A delicate balance between rejection and BK polyomavirus associated nephropathy; A retrospective cohort study in renal transplant recipients.

Lilli Gard,Willem Van Doesum,Willem J Van Son,Annelies Riezebos-Brilman,Henk Groen,Jan Stephan Sanders,Coen A Stegeman,Hubert G M Niesters,Arjan Diepstra

doi:10.1371/journal.pone.0178801

Abstract

BackgroundThe immunosuppressive agents mycophenolate acid (MPA) and tacrolimus (Tac) are associated with a higher incidence of BK polyomavirus nephropathy (BKPyVAN).In this observational retrospective cohort study, the frequency of BK polyomavirus (BKPyV) complications over a 24-month period was studied.Methods358 renal transplant recipients (RTR) treated with MPA, with either cyclosporine A (CsA) (CsAM group) or Tac (TacM group) and mostly prednisolone, were included.ResultsIncidence of BKPyV-viremia was not significantly different between the CsAM (n = 42/191) (22.0%) and the TacM (n = 36/167) (21.6%) group. Biopsy proven BKPyVAN occurred more often in the TacM group (6.6%) versus the CsAM group (2.1%) (p = 0.03). Longitudinal data analysis showed a significant earlier decline of viral load in plasma in the CsAM group compared to the TacM group (p = 0.005).The incidence of biopsy proven acute rejection (BPAR) was significantly higher in the CsAM (19.9%) compared to the TacM (10.8%) (p = 0.02) group. Graft loss, estimated glomerular filtration rate and mortality rate did not differ in both treatment groups.ConclusionIn conclusion, this study shows that immunosuppressive treatment with Tac and MPA compared to CsA and MPA is associated with a lower incidence of BPAR, but at the cost of an increased risk of developing BKPyVAN in the first two years post-transplant.

Highlights

Increasing rates of BK polyomavirus nephropathy (BKPyVAN) have been observed in renal transplant recipients (RTR) over the last decades
Biopsy proven BKPyVAN occurred more often in the TacM group (6.6%) versus the CsAM group (2.1%) (p = 0.03)
This study shows that immunosuppressive treatment with Tac and mycophenolate acid (MPA) compared to cyclosporine A (CsA) and MPA is associated with a lower incidence of biopsy proven acute rejection (BPAR), but at the cost of an increased risk of developing BKPyVAN in the first two years post-transplant

Summary

Introduction

Increasing rates of BK polyomavirus nephropathy (BKPyVAN) have been observed in renal transplant recipients (RTR) over the last decades. Cyclosporine A (CsA) seems to suppress BKPyV replication in-vitro [9], but it is unclear whether this antiviral effect is present in RTR This suggests that the choice of immunosuppression plays a role in the increasing cases of BKPyVAN in the last decades, since most RTR receive immune suppressive therapy with Tac after renal transplantation [10,11]. The immunosuppressive agents mycophenolate acid (MPA) and tacrolimus (Tac) are associated with a higher incidence of BK polyomavirus nephropathy (BKPyVAN). In this observational retrospective cohort study, the frequency of BK polyomavirus (BKPyV) complications over a 24-month period was studied

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