Screening for BK virus nephropathy in kidney transplant recipients: comparison of diagnostic tests

Abstract

Urine cytology and qPCR in blood and urine are commonly used to screen renal transplant recipients for polyomavirus-associated nephropathy (PVAN). Few studies, however, have directly compared these two diagnostic tests, in terms of their performance to predict PVAN. This was a systematic review in which adult (≥ 18 years old) renal transplant recipients were studied. A structured Pubmed search was used to identify studies comparing urine cytology and/or qPCR in urine and plasma samples for detecting PVAN with renal biopsy as the gold standard for diagnosis. From 707 potential papers, there were only twelve articles that matched the inclusion criteria and were analyzed in detail. Among 1694 renal transplant recipients that were included in the review, there were 115 (6.8%) patients with presumptive PVAN and 57 (3.4%) PVAN confirmed. In this systematic review, the qPCR in plasma had better performance for PVAN compared to urine cytopathology. Resumo A citologia urinária e a reação da cadeia da polimerase em tempo real (qPCR) em amostras de sangue e/ou urina são comumente utilizados para rastrear nefropatia associada ao polyomavirus (PVAN), em pacientes transplantados renais. Entretanto, poucos estudos comparam diretamente esses testes diagnósticos quanto ao desempenho para predizer esta complicação. Aqui realizamos uma revisão sistemática na qual foram estudados pacientes transplantados renais adultos (≥ 18 anos). Uma pesquisa estruturada Pubmed foi utilizada para identificar estudos comparando citologia urinária e/ou qPCR em amostras de urina e plasma para detectar PVAN, utilizando a biópsia renal como padrão-ouro para o diagnóstico. Dentre os 707 artigos em potencial, apenas 12 atendiam aos critérios de inclusão e foram analisados em maior detalhe. Foram incluídos 1694 pacientes transplantados renais, entre os quais 115 (6,8%) classificados com PVAN presuntivo e 57 (3,4%) PVAN confirmado. Nessa revisão sistemática, o qPCR no plasma tive melhor desempenho para PVAN em comparação com citopatologia urinária.

Clinical characteristics and outcomes of late‐onset BK virus nephropathy in kidney and kidney‐pancreas transplant recipients

“…The study was retrospective and single center and these results should therefore be confirmed at other centers using different immunosuppression and other clinical protocols. The majority of BKPyVAN cases were presumptively diagnosed based on viral load threshold rather than by biopsy, but a well‐validated virologic threshold was used for diagnosis, and the characteristics and outcomes of those with presumptive and proven BKPyVAN were similar (Table ). The inclusion of both presumptive and biopsy‐proven cases allowed an analysis reflective of the full clinical spectrum of BKPyVAN and avoided inappropriate misclassification of cases with false negative biopsies .…”

“…Biopsy‐proven BKPyVAN was diagnosed by renal allograft biopsy that demonstrated typical viral inclusions that were positive for SV40 antigen as described previously . Presumptive BKPyVAN was defined as a plasma BKPyV load >10 000 BKPyV DNA copies/mL, a well‐validated, sensitive, and specific threshold for biopsy‐proven BKPyVAN, as previously described . Proven and presumed cases were pooled for analysis to reflect the entire spectrum of clinical BKPyVAN, to include true cases of BKPyVAN that might have been missed because of a falsely negative biopsy, and because these clinical entities have been shown to have a generally similar histologic and clinical course .…”

Analysis of diagnostic methods as a screening test to detect BK virus nephropathy in kidney transplant patients

“…1,2 NAT in urine, in the absence of an elevated BKPyV plasma load is not associated with an increased risk for BKPyVAN. Pinto et al 7 concluded that positive BKPyV in two or more urine samples was helpful to predict BKPyV viremia with 100% sensitivity, 94% specificity and a PPV of 50% and NPV of 100%. Plasma NAT has the best PPV for BKPyVAN and has been used for most transplant centers for BKPyV screening; the sensitivity to predict BKPyVAN was 60-100%, specificity was 33-100%, and PPV was 72-100%.…”

“…As reported by Pinto et al, the different techniques limit the comparison between quantitative NATs and there is a need for standardization for BKPyV-related tests. 7 PCRs with primers and probes targeting the variable regions of the genome, like the NCCR or VP1 regions, may give false negative results or incorrect viral loads when samples contain rare genotypes. 10 In addition, urine "decoy cells" detection presents a considerable pre-analytical logistics and an analytical laboratory expertise; the exam should be performed in fresh urine, and inconclusive results are frequent during the first months post-transplant due the high urinary sediment.…”

“…that directly compared the analytical performance of screening methods to predict the diagnosis of BKPyVAN proven by histopathology. 7 From 707 potential articles initially identified, only 12 met inclusion criteria and were included in the final analysis, representing the paucity of data in the literature regarding this issue and the lack of quality data. The authors have demonstrated a better diagnostic performance of quantitative NAT than urine cytopathology for the detection of BKPyVAN.…”