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    "textoCompleto" => "<p class="elsevierStylePara">Renal transplant patients must receive immunosuppressants for a long time to prevent graft rejection&#59; these medications make them susceptible to infections and neoplasms&#44; which still are an important morbimortality cause in patients receiving solid organ transplants&#46;<span class="elsevierStyleSup">1</span></p><p class="elsevierStylePara">Recently&#44; the BK virus&#44; which belongs to the polyoma family and has a special affinity for the urinary tract&#44; has been recognized as an agent that may cause loss or dysfunction of the kidney graft&#46;<span class="elsevierStyleSup">2-4</span> Polyoma viruses are icosahedral 40- nm big viruses with an approximately 5&#44;300 base pairs long DNA&#46;</p><p class="elsevierStylePara">BK &#40;BKV&#41; and JC &#40;JCV&#41; viruses were initially named upon the initials of the patients in whom they were described for the first time&#58; BKV was found in the urine of a renal transplant patient that had urethral stenosis<span class="elsevierStyleSup">5</span> and JCV in the brain of a patient with progressive multifocal leukoencephalopathy&#46;<span class="elsevierStyleSup">6</span> BKV and JCV share 75&#37; homology in their nucleotide sequence&#46; The simian virus 40 &#40;SV40&#41; also belongs to the polyoma virus family and may infect humans&#44; and shares 70&#37; homology in the nucleotide sequence with BKV&#46;<span class="elsevierStyleSup">7&#44; 8</span></p><p class="elsevierStylePara">The BKV genome is functionally divided into three regions&#58; 1&#41; a non-codifying regulatory region&#59; 2&#41; an early region codifying for proteins t and T&#44; which are transcribed before virus replication&#59; and 3&#41; a late region codifying for the agnoprotein and the capsid proteins VP1&#44; VP2&#44; and VP3&#44; which are transcribed after virus replication&#46;<span class="elsevierStyleSup">9&#44; 10</span></p><p class="elsevierStylePara"><span class="elsevierStyleSup"></span><span class="elsevierStyleBold">CLINICAL MANIFESTATIONS</span></p><p class="elsevierStylePara">Primary infection by BKV occurs during the childhood either through the gastrointestinal or respiratory tracts&#44; is generally asymptomatic&#44; although it may occasionally produce upper respiratory or urinary symptoms&#46; After the primary infection&#44; the virus remains latent at different locations inside the host&#44; mainly within the urinary tract &#40;kidneys&#44; bladder&#44; prostate&#44; cervix&#44; vulva&#44; testis&#41; and within the hemato-lymphoid tissues &#40;tonsils&#44; peripheral blood mononuclear cells&#41;&#44; and may be reactivated by immunosuppressive events&#46; Eighty to ninety percent of the adult population is BKV-seropositive&#44;<span class="elsevierStyleSup">11&#44;12</span> whereas in children the seropositivity rate reaches 80&#37;-90&#37; at 10 years of age&#46;<span class="elsevierStyleSup">13&#44; 14</span></p><p class="elsevierStylePara">In bone marrow transplants&#44; BKV presents as hemorrhagic cystitis&#44; whereas in kidney transplant patients it may produce hematuria&#44; urethral stenosis and&#47;or tubulointerstitial nephritis with the risk for progression to graft loss&#46; Patients receiving transplantation of other solid organs and those immunocompromised for any other reason &#40;acquired immunodeficiency syndrome&#44; systemic lupus erythematous&#41; may also present with polyoma-induced nephritis&#46;<span class="elsevierStyleSup">15-18</span></p><p class="elsevierStylePara">Most of polyoma-induced nephrites occur within the first year post-transplantation&#44; although 25&#37; of the cases are diagnosed later on&#46;<span class="elsevierStyleSup">19</span> Graft-loss rates vary 10&#37;-80&#37; according to the different series&#44; and it seems to be lower in those centers with active surveillance programs&#46; BKV accounts for most of the cases of cystitis and nephritis&#44; although JCV has also been reported&#44;<span class="elsevierStyleSup">18</span> and occasionally SV40&#46;<span class="elsevierStyleSup">20</span></p><p class="elsevierStylePara">In pediatric patients with renal transplant there is a special interest for BKV since this population is more likely to present a primary infection&#44; and the virus may be quiescent within the urothelium of the donated graft&#46; Viruria has been confirmed in 20&#37;-50&#37; of pediatric patients and nephritis in 2&#37;-8&#37;&#46;<span class="elsevierStyleSup">13&#44; 21&#44; 22</span> In a prospective multicenter study carried out in our country&#44; it has been observed that pediatric patients have a two-fold virus replication rate in the urine as compared with adults within the first 6 months after renal transplant&#46;<span class="elsevierStyleSup">23</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Risk factors for post-transplantation infection</span></p><p class="elsevierStylePara">The risk factors that have been reported include factors inherent to the donor&#44; the recipient&#44; the graft&#44; and the type of immunosuppression regimen&#46;<span class="elsevierStyleSup">24-26</span> So that the factors relating to the donor include&#58; the presence of active BKV infection&#44; cytomegalovirus &#40;CMV&#41; infection&#44; BKV seropositivity &#191;which has been implicated in the development of viruria&#44; viremia&#44; or nephritis in the pediatric and adult transplanted populations&#191;&#44; the absence of HLA-C7&#44; as well as dead donor versus living donor&#46;<span class="elsevierStyleSup">25&#44; 27</span> On the other hand&#44; recipient-related risk factors include&#58; older age&#44; male gender&#44; CMV infection&#44; diabetes mellitus&#44; recipient&#191;s seronegativity for BKV&#44; absence of HLAC7&#44; and Caucasian origin&#46; The graft-related risk factors include&#58; organ collection-related damage&#44; time of cold ischemia&#44; and late onset of graft function&#46; One of the issues commonly cited as the risk factors favoring BKV infection is immunosuppression&#44; especially maintenance therapy with the combination tacrolimus-mofetil mycofenolate&#44; as well as the use of anti-lymphocytic therapy for managing acute rejection&#46; <span class="elsevierStyleSup">28&#44; 29</span> The real impact of the type of immunosuppressants&#44; and particularly their combinations&#44; is clearly studied in a prospective study by Brennan and coworkers&#44; whose data point out that it is the intensity of immunosuppression&#44; more than the type of immunosuppressant&#44; what confers the highest risk for BKV infection&#44; and thus for BKV-associated nephritis &#40;BKVN&#41;&#46;<span class="elsevierStyleSup">26</span> The analyses carried out in that study indicate that the selection of a calcineurin inhibitor or of the adjuvant immunosuppressant did not independently affect BKV viruria or viremia levels&#46; However&#44; the highest viruria ranges were observed with the combination tacrolimus-mofetil mycofenolate and the lowest ones with cyclosporin-mofetil mycofenolate&#46; In addition the study specifically shows how monitoring and early withdrawal of the anti-metabolite agent upon detecting the viremia was associated to viremia resolution and absence of BKVN without occurrence of acute rejection events or graft loss&#46; With no doubt&#44; the type and intensity of immunosuppression exceed whatever risk factor &#191;individual or combined&#191; and represent the most easily modifiable ones among all mentioned&#46; It is evident that a strategy of this nature requires a follow-up with viral markers&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">DEFINITIONS AND DIAGNOSIS</span></p><p class="elsevierStylePara">Polyoma virus infection&#46;- Evidence of exposure to the virus without differentiating between latency and active replication&#46;<span class="elsevierStyleSup">24</span></p><p class="elsevierStylePara">Polyoma virus replication&#46;- Evidence of viral multiplication &#40;lytic or active infection&#41; detected by viral culture&#44; polyoma particles by electron microscopy&#44; polyoma structural proteins by immunohistochemistry&#44; expression of messenger RNA of late virus genes &#40;e&#46;g&#46; VP1&#41;&#59; viral DNA at non-quiescent sites &#40;e&#46;g&#46;&#44; plasma&#41;&#59; cytological &#40;lure cells&#41; or histological evidence of polyoma replication&#46;<span class="elsevierStyleSup">24&#44; 30</span></p><p class="elsevierStylePara">The infection may be primary of secondary depending on whether replication is detected in a seronegative or seropositive individual&#44; respectively&#46;</p><p class="elsevierStylePara">Polyoma virus disease is defined as the histopathological or ultra-structural evidence of virus-induced cytopathic and organ damage&#46;</p><p class="elsevierStylePara">Direct visualization techniques have the drawback of not being able to differentiate between the three types of polyoma virus that infect humans &#40;JCV&#44; BKV&#44; and SV40&#41;&#44; in addition to the potential mistake with other virus such as cytomegalovirus and adenovirus&#46;<span class="elsevierStyleSup">31</span> Detection in the urine of lure cells &#40;fig&#46; 1&#41; indicates active replication of the polyoma virus within the genitourinary tract&#44; and although it is a simple method with a 100&#37; sensitivity rate&#44; its specificity for BKVN diagnosis is rather low &#40;71&#37;&#41;&#59; even though&#44; it is recommended as the screening method&#46;<span class="elsevierStyleSup">32</span></p><p class="elsevierStylePara">The major limiting aspect of the methods based on viral DNA detection is that they cannot differentiate between quiescent infection and reactivation&#46; The use of real-time PCR studying mRNA instead of DNA in cells from the urine sediment has been described as an accurate and non-invasive method for establishing the presumption diagnosis of BKVN in adult kidney transplant patients&#46; By using the cutoff value of 6&#46;5 &#215; 105 copies of the BKV VP1 region per nanogram of total RNA in urine&#44; nephritis may be predicted with 93&#46;8&#37; sensitivity and 93&#46;9&#37; specificity&#46;<span class="elsevierStyleSup">33</span> We may say that the use of urinary sediment RNA has been successfully used for diagnosing acute renal graft rejection<span class="elsevierStyleSup">34</span> and the technique of urine collection has been described in detail&#46;<span class="elsevierStyleSup">35</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">HISTOPATHOLOGY</span></p><p class="elsevierStylePara">The gold standard for diagnosing viral nephritis still is detailed evaluation of the renal biopsy&#46; According to the recommendations of Banff&#191;s classification&#44;<span class="elsevierStyleSup">36</span> two tissular sections must be examined&#44; which must contain medullary parenchyma in order to increase the sensitivity&#46; The histopathological findings include intranuclear inclusion bodies within the epithelial cells&#44; tubular cytopathic changes&#44; and interstitial infiltrate &#40;figs&#46; 2-3&#41;&#46;<span class="elsevierStyleSup">32</span> The infiltrate may be mistaken with allograft rejection and with drug-induced nephrotoxicity&#46; Renal tissue assessment by electron microscopy<span class="elsevierStyleSup">37</span> or the use of immunohistochemistry firmly establishes the diagnosis &#40;fig&#46; 4&#41;&#46; Given that BKVN may be focal&#44; there is the potential for sampling errors and a negative biopsy should not completely rule out the possibility of BKV-induced nephritis&#46; In those cases in which BKV is suspected&#44; with replication levels above the cut-off values&#44; it is recommended to perform immunohistochemistry&#44; and if negative a new renal biopsy&#46;</p><p class="elsevierStylePara">It has been proposed that the histopathology report should include the following items&#58;</p><p class="elsevierStylePara">1&#41; Semi-quantitative assessment of cytopathic viral changes and their location&#44; either at the cortex or the medulla&#44; and assessment of interstitial fibrosis&#44; tubular atrophy and inflammation according to Banff&#191;s classification &#40;table I&#41;&#46;</p><p class="elsevierStylePara">2&#41; Classification of the semi-quantitative assessment by nephritis patterns&#58; A&#44; early or limited stage&#59; B&#44; blown or developed stage&#59; and C&#44; late stage &#40;table II&#41;&#46;</p><p class="elsevierStylePara">The differential diagnosis should be made with acute graft rejection and with drug-induced nephrotoxicity&#59; both conditions may be present simultaneously&#46; It may be very difficult to differentiate the tubulointerstitial infiltrate of rejection &#40;Banff type I&#41; from BKV-induced nephritis&#46;<span class="elsevierStyleSup">38&#44; 39</span> If endarteritis&#44; fibrinoid vascular necrosis and glomerulitis are present &#40;Banff types II and III&#41;&#44; as well as C4d deposition within the peritubular capillaries&#44; then there is no doubt about the coexistence of acute rejection&#46;</p><p class="elsevierStylePara">Once established&#44; BKVN may lead to renal graft loss in 10&#37;-80&#37; of the cases according to the different series&#46;<span class="elsevierStyleSup">4&#44;40</span> This is why there has been an emphasis on new diagnostic strategies allowing for early identification of this condition&#46;</p><p class="elsevierStylePara">It has been observed that the greater the immunosuppression levels the higher the frequency of viruria&#46;<span class="elsevierStyleSup">41&#44; 42</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">MANAGEMENT</span></p><p class="elsevierStylePara">BKVN management is not completely satisfactory because of two reasons&#58; we still do not count on a uniformly effective anti-viral therapy&#44; and there have not been controlled prospective studies conclusively showing the best treatment strategy&#46;<span class="elsevierStyleSup">40&#44; 43</span> In most of the nephrology centers&#44; the first approach is to decrease the immunosuppression level&#44; although it has also been suggested to discontinue treatment with tacrolimus and start on sirolimus&#46;<span class="elsevierStyleSup">44</span> Some groups have used idofovir as antiviral therapy&#44; with the drawback of being a nephro- and hepatotoxic drug&#46;<span class="elsevierStyleSup">45&#44; 46</span></p><p class="elsevierStylePara">BKVN management is bi-faceted&#58; on the one hand&#44; immunosuppression reduction in order to restore the anti-viral immunity&#44; and on the other hand&#44; specific anti-viral therapy&#46;<span class="elsevierStyleSup">47</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Modification of immunosuppression</span></p><p class="elsevierStylePara">Modification of immunosuppressive therapy has been the main therapeutic strategy even before the development of anti-viral therapy&#46;<span class="elsevierStyleSup">24</span> This strategy has been focused on immunosuppression reduction when making the diagnosis of BKVN on the one hand&#44; and continuous surveillance from the moment of transplantation and modification of immunosuppressive therapy upon detection of viral replication in plasma and urine&#46;</p><p class="elsevierStylePara">About modification of immunosuppression upon making the diagnosis of BKVN we must comment on the study performed by Vasudev and coworkers&#46;<span class="elsevierStyleSup">48</span> They included 41 adult patients receiving a renal transplant &#40;36 cases&#41; or combined renal-pancreas transplant &#40;five cases&#41;&#44; diagnosed with BKVN confirmed by characteristic histological and immunohistochemical findings &#40;staining for SV<span class="elsevierStyleSup">40 </span>by the peroxidase method&#41; in the renal biopsy&#46; Most of the patients were on triple therapy with prednisone&#44; tacrolimus&#44; and mofetil mycofenolate&#46; The time elapsed from transplantation to diagnosis of BKVN was 318 days on average &#40;variation of 48-1&#44;356 days&#41;&#46; Reduction of immunosuppressive therapy &#40;reduction of the dose of immunosuppressants or switch from triple to double therapy&#41; allowed decreasing the renal function loss rate from a creatinine clearance value of 4&#46;8 mL&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span>&#47;month before the diagnosis of BKVN to 0&#46;7 mL&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span> during the control following the diagnosis&#46; However&#44; graft loss was observed in 46&#37; of the patients studied&#44; which shows the negative impact of BKV infection on patients with renal transplant&#46; Upon reducing immunosuppression&#44; three patients presented acute rejection&#44; two of them loosing the function of the renal graft&#46;</p><p class="elsevierStylePara">In the study mentioned&#44; better stabilization of renal function was observed with reduction or discontinuation of the therapy with calcineurin inhibitors&#44; relative to global reduction of immunosuppression&#46; The authors<span class="elsevierStyleSup">48</span> mentioned that&#44; although it may be difficult differentiating between the immunosuppressive effect and the nephrotoxic effect of calcineurin inhibitors&#44; in this study they observed that the favorable effect of discontinuation or dose reduction was not observed immediately&#44; as it would have happened had the arteriolar vasoconstrictor effect be the only effect to be suppressed&#46; In this regard&#44; it has been suggested that calcineurin inhibitors may have a permissive effect on viral replication because of their toxic effect on the renal epithelium&#46;<span class="elsevierStyleSup">43</span></p><p class="elsevierStylePara">In a study carried out in children&#44; Hymes and coworkers<span class="elsevierStyleSup">49</span> observed that 20 &#40;16&#37;&#41; out of 122 patients receiving a renal transplant developed a positive reaction with the polymerase chain reaction &#40;PCR&#41; for serum viral DNA at an average of 467 days &#40;variation 23-1&#44;410 days&#41; post-transplantation&#46; By comparing the immunosuppression regimens &#40;all children received induction therapy with basiliximab and maintenance therapy with tacrolimus&#44; prednisone&#44; and mofetil mycofenolate or azathioprine or sirolimus&#41; that the patients received&#44; either they developed viral DNA positivity or not&#44; the authors did not find differences between both groups of patients&#46; In all cases immunosuppression reduction was indicated&#44; and seven out of eight children that presented BKVN upon examination of the renal biopsy received in addition therapy with cidofovir&#46; Thirteen &#40;65&#37;&#41; of the treated patients remained PCR-positive&#44; renal function was kept stable in 16 &#40;80&#37;&#41; of them at 13 &#177; 6 months after initiating the therapy&#59; the four remaining patients &#40;20&#37;&#41;&#44; all with BKVN&#44; presented progressive renal function deterioration&#46;</p><p class="elsevierStylePara">Recently&#44; Trofe and coworkers<span class="elsevierStyleSup">50</span> have presented a summary of the strategies followed in several studies aimed at reducing immunosuppression in recipients of renal transplant diagnosed with BKVN &#40;table III&#41;&#46;</p><p class="elsevierStylePara">If acute graft rejection occurs as a result of reduction of immunosuppressive therapy&#44; it is recommended to administer methylprednisolone at a dose of 500 mg&#47;day or 10 mg&#47;kg&#47;day i&#46;v&#46; for three days&#44; and then initiating reduction of the corticosteroid therapy p&#46;o&#46;&#46; In these cases&#44; treatment with anti-lymphocytic preparations is not recommended because it induces a more severe immune dysfunction&#44; which may promote reactivation of the polyomavirus&#46; On the other hand&#44; it has not been observed that treatment of acute graft rejection with corticosteroids may favor the recurrence of BKVN&#46;<span class="elsevierStyleSup">26&#44; 51</span></p><p class="elsevierStylePara">The second strategy in immunosuppression reduction has been recently described by Brennan and coworkers<span class="elsevierStyleSup">26</span> in a prospective study carried out in 200 patients receiving a renal transplant&#46; All the patients received induction therapy with rabbit anti-thymocyte globulin&#44; and then treatment with tacrolimus or cyclosporin&#44; prednisone and azathioprine or mofetil mycofenolate&#46; The patients were prospectively assessed to detect replication of BKV in plasma and urine by means of PCR&#46; In patients with BKV viremia&#44; azathioprine or mofetil mycofenolate therapy was discontinued&#59; were this insufficient to render the viremia negative&#44; it was indicated to reduce the dose of calcineurin inhibitors&#46; Twenty-three &#40;11&#46;5&#37;&#41; patients developed BKV viremia and 70 &#40;35&#37;&#41; presented viruria&#46; In twenty two out of 23 patients the viremia became negative with reduction of immunosuppression&#58; seven responded to discontinuation of only azathioprine&#47;mofetil mycofenolate&#44; two to discontinuation of only the calcineurin inhibitor&#44; seven to both therapeutic procedures&#44; and the remaining seven to the usual post-transplantation reduction of immunosuppression&#46; However&#44; in only five out of 23 patients the viremia became negative&#46; Reduction of immunosuppression was accompanied by an episode of acute rejection&#46;</p><p class="elsevierStylePara">In the study described<span class="elsevierStyleSup">26</span> there were no cases of renal biopsy-proven BKVN&#44; although this procedure was only performed in the presence of graft functional impairment&#44; so that it may possible that mild cases of intrarenal viral replication were not diagnosed&#46;</p><p class="elsevierStylePara">A new strategy recently described is based on ex vivo manipulation of T cells to increase the specific immunity against BKV&#46;<span class="elsevierStyleSup">52</span> This would make possible to provide specific immunity against the virus preventing the risk for acute rejection associated to reduction of immunosuppression&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Specific antiviral therapy</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Cidofovir</span></p><p class="elsevierStylePara">Cidofovir is cytosine analogue nucleotide that inhibits viral DNA synthesis&#46;<span class="elsevierStyleSup">53&#44;54</span> Many of the clinical experience comes from managing cytomegalovirus infection&#46; Cidofovir is cleared mainly by the kidney and its main adverse effect is nephrotoxicity&#44; and patients with renal dysfunction require lower doses&#46; For this reason&#44; the doses used in BKVN management are lower than those used in managing CMV infection&#46; By contrast with the treatment for patients with CMV retinitis&#44; cidofovir in BKVN patients has not been associated to the use of probenecid&#46; Probenecid inhibits renal tubular excretion of cidofovir and allows increasing the plasma levels with lower administered doses&#46; However&#44; in BKVN patients&#44; the lower intratubular excretion of cidofovir may potentially reduce the drug concentration at the tissue carrying the highest viral load in this disease&#46;<span class="elsevierStyleSup">55</span> In this regard&#44; it has been observed that given its intrinsic nephrotoxicity&#44; cidofovir is used in BKVN patients at a dose representing 10&#37;-25&#37; of the effective dose used to treat CMV retinitis&#46; In vitro studies have shown that at the doses used in renal transplant&#44; the serum peak concentration is approximately one tenth of the in vitro effective level and one twentieth of the 50&#37; inhibitory concentration&#46;<span class="elsevierStyleSup">50</span></p><p class="elsevierStylePara">There are reports published on the favorable effect of treating BKV-induced nephritis with cidofovir at a dose 0&#46;25-1 mg&#47;kg i&#46;v&#46;&#44; every one to three weeks&#44; with previous hydration to reduce the nephrotoxic effects&#46;<span class="elsevierStyleSup">43&#44; 45&#44; 56</span> In a study carried out in children&#44; Hymes and coworkers49 prescribed cidofovir at a dose of 0&#46;3 mg&#47;kg fortnightly for eight weeks&#46; In another pediatric study&#44; Araya and coworkers<span class="elsevierStyleSup">57</span> have used &#171;intermediate&#187; doses at 0&#46;75-1&#46;0 mg&#47;kg&#47;dose&#44; for five doses administered fortnightly&#44; without probenecid and no evidence of nephrotoxicity&#46; Kuypers and coworkers used cidofovir at a dose of 0&#46;5 mg&#47;kg weekly for 4-10 weeks in 8 adult patients&#59; after an average follow-up of 24 months no patient lost the graft for this reason&#46;<span class="elsevierStyleSup">58</span></p><p class="elsevierStylePara">In treated patients it has also been reported a reduction in the dose of immunosuppressants&#59; thus&#44; it has been argued that it is difficult to differentiate the antiviral effect of treatment with cidofovir from that obtained by improving the host immune response&#46;<span class="elsevierStyleSup">43</span> On the other hand&#44; in some patients treated with cidofovir renal interstitial fibrosis has been observed&#44; as well as worsening of renal dysfunction&#46;<span class="elsevierStyleSup">43</span></p><p class="elsevierStylePara">In spite of all this&#44; cidofovir is currently considered as being a therapeutic alternative in BKVN patients having not responded to reduction of immunosuppression and showing evidences of progressive renal function deterioration&#46;<span class="elsevierStyleSup">24&#44; 55</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Leflunomide</span></p><p class="elsevierStylePara">Leflunomide is metabolized to its active metabolite A771726&#44; which inhibits pyrimidine synthesis&#59; besides&#44; its inhibitory effect of protein phosphorylation may be responsible of its antiviral effect&#46;<span class="elsevierStyleSup">59</span></p><p class="elsevierStylePara">In a recent study&#44; Williams and coworkers<span class="elsevierStyleSup">60</span> reported on the evolution of 17 BKVN patients treated with leflunomide&#59; viremia negative conversion and a reduction of the viral load were observed in seven patients and eight additional patients&#44; respectively&#59; in these 15 patients&#44; stabilization or improvement in serum creatinine levels was observed&#46; The collateral effects observed were leukopenia&#44; skin rash&#44; and hair loss&#46;</p><p class="elsevierStylePara">In another study&#44; Josephson and coworkers<span class="elsevierStyleSup">61</span> reported on leflunomide therapy in 26 BKVN patients&#44; in seven of them associated to cidofovir&#46; After six months of therapy&#44; the BKV viral load in the blood and urine was significantly lower than the baseline level in both groups of patients&#59; the virus was undetectable in the blood of 11 patients&#59; in eight of them&#44; viruria also became negative&#46; After 40 months of follow-up&#44; graft loss was observed in four patients&#44; all of whom had showed advanced levels of inflammation and renal damage at baseline renal biopsy&#46; No serious adverse events from the therapy were observed in this study&#46;<span class="elsevierStyleSup">61</span></p><p class="elsevierStylePara">In adults&#44; leflunomide has been used at a dose of 100 mg&#47;day for five days&#44; being further reduced to 20-60 mg&#47;day&#44; trying to keep blood levels at 50-100 &#956;g&#47;mL&#46;<span class="elsevierStyleSup">47</span> Prolonged therapy &#40;for more than six months&#41; and maintaining minimal blood levels &#40;not lower than 40 &#956;g&#47;mL&#41; is required&#59; on the other hand&#44; the drug pharmacokinetics may vary considerably between the different patients&#46;<span class="elsevierStyleSup">46&#44; 50&#44; 55</span></p><p class="elsevierStylePara">The immunosuppressant FK 778&#44; a leflunomide derivative&#44; has been recently investigated&#44; showing in vitro activity against BKV&#46;<span class="elsevierStyleSup">50</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Intravenous immunoglobulin</span></p><p class="elsevierStylePara">Intravenous immunoglobulin &#40;IVIG&#41; is used to treat patients with immunodeficiencies&#44; as well as those with other autoimmune or inflammatory diseases&#59;<span class="elsevierStyleSup">62</span> in renal transplant patients&#44; it has been used to treat steroid-resistant rejection&#44; in desensitization protocols&#44; and as a maintenance immunosuppressant&#46; <span class="elsevierStyleSup">63-65</span> The mechanism of action is complex and transcends antibodies transference&#44; including modulation and expression of Fc receptors&#44; inhibition of complement-mediated damage&#44; interference with the inflammatory cytokines network&#44; effects on activation&#44; differentiation and effector function of dendritic cells&#44; macrophages&#44; and T and B lymphocytes&#46;<span class="elsevierStyleSup">66&#44; 67</span> The immunomodulatory effects of IVIG might prevent rejection occurrence by decreasing the immunosuppressive therapy&#46; The titer of neutralizing antibodies against the BK virus in IVIG-containing preparations is 2&#44;048 hemagglutination units on average &#40;variation of 2&#44;048-4&#44;096&#41;&#44; much lower than the levels presented by BKVN patients that have on average 8&#44;192 hemagglutination units &#40;variation 2&#44;048-65&#44;536&#41;&#46;<span class="elsevierStyleSup">68</span></p><p class="elsevierStylePara">There exist several reports on BKVN patients treated with IVIG&#44; either as single therapy or associated to antiviral agents&#46;</p><p class="elsevierStylePara">Wadei and coworkers reported on 55 BKVN patients&#44; twelve of whom received IVIG therapy&#44; two doses of 1&#46;25 mg&#47;kg administered 48 hours apart&#44; ten received cidofovir in addition&#59; the authors did not find differences in renal function worsening at 30 months in the IVIG-treated group vs patients without IVIG&#46;<span class="elsevierStyleSup">69</span></p><p class="elsevierStylePara">Sener and coworkers reported on eight BKVN patients treated with IVIG 2g&#47;kg at divided doses to two or five days and reduction of immunosuppression by 50&#37;&#59; after an average follow-up of 15 months&#44; 88&#37; showed stable renal function&#46;<span class="elsevierStyleSup">70</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Quinolones</span></p><p class="elsevierStylePara">It has been shown that quinolones may inhibit the BK virus replication in vitro&#46;<span class="elsevierStyleSup">71</span> In a pilot study presented by Josephson and coworkers&#44;<span class="elsevierStyleSup">55</span> gatifloxacin &#40;400 mg&#47;day p&#46;o&#46;&#41; was prescribed for 10 days&#44; in 10 patients with renal transplant that presented on two occasions &#191;lure&#191; cells in the urine&#46; The immunosuppression regimen was not modified&#46; Seven out of 10 treated patients showed viremia reduction greater than 80&#37; and in all of them disappearance of lure cells in the urine was observed&#46; The authors mention that gatifloxacin use was decided given its in vitro potency against polyomavirus and also because it concentrates at and clears through the kidney&#59; in this way&#44; tubular renal cells&#44; where viral replication takes place&#44; are exposed to high levels of the quinolone&#46;</p><p class="elsevierStylePara">Similarly&#44; the use of a fluoroquinolone&#44; ciprofloxacin&#44; in patients with hematopoietic cells transplant has been associated to reduction in the incidence of BKV viruria&#46;<span class="elsevierStyleSup">72</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Re-transplant</span></p><p class="elsevierStylePara">It has been described in the literature 15 patients receiving a new renal transplant after having lost their graft due to BKVN&#59; infection recurrence was observed in two patients &#40;13&#37;&#41;&#46; Most of the patients &#40;11&#59; 73&#37;&#41; received the same immunosuppressant regimen than the one used in the first transplant&#59; nephrectomy of the first transplant was done in 11 patients&#44; although this did not protect from further development of BKVN&#46;<span class="elsevierStyleSup">40</span> In theses cases&#44; it has been recommended to reduce the immunosuppression intensity and avoid retransplantation in the presence of BKV replication&#46;<span class="elsevierStyleSup">73</span></p><p class="elsevierStylePara">On the other hand&#44; Womer and coworkers<span class="elsevierStyleSup">74</span> have recently performed re-transplantation concurrently with nephrectomy of the first transplant in two patients&#44; with adequate renal function of the re-transplanted graft within one year of follow- up&#46; However&#44; it is still suggested that it is more appropriate to reduce immunosuppression &#40;in order to promote the development of an antiviral immune response&#41; before performing a new renal transplant&#46;<span class="elsevierStyleSup">74</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">SCREENING FOR APPROPRIATE DETECTION OF BK VIRUS INFECTION IN PATIENTS WITH RENAL TRANSPLANT</span></p><p class="elsevierStylePara">Regular screening searching BK virus replication is recommended in renal transplant patients with viruria determination&#44; either through cytology for lure cells or by electronic microscopy&#44; and preferably through quantitative PCR&#44; or through viremia according to the resources of each transplantation center&#44; monthly for the first 6 months post-renal transplant&#44; and then quarterly or whenever graft dysfunction is detected &#40;fig&#46; 4&#41;&#46; In case of a positive viremia&#44; performing a renal biopsy should be considered&#44; mainly in those cases with graft dysfunction&#46; If there is evidence of BKV-induced nephritis&#44; immunosuppression should be decreased and therapy with leflunomide or cidofovir be considered&#46;</p><p class="elsevierStylePara">As previously discussed&#44; the advantage of the follow-up with viremia determination is that it brings the opportunity of assessing the impact on viral load reduction by reducing immunosuppression and administering antiviral therapy&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">ACKNOWLEDGEMENTS</span></p><p class="elsevierStylePara">Support from the Sectorial Project on Investigation on Health and Social Security 2004-C01-193&#46; <br></br></p>"
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                  "referenciaCompleta" => "Fishman JA. Infection in solid-organ transplant recipients. N Engl J Med 2007; 357 (25): 2601-14. <a href="http://www.ncbi.nlm.nih.gov/pubmed/18094380" target="_blank">[Pubmed]</a>"
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                  "referenciaCompleta" => "Lin PL, Vats AN, Green M. BK virus infection in renal transplant recipients. Pediatr Transplant 2001; 5 (6): 398-405. <a href="http://www.ncbi.nlm.nih.gov/pubmed/11737764" target="_blank">[Pubmed]</a>"
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                  "referenciaCompleta" => "Mylonakis E, Goes N, Rubin RH, Cosimi AB, Colvin RB, Fishman JA. BK virus in solid organ transplant recipients: an emerging syndrome. Transplantation 2001; 72 (10): 1587-92. <a href="http://www.ncbi.nlm.nih.gov/pubmed/11726814" target="_blank">[Pubmed]</a>"
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                  "referenciaCompleta" => "Binet I, Nickeleit V, Hirsch HH y cols. Polyomavirus disease under new immunosuppressive drugs: a cause of renal graft dysfunction and graft loss. Transplantation 1999; 67 (6): 918-22. <a href="http://www.ncbi.nlm.nih.gov/pubmed/10199744" target="_blank">[Pubmed]</a>"
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                  "referenciaCompleta" => "Gardner SD, Field AM, Coleman DV, Hulme B. New human papovavirus (BK) isolated from urine after renal transplantation. Lancet 1971; 1 (7712): 1253-7. <a href="http://www.ncbi.nlm.nih.gov/pubmed/4104714" target="_blank">[Pubmed]</a>"
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                  "referenciaCompleta" => "Padgett BL, Walker DL, ZuRhein GM, Eckroade RJ, Dessel BH. Cultivation of papova-like virus from human brain with progressive multifocal leucoencephalopathy. Lancet 1971; 1 (7712): 1257-60. <a href="http://www.ncbi.nlm.nih.gov/pubmed/48894" target="_blank">[Pubmed]</a>"
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                  "referenciaCompleta" => "Acott PD. Polyoma virus in pediatric renal transplantation. Pediatr Transplant 2006; 10 (7): 856-60. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17032436" target="_blank">[Pubmed]</a>"
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                  "referenciaCompleta" => "Barbanti-Brodano G, Trabanelli C, Lazzarin L y cols. [SV40 as a possible cofactor in the etiopathogenesis of mesothelioma and other human tumors]. G Ital Med Lav Ergon 1998; 20 (4): 218-24. <a href="http://www.ncbi.nlm.nih.gov/pubmed/9987613" target="_blank">[Pubmed]</a>"
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              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Cole CN, Conzen SD. Polyomaviridae: The viruses and their replication. En: Knipe DM, Howley PM, eds. Fields¿ Virology. 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2001: 2141-2174."
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib10"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Major EO. Human Polyomavirus. En: Knipe DM, Howley PM, eds. Fields¿ Virology. Philadelphia: Lippincot Williams & Wilkins, 2001: 2175-2196."
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:1 [
                        "itemHostRev" => array:3 [
                          "pii" => "S014067360567626X"
                          "estado" => "S300"
                          "issn" => "01406736"
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                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib11"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Shah KV. Human polyomavirus BKV and renal disease. Nephrol Dial Transplant 2000; 15 (6): 754-5. <a href="http://www.ncbi.nlm.nih.gov/pubmed/10831621" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib12"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Shah K, Daniel R, Madden D, Stagno S. Serological investigation of BK papovavirus infection in pregnant women and their offspring. Infect Immun 1980; 30 (1): 29-35. <a href="http://www.ncbi.nlm.nih.gov/pubmed/6254883" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib13"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Acott PD, Hirsch HH. BKV infection, replication and diseases in pediatric kidney transplantation. Pediatr Nephrol 2007; 22 (9): 1243-1250. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17377822" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib14"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Taguchi F, Kajioka J, Miyamura T. Prevalence rate and age of acquisition of antibodies against JC virus and BK virus in human sera. Microbiol Immunol 1982; 26 (11): 1057-64. <a href="http://www.ncbi.nlm.nih.gov/pubmed/6300615" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib15"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Randhawa P, Vats A, Shapiro R. The pathobiology of polyomavirus infection in man. Adv Exp Med Biol 2006; 577: 148-59. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16626033" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib16"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Taguchi F, Hara K, Kajioka J, Nagaki D. Isolation of BK virus from a patient with systemic lupus erythematosus (SLE). Microbiol Immunol 1979; 23 (11): 1131-2. <a href="http://www.ncbi.nlm.nih.gov/pubmed/231184" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib17"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Sundsfjord A, Osei A, Rosenqvist H y cols. BK and JC viruses in patients with systemic lupus erythematosus: prevalent and persistent BK viruria, sequence stability of the viral regulatory regions, and nondetectable viremia. J Infect Dis 1999; 180 (1): 1-9. <a href="http://www.ncbi.nlm.nih.gov/pubmed/10353854" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib18"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Randhawa P, Uhrmacher J, Pasculle W y cols. A comparative study of BK and JC virus infections in organ transplant recipients. J Med Virol 2005; 77 (2): 238-43. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16121361" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib19"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Buehrig CK, Lager DJ, Stegall MD y cols. Influence of surveillance renal allograft biopsy on diagnosis and prognosis of polyomavirusassociated nephropathy. Kidney Int 2003; 64 (2): 665-73. <a href="http://www.ncbi.nlm.nih.gov/pubmed/12846764" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib20"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Comar M, D¿Agaro P, Andolina M y cols. Hemorrhagic cystitis in children undergoing bone marrow transplantation: a putative role for simian virus 40. Transplantation 2004; 78 (4): 544-8. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15446313" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib21"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Ginevri F, Azzi A, Hirsch HH y cols. Prospective monitoring of polyomavirus BK replication and impact of pre-emptive intervention in pediatric kidney recipients. Am J Transplant 2007; 7 (12): 2727-35. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17908275" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib22"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Herman J, Van Ranst M, Snoeck R, Beuselinck K, Lerut E, Van Damme-Lombaerts R. Polyomavirus infection in pediatric renal transplant recipients: Evaluation using a quantitative real-time PCR technique. Pediatr Transplant 2004; 8 (5): 485-92. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15367285" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib23"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Abstracts of the 4th Congress of the International Pediatric Transplant Association. Cancun, Mexico. March 17-21, 2007. Pediatr Transplant 2007; 11 Supl.: 136-114."
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:1 [
                        "itemHostRev" => array:3 [
                          "pii" => "S0140673600020626"
                          "estado" => "S300"
                          "issn" => "01406736"
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                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib24"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Hirsch HH, Brennan DC, Drachenberg CB y cols. Polyomavirus-associated nephropathy in renal transplantation: interdisciplinary analyses and recommendations. Transplantation 2005; 79 (10): 1277-86. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15912088" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib25"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Bohl DL, Storch GA, Ryschkewitsch C y cols. Donor origin of BK virus in renal transplantation and role of HLA C7 in susceptibility to sustained BK viremia. Am J Transplant 2005; 5(9): 2213-21. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16095500" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib26"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Brennan DC, Agha I, Bohl DL y cols. Incidence of BK with tacrolimus versus cyclosporine and impact of preemptive immunosuppression reduction. Am J Transplant 2005; 5 (3): 582-94. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15707414" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib27"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Ginevri F, De Santis R, Comoli P y cols. Polyomavirus BK infection in pediatric kidney-allograft recipients: a single-center analysis of incidence, risk factors, and novel therapeutic approaches. Transplantation 2003; 75 (8): 1266-70. <a href="http://www.ncbi.nlm.nih.gov/pubmed/12717214" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib28"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Mengel M, Marwedel M, Radermacher J y cols. Incidence of polyomavirus- nephropathy in renal allografts: influence of modern immunosuppressive drugs. Nephrol Dial Transplant 2003; 18 (6): 1190-6. <a href="http://www.ncbi.nlm.nih.gov/pubmed/12748354" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib29"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Barri YM, Ahmad I, Ketel BL y cols. Polyoma viral infection in renal transplantation: the role of immunosuppressive therapy. Clin Transplant 2001; 15 (4): 240-6. <a href="http://www.ncbi.nlm.nih.gov/pubmed/11683817" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib30"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Arthur RR, Shah KV. Polyomaviruses BK and JC. En: Lennete EH, Smith TF, eds. Laboratory diagnosis of viral infections. New York: Marcel Dekker Inc., 1999: 721-730."
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:1 [
                        "itemHostRev" => array:3 [
                          "pii" => "S014067361161221X"
                          "estado" => "S300"
                          "issn" => "01406736"
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                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib31"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Kwak EJ, Vílchez RA, Randhawa P, Shapiro R, Butel JS, Kusne S. Pathogenesis and Management of Polyomavirus Infection in Transplant Recipients. Clin Infect Dis 2002; 35: 1081-1087. <a href="http://www.ncbi.nlm.nih.gov/pubmed/12384842" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib32"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Nickeleit V, Singh HK, Mihatsch MJ. Polyomavirus nephropathy: morphology, pathophysiology, and clinical management. Curr Opin Nephrol Hypertens 2003; 12 (6): 599-605. <a href="http://www.ncbi.nlm.nih.gov/pubmed/14564196" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib33"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Ding R, Medeiros M, Dadhania D y cols. Noninvasive diagnosis of BK virus nephritis by measurement of messenger RNA for BK virus VP1 in urine. Transplantation 2002; 74 (7): 987-94. <a href="http://www.ncbi.nlm.nih.gov/pubmed/12394843" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:1 [
                        "itemHostRev" => array:3 [
                          "pii" => "S014067361060517X"
                          "estado" => "S300"
                          "issn" => "01406736"
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                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib34"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Li B, Hartono C, Ding R y cols. Noninvasive diagnosis of renal-allograft rejection by measurement of messenger RNA for perforin and granzyme B in urine. N Engl J Med 2001; 344 (13): 947-54. <a href="http://www.ncbi.nlm.nih.gov/pubmed/11274620" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:1 [
                        "itemHostRev" => array:3 [
                          "pii" => "S0140673611610556"
                          "estado" => "S300"
                          "issn" => "01406736"
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                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib35"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Medeiros M, Sharma VK, Ding R y cols. Optimization of RNA yield, purity and mRNA copy number by treatment of urine cell pellets with RNAlater. J Immunol Methods 2003; 279 (1-2): 135-42. <a href="http://www.ncbi.nlm.nih.gov/pubmed/12969554" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:1 [
                        "itemHostRev" => array:3 [
                          "pii" => "S0140673600031391"
                          "estado" => "S300"
                          "issn" => "01406736"
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                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib36"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Racusen LC, Colvin RB, Solez K y cols. Antibody-mediated rejection criteria ¿an addition to the Banff 97 classification of renal allograft rejection. Am J Transplant 2003; 3 (6): 708-14. <a href="http://www.ncbi.nlm.nih.gov/pubmed/12780562" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib37"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Howell DN, Smith SR, Butterly DW y cols. Diagnosis and management of BK polyomavirus interstitial nephritis in renal transplant recipients. Transplantation 1999; 68 (9): 1279-88. <a href="http://www.ncbi.nlm.nih.gov/pubmed/10573064" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib38"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Nickeleit V, Mihatsch MJ. Polyomavirus allograft nephropathy and concurrent acute rejection: a diagnostic and therapeutic challenge. Am J Transplant 2004; 4 (5): 838-9. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15084184" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib39"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Liptak P, Kemeny E, Ivanyi B. Primer: histopathology of polyomavirus- associated nephropathy in renal allografts. Nat Clin Pract Nephrol 2006; 2 (11): 631-6. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17066055" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib40"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Randhawa P, Brennan DC. BK virus infection in transplant recipients: an overview and update. Am J Transplant 2006; 6 (9): 2000-5. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16771813" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:1 [
                        "itemHostRev" => array:3 [
                          "pii" => "S0140673609600982"
                          "estado" => "S300"
                          "issn" => "01406736"
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                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib41"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Randhawa P, Ho A, Shapiro R y cols. Correlates of quantitative measurement of BK polyomavirus (BKV) DNA with clinical course of BKV infection in renal transplant patients. J Clin Microbiol 2004; 42 (3):1176-80. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15004071" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib42"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Haysom L, Rosenberg AR, Kainer G y cols. BK viral infection in an Australian pediatric renal transplant population. Pediatr Transplant 2004; 8 (5): 480-4. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15367284" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib43"
              "etiqueta" => "43"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Crew RJ, Markowitz G, Radhakrishnan J. Therapeutic options in BK virus-associated interstitial nephritis. Kidney Int 2006; 70 (2): 399- 402. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16775604" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib44"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Ramos E, Vincenti F, Lu WX y cols. Retransplantation in patients with graft loss caused by polyoma virus nephropathy. Transplantation 2004; 77 (1): 131-3. <a href="http://www.ncbi.nlm.nih.gov/pubmed/14724448" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib45"
              "etiqueta" => "45"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Vats A, Shapiro R, Singh R. Quantitative viral load monitoring and cidofovir therapy for the management of BK virus-associated nephropathy in children and adults. Transplantation 2003; (75): 105-112."
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib46"
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                  "referenciaCompleta" => "Josephson MA, Gillen D, Javaid B y cols. Treatment of renal allograft polyoma BK virus infection with leflunomide. Transplantation 2006; 81 (5): 704-10. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16534472" target="_blank">[Pubmed]</a>"
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                0 => array:3 [
                  "referenciaCompleta" => "Hariharan S. BK virus nephritis after renal transplantation. Kidney Int 2006; 69 (4): 655-62.  <a href="http://www.ncbi.nlm.nih.gov/pubmed/16395271" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
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                  "referenciaCompleta" => "Vasudev B, Hariharan S, Hussain SA, Zhu YR, Bresnahan BA, Cohen EP. BK virus nephritis: risk factors, timing, and outcome in renal transplant recipients. Kidney Int 2005; 68 (4): 1834-9. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16164661" target="_blank">[Pubmed]</a>"
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              "etiqueta" => "49"
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                0 => array:3 [
                  "referenciaCompleta" => "Hymes LC, Warshaw BL. Polyomavirus (BK) in pediatric renal transplants: evaluation of viremic patients with and without BK associated nephritis. Pediatr Transplant 2006; 10 (8): 920-2. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17096758" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
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              "etiqueta" => "50"
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                0 => array:3 [
                  "referenciaCompleta" => "Trofe J, Hirsch HH, Ramos E. Polyomavirus-associated nephropathy: update of clinical management in kidney transplant patients. Transpl Infect Dis 2006; 8 (2): 76-85. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16734630" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
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            50 => array:3 [
              "identificador" => "bib51"
              "etiqueta" => "51"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Hirsch HH. Virus infections post transplant: risk and immunity. Transpl Infect Dis 2005; 7 (3-4): 97-8. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16390396" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
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            51 => array:3 [
              "identificador" => "bib52"
              "etiqueta" => "52"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Comoli P, Basso S, Azzi A y cols. Dendritic cells pulsed with polyomavirus BK antigen induce ex vivo polyoma BK virus-specific cytotoxic T-cell lines in seropositive healthy individuals and renal transplant recipients. J Am Soc Nephrol 2003; 14 (12): 3197-204. <a href="http://www.ncbi.nlm.nih.gov/pubmed/14638918" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
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                  "host" => array:1 [
                    0 => null
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              ]
            ]
            52 => array:3 [
              "identificador" => "bib53"
              "etiqueta" => "53"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Cundy KC. Clinical pharmacokinetics of the antiviral nucleotide analogues cidofovir and adefovir. Clin Pharmacokinet 1999; 36 (2): 127-43. <a href="http://www.ncbi.nlm.nih.gov/pubmed/10092959" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
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                  "host" => array:1 [
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            53 => array:3 [
              "identificador" => "bib54"
              "etiqueta" => "54"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Farasati NA, Shapiro R, Vats A, Randhawa P. Effect of leflunomide and cidofovir on replication of BK virus in an in vitro culture system. Transplantation 2005; 79 (1): 116-8. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15714178" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
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                  "host" => array:1 [
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            54 => array:3 [
              "identificador" => "bib55"
              "etiqueta" => "55"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Josephson MA, Williams JW, Chandraker A, Randhawa PS. Polyomavirus- associated nephropathy: update on antiviral strategies. Transpl Infect Dis 2006; 8 (2): 95-101. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16734632" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
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                0 => array:3 [
                  "referenciaCompleta" => "Bjorang O, Tveitan H, Midtvedt K, Broch LU, Scott H, Andresen PA. Treatment of polyomavirus infection with cidofovir in a renal-transplant recipient. Nephrol Dial Transplant 2002; 17 (11): 2023-5. <a href="http://www.ncbi.nlm.nih.gov/pubmed/12401867" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
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                  "host" => array:1 [
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            56 => array:3 [
              "identificador" => "bib57"
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              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Araya CE, Lew JF, Fennell RS, 3rd, Neiberger RE, Dharnidharka VR. Intermediate- dose cidofovir without probenecid in the treatment of BK virus allograft nephropathy. Pediatr Transplant 2006; 10 (1): 32-7. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16499584" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
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              "identificador" => "bib58"
              "etiqueta" => "58"
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                0 => array:3 [
                  "referenciaCompleta" => "Kuypers DR, Vandooren AK, Lerut E y cols. Adjuvant low-dose cidofovir therapy for BK polyomavirus interstitial nephritis in renal transplant recipients. Am J Transplant 2005; 5 (8): 1997-2004. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15996251" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
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                0 => array:3 [
                  "referenciaCompleta" => "Knight DA, Hejmanowski AQ, Dierksheide JE, Williams JW, Chong AS, Waldman WJ. Inhibition of herpes simplex virus type 1 by the experimental immunosuppressive agent leflunomide. Transplantation 2001; 71 (1): 170-4. <a href="http://www.ncbi.nlm.nih.gov/pubmed/11211189" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
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            59 => array:3 [
              "identificador" => "bib60"
              "etiqueta" => "60"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Williams JW, Javaid B, Kadambi PV y cols. Leflunomide for polyomavirus type BK nephropathy. N Engl J Med 2005; 352 (11): 1157-8. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15784677" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
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              "identificador" => "bib61"
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              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Josephson MA, Javaid B, Kadambi PV, Meehan SM, Williams JW. Leflunomide in solid organ transplantation and polyoma virus infection. Adv Exp Med Biol 2006; 577: 255-65. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16626041" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
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            61 => array:3 [
              "identificador" => "bib62"
              "etiqueta" => "62"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Negi VS, Elluru S, Siberil S y cols. Intravenous immunoglobulin: an update on the clinical use and mechanisms of action. J Clin Immunol 2007; 27 (3): 233-45. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17351760" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
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                  "host" => array:1 [
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            62 => array:3 [
              "identificador" => "bib63"
              "etiqueta" => "63"
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                0 => array:3 [
                  "referenciaCompleta" => "Jordan S, Cunningham-Rundles C, McEwan R. Utility of intravenous immune globulin in kidney transplantation: efficacy, safety, and cost implications. Am J Transplant 2003; 3 (6): 653-64. <a href="http://www.ncbi.nlm.nih.gov/pubmed/12780556" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
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            63 => array:3 [
              "identificador" => "bib64"
              "etiqueta" => "64"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Jordan SC, Vo AA, Peng A, Toyoda M, Tyan D. Intravenous gammaglobulin (IVIG): a novel approach to improve transplant rates and outcomes in highly HLA-sensitized patients. Am J Transplant 2006;6 (3): 459-66. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16468954" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
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              ]
            ]
            64 => array:3 [
              "identificador" => "bib65"
              "etiqueta" => "65"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "De Gracia R, Jiménez C, Gil F, Escuin F, Castell J, Sanz A. [Intravenous immunoglobulin: another therapeutic application]. Nefrologia 2007; 27 (2): 214-6. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17564568" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
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              "identificador" => "bib66"
              "etiqueta" => "66"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Siberil S, Elluru S, Graff-Dubois S y cols. Intravenous immunoglobulins in autoimmune and inflammatory diseases: a mechanistic perspective. Ann N Y Acad Sci 2007; 1110: 497-506. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17911465" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
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                0 => array:3 [
                  "referenciaCompleta" => "Kessel A, Ammuri H, Peri R y cols. Intravenous immunoglobulin therapy affects T regulatory cells by increasing their suppressive function. J Immunol 2007; 179 (8): 5571-5. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17911644" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
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            67 => array:3 [
              "identificador" => "bib68"
              "etiqueta" => "68"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Trofe J, Roy-Chaudhury P, Gordon J y cols. Outcomes of patients with rejection post-polyomavirus nephropathy. Transplant Proc 2005; 37 (2): 942-4. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15848582" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
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            68 => array:3 [
              "identificador" => "bib69"
              "etiqueta" => "69"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Wadei HM, Rule AD, Lewin M y cols. Kidney transplant function and histological clearance of virus following diagnosis of polyomavirus- associated nephropathy (PVAN). Am J Transplant 2006; 6:1025-1032. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16611340" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
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            69 => array:3 [
              "identificador" => "bib70"
              "etiqueta" => "70"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Sener A, House AA, Jevnikar AM y cols. Intravenous immunoglobulin as a treatment for BK virus associated nephropathy: one-year follow- up of renal allograft recipients. Transplantation 2006; 81 (1): 117-20. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16421486" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
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              "identificador" => "bib71"
              "etiqueta" => "71"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Randhawa PS. Anti-BK virus activity of ciprofloxacin and related antibiotics. Clin Infect Dis 2005; 41 (9): 1366-7; author reply 1367."
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
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                0 => array:3 [
                  "referenciaCompleta" => "Leung AY, Chan MT, Yuen KY y cols. Ciprofloxacin decreased polyoma BK virus load in patients who underwent allogeneic hematopoietic stem cell transplantation. Clin Infect Dis 2005; 40 (4): 528-37. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15712075" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
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              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Hirsch HH, Ramos E. Retransplantation after polyomavirus-associated nephropathy: just do it? Am J Transplant 2006; 6 (1): 7-9. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16433749" target="_blank">[Pubmed]</a>"
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                0 => array:3 [
                  "referenciaCompleta" => "Womer KL, Meier-Kriesche HU, Patton PR y cols. Preemptive retransplantation for BK virus nephropathy: successful outcome despite active viremia. Am J Transplant 2006; 6 (1): 209-13. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16433777" target="_blank">[Pubmed]</a>"
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Polyoma virus in transplant recipients
Virus polioma en trasplante renal
Mara Medeirosa, J.. Alberúa, G. R.. Garcíaa, Y.. Fuentesa, L.. Velasqueza
a Departamentos de Nefrología y Patología; Departamento de Trasplantes, Hospital Infantil de México Federico Gómez; Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México,
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    "textoCompleto" => "<p class="elsevierStylePara">Renal transplant patients must receive immunosuppressants for a long time to prevent graft rejection&#59; these medications make them susceptible to infections and neoplasms&#44; which still are an important morbimortality cause in patients receiving solid organ transplants&#46;<span class="elsevierStyleSup">1</span></p><p class="elsevierStylePara">Recently&#44; the BK virus&#44; which belongs to the polyoma family and has a special affinity for the urinary tract&#44; has been recognized as an agent that may cause loss or dysfunction of the kidney graft&#46;<span class="elsevierStyleSup">2-4</span> Polyoma viruses are icosahedral 40- nm big viruses with an approximately 5&#44;300 base pairs long DNA&#46;</p><p class="elsevierStylePara">BK &#40;BKV&#41; and JC &#40;JCV&#41; viruses were initially named upon the initials of the patients in whom they were described for the first time&#58; BKV was found in the urine of a renal transplant patient that had urethral stenosis<span class="elsevierStyleSup">5</span> and JCV in the brain of a patient with progressive multifocal leukoencephalopathy&#46;<span class="elsevierStyleSup">6</span> BKV and JCV share 75&#37; homology in their nucleotide sequence&#46; The simian virus 40 &#40;SV40&#41; also belongs to the polyoma virus family and may infect humans&#44; and shares 70&#37; homology in the nucleotide sequence with BKV&#46;<span class="elsevierStyleSup">7&#44; 8</span></p><p class="elsevierStylePara">The BKV genome is functionally divided into three regions&#58; 1&#41; a non-codifying regulatory region&#59; 2&#41; an early region codifying for proteins t and T&#44; which are transcribed before virus replication&#59; and 3&#41; a late region codifying for the agnoprotein and the capsid proteins VP1&#44; VP2&#44; and VP3&#44; which are transcribed after virus replication&#46;<span class="elsevierStyleSup">9&#44; 10</span></p><p class="elsevierStylePara"><span class="elsevierStyleSup"></span><span class="elsevierStyleBold">CLINICAL MANIFESTATIONS</span></p><p class="elsevierStylePara">Primary infection by BKV occurs during the childhood either through the gastrointestinal or respiratory tracts&#44; is generally asymptomatic&#44; although it may occasionally produce upper respiratory or urinary symptoms&#46; After the primary infection&#44; the virus remains latent at different locations inside the host&#44; mainly within the urinary tract &#40;kidneys&#44; bladder&#44; prostate&#44; cervix&#44; vulva&#44; testis&#41; and within the hemato-lymphoid tissues &#40;tonsils&#44; peripheral blood mononuclear cells&#41;&#44; and may be reactivated by immunosuppressive events&#46; Eighty to ninety percent of the adult population is BKV-seropositive&#44;<span class="elsevierStyleSup">11&#44;12</span> whereas in children the seropositivity rate reaches 80&#37;-90&#37; at 10 years of age&#46;<span class="elsevierStyleSup">13&#44; 14</span></p><p class="elsevierStylePara">In bone marrow transplants&#44; BKV presents as hemorrhagic cystitis&#44; whereas in kidney transplant patients it may produce hematuria&#44; urethral stenosis and&#47;or tubulointerstitial nephritis with the risk for progression to graft loss&#46; Patients receiving transplantation of other solid organs and those immunocompromised for any other reason &#40;acquired immunodeficiency syndrome&#44; systemic lupus erythematous&#41; may also present with polyoma-induced nephritis&#46;<span class="elsevierStyleSup">15-18</span></p><p class="elsevierStylePara">Most of polyoma-induced nephrites occur within the first year post-transplantation&#44; although 25&#37; of the cases are diagnosed later on&#46;<span class="elsevierStyleSup">19</span> Graft-loss rates vary 10&#37;-80&#37; according to the different series&#44; and it seems to be lower in those centers with active surveillance programs&#46; BKV accounts for most of the cases of cystitis and nephritis&#44; although JCV has also been reported&#44;<span class="elsevierStyleSup">18</span> and occasionally SV40&#46;<span class="elsevierStyleSup">20</span></p><p class="elsevierStylePara">In pediatric patients with renal transplant there is a special interest for BKV since this population is more likely to present a primary infection&#44; and the virus may be quiescent within the urothelium of the donated graft&#46; Viruria has been confirmed in 20&#37;-50&#37; of pediatric patients and nephritis in 2&#37;-8&#37;&#46;<span class="elsevierStyleSup">13&#44; 21&#44; 22</span> In a prospective multicenter study carried out in our country&#44; it has been observed that pediatric patients have a two-fold virus replication rate in the urine as compared with adults within the first 6 months after renal transplant&#46;<span class="elsevierStyleSup">23</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Risk factors for post-transplantation infection</span></p><p class="elsevierStylePara">The risk factors that have been reported include factors inherent to the donor&#44; the recipient&#44; the graft&#44; and the type of immunosuppression regimen&#46;<span class="elsevierStyleSup">24-26</span> So that the factors relating to the donor include&#58; the presence of active BKV infection&#44; cytomegalovirus &#40;CMV&#41; infection&#44; BKV seropositivity &#191;which has been implicated in the development of viruria&#44; viremia&#44; or nephritis in the pediatric and adult transplanted populations&#191;&#44; the absence of HLA-C7&#44; as well as dead donor versus living donor&#46;<span class="elsevierStyleSup">25&#44; 27</span> On the other hand&#44; recipient-related risk factors include&#58; older age&#44; male gender&#44; CMV infection&#44; diabetes mellitus&#44; recipient&#191;s seronegativity for BKV&#44; absence of HLAC7&#44; and Caucasian origin&#46; The graft-related risk factors include&#58; organ collection-related damage&#44; time of cold ischemia&#44; and late onset of graft function&#46; One of the issues commonly cited as the risk factors favoring BKV infection is immunosuppression&#44; especially maintenance therapy with the combination tacrolimus-mofetil mycofenolate&#44; as well as the use of anti-lymphocytic therapy for managing acute rejection&#46; <span class="elsevierStyleSup">28&#44; 29</span> The real impact of the type of immunosuppressants&#44; and particularly their combinations&#44; is clearly studied in a prospective study by Brennan and coworkers&#44; whose data point out that it is the intensity of immunosuppression&#44; more than the type of immunosuppressant&#44; what confers the highest risk for BKV infection&#44; and thus for BKV-associated nephritis &#40;BKVN&#41;&#46;<span class="elsevierStyleSup">26</span> The analyses carried out in that study indicate that the selection of a calcineurin inhibitor or of the adjuvant immunosuppressant did not independently affect BKV viruria or viremia levels&#46; However&#44; the highest viruria ranges were observed with the combination tacrolimus-mofetil mycofenolate and the lowest ones with cyclosporin-mofetil mycofenolate&#46; In addition the study specifically shows how monitoring and early withdrawal of the anti-metabolite agent upon detecting the viremia was associated to viremia resolution and absence of BKVN without occurrence of acute rejection events or graft loss&#46; With no doubt&#44; the type and intensity of immunosuppression exceed whatever risk factor &#191;individual or combined&#191; and represent the most easily modifiable ones among all mentioned&#46; It is evident that a strategy of this nature requires a follow-up with viral markers&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">DEFINITIONS AND DIAGNOSIS</span></p><p class="elsevierStylePara">Polyoma virus infection&#46;- Evidence of exposure to the virus without differentiating between latency and active replication&#46;<span class="elsevierStyleSup">24</span></p><p class="elsevierStylePara">Polyoma virus replication&#46;- Evidence of viral multiplication &#40;lytic or active infection&#41; detected by viral culture&#44; polyoma particles by electron microscopy&#44; polyoma structural proteins by immunohistochemistry&#44; expression of messenger RNA of late virus genes &#40;e&#46;g&#46; VP1&#41;&#59; viral DNA at non-quiescent sites &#40;e&#46;g&#46;&#44; plasma&#41;&#59; cytological &#40;lure cells&#41; or histological evidence of polyoma replication&#46;<span class="elsevierStyleSup">24&#44; 30</span></p><p class="elsevierStylePara">The infection may be primary of secondary depending on whether replication is detected in a seronegative or seropositive individual&#44; respectively&#46;</p><p class="elsevierStylePara">Polyoma virus disease is defined as the histopathological or ultra-structural evidence of virus-induced cytopathic and organ damage&#46;</p><p class="elsevierStylePara">Direct visualization techniques have the drawback of not being able to differentiate between the three types of polyoma virus that infect humans &#40;JCV&#44; BKV&#44; and SV40&#41;&#44; in addition to the potential mistake with other virus such as cytomegalovirus and adenovirus&#46;<span class="elsevierStyleSup">31</span> Detection in the urine of lure cells &#40;fig&#46; 1&#41; indicates active replication of the polyoma virus within the genitourinary tract&#44; and although it is a simple method with a 100&#37; sensitivity rate&#44; its specificity for BKVN diagnosis is rather low &#40;71&#37;&#41;&#59; even though&#44; it is recommended as the screening method&#46;<span class="elsevierStyleSup">32</span></p><p class="elsevierStylePara">The major limiting aspect of the methods based on viral DNA detection is that they cannot differentiate between quiescent infection and reactivation&#46; The use of real-time PCR studying mRNA instead of DNA in cells from the urine sediment has been described as an accurate and non-invasive method for establishing the presumption diagnosis of BKVN in adult kidney transplant patients&#46; By using the cutoff value of 6&#46;5 &#215; 105 copies of the BKV VP1 region per nanogram of total RNA in urine&#44; nephritis may be predicted with 93&#46;8&#37; sensitivity and 93&#46;9&#37; specificity&#46;<span class="elsevierStyleSup">33</span> We may say that the use of urinary sediment RNA has been successfully used for diagnosing acute renal graft rejection<span class="elsevierStyleSup">34</span> and the technique of urine collection has been described in detail&#46;<span class="elsevierStyleSup">35</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">HISTOPATHOLOGY</span></p><p class="elsevierStylePara">The gold standard for diagnosing viral nephritis still is detailed evaluation of the renal biopsy&#46; According to the recommendations of Banff&#191;s classification&#44;<span class="elsevierStyleSup">36</span> two tissular sections must be examined&#44; which must contain medullary parenchyma in order to increase the sensitivity&#46; The histopathological findings include intranuclear inclusion bodies within the epithelial cells&#44; tubular cytopathic changes&#44; and interstitial infiltrate &#40;figs&#46; 2-3&#41;&#46;<span class="elsevierStyleSup">32</span> The infiltrate may be mistaken with allograft rejection and with drug-induced nephrotoxicity&#46; Renal tissue assessment by electron microscopy<span class="elsevierStyleSup">37</span> or the use of immunohistochemistry firmly establishes the diagnosis &#40;fig&#46; 4&#41;&#46; Given that BKVN may be focal&#44; there is the potential for sampling errors and a negative biopsy should not completely rule out the possibility of BKV-induced nephritis&#46; In those cases in which BKV is suspected&#44; with replication levels above the cut-off values&#44; it is recommended to perform immunohistochemistry&#44; and if negative a new renal biopsy&#46;</p><p class="elsevierStylePara">It has been proposed that the histopathology report should include the following items&#58;</p><p class="elsevierStylePara">1&#41; Semi-quantitative assessment of cytopathic viral changes and their location&#44; either at the cortex or the medulla&#44; and assessment of interstitial fibrosis&#44; tubular atrophy and inflammation according to Banff&#191;s classification &#40;table I&#41;&#46;</p><p class="elsevierStylePara">2&#41; Classification of the semi-quantitative assessment by nephritis patterns&#58; A&#44; early or limited stage&#59; B&#44; blown or developed stage&#59; and C&#44; late stage &#40;table II&#41;&#46;</p><p class="elsevierStylePara">The differential diagnosis should be made with acute graft rejection and with drug-induced nephrotoxicity&#59; both conditions may be present simultaneously&#46; It may be very difficult to differentiate the tubulointerstitial infiltrate of rejection &#40;Banff type I&#41; from BKV-induced nephritis&#46;<span class="elsevierStyleSup">38&#44; 39</span> If endarteritis&#44; fibrinoid vascular necrosis and glomerulitis are present &#40;Banff types II and III&#41;&#44; as well as C4d deposition within the peritubular capillaries&#44; then there is no doubt about the coexistence of acute rejection&#46;</p><p class="elsevierStylePara">Once established&#44; BKVN may lead to renal graft loss in 10&#37;-80&#37; of the cases according to the different series&#46;<span class="elsevierStyleSup">4&#44;40</span> This is why there has been an emphasis on new diagnostic strategies allowing for early identification of this condition&#46;</p><p class="elsevierStylePara">It has been observed that the greater the immunosuppression levels the higher the frequency of viruria&#46;<span class="elsevierStyleSup">41&#44; 42</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">MANAGEMENT</span></p><p class="elsevierStylePara">BKVN management is not completely satisfactory because of two reasons&#58; we still do not count on a uniformly effective anti-viral therapy&#44; and there have not been controlled prospective studies conclusively showing the best treatment strategy&#46;<span class="elsevierStyleSup">40&#44; 43</span> In most of the nephrology centers&#44; the first approach is to decrease the immunosuppression level&#44; although it has also been suggested to discontinue treatment with tacrolimus and start on sirolimus&#46;<span class="elsevierStyleSup">44</span> Some groups have used idofovir as antiviral therapy&#44; with the drawback of being a nephro- and hepatotoxic drug&#46;<span class="elsevierStyleSup">45&#44; 46</span></p><p class="elsevierStylePara">BKVN management is bi-faceted&#58; on the one hand&#44; immunosuppression reduction in order to restore the anti-viral immunity&#44; and on the other hand&#44; specific anti-viral therapy&#46;<span class="elsevierStyleSup">47</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Modification of immunosuppression</span></p><p class="elsevierStylePara">Modification of immunosuppressive therapy has been the main therapeutic strategy even before the development of anti-viral therapy&#46;<span class="elsevierStyleSup">24</span> This strategy has been focused on immunosuppression reduction when making the diagnosis of BKVN on the one hand&#44; and continuous surveillance from the moment of transplantation and modification of immunosuppressive therapy upon detection of viral replication in plasma and urine&#46;</p><p class="elsevierStylePara">About modification of immunosuppression upon making the diagnosis of BKVN we must comment on the study performed by Vasudev and coworkers&#46;<span class="elsevierStyleSup">48</span> They included 41 adult patients receiving a renal transplant &#40;36 cases&#41; or combined renal-pancreas transplant &#40;five cases&#41;&#44; diagnosed with BKVN confirmed by characteristic histological and immunohistochemical findings &#40;staining for SV<span class="elsevierStyleSup">40 </span>by the peroxidase method&#41; in the renal biopsy&#46; Most of the patients were on triple therapy with prednisone&#44; tacrolimus&#44; and mofetil mycofenolate&#46; The time elapsed from transplantation to diagnosis of BKVN was 318 days on average &#40;variation of 48-1&#44;356 days&#41;&#46; Reduction of immunosuppressive therapy &#40;reduction of the dose of immunosuppressants or switch from triple to double therapy&#41; allowed decreasing the renal function loss rate from a creatinine clearance value of 4&#46;8 mL&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span>&#47;month before the diagnosis of BKVN to 0&#46;7 mL&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span> during the control following the diagnosis&#46; However&#44; graft loss was observed in 46&#37; of the patients studied&#44; which shows the negative impact of BKV infection on patients with renal transplant&#46; Upon reducing immunosuppression&#44; three patients presented acute rejection&#44; two of them loosing the function of the renal graft&#46;</p><p class="elsevierStylePara">In the study mentioned&#44; better stabilization of renal function was observed with reduction or discontinuation of the therapy with calcineurin inhibitors&#44; relative to global reduction of immunosuppression&#46; The authors<span class="elsevierStyleSup">48</span> mentioned that&#44; although it may be difficult differentiating between the immunosuppressive effect and the nephrotoxic effect of calcineurin inhibitors&#44; in this study they observed that the favorable effect of discontinuation or dose reduction was not observed immediately&#44; as it would have happened had the arteriolar vasoconstrictor effect be the only effect to be suppressed&#46; In this regard&#44; it has been suggested that calcineurin inhibitors may have a permissive effect on viral replication because of their toxic effect on the renal epithelium&#46;<span class="elsevierStyleSup">43</span></p><p class="elsevierStylePara">In a study carried out in children&#44; Hymes and coworkers<span class="elsevierStyleSup">49</span> observed that 20 &#40;16&#37;&#41; out of 122 patients receiving a renal transplant developed a positive reaction with the polymerase chain reaction &#40;PCR&#41; for serum viral DNA at an average of 467 days &#40;variation 23-1&#44;410 days&#41; post-transplantation&#46; By comparing the immunosuppression regimens &#40;all children received induction therapy with basiliximab and maintenance therapy with tacrolimus&#44; prednisone&#44; and mofetil mycofenolate or azathioprine or sirolimus&#41; that the patients received&#44; either they developed viral DNA positivity or not&#44; the authors did not find differences between both groups of patients&#46; In all cases immunosuppression reduction was indicated&#44; and seven out of eight children that presented BKVN upon examination of the renal biopsy received in addition therapy with cidofovir&#46; Thirteen &#40;65&#37;&#41; of the treated patients remained PCR-positive&#44; renal function was kept stable in 16 &#40;80&#37;&#41; of them at 13 &#177; 6 months after initiating the therapy&#59; the four remaining patients &#40;20&#37;&#41;&#44; all with BKVN&#44; presented progressive renal function deterioration&#46;</p><p class="elsevierStylePara">Recently&#44; Trofe and coworkers<span class="elsevierStyleSup">50</span> have presented a summary of the strategies followed in several studies aimed at reducing immunosuppression in recipients of renal transplant diagnosed with BKVN &#40;table III&#41;&#46;</p><p class="elsevierStylePara">If acute graft rejection occurs as a result of reduction of immunosuppressive therapy&#44; it is recommended to administer methylprednisolone at a dose of 500 mg&#47;day or 10 mg&#47;kg&#47;day i&#46;v&#46; for three days&#44; and then initiating reduction of the corticosteroid therapy p&#46;o&#46;&#46; In these cases&#44; treatment with anti-lymphocytic preparations is not recommended because it induces a more severe immune dysfunction&#44; which may promote reactivation of the polyomavirus&#46; On the other hand&#44; it has not been observed that treatment of acute graft rejection with corticosteroids may favor the recurrence of BKVN&#46;<span class="elsevierStyleSup">26&#44; 51</span></p><p class="elsevierStylePara">The second strategy in immunosuppression reduction has been recently described by Brennan and coworkers<span class="elsevierStyleSup">26</span> in a prospective study carried out in 200 patients receiving a renal transplant&#46; All the patients received induction therapy with rabbit anti-thymocyte globulin&#44; and then treatment with tacrolimus or cyclosporin&#44; prednisone and azathioprine or mofetil mycofenolate&#46; The patients were prospectively assessed to detect replication of BKV in plasma and urine by means of PCR&#46; In patients with BKV viremia&#44; azathioprine or mofetil mycofenolate therapy was discontinued&#59; were this insufficient to render the viremia negative&#44; it was indicated to reduce the dose of calcineurin inhibitors&#46; Twenty-three &#40;11&#46;5&#37;&#41; patients developed BKV viremia and 70 &#40;35&#37;&#41; presented viruria&#46; In twenty two out of 23 patients the viremia became negative with reduction of immunosuppression&#58; seven responded to discontinuation of only azathioprine&#47;mofetil mycofenolate&#44; two to discontinuation of only the calcineurin inhibitor&#44; seven to both therapeutic procedures&#44; and the remaining seven to the usual post-transplantation reduction of immunosuppression&#46; However&#44; in only five out of 23 patients the viremia became negative&#46; Reduction of immunosuppression was accompanied by an episode of acute rejection&#46;</p><p class="elsevierStylePara">In the study described<span class="elsevierStyleSup">26</span> there were no cases of renal biopsy-proven BKVN&#44; although this procedure was only performed in the presence of graft functional impairment&#44; so that it may possible that mild cases of intrarenal viral replication were not diagnosed&#46;</p><p class="elsevierStylePara">A new strategy recently described is based on ex vivo manipulation of T cells to increase the specific immunity against BKV&#46;<span class="elsevierStyleSup">52</span> This would make possible to provide specific immunity against the virus preventing the risk for acute rejection associated to reduction of immunosuppression&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Specific antiviral therapy</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Cidofovir</span></p><p class="elsevierStylePara">Cidofovir is cytosine analogue nucleotide that inhibits viral DNA synthesis&#46;<span class="elsevierStyleSup">53&#44;54</span> Many of the clinical experience comes from managing cytomegalovirus infection&#46; Cidofovir is cleared mainly by the kidney and its main adverse effect is nephrotoxicity&#44; and patients with renal dysfunction require lower doses&#46; For this reason&#44; the doses used in BKVN management are lower than those used in managing CMV infection&#46; By contrast with the treatment for patients with CMV retinitis&#44; cidofovir in BKVN patients has not been associated to the use of probenecid&#46; Probenecid inhibits renal tubular excretion of cidofovir and allows increasing the plasma levels with lower administered doses&#46; However&#44; in BKVN patients&#44; the lower intratubular excretion of cidofovir may potentially reduce the drug concentration at the tissue carrying the highest viral load in this disease&#46;<span class="elsevierStyleSup">55</span> In this regard&#44; it has been observed that given its intrinsic nephrotoxicity&#44; cidofovir is used in BKVN patients at a dose representing 10&#37;-25&#37; of the effective dose used to treat CMV retinitis&#46; In vitro studies have shown that at the doses used in renal transplant&#44; the serum peak concentration is approximately one tenth of the in vitro effective level and one twentieth of the 50&#37; inhibitory concentration&#46;<span class="elsevierStyleSup">50</span></p><p class="elsevierStylePara">There are reports published on the favorable effect of treating BKV-induced nephritis with cidofovir at a dose 0&#46;25-1 mg&#47;kg i&#46;v&#46;&#44; every one to three weeks&#44; with previous hydration to reduce the nephrotoxic effects&#46;<span class="elsevierStyleSup">43&#44; 45&#44; 56</span> In a study carried out in children&#44; Hymes and coworkers49 prescribed cidofovir at a dose of 0&#46;3 mg&#47;kg fortnightly for eight weeks&#46; In another pediatric study&#44; Araya and coworkers<span class="elsevierStyleSup">57</span> have used &#171;intermediate&#187; doses at 0&#46;75-1&#46;0 mg&#47;kg&#47;dose&#44; for five doses administered fortnightly&#44; without probenecid and no evidence of nephrotoxicity&#46; Kuypers and coworkers used cidofovir at a dose of 0&#46;5 mg&#47;kg weekly for 4-10 weeks in 8 adult patients&#59; after an average follow-up of 24 months no patient lost the graft for this reason&#46;<span class="elsevierStyleSup">58</span></p><p class="elsevierStylePara">In treated patients it has also been reported a reduction in the dose of immunosuppressants&#59; thus&#44; it has been argued that it is difficult to differentiate the antiviral effect of treatment with cidofovir from that obtained by improving the host immune response&#46;<span class="elsevierStyleSup">43</span> On the other hand&#44; in some patients treated with cidofovir renal interstitial fibrosis has been observed&#44; as well as worsening of renal dysfunction&#46;<span class="elsevierStyleSup">43</span></p><p class="elsevierStylePara">In spite of all this&#44; cidofovir is currently considered as being a therapeutic alternative in BKVN patients having not responded to reduction of immunosuppression and showing evidences of progressive renal function deterioration&#46;<span class="elsevierStyleSup">24&#44; 55</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Leflunomide</span></p><p class="elsevierStylePara">Leflunomide is metabolized to its active metabolite A771726&#44; which inhibits pyrimidine synthesis&#59; besides&#44; its inhibitory effect of protein phosphorylation may be responsible of its antiviral effect&#46;<span class="elsevierStyleSup">59</span></p><p class="elsevierStylePara">In a recent study&#44; Williams and coworkers<span class="elsevierStyleSup">60</span> reported on the evolution of 17 BKVN patients treated with leflunomide&#59; viremia negative conversion and a reduction of the viral load were observed in seven patients and eight additional patients&#44; respectively&#59; in these 15 patients&#44; stabilization or improvement in serum creatinine levels was observed&#46; The collateral effects observed were leukopenia&#44; skin rash&#44; and hair loss&#46;</p><p class="elsevierStylePara">In another study&#44; Josephson and coworkers<span class="elsevierStyleSup">61</span> reported on leflunomide therapy in 26 BKVN patients&#44; in seven of them associated to cidofovir&#46; After six months of therapy&#44; the BKV viral load in the blood and urine was significantly lower than the baseline level in both groups of patients&#59; the virus was undetectable in the blood of 11 patients&#59; in eight of them&#44; viruria also became negative&#46; After 40 months of follow-up&#44; graft loss was observed in four patients&#44; all of whom had showed advanced levels of inflammation and renal damage at baseline renal biopsy&#46; No serious adverse events from the therapy were observed in this study&#46;<span class="elsevierStyleSup">61</span></p><p class="elsevierStylePara">In adults&#44; leflunomide has been used at a dose of 100 mg&#47;day for five days&#44; being further reduced to 20-60 mg&#47;day&#44; trying to keep blood levels at 50-100 &#956;g&#47;mL&#46;<span class="elsevierStyleSup">47</span> Prolonged therapy &#40;for more than six months&#41; and maintaining minimal blood levels &#40;not lower than 40 &#956;g&#47;mL&#41; is required&#59; on the other hand&#44; the drug pharmacokinetics may vary considerably between the different patients&#46;<span class="elsevierStyleSup">46&#44; 50&#44; 55</span></p><p class="elsevierStylePara">The immunosuppressant FK 778&#44; a leflunomide derivative&#44; has been recently investigated&#44; showing in vitro activity against BKV&#46;<span class="elsevierStyleSup">50</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Intravenous immunoglobulin</span></p><p class="elsevierStylePara">Intravenous immunoglobulin &#40;IVIG&#41; is used to treat patients with immunodeficiencies&#44; as well as those with other autoimmune or inflammatory diseases&#59;<span class="elsevierStyleSup">62</span> in renal transplant patients&#44; it has been used to treat steroid-resistant rejection&#44; in desensitization protocols&#44; and as a maintenance immunosuppressant&#46; <span class="elsevierStyleSup">63-65</span> The mechanism of action is complex and transcends antibodies transference&#44; including modulation and expression of Fc receptors&#44; inhibition of complement-mediated damage&#44; interference with the inflammatory cytokines network&#44; effects on activation&#44; differentiation and effector function of dendritic cells&#44; macrophages&#44; and T and B lymphocytes&#46;<span class="elsevierStyleSup">66&#44; 67</span> The immunomodulatory effects of IVIG might prevent rejection occurrence by decreasing the immunosuppressive therapy&#46; The titer of neutralizing antibodies against the BK virus in IVIG-containing preparations is 2&#44;048 hemagglutination units on average &#40;variation of 2&#44;048-4&#44;096&#41;&#44; much lower than the levels presented by BKVN patients that have on average 8&#44;192 hemagglutination units &#40;variation 2&#44;048-65&#44;536&#41;&#46;<span class="elsevierStyleSup">68</span></p><p class="elsevierStylePara">There exist several reports on BKVN patients treated with IVIG&#44; either as single therapy or associated to antiviral agents&#46;</p><p class="elsevierStylePara">Wadei and coworkers reported on 55 BKVN patients&#44; twelve of whom received IVIG therapy&#44; two doses of 1&#46;25 mg&#47;kg administered 48 hours apart&#44; ten received cidofovir in addition&#59; the authors did not find differences in renal function worsening at 30 months in the IVIG-treated group vs patients without IVIG&#46;<span class="elsevierStyleSup">69</span></p><p class="elsevierStylePara">Sener and coworkers reported on eight BKVN patients treated with IVIG 2g&#47;kg at divided doses to two or five days and reduction of immunosuppression by 50&#37;&#59; after an average follow-up of 15 months&#44; 88&#37; showed stable renal function&#46;<span class="elsevierStyleSup">70</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Quinolones</span></p><p class="elsevierStylePara">It has been shown that quinolones may inhibit the BK virus replication in vitro&#46;<span class="elsevierStyleSup">71</span> In a pilot study presented by Josephson and coworkers&#44;<span class="elsevierStyleSup">55</span> gatifloxacin &#40;400 mg&#47;day p&#46;o&#46;&#41; was prescribed for 10 days&#44; in 10 patients with renal transplant that presented on two occasions &#191;lure&#191; cells in the urine&#46; The immunosuppression regimen was not modified&#46; Seven out of 10 treated patients showed viremia reduction greater than 80&#37; and in all of them disappearance of lure cells in the urine was observed&#46; The authors mention that gatifloxacin use was decided given its in vitro potency against polyomavirus and also because it concentrates at and clears through the kidney&#59; in this way&#44; tubular renal cells&#44; where viral replication takes place&#44; are exposed to high levels of the quinolone&#46;</p><p class="elsevierStylePara">Similarly&#44; the use of a fluoroquinolone&#44; ciprofloxacin&#44; in patients with hematopoietic cells transplant has been associated to reduction in the incidence of BKV viruria&#46;<span class="elsevierStyleSup">72</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Re-transplant</span></p><p class="elsevierStylePara">It has been described in the literature 15 patients receiving a new renal transplant after having lost their graft due to BKVN&#59; infection recurrence was observed in two patients &#40;13&#37;&#41;&#46; Most of the patients &#40;11&#59; 73&#37;&#41; received the same immunosuppressant regimen than the one used in the first transplant&#59; nephrectomy of the first transplant was done in 11 patients&#44; although this did not protect from further development of BKVN&#46;<span class="elsevierStyleSup">40</span> In theses cases&#44; it has been recommended to reduce the immunosuppression intensity and avoid retransplantation in the presence of BKV replication&#46;<span class="elsevierStyleSup">73</span></p><p class="elsevierStylePara">On the other hand&#44; Womer and coworkers<span class="elsevierStyleSup">74</span> have recently performed re-transplantation concurrently with nephrectomy of the first transplant in two patients&#44; with adequate renal function of the re-transplanted graft within one year of follow- up&#46; However&#44; it is still suggested that it is more appropriate to reduce immunosuppression &#40;in order to promote the development of an antiviral immune response&#41; before performing a new renal transplant&#46;<span class="elsevierStyleSup">74</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">SCREENING FOR APPROPRIATE DETECTION OF BK VIRUS INFECTION IN PATIENTS WITH RENAL TRANSPLANT</span></p><p class="elsevierStylePara">Regular screening searching BK virus replication is recommended in renal transplant patients with viruria determination&#44; either through cytology for lure cells or by electronic microscopy&#44; and preferably through quantitative PCR&#44; or through viremia according to the resources of each transplantation center&#44; monthly for the first 6 months post-renal transplant&#44; and then quarterly or whenever graft dysfunction is detected &#40;fig&#46; 4&#41;&#46; In case of a positive viremia&#44; performing a renal biopsy should be considered&#44; mainly in those cases with graft dysfunction&#46; If there is evidence of BKV-induced nephritis&#44; immunosuppression should be decreased and therapy with leflunomide or cidofovir be considered&#46;</p><p class="elsevierStylePara">As previously discussed&#44; the advantage of the follow-up with viremia determination is that it brings the opportunity of assessing the impact on viral load reduction by reducing immunosuppression and administering antiviral therapy&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">ACKNOWLEDGEMENTS</span></p><p class="elsevierStylePara">Support from the Sectorial Project on Investigation on Health and Social Security 2004-C01-193&#46; <br></br></p>"
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                  "referenciaCompleta" => "Fishman JA. Infection in solid-organ transplant recipients. N Engl J Med 2007; 357 (25): 2601-14. <a href="http://www.ncbi.nlm.nih.gov/pubmed/18094380" target="_blank">[Pubmed]</a>"
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                  "referenciaCompleta" => "Lin PL, Vats AN, Green M. BK virus infection in renal transplant recipients. Pediatr Transplant 2001; 5 (6): 398-405. <a href="http://www.ncbi.nlm.nih.gov/pubmed/11737764" target="_blank">[Pubmed]</a>"
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                  "referenciaCompleta" => "Mylonakis E, Goes N, Rubin RH, Cosimi AB, Colvin RB, Fishman JA. BK virus in solid organ transplant recipients: an emerging syndrome. Transplantation 2001; 72 (10): 1587-92. <a href="http://www.ncbi.nlm.nih.gov/pubmed/11726814" target="_blank">[Pubmed]</a>"
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                0 => array:3 [
                  "referenciaCompleta" => "Binet I, Nickeleit V, Hirsch HH y cols. Polyomavirus disease under new immunosuppressive drugs: a cause of renal graft dysfunction and graft loss. Transplantation 1999; 67 (6): 918-22. <a href="http://www.ncbi.nlm.nih.gov/pubmed/10199744" target="_blank">[Pubmed]</a>"
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                    0 => null
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                0 => array:3 [
                  "referenciaCompleta" => "Gardner SD, Field AM, Coleman DV, Hulme B. New human papovavirus (BK) isolated from urine after renal transplantation. Lancet 1971; 1 (7712): 1253-7. <a href="http://www.ncbi.nlm.nih.gov/pubmed/4104714" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
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                0 => array:3 [
                  "referenciaCompleta" => "Padgett BL, Walker DL, ZuRhein GM, Eckroade RJ, Dessel BH. Cultivation of papova-like virus from human brain with progressive multifocal leucoencephalopathy. Lancet 1971; 1 (7712): 1257-60. <a href="http://www.ncbi.nlm.nih.gov/pubmed/48894" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
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                    0 => null
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              "identificador" => "bib7"
              "etiqueta" => "7"
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                0 => array:3 [
                  "referenciaCompleta" => "Acott PD. Polyoma virus in pediatric renal transplantation. Pediatr Transplant 2006; 10 (7): 856-60. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17032436" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
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                0 => array:3 [
                  "referenciaCompleta" => "Barbanti-Brodano G, Trabanelli C, Lazzarin L y cols. [SV40 as a possible cofactor in the etiopathogenesis of mesothelioma and other human tumors]. G Ital Med Lav Ergon 1998; 20 (4): 218-24. <a href="http://www.ncbi.nlm.nih.gov/pubmed/9987613" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
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              "identificador" => "bib9"
              "etiqueta" => "9"
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                0 => array:3 [
                  "referenciaCompleta" => "Cole CN, Conzen SD. Polyomaviridae: The viruses and their replication. En: Knipe DM, Howley PM, eds. Fields¿ Virology. 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2001: 2141-2174."
                  "contribucion" => array:1 [
                    0 => null
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                    0 => null
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              "identificador" => "bib10"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Major EO. Human Polyomavirus. En: Knipe DM, Howley PM, eds. Fields¿ Virology. Philadelphia: Lippincot Williams & Wilkins, 2001: 2175-2196."
                  "contribucion" => array:1 [
                    0 => null
                  ]
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            10 => array:3 [
              "identificador" => "bib11"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Shah KV. Human polyomavirus BKV and renal disease. Nephrol Dial Transplant 2000; 15 (6): 754-5. <a href="http://www.ncbi.nlm.nih.gov/pubmed/10831621" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
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                  "host" => array:1 [
                    0 => null
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            11 => array:3 [
              "identificador" => "bib12"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Shah K, Daniel R, Madden D, Stagno S. Serological investigation of BK papovavirus infection in pregnant women and their offspring. Infect Immun 1980; 30 (1): 29-35. <a href="http://www.ncbi.nlm.nih.gov/pubmed/6254883" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
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                    0 => null
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            ]
            12 => array:3 [
              "identificador" => "bib13"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Acott PD, Hirsch HH. BKV infection, replication and diseases in pediatric kidney transplantation. Pediatr Nephrol 2007; 22 (9): 1243-1250. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17377822" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
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                  "host" => array:1 [
                    0 => null
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              ]
            ]
            13 => array:3 [
              "identificador" => "bib14"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Taguchi F, Kajioka J, Miyamura T. Prevalence rate and age of acquisition of antibodies against JC virus and BK virus in human sera. Microbiol Immunol 1982; 26 (11): 1057-64. <a href="http://www.ncbi.nlm.nih.gov/pubmed/6300615" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
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                  "host" => array:1 [
                    0 => null
                  ]
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              ]
            ]
            14 => array:3 [
              "identificador" => "bib15"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Randhawa P, Vats A, Shapiro R. The pathobiology of polyomavirus infection in man. Adv Exp Med Biol 2006; 577: 148-59. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16626033" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib16"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Taguchi F, Hara K, Kajioka J, Nagaki D. Isolation of BK virus from a patient with systemic lupus erythematosus (SLE). Microbiol Immunol 1979; 23 (11): 1131-2. <a href="http://www.ncbi.nlm.nih.gov/pubmed/231184" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib17"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Sundsfjord A, Osei A, Rosenqvist H y cols. BK and JC viruses in patients with systemic lupus erythematosus: prevalent and persistent BK viruria, sequence stability of the viral regulatory regions, and nondetectable viremia. J Infect Dis 1999; 180 (1): 1-9. <a href="http://www.ncbi.nlm.nih.gov/pubmed/10353854" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib18"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Randhawa P, Uhrmacher J, Pasculle W y cols. A comparative study of BK and JC virus infections in organ transplant recipients. J Med Virol 2005; 77 (2): 238-43. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16121361" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib19"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Buehrig CK, Lager DJ, Stegall MD y cols. Influence of surveillance renal allograft biopsy on diagnosis and prognosis of polyomavirusassociated nephropathy. Kidney Int 2003; 64 (2): 665-73. <a href="http://www.ncbi.nlm.nih.gov/pubmed/12846764" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib20"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Comar M, D¿Agaro P, Andolina M y cols. Hemorrhagic cystitis in children undergoing bone marrow transplantation: a putative role for simian virus 40. Transplantation 2004; 78 (4): 544-8. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15446313" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib21"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Ginevri F, Azzi A, Hirsch HH y cols. Prospective monitoring of polyomavirus BK replication and impact of pre-emptive intervention in pediatric kidney recipients. Am J Transplant 2007; 7 (12): 2727-35. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17908275" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib22"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Herman J, Van Ranst M, Snoeck R, Beuselinck K, Lerut E, Van Damme-Lombaerts R. Polyomavirus infection in pediatric renal transplant recipients: Evaluation using a quantitative real-time PCR technique. Pediatr Transplant 2004; 8 (5): 485-92. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15367285" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib23"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Abstracts of the 4th Congress of the International Pediatric Transplant Association. Cancun, Mexico. March 17-21, 2007. Pediatr Transplant 2007; 11 Supl.: 136-114."
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:1 [
                        "itemHostRev" => array:3 [
                          "pii" => "S0140673600020626"
                          "estado" => "S300"
                          "issn" => "01406736"
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                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib24"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Hirsch HH, Brennan DC, Drachenberg CB y cols. Polyomavirus-associated nephropathy in renal transplantation: interdisciplinary analyses and recommendations. Transplantation 2005; 79 (10): 1277-86. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15912088" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib25"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Bohl DL, Storch GA, Ryschkewitsch C y cols. Donor origin of BK virus in renal transplantation and role of HLA C7 in susceptibility to sustained BK viremia. Am J Transplant 2005; 5(9): 2213-21. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16095500" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib26"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Brennan DC, Agha I, Bohl DL y cols. Incidence of BK with tacrolimus versus cyclosporine and impact of preemptive immunosuppression reduction. Am J Transplant 2005; 5 (3): 582-94. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15707414" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib27"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Ginevri F, De Santis R, Comoli P y cols. Polyomavirus BK infection in pediatric kidney-allograft recipients: a single-center analysis of incidence, risk factors, and novel therapeutic approaches. Transplantation 2003; 75 (8): 1266-70. <a href="http://www.ncbi.nlm.nih.gov/pubmed/12717214" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib28"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Mengel M, Marwedel M, Radermacher J y cols. Incidence of polyomavirus- nephropathy in renal allografts: influence of modern immunosuppressive drugs. Nephrol Dial Transplant 2003; 18 (6): 1190-6. <a href="http://www.ncbi.nlm.nih.gov/pubmed/12748354" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib29"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Barri YM, Ahmad I, Ketel BL y cols. Polyoma viral infection in renal transplantation: the role of immunosuppressive therapy. Clin Transplant 2001; 15 (4): 240-6. <a href="http://www.ncbi.nlm.nih.gov/pubmed/11683817" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib30"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Arthur RR, Shah KV. Polyomaviruses BK and JC. En: Lennete EH, Smith TF, eds. Laboratory diagnosis of viral infections. New York: Marcel Dekker Inc., 1999: 721-730."
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:1 [
                        "itemHostRev" => array:3 [
                          "pii" => "S014067361161221X"
                          "estado" => "S300"
                          "issn" => "01406736"
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                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib31"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Kwak EJ, Vílchez RA, Randhawa P, Shapiro R, Butel JS, Kusne S. Pathogenesis and Management of Polyomavirus Infection in Transplant Recipients. Clin Infect Dis 2002; 35: 1081-1087. <a href="http://www.ncbi.nlm.nih.gov/pubmed/12384842" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib32"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Nickeleit V, Singh HK, Mihatsch MJ. Polyomavirus nephropathy: morphology, pathophysiology, and clinical management. Curr Opin Nephrol Hypertens 2003; 12 (6): 599-605. <a href="http://www.ncbi.nlm.nih.gov/pubmed/14564196" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib33"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Ding R, Medeiros M, Dadhania D y cols. Noninvasive diagnosis of BK virus nephritis by measurement of messenger RNA for BK virus VP1 in urine. Transplantation 2002; 74 (7): 987-94. <a href="http://www.ncbi.nlm.nih.gov/pubmed/12394843" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:1 [
                        "itemHostRev" => array:3 [
                          "pii" => "S014067361060517X"
                          "estado" => "S300"
                          "issn" => "01406736"
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                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib34"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Li B, Hartono C, Ding R y cols. Noninvasive diagnosis of renal-allograft rejection by measurement of messenger RNA for perforin and granzyme B in urine. N Engl J Med 2001; 344 (13): 947-54. <a href="http://www.ncbi.nlm.nih.gov/pubmed/11274620" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:1 [
                        "itemHostRev" => array:3 [
                          "pii" => "S0140673611610556"
                          "estado" => "S300"
                          "issn" => "01406736"
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                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib35"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Medeiros M, Sharma VK, Ding R y cols. Optimization of RNA yield, purity and mRNA copy number by treatment of urine cell pellets with RNAlater. J Immunol Methods 2003; 279 (1-2): 135-42. <a href="http://www.ncbi.nlm.nih.gov/pubmed/12969554" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:1 [
                        "itemHostRev" => array:3 [
                          "pii" => "S0140673600031391"
                          "estado" => "S300"
                          "issn" => "01406736"
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                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib36"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Racusen LC, Colvin RB, Solez K y cols. Antibody-mediated rejection criteria ¿an addition to the Banff 97 classification of renal allograft rejection. Am J Transplant 2003; 3 (6): 708-14. <a href="http://www.ncbi.nlm.nih.gov/pubmed/12780562" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib37"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Howell DN, Smith SR, Butterly DW y cols. Diagnosis and management of BK polyomavirus interstitial nephritis in renal transplant recipients. Transplantation 1999; 68 (9): 1279-88. <a href="http://www.ncbi.nlm.nih.gov/pubmed/10573064" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib38"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Nickeleit V, Mihatsch MJ. Polyomavirus allograft nephropathy and concurrent acute rejection: a diagnostic and therapeutic challenge. Am J Transplant 2004; 4 (5): 838-9. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15084184" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib39"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Liptak P, Kemeny E, Ivanyi B. Primer: histopathology of polyomavirus- associated nephropathy in renal allografts. Nat Clin Pract Nephrol 2006; 2 (11): 631-6. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17066055" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib40"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Randhawa P, Brennan DC. BK virus infection in transplant recipients: an overview and update. Am J Transplant 2006; 6 (9): 2000-5. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16771813" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:1 [
                        "itemHostRev" => array:3 [
                          "pii" => "S0140673609600982"
                          "estado" => "S300"
                          "issn" => "01406736"
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                      ]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib41"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Randhawa P, Ho A, Shapiro R y cols. Correlates of quantitative measurement of BK polyomavirus (BKV) DNA with clinical course of BKV infection in renal transplant patients. J Clin Microbiol 2004; 42 (3):1176-80. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15004071" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib42"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Haysom L, Rosenberg AR, Kainer G y cols. BK viral infection in an Australian pediatric renal transplant population. Pediatr Transplant 2004; 8 (5): 480-4. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15367284" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib43"
              "etiqueta" => "43"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Crew RJ, Markowitz G, Radhakrishnan J. Therapeutic options in BK virus-associated interstitial nephritis. Kidney Int 2006; 70 (2): 399- 402. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16775604" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib44"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Ramos E, Vincenti F, Lu WX y cols. Retransplantation in patients with graft loss caused by polyoma virus nephropathy. Transplantation 2004; 77 (1): 131-3. <a href="http://www.ncbi.nlm.nih.gov/pubmed/14724448" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib45"
              "etiqueta" => "45"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Vats A, Shapiro R, Singh R. Quantitative viral load monitoring and cidofovir therapy for the management of BK virus-associated nephropathy in children and adults. Transplantation 2003; (75): 105-112."
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib46"
              "etiqueta" => "46"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Josephson MA, Gillen D, Javaid B y cols. Treatment of renal allograft polyoma BK virus infection with leflunomide. Transplantation 2006; 81 (5): 704-10. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16534472" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib47"
              "etiqueta" => "47"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Hariharan S. BK virus nephritis after renal transplantation. Kidney Int 2006; 69 (4): 655-62.  <a href="http://www.ncbi.nlm.nih.gov/pubmed/16395271" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            47 => array:3 [
              "identificador" => "bib48"
              "etiqueta" => "48"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Vasudev B, Hariharan S, Hussain SA, Zhu YR, Bresnahan BA, Cohen EP. BK virus nephritis: risk factors, timing, and outcome in renal transplant recipients. Kidney Int 2005; 68 (4): 1834-9. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16164661" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            48 => array:3 [
              "identificador" => "bib49"
              "etiqueta" => "49"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Hymes LC, Warshaw BL. Polyomavirus (BK) in pediatric renal transplants: evaluation of viremic patients with and without BK associated nephritis. Pediatr Transplant 2006; 10 (8): 920-2. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17096758" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            49 => array:3 [
              "identificador" => "bib50"
              "etiqueta" => "50"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Trofe J, Hirsch HH, Ramos E. Polyomavirus-associated nephropathy: update of clinical management in kidney transplant patients. Transpl Infect Dis 2006; 8 (2): 76-85. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16734630" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            50 => array:3 [
              "identificador" => "bib51"
              "etiqueta" => "51"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Hirsch HH. Virus infections post transplant: risk and immunity. Transpl Infect Dis 2005; 7 (3-4): 97-8. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16390396" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            51 => array:3 [
              "identificador" => "bib52"
              "etiqueta" => "52"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Comoli P, Basso S, Azzi A y cols. Dendritic cells pulsed with polyomavirus BK antigen induce ex vivo polyoma BK virus-specific cytotoxic T-cell lines in seropositive healthy individuals and renal transplant recipients. J Am Soc Nephrol 2003; 14 (12): 3197-204. <a href="http://www.ncbi.nlm.nih.gov/pubmed/14638918" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            52 => array:3 [
              "identificador" => "bib53"
              "etiqueta" => "53"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Cundy KC. Clinical pharmacokinetics of the antiviral nucleotide analogues cidofovir and adefovir. Clin Pharmacokinet 1999; 36 (2): 127-43. <a href="http://www.ncbi.nlm.nih.gov/pubmed/10092959" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            53 => array:3 [
              "identificador" => "bib54"
              "etiqueta" => "54"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Farasati NA, Shapiro R, Vats A, Randhawa P. Effect of leflunomide and cidofovir on replication of BK virus in an in vitro culture system. Transplantation 2005; 79 (1): 116-8. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15714178" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            54 => array:3 [
              "identificador" => "bib55"
              "etiqueta" => "55"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Josephson MA, Williams JW, Chandraker A, Randhawa PS. Polyomavirus- associated nephropathy: update on antiviral strategies. Transpl Infect Dis 2006; 8 (2): 95-101. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16734632" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            55 => array:3 [
              "identificador" => "bib56"
              "etiqueta" => "56"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Bjorang O, Tveitan H, Midtvedt K, Broch LU, Scott H, Andresen PA. Treatment of polyomavirus infection with cidofovir in a renal-transplant recipient. Nephrol Dial Transplant 2002; 17 (11): 2023-5. <a href="http://www.ncbi.nlm.nih.gov/pubmed/12401867" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            56 => array:3 [
              "identificador" => "bib57"
              "etiqueta" => "57"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Araya CE, Lew JF, Fennell RS, 3rd, Neiberger RE, Dharnidharka VR. Intermediate- dose cidofovir without probenecid in the treatment of BK virus allograft nephropathy. Pediatr Transplant 2006; 10 (1): 32-7. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16499584" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            57 => array:3 [
              "identificador" => "bib58"
              "etiqueta" => "58"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Kuypers DR, Vandooren AK, Lerut E y cols. Adjuvant low-dose cidofovir therapy for BK polyomavirus interstitial nephritis in renal transplant recipients. Am J Transplant 2005; 5 (8): 1997-2004. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15996251" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            58 => array:3 [
              "identificador" => "bib59"
              "etiqueta" => "59"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Knight DA, Hejmanowski AQ, Dierksheide JE, Williams JW, Chong AS, Waldman WJ. Inhibition of herpes simplex virus type 1 by the experimental immunosuppressive agent leflunomide. Transplantation 2001; 71 (1): 170-4. <a href="http://www.ncbi.nlm.nih.gov/pubmed/11211189" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            59 => array:3 [
              "identificador" => "bib60"
              "etiqueta" => "60"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Williams JW, Javaid B, Kadambi PV y cols. Leflunomide for polyomavirus type BK nephropathy. N Engl J Med 2005; 352 (11): 1157-8. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15784677" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            60 => array:3 [
              "identificador" => "bib61"
              "etiqueta" => "61"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Josephson MA, Javaid B, Kadambi PV, Meehan SM, Williams JW. Leflunomide in solid organ transplantation and polyoma virus infection. Adv Exp Med Biol 2006; 577: 255-65. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16626041" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            61 => array:3 [
              "identificador" => "bib62"
              "etiqueta" => "62"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Negi VS, Elluru S, Siberil S y cols. Intravenous immunoglobulin: an update on the clinical use and mechanisms of action. J Clin Immunol 2007; 27 (3): 233-45. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17351760" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            62 => array:3 [
              "identificador" => "bib63"
              "etiqueta" => "63"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Jordan S, Cunningham-Rundles C, McEwan R. Utility of intravenous immune globulin in kidney transplantation: efficacy, safety, and cost implications. Am J Transplant 2003; 3 (6): 653-64. <a href="http://www.ncbi.nlm.nih.gov/pubmed/12780556" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            63 => array:3 [
              "identificador" => "bib64"
              "etiqueta" => "64"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Jordan SC, Vo AA, Peng A, Toyoda M, Tyan D. Intravenous gammaglobulin (IVIG): a novel approach to improve transplant rates and outcomes in highly HLA-sensitized patients. Am J Transplant 2006;6 (3): 459-66. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16468954" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            64 => array:3 [
              "identificador" => "bib65"
              "etiqueta" => "65"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "De Gracia R, Jiménez C, Gil F, Escuin F, Castell J, Sanz A. [Intravenous immunoglobulin: another therapeutic application]. Nefrologia 2007; 27 (2): 214-6. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17564568" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            65 => array:3 [
              "identificador" => "bib66"
              "etiqueta" => "66"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Siberil S, Elluru S, Graff-Dubois S y cols. Intravenous immunoglobulins in autoimmune and inflammatory diseases: a mechanistic perspective. Ann N Y Acad Sci 2007; 1110: 497-506. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17911465" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            66 => array:3 [
              "identificador" => "bib67"
              "etiqueta" => "67"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Kessel A, Ammuri H, Peri R y cols. Intravenous immunoglobulin therapy affects T regulatory cells by increasing their suppressive function. J Immunol 2007; 179 (8): 5571-5. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17911644" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            67 => array:3 [
              "identificador" => "bib68"
              "etiqueta" => "68"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Trofe J, Roy-Chaudhury P, Gordon J y cols. Outcomes of patients with rejection post-polyomavirus nephropathy. Transplant Proc 2005; 37 (2): 942-4. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15848582" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            68 => array:3 [
              "identificador" => "bib69"
              "etiqueta" => "69"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Wadei HM, Rule AD, Lewin M y cols. Kidney transplant function and histological clearance of virus following diagnosis of polyomavirus- associated nephropathy (PVAN). Am J Transplant 2006; 6:1025-1032. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16611340" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            69 => array:3 [
              "identificador" => "bib70"
              "etiqueta" => "70"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Sener A, House AA, Jevnikar AM y cols. Intravenous immunoglobulin as a treatment for BK virus associated nephropathy: one-year follow- up of renal allograft recipients. Transplantation 2006; 81 (1): 117-20. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16421486" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
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                ]
              ]
            ]
            70 => array:3 [
              "identificador" => "bib71"
              "etiqueta" => "71"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Randhawa PS. Anti-BK virus activity of ciprofloxacin and related antibiotics. Clin Infect Dis 2005; 41 (9): 1366-7; author reply 1367."
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
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              "etiqueta" => "72"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Leung AY, Chan MT, Yuen KY y cols. Ciprofloxacin decreased polyoma BK virus load in patients who underwent allogeneic hematopoietic stem cell transplantation. Clin Infect Dis 2005; 40 (4): 528-37. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15712075" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
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            72 => array:3 [
              "identificador" => "bib73"
              "etiqueta" => "73"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Hirsch HH, Ramos E. Retransplantation after polyomavirus-associated nephropathy: just do it? Am J Transplant 2006; 6 (1): 7-9. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16433749" target="_blank">[Pubmed]</a>"
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                0 => array:3 [
                  "referenciaCompleta" => "Womer KL, Meier-Kriesche HU, Patton PR y cols. Preemptive retransplantation for BK virus nephropathy: successful outcome despite active viremia. Am J Transplant 2006; 6 (1): 209-13. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16433777" target="_blank">[Pubmed]</a>"
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ISSN: 20132514
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