Impact of HMG‐CoA reductase inhibitors on the incidence of polyomavirus‐associated nephropathy in renal transplant recipients with human BK polyomavirus viremia

Abstract

Introduction Up to 20% of renal transplant recipients (RTR) will develop human BK polyomavirus (BKPyV) viremia. BKPyV viremia is a pre-requisite of polyomavirus-associated nephropathy (PyVAN). Risk of BKPyV infections increases with immunosuppression. Currently, the only effective therapy against PyVAN is reductions in immunosuppression; but this may increase the risk of rejection. In vitro data have shown that pravastatin dramatically decreased caveolin-1 expression in human renal proximal tubular epithelial cells (HRPTEC) and suppressed BKPyV infection in these cells. Based on these data, we postulated that statin therapy may prevent the progression of BKPyV viremia to PyVAN. Patients and methods A multicenter, retrospective study was conducted in adult RTR transplanted between July 2005 and March 2012. All patients with documented BKPyV viremia (viral load >500 copies/mL on 2 consecutive tests) were included. Group I consisted of patients taking a statin before the BKPyV viremia diagnosis (n = 32), and Group II had no statin exposure before or after the BKPyV viremia diagnosis (n = 36). The primary endpoint was the incidence of PyVAN. Results Demographic data, transplant characteristics, and the degree of immunosuppression (i.e., induction/maintenance therapies, rejection treatment) were similar between the groups, with the exception of more diabetics in Group I. The incidence of PyVAN was comparable between the 2 groups (Group I = 28.1% vs. Group II = 41.7%; P = 0.312). Conclusions Despite the proven in vitro effectiveness of pravastatin preventing BKPyV infection in HRPTEC, statins at doses maximized for cholesterol lowering, in RTR with BKPyV viremia, did not prevent progression to PyVAN.

Caveolin- and clathrin-independent entry of BKPyV into primary human proximal tubule epithelial cells

“…Second, our lab showed that SV40 trafficking is cell type-dependent (Bennett et al, 2013). Third, an in vitro study showed that the 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitor Pravastatin, which inhibits cholesterol synthesis, prevents BKPyV infection by depleting caveolin 1 protein in RPTE cells (Moriyama et al, 2008); however, a clinical trial using Pravastatin failed to protect patients from PVAN at the maximum effective dose (Gabardi et al, 2015). Lastly, a study focused on BKPyV trafficking in human kidney cells supported the previous animal model that BKPyV entry is caveolin-dependent (Moriyama et al, 2007); however, we were unable to reproduce the results of Moriyama et al by exactly following their reported protocol.…”

Lipid homeostasis and mevalonate pathway in COVID-19: Basic concepts and potential therapeutic targets

“…In the light of in vitro findings suggesting that statins prevent caveolar-dependent entry of BK virus (BKV), a Polyomaviridae member, into proximal tubular epithelial cells [ 23 ], and clinical studies reporting that statins reduced proteinuria and the progression of kidney disease by improving renal function [ 135 ], a retrospective study was conducted in renal transplant recipients with documented BKV viremia taking or not statins to treat hyperlipidaemia. The study failed to demonstrate a beneficial effect of statins, at least at doses maximized for cholesterol lowering, and the authors highlighted the need to perform studies other than Randomized Clinical Trials (RCT) to identify the statins’ doses able to counteract the virus progression [ 136 ].…”

BK nephropathy in the native kidneys of patients with organ transplants: Clinical spectrum of BK infection

“…HMG-CoA reductase inhibitors are another class of drugs that has been tried unsuccessfully for the treatment of BKV infection. After the original in vitro observation that pravastatin blocks BKV cellular entry[ 449 ], a retrospective multicenter study failed to show any effect of statin doses that maximize their cholesterol-lowering effect on BK viruria or the development of BKN in renal transplant recipients[ 479 ]. Intravenous ( i.v .)…”