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          "en" => "N&#186; Miss Match&#44; Viruria&#44; Viremia&#44; Funci&#243;n Renal y Biopsia en pacientes con infecci&#243;n activa por el Virus BK"
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    "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">To the Editor&#44;</span></p><p class="elsevierStylePara">BK virus &#40;BKV&#41; has a high prevalence in the world population &#40;&#62; 80&#37;&#41;&#46; Although it does not cause disease in immunocompetent patients&#44; it remains latent in the kidneys and urinary tract<span class="elsevierStyleSup">1</span>&#46;</p><p class="elsevierStylePara">Its reactivation in renal transplant recipients can lead to BKV-associated nephropathy &#40;BKVAN&#41;&#46; There is no specific treatment and the therapeutic strategy consists on the change of immunosuppressive drugs or dose adjustment&#46; The correct detection and monitoring of this virus is crucial&#44; since early intervention could prevent development of disease<span class="elsevierStyleSup">2</span>&#46;</p><p class="elsevierStylePara">Active viral infection may be confused or coexist with cellular rejection&#44; but they are two opposing entities&#44; so it is essential to differentiate them&#46;</p><p class="elsevierStylePara">Renal biopsy is the gold standard for BKVAN diagnosis<span class="elsevierStyleSup">2&#44;3</span>&#46; However&#44; real time PCR &#40;polymerase chain reaction&#41; makes it possible to quantify viral load and detect patients at risk for nephropathy before tissue damage occurs<span class="elsevierStyleSup">4&#44;5</span>&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Objective&#58; </span>To analyse the incidence of active BKV infection and the development of BKVAN in patients during their first two years after renal transplantation&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">MATERIAL AND METHOD</span></p><p class="elsevierStylePara">We studied 70 kidney recipients in the Renal Transplant Unit of Dr&#46; Julio C&#46; Perrando Hospital&#59; 62 of them received kidneys from cadaveric donors&#46; Urine samples were included for BKV screening in patients who were in their first two years post-transplantation &#40;viruria was monitored every three months during the first two years&#59; if levels of viruria &#62;10<span class="elsevierStyleSup">7</span> copies&#47;mL&#44; plasma detection was performed&#41;&#46;</p><p class="elsevierStylePara">Patients received induction with daclizumab&#47;baxilzumab-methylprednisolone-mycophenolate-mofetil &#40;MMF&#41; and maintenance with tacrolimus-MMF-steroids&#46;</p><p class="elsevierStylePara">DNAs were extracted using commercial columns &#40;Quick-gDNA MiniPrep&#44; Zymo Research&#44; U&#46;S&#46;A&#46;&#41;&#46;</p><p class="elsevierStylePara">Qualitative real-time PCR was performed&#44; using primers according to Randhawa et al<span class="elsevierStyleSup">5</span>&#46; Positive samples were quantified by commercial Q-PCR Alert &#40;Nanogen Advanced Diagnostics SRL<span class="elsevierStyleSup">&#174;</span>&#41;&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">RESULTS</span></p><p class="elsevierStylePara">Viruria was detected &#62;10<span class="elsevierStyleSup">7</span> copies&#47;mL in 12 of the 70 patients &#40;17&#37;&#41;&#44; but only 5 had persistent viruria&#44; the others were transient&#46;</p><p class="elsevierStylePara">Active infection was between 3 and 24 months after transplantation&#44; with positive viraemia after 12 months&#46;</p><p class="elsevierStylePara">Half of patients with viruria also suffered from renal function deterioration &#40;creatinine &#62; 1&#46;4mg&#47;dL&#41;&#46;</p><p class="elsevierStylePara">Table 1 shows the number of missmatch&#44; renal function&#44; biopsy&#44; viruria and viraemia in patients with persistent levels of viruria&#46;</p><p class="elsevierStylePara">BKVAN was confirmed by biopsy in 1 patient&#44; and therefore had an incidence of 1&#46;4&#37; in our centre&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Case report</span></p><p class="elsevierStylePara">55 year-old patient who received a cadaveric transplant&#46; Induction&#58; daclizumab-tacrolimus-MMF-steroids&#46; Maintenance&#58; tacrolimus-MMF-steroids&#46; Creatinine 1mg&#47;dL and 1&#46;2mg&#47;dL&#59; creatinine clearance&#58; 96mL&#44; no proteinuria&#46; Nine months after transplantation&#44; the patient presented viruria &#40;10<span class="elsevierStyleSup">7</span> copies&#47;mL&#41; for BKV without renal dysfunction and with negative viraemia&#46; High levels of viruria persisted with negative viraemia&#44; which became positive at month 12 &#40;&#62; 10<span class="elsevierStyleSup">4 </span>copies&#47;mL&#41;&#59; biopsy findings&#58; interstitial nephritis&#44; tubular nuclear alterations related to BKV&#46; The immunosupressive treatment was switched to sirolimus 2mg&#47;day and ciprofloxacin 500mg&#47;day &#40;10 days&#41; is added&#46; The patient maintained stable renal function values&#44; clearance 86mL&#44; without proteinuria and decreased viral load in blood and urine&#46; Currently&#44; the patient has still his kidney and does not require dialysis&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara">The prevalence of BKV in the urine of renal transplant patients ranges from 18&#37;-40&#37;&#58; Shenagari et al&#46;<span class="elsevierStyleSup">6</span> report 40&#37;&#44; Costa et al&#46; 18&#44;3&#37;<span class="elsevierStyleSup">7</span> and Viscount et al&#46; 24&#37;<span class="elsevierStyleSup">4</span>&#46; Reactivation usually occurs within the first two months post-transplant<span class="elsevierStyleSup">8</span>&#46; In our study&#44; we determined viral load in plasma in the 5 patients with persistent viruria&#44; 2 had viral loads&#62; 10<span class="elsevierStyleSup">4</span> copies&#47;mL&#44; similar to other reports&#44; in one patient BKVAN was found by biopsy&#44; and the other patient had a non-conclusive biopsy&#46; BKVAN lesions are multifocal with random distribution&#44; and can give false negatives<span class="elsevierStyleSup">3</span>&#46;</p><p class="elsevierStylePara">Hirsch et al&#46;<span class="elsevierStyleSup">9</span> monitored BKV replication during the first year after transplant&#44; and found the highest values of viruria and viraemia &#40;25&#46;4&#37; and 13&#46;7&#37;&#44; respectively&#41; 6 months after transplantation&#46;</p><p class="elsevierStylePara">Babel et al&#46;<span class="elsevierStyleSup">10</span> showed that 21&#46;4&#37; of patients with persistent viruria developed BKVAN between 5 and 11 weeks after reactivation in urine and blood&#46; In our patient with BKVAN&#44; viruria appeared 12 weeks before viraemia and this became positive almost simultaneously with biopsy findings&#44; without clinical signs of renal dysfunction &#40;no protocol biopsies performed in the centre&#41;&#46;</p><p class="elsevierStylePara">In addition to immunosuppression&#44; other factors such as inflammation and host immunity should be considered in the pathogenesis of BKVAN&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">CONCLUSIONS</span></p><p class="elsevierStylePara">The positivity of PCR in urine may be the first finding indicative of BKV reactivation&#46; In our patient&#44; screening determined a significant and persistent viral load in urine 12 weeks before viraemia&#44; which could be an advantage for early detection of reactivation and allow adjustment of immunosuppression&#44; although viraemia is more strongly associated with the development nephropathy&#46; The data reported are useful&#44; since so far no literature has been published on the incidence of BKV reactivation in renal transplantation in Argentina&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Conflicts of interest</span></p><p class="elsevierStylePara">The authors declare that they have no conflicts of interest related to the contents of this article&#46;</p><p class="elsevierStylePara"><a href="grande&#47;12657&#95;19904&#95;60062&#95;es&#95;12657&#95;t1&#46;jpg" class="elsevierStyleCrossRefs"><img src="12657_19904_60062_es_12657_t1.jpg" alt="N&#186; Miss Match&#44; Viruria&#44; Viremia&#44; Funci&#243;n Renal y Biopsia en pacientes con infecci&#243;n activa por el Virus BK"></img></a></p><p class="elsevierStylePara">Tabla 1&#46; N&#186; Miss Match&#44; Viruria&#44; Viremia&#44; Funci&#243;n Renal y Biopsia en pacientes con infecci&#243;n activa por el Virus BK</p>"
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