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

被引:7
作者
Gabardi, S. [1 ,2 ,3 ,4 ]
Ramasamy, S. [2 ]
Kim, M. [2 ,5 ]
Klasek, R. [2 ]
Carter, D. [2 ]
Mackenzie, M. R. [6 ]
Chandraker, A. [3 ,4 ,7 ]
Tan, C. S. [4 ,6 ,8 ]
机构
[1] Brigham & Womens Hosp, Dept Transplant Surg, Boston, MA 02115 USA
[2] Brigham & Womens Hosp, Dept Pharm Serv, Boston, MA 02115 USA
[3] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA
[4] Harvard Univ, Sch Med, Boston, MA USA
[5] Brigham & Womens Hosp, Dept Cardiol, Boston, MA 02115 USA
[6] Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA
[7] Brigham & Womens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA
[8] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA
关键词
BK virus; BKPyV viremia; polyomavirus; polyomavirus-associated nephropathy; renal transplantation; statins; TUBULAR EPITHELIAL-CELLS; LOW-DOSE CIDOFOVIR; VIRUS-INFECTION; REPLICATION; MANAGEMENT; NEPHRITIS; KIDNEY; UPDATE; HEART;
D O I
10.1111/tid.12402
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
BackgroundUp 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 methodsA 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. ResultsDemographic 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). ConclusionsDespite the proven invitro 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.
引用
收藏
页码:536 / 543
页数:8
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