#40;c<span class="elsevierStyleSup">2 </span>model 2&#46;63&#44; <span class="elsevierStyleItalic">P&#61;</span>&#46;76&#41;&#46;</p><p class="elsevierStylePara">Table 4 displays the histopathological results of the renal biopsies&#46; Nine episodes of AR were found in the protocol biopsies carried out within the first 3 months after transplantation&#59; of the patients in the ESW-C&#44; 3 had borderline AR and 2 had Banff IA AR&#44; while the controls had 2 Banff IA AR&#44; 1 Banff IIA AR and 1 acute humoral rejection&#46; In the biopsies carried out after between 9 and 12 months &#40;whether by protocol or indicated&#41;&#44; of the patients in the ESW-C&#44; 1 had Banff IA AR&#44; while of those in the C-C&#44; 5 had borderline AR and 3 had Banff IA AR&#46; The latter findings were significantly different between cohorts &#40;<span class="elsevierStyleItalic">P</span>&#61;&#46;006&#41;&#46; Three C-C patients had chronic vascular disease of the graft in the biopsies conducted after 1 year of follow-up&#46; Moreover&#44; toxicity due to TAC was found in 23 patients &#40;36 events of toxicity&#41;&#58; 14 patients &#40;61&#37;&#41; of the ESW-C and 9 patients &#40;39&#37;&#41; of the C-C &#40;<span class="elsevierStyleItalic">P</span>&#61;&#46;21&#41;&#46; Of these&#44; 10 patients &#40;4 of the ESW-C&#47;6 of the C-C&#41; were changed to sirolimus and the GFR was not different between these two groups <span class="elsevierStyleBold">&#40;72&#46;31&#177;22&#46;80&#44; 74&#46;37&#177;19&#46;75&#44; <span class="elsevierStyleItalic">p</span>&#61;&#46;82&#41;</span>&#44; and none had AR&#46;</p><p class="elsevierStylePara">Despite the higher frequency of toxicity by TAC &#40;confirmed by biopsy&#41; in the ESW-C&#44; levels of the drug in blood were not significantly different between the cohorts and they were within the therapeutic range in all cases &#40;Table 3&#41;&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Corticosteroids are currently used in most renal transplantation centres around the world&#46; However&#44; there is a growing tendency to avoid their use due to their side effects and the negative impact on graft and patient survival&#44; even at low doses&#46;<span class="elsevierStyleSup">18-20 </span>Results of various studies in which steroids have been withdrawn have been controversial&#44; probably due to the heterogeneity of the different immunosuppression protocol used&#44; based on cyclosporine&#44; TAC&#44; azathioprine&#44; MMF&#44; rapamycin or everolimus&#44;<span class="elsevierStyleSup">12&#44;21 </span>with or without antibodies &#40;monoclonal or polyclonal&#41;&#46;<span class="elsevierStyleSup">13&#44;22-24 </span>In the Latin American population&#44; there are no data available for this intervention&#44; especially with homogeneous immunosuppression regimens based on TAC and MMF&#46; Nowadays&#44; there is a documented higher risk in the development of obesity and diabetes in various populations&#44;<span class="elsevierStyleSup">8&#44;9 </span>which could be exacerbated after renal transplantation &#40;and corticosteroids could be a major risk factor&#41;&#46; In our setting&#44; a higher risk of <span class="elsevierStyleItalic">de novo</span> diabetes after transplantation was associated with corticosteroid use&#59;<span class="elsevierStyleSup">10 </span>medical interventions such as ESW may be beneficial in transplant recipients&#46; Obviously&#44; this intervention must not increase the risk of AR or decrease renal function&#46; Initially&#44; only patients with a low immunological risk and who ideally use potent immunosuppressive drugs would be candidates for steroid withdrawal&#46;</p><p class="elsevierStylePara">We included patients who met these requirements and our results were similar to those of other studies carried out in similar conditions&#46;<span class="elsevierStyleSup">25 </span>One of the main concerns with the withdrawal of corticosteroids was the greater risk of AR&#46; The results of some studies that have reported a high rate<span class="elsevierStyleSup">13 </span>of AR are questionable&#44; since a significant number of them did not perform renal biopsies &#40;gold standard&#41; or even reported the methodology for diagnosing AR&#44; which could explain the results of a higher AR rate&#46; In this study&#44; AR was documented with protocol or indicated biopsies&#44; and as such&#44; both subclinical and clinical rejections were identified&#46; Our results with ESW did not predict the development of AR or the incidence of AR during the first year and this was consistent with that reported by other hospitals&#46;<span class="elsevierStyleSup">26 </span>Most late episodes of AR were documented in biopsies carried out due to an increase in serum creatinine and were more common in C-C &#40;29&#37;&#41; than in ESW-C &#40;3&#37;&#41;&#46; A possible explanation for this result is that the ESW-C had higher toxicity due to TAC documented histopathologically than the C-C&#44; in spite of patients in the ESW-C receiving lower doses of TAC &#40;data not displayed&#41;&#46; From a pharmacological point of view&#44; corticosteroids are cytochrome P450 inducer stimulants &#40;isoenzyme CYA4&#41; responsible for the biotransformation of TAC&#44; and in ESW&#44; this favours greater bioavailability of TAC&#44; which may explain why patients with ESW had greater toxicity due to TAC and a lower rate of AR&#46;<span class="elsevierStyleSup">27&#44;28 </span>In the C-C&#44; the eGFR was lower in comparison with that of the ESW-C&#44; which could be explained by the higher rate of AR observed in this group during follow-up&#46; The withdrawal of steroids could potentially improve the haemodynamic and metabolic profile&#46; Gonz&#225;lez-Molina et al&#46;<span class="elsevierStyleSup">29</span> retrospectively assessed 923 kidney recipients &#40;deceased donor&#41; with steroid withdrawal and found lower blood pressure&#44; total cholesterol and triglycerides&#46; In this study&#44; both groups had an appropriate control of blood pressure and serum lipids&#59; however&#44; ESW-C achieved this control with the use of a lower dose and frequency of drugs and these results were consistent with other studies&#46;<span class="elsevierStyleSup">13 </span>These results have encouraged us to continue this intervention in our population through clinical trials to test these findings&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">CONCLUSION</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">In patients with a low immunological risk&#44; with an immunosuppression regimen based on TAC and MMF&#44; ESW does not change graft survival&#44; renal function or the rate of AR in this cohort&#46; Toxicity due to TAC &#40;confirmed by biopsy&#41; tends to be more common in ESW-C than in the controls and the reason for this merits further research&#46; ESW-C patients had a lower requirement for antihypertensive drugs and hypolipidaemic agents in comparison with the C-C&#44; which suggests a better metabolic profile&#46; Our findings require further clinical trials in homogenous populations in order to avoid controversy with this type of intervention&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Conflicts of interest</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The authors declare that they have no conflicts of interest related to the contents of this article&#46;</p><p class="elsevierStylePara"><a href="grande&#47;12028&#95;16025&#95;56435&#95;en&#95;t110&#46;12028&#95;i&#46;jpg" class="elsevierStyleCrossRefs"><img src="12028_16025_56435_en_t110.12028_i.jpg" alt="Demographic and transplantation characteristics&#46;"></img></a></p><p class="elsevierStylePara">Table 1&#46; Demographic and transplantation characteristics&#46;</p><p class="elsevierStylePara"><a href="grande&#47;12028&#95;16025&#95;56436&#95;en&#95;t210&#46;12028&#95;i2&#46;jpg" class="elsevierStyleCrossRefs"><img src="12028_16025_56436_en_t210.12028_i2.jpg" alt="Clinical and biochemical comparisons between the cohorts at the start and end of follow-up&#46;"></img></a></p><p class="elsevierStylePara">Table 2&#46; Clinical and biochemical comparisons between the cohorts at the start and end of follow-up&#46;</p><p class="elsevierStylePara"><a href="grande&#47;12028&#95;16025&#95;56437&#95;en&#95;t3&#95;10&#46;12028&#95;i4&#46;jpg" class="elsevierStyleCrossRefs"><img src="12028_16025_56437_en_t3_10.12028_i4.jpg" alt="Comparison of renal function between cohorts at the start and end of follow-up&#46;"></img></a></p><p class="elsevierStylePara">Table 3&#46; Comparison of renal function between cohorts at the start and end of follow-up&#46;</p><p class="elsevierStylePara"><a href="grande&#47;12028&#95;16025&#95;56438&#95;en&#95;t4&#95;10&#46;12028&#95;i4&#46;jpg" class="elsevierStyleCrossRefs"><img src="12028_16025_56438_en_t4_10.12028_i4.jpg" alt="Histopathological findings in renal biopsies carried out after 3 or &#38;"></img></a></p><p class="elsevierStylePara">Table 4&#46; Histopathological findings in renal biopsies carried out after 3 or &#38;</p><p class="elsevierStylePara"><a href="grande&#47;12028&#95;16025&#95;56439&#95;en&#95;f1&#95;10&#46;12028&#95;i3&#46;jpg" class="elsevierStyleCrossRefs"><img src="12028_16025_56439_en_f1_10.12028_i3.jpg" alt="Comparison of survival in accordance with the study cohort&#46; B&#46; Comparison of renal function in each cohort&#46;"></img></a></p><p class="elsevierStylePara">Figure 1&#46; Comparison of survival in accordance with the study cohort&#46; B&#46; Comparison of renal function in each cohort&#46;</p>"
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        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Antecedentes&#58; </span>No hay suficiente evidencia sobre la frecuencia de rechazo agudo y la funci&#243;n del injerto en los pacientes con retiro temprano de esteroides &#40;RTE&#41;&#46; El objetivo del presente estudio es comparar el efecto del RTE sobre la tasa de filtrado glomerular &#40;TFG&#41;&#44; la supervivencia&#47;rechazo del injerto en receptores de una cohorte de tratados con tacrolimus&#47;mofetil micofenolato&#44; comparada con un grupo control&#46; <span class="elsevierStyleBold">Material y m&#233;todos&#58;</span> Cohorte retrospectiva en 60 receptores de bajo riesgo inmunol&#243;gico entre diciembre de 2005 y julio de 2010&#46; Cohorte del estudio &#40;C-RTE&#59; N&#160;&#61;&#160;32&#41;&#44; el RTE se hizo el 5&#186; d&#237;a mientras recib&#237;an tacrolimus&#47;mofetil micofenolato&#46; La cohorte control &#40;C-C&#44; N &#61; 28&#41; recibi&#243; prednisona&#47;tacrolimus&#47;mofetil micofenolato&#46; Las variables cl&#237;nicas&#44; bioqu&#237;micas e histol&#243;gicas fueron evaluadas al inicio del estudio&#44; y a los 3&#44; 6 y 12 meses de seguimiento&#46; Se utiliz&#243; Kaplan-Meier y el modelo de riesgos proporcionales de Cox para evaluar la supervivencia&#46; Las comparaciones entre cohortes fueron hechas por la <span class="elsevierStyleItalic">t</span> de Student y <span class="elsevierStyleItalic">c<span class="elsevierStyleSup">2</span></span>&#46; <span class="elsevierStyleBold">Resultados</span><span class="elsevierStyleBold">&#58;</span> Durante el seguimiento&#44; la C-C muestra presi&#243;n sangu&#237;nea significativamente mayor tanto sist&#243;lica &#40;125&#160;&#177;&#160;10 frente a 114&#160;&#177;&#160;8&#41; como diast&#243;lica &#40;81&#160;&#177;&#160;8 frente a 72&#160;&#177;&#160;7&#41;&#44; glucosa s&#233;rica &#40;96&#160;&#177;&#160;13 frente a 86&#160;&#177;&#160;10&#41;&#44; triglic&#233;ridos &#40;177&#160;&#177;&#160;61 frente a 129&#160;&#177;&#160;34&#41;&#44; colesterol total &#40;183&#160;&#177;&#160;43 frente a 148&#160;&#177;&#160;34&#41; y colesterol LDL &#40;100&#160;&#177;&#160;22 frente a 87&#160;&#177;&#160;25&#41;&#46; La C-C present&#243; una mayor proporci&#243;n de uso de antihipertensivos &#40;57 frente a 13&#160;&#37;&#41; y de estatinas &#40;27 frente a 9&#160;&#37;&#41;&#46; La TFGe fue mejor en la C-RTE que en la C-C &#40;85&#44;4&#160;&#177;&#160;20&#44;6 frente a 70&#44;6&#160;&#177;&#160;17&#44;0&#44; <span class="elsevierStyleBold">p</span>&#160;<span class="elsevierStyleBold">&#61;</span>&#160;<span class="elsevierStyleBold">0&#44;004</span>&#41;&#46; La frecuencia de rechazo agudo fue menor en la C-RTE&#46; <span class="elsevierStyleBold">Conclusiones</span><span class="elsevierStyleBold">&#58;</span> La supervivencia del injerto&#44; la TFG&#44; la tasa de rechazo agudo y el perfil metab&#243;lico fueron mejores en la C-RTE que en la C-C&#46;</p>"
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        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Background&#58;</span> Acute rejection and graft function have not been completely clarified in early-steroid-withdrawal &#40;ESW&#41; patients&#46; The objective of this study was to compare the effect of early steroid withdrawal on GFR&#44; graft survival&#47;rejection in recipients in a cohort treated with tacrolimus&#47;mycophenolate mofetil compared to a control cohort&#46; <span class="elsevierStyleBold">Material and method&#58;</span> Retrospective cohort&#44; in 60 low immunological risk recipients between December 2005 and July 2010&#46; Study cohort &#40;ESW-C N&#61;32&#41;&#44; steroid withdrawal was carried out after 5 days&#44; while they were receiving tacrolimus&#47;mycophenolate mofetil&#46; The control cohort &#40;C-C&#44; N&#61;28&#41; received prednisone&#47;tacrolimus&#47;mycophenolate mofetil&#46; Clinical&#44; biochemical and histological variables were assessed at baseline and after 3&#44; 6&#44; and 12 months of follow-up&#46; Kaplan-Meier and the Cox proportional hazards model were used to assess survival&#46; Comparisons between cohorts were carried out by the Student&#8217;s t and <span class="elsevierStyleItalic">c<span class="elsevierStyleSup">2</span></span> tests&#46; <span class="elsevierStyleBold">Results&#58;</span> At follow-up&#44; C-C displayed significantly higher systolic &#40;125&#177;10 <span class="elsevierStyleItalic">vs&#46;</span> 114&#177;8&#41; and diastolic &#40;81&#177;8 <span class="elsevierStyleItalic">vs&#46;</span> 72&#177;7&#41; blood pressure&#44; serum glucose &#40;96&#177;13 vs&#46; 86&#177;10&#41;&#44; triglycerides &#40;177&#177;61 <span class="elsevierStyleItalic">vs&#46;</span> 129&#177;34&#41;&#44; total &#40;183&#177;43 <span class="elsevierStyleItalic">vs&#46;</span><span class="elsevierStyleItalic"> </span>148&#177;34&#41; and LDL-cholesterol &#40;100&#177;22 <span class="elsevierStyleItalic">vs&#46;</span> 87&#177;25&#41;&#46; C-C had a higher proportion of antihypertensive &#40;57 <span class="elsevierStyleItalic">vs&#46;</span> 13&#37;&#41;&#44; and statins &#40;27 <span class="elsevierStyleItalic">vs&#46;</span> 9&#37;&#41; use&#46; eGFR was better in ESW-C than in C-C &#40;85&#46;4&#177;20&#46;6 <span class="elsevierStyleItalic">vs&#46;</span> 70&#46;6&#177;17&#46;0&#44; <span class="elsevierStyleBold"><span class="elsevierStyleItalic">p</span></span><span class="elsevierStyleBold">&#61;&#46;004</span>&#41;&#46; AR frequency was lower in ESW-C&#46; <span class="elsevierStyleBold">Conclusions&#58;</span><span class="elsevierStyleItalic"><span class="elsevierStyleBold"> </span></span>Graft survival&#44; GFR&#44; AR rate and metabolic profile were better in the ESW-C than in C-C&#46;</p>"
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