Risk Factors for Developing BK Virus-Associated Nephropathy: A Single-Center Retrospective Cohort Study of Kidney Transplant Recipients

Abstract

Background BK virus (BKV) infection after kidney transplantation leads to BKV-associated nephropathy (BKVAN) in up to 10% of recipients, and is associated with an increased risk of allograft dysfunction or loss. The objective of this study was to estimate the incidence of BKVAN and to analyze whether enhanced induction is associated with an increased risk of BKVAN, possibly justifying more intensive surveillance. Material/Methods This was a single-center retrospective cohort study. All patients who underwent kidney transplantation or simultaneous pancreas and kidney transplantation at the Uppsala University Hospital in Sweden between 2005 and 2014 were included, a period when BKV screening was not yet implemented. The effect of enhanced induction, defined as treatment with thymoglobulin, rituximab, and/or eculizumab, often in combination with IVIg and glycosorb, immunoadsorption and/or plasmapheresis/apheresis, was analyzed in a multivariable Cox proportional hazards model together with sex, age, cytomegalovirus mismatch (donor+/recipient−) and rejection treatment as co-predictors. Further, the effects of BKVAN on graft survival was analyzed in a univariable Cox proportional hazards model. Results In total 44 of 928 (4.7%) patients developed a biopsy-verified BKVAN 4.8 (1.5–34.2) months after transplantation. Male sex was identified as a risk factor (HR 2.02, P =0.04) but not enhanced induction. Patients with BKVAN experienced a significantly higher risk of graft loss (HR 4.37, P <0.001). Conclusions Male sex, but not enhanced induction, was found to be a risk factor for BKVAN development after kidney transplantation. BKVAN is associated with an increased risk of graft loss.

Detection of JCV or BKV viruria and viremia after kidney transplantation is not associated with unfavorable outcomes

“…Radtke et al 24 found that neither induction nor maintenance immunosuppressive therapy influenced BKV infection. The same results were recently found by Lorant et al 25 Authors studied 44 patients with biopsy-proven PVAN and found that enhanced induction (including thymoglobulin), was not associated with BKV PVAN development after KT. We postulated that the use of modern low-dose concepts of immunosuppression in KT, merely impacts polyomavirus replication after KT.…”

Antiviral prophylaxis, male gender and killer immunoglobulin-like receptor KIR2DL3 as markers for stratifying the risk of BK polyomavirus-associated nephropathy in kidney transplant recipients

“…Finally, in a multivariable analysis, we confirmed the previously reported and widely recognized association between male age, acute rejection episodes, and the onset of PyVAN [33][34][35][36]. The present study has some limitations, mainly concerning the limited sample size, the lack of information about the expression of KIRs, the lack of analyses on NK cells subsets expressing the KIRs most relevant for PyVAN development and matched-pair randomized groups of recipients.…”

BK Virus Infection and BK-Virus-Associated Nephropathy in Renal Transplant Recipients

“…Indeed, when the immune system is suppressed (as in RTRs and in transplanted individuals in general), the virus may reactivate and, as a consequence of its replication, trigger a series of effects that begin with tubular cell lysis and the excretion of BKV in urine. Thereafter, BKV replicates in the interstitial cells and crosses the peritubular endothelial barrier, reaching the bloodstream and eventually the allograft, causing different tubular and interstitial damages with consequent serious complications, such as BKVN [ 15 ]. BKVN can induce the degeneration of transplanted kidney and graft failure [ 16 ], and patient outcome is determined by the severity of injury with consequent inflammatory and fibrosis pictures.…”

“…It was reported recently in a single-center retrospective study the effects of the so-called enhanced induction, (based upon the administration of thymoglobulin, rituximab, and/or eculizumab), together with age, sex, cytomegalovirus mismatch (donor +/recipient−) and transplant failure treatment as risk factors for developing BKVN. Results show that male gender, but not enhanced induction, represents a hazard for developing BKVN [ 15 ]. Moreover, in another very recent research work has been assessed the relationship between laboratory data and a higher risk of BKV activation.…”