BK viremia and polyomavirus nephropathy in 352 kidney transplants; risk factors and potential role of mTOR inhibition

Abstract

BackgroundPolyomavirus BK nephropathy (PyVAN) remains an important cause of early graft dysfunction and graft loss in kidney transplantation.MethodsIn this retrospective, single centre cohort study we studied the incidence and outcome of BK viral infection in 352 patients transplanted in 2008–2011.ResultsDuring follow-up viral replication was detected in 48 patients (13.6%); 22 patients (6.2%) had biopsy proven PyVAN.In multivariate logistic regression analyses risk factors for BK-viremia were lack of enrolment into randomized controlled trials (RCTs), biopsy proven acute rejections, cytomegaly virus (CMV) serostatus of both donor and recipient and previous transplantation.In patients without PyVAN reduction or switch of immunosuppression was associated with rapid viral clearance and stable graft function. In contrast, in most patients with PyVAN graft function deteriorated and 5 patients prematurely lost their allograft. Switch of immunosuppression to a low dose cyclosporine plus mTOR inhibitor based regimen in patients with PyVAN was safe, well tolerated and tended to be associated with a better short-term outcome in terms of graft function compared to reduction of existing immunosuppression alone.ConclusionsWith the lack of licensed anti-polyoma viral drugs reduction or conversion of immunosuppression remains the mainstay of therapy in patients with PyVAN. The combination of low dose cyclosporine plus mTOR inhibition appears to be safe and warrants further investigation.

Impact of low‐level BK polyomavirus viremia on intermediate‐term renal allograft function

“…In patients with negative screening for BKPyV, the authors observed an improved renal allograft function within the first year after transplantation compared to patients with BKPyV viremia and/or PyVAN. However, the patients with BKPyV viremia were not subdivided into groups based on quantified BKPyV viral load in serum . In the current study, patients with BKPyV viremia were subdivided according to their maximal detected BKPyV load in serum until 24 months after transplantation.…”

“…The impact of serum BKPyV viremia ≤10 4 copies/mL was not previously evaluated in the literature. A retrospective study by Jacobi et al observed an impact of the BKPyV viremia on the graft function. In patients with negative screening for BKPyV, the authors observed an improved renal allograft function within the first year after transplantation compared to patients with BKPyV viremia and/or PyVAN.…”

“…However, graft function was not described separately for patients with low‐level BKPyV viremia . These findings could be used in clinical praxis, as there seems to be no need for reduction of immunosuppression in patients with low‐level viremia in contrast to patients with high‐level viremia …”

m-TOR Inhibitors in Kidney Transplantation: A Comprehensive Review

“…Moreover, they are associated with lesser CMV viremia [69], and everolimus was shown to be superior to MMF in that aspect in a pooled analysis of three clinical trials [70]. Additionally, mTOR-I showed favourable effect in BK viremia/BK associated nephropathy [71,72] and post-transplant encapsulating peritoneal sclerosis [73][74][75].…”

Clinical and Pathological Study of Polyomavirus-Associated Nephropathy after Renal Transplantation

“…The issue has become more important in recent years, as several new immunosuppressant agents have been introduced for treating renal transplant recipients. PVAN is an aggressively destructive disease occurring in up to 8% of kidney allograft recipients [3], with one-year graft-loss rate ranging from 30% to 65% [4]. PVAN has become an important cause of allograft loss in renal transplantation, but only limited information is available regarding its pathogenesis.…”