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

S Gabardi; S Ramasamy; M Kim; R Klasek; D Carter; M R Mackenzie; A Chandraker; C S Tan

doi:10.1111/tid.12402

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

Journal article

Peer reviewed

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

S Gabardi, S Ramasamy, M Kim, R Klasek, D Carter, M R Mackenzie, A Chandraker and C S Tan

Transplant infectious disease, Vol.17(4), pp.536-543

08/2015

DOI: 10.1111/tid.12402

PMCID: PMC4529764

PMID: 25989423

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Abstract

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. 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. 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). 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.

Adult

Aged

BK Virus - isolation & purification

Disease Progression

Female

Humans

Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use

Incidence

Kidney Diseases - diagnosis

Kidney Diseases - epidemiology

Kidney Diseases - etiology

Kidney Diseases - prevention & control

Kidney Diseases - virology

Kidney Transplantation

Male

Middle Aged

Polyomavirus Infections - diagnosis

Polyomavirus Infections - epidemiology

Polyomavirus Infections - etiology

Polyomavirus Infections - prevention & control

Polyomavirus Infections - virology

Postoperative Complications - diagnosis

Postoperative Complications - epidemiology

Postoperative Complications - prevention & control

Pravastatin - therapeutic use

Treatment Outcome

Tumor Virus Infections - diagnosis

Tumor Virus Infections - epidemiology

Tumor Virus Infections - etiology

Tumor Virus Infections - prevention & control

Viremia - diagnosis

Viremia - epidemiology

Viremia - etiology

Viremia - prevention & control

Details

Title: Subtitle: Impact of HMG-CoA reductase inhibitors on the incidence of polyomavirus-associated nephropathy in renal transplant recipients with human BK polyomavirus viremia
Creators: S Gabardi - Brigham and Women's Hospital
S Ramasamy - Brigham and Women's Hospital
M Kim - Brigham and Women's Hospital
R Klasek - Brigham and Women's Hospital
D Carter - Brigham and Women's Hospital
M R Mackenzie - Beth Israel Deaconess Medical Center
A Chandraker - Harvard University
C S Tan - Beth Israel Deaconess Medical Center
Resource Type: Journal article
Publication Details: Transplant infectious disease, Vol.17(4), pp.536-543
DOI: 10.1111/tid.12402
PMID: 25989423
PMCID: PMC4529764
ISSN: 1398-2273
eISSN: 1399-3062
Grant note: K08 NS064215 / NINDS NIH HHS
Language: English
Date published: 08/2015
Academic Unit: Iowa Neuroscience Institute; Internal Medicine
Record Identifier: 9984366289702771

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