Clinical Relevance of Absolute BK Polyoma Viral Load Kinetics in Patients With Biopsy Proven BK Polyomavirus Associated Nephropathy.

Haris Omić,Lukas Weseslindtner,Stephan W Aberle,Bruno Watschinger,Gregor Bond,Johannes Phillip Kläger,Heinz Regele,Tarek Arno Schrag,Johannes Werzowa,Željko Kikić,Michael Eder,Katharina Hohenstein,Harald Herkner,Robert Strassl

doi:10.3389/fmed.2021.791087

Abstract

Introduction: The absolute BK viral load is an important diagnostic surrogate for BK polyomavirus associated nephropathy (PyVAN) after renal transplant (KTX) and serial assessment of BK viremia is recommended. However, there is no data indicating which particular viral load change, i.e., absolute vs. relative viral load changes (copies/ml; percentage of the preceding viremia) is associated with worse renal graft outcomes.Materials and Methods: In this retrospective study of 91 biopsy proven PyVAN, we analyzed the interplay of exposure time, absolute and relative viral load kinetics, baseline risk, and treatment strategies as risk factors for graft loss after 2 years using a multivariable Poisson-model.Results: We compared two major treatment strategies: standardized immunosuppression (IS) reduction (n = 53) and leflunomide (n = 30). The median viral load at the index biopsy was 2.15E+04 copies/ml (interquartile range [IQR] 1.70E+03–1.77E+05) and median peak viremia was 3.6E+04 copies/ml (IQR 2.7E+03–3.3E+05). Treatment strategies and IS-levels were not related to graft loss. After correction for baseline viral load and estimated glomerular filtration rate (eGFR), absolute viral load decrease/unit remained an independent risk factor for graft loss [incidence rate ratios [IRR] = 0.77, (95% CI 0.61–0.96), p = 0.02].Conclusion: This study provides evidence for the prognostic importance of absolute BK viremia kinetics as a dynamic parameter indicating short-term graft survival independently of other established risk factors.

Highlights

The absolute BK viral load is an important diagnostic surrogate for BK polyomavirus associated nephropathy (PyVAN) after renal transplant (KTX) and serial assessment of BK viremia is recommended
Following criteria were applied for study inclusion: (a) all patients with biopsy proven PyVAN between 2001 and 2018 supported by compatible histopathological findings and immunohistochemical staining of simian virus 40 (SV40); (b) two or more positive BK virus- polymerase chain reaction (PCR) findings during the post-transplantation (TX) period; and (c) a follow-up of at least 2 years after index biopsy
Even after correction for baseline viral load and baseline eGFR, the absolute viral load change remained an independent protective factor for graft loss (IRR = 0.77, 95% CI 0.61–0.96, p = 0.02) (Figure 3)

Summary

Introduction

The absolute BK viral load is an important diagnostic surrogate for BK polyomavirus associated nephropathy (PyVAN) after renal transplant (KTX) and serial assessment of BK viremia is recommended. The viral reactivation of BK Virus in an immunocompromised patient may induce BK polyoma virus associated nephropathy (PyVAN) as a serious complication following renal transplantation. The histomorphological phenotype of PyVAN is characterized by tubulointerstitial nephritis including the detection of virusinfected tubular epithelial cells by immunohistochemical staining using BK large T-antigen raised against SV40 [7]. A more recent diagnostic option is gene expression analysis from biopsy to distinguish PyVAN from T-cell-mediated rejection (TCMR) [8]. Untreated PyVAN can lead to progressive graft damage and presents clinically in the form of an asymptomatic deterioration of graft function causing graft failure in up to 10–30% of the patients [3, 9,10,11]

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