Tenofovir is not associated with renal dysfunction following solid organ transplantation
Year of Publication
Roland, M; Barin, B; Blumberg, E; Feinberg, J; Fox, L; Huprikar, S; Wong, M; Diego, J; Simon, D; Stock, P
HIV virus; kidney transplantation; liver transplantation; Renal function
Background: As kidney (KT) and liver (LT) transplantation (TX) become an accepted option for HIV-infected (+) individuals, we must develop clinical management guidance. Potentially nephrotoxic agents are used post-TX to prevent rejection and OIs and to control HIV and HBV. It is not known if tenofovir (TDF) can be used safely.Methods: Post-transplant antiretroviral management in a prospective study of KT/LT was at the discretion of investigators in collaboration with referring HIV providers. We evaluated the following predictors of post-TX creatinine (Cr) quarterly over 2.5 yrs in univariate (UV) and multivariate (MV) linear repeated measures models: baseline Cr, age, gender, race, detectable HIV RNA pre-TX [LT only], HCV status, donor source and age, marginal donor, and, as time-dependent covariates, detectable HIV RNA, protease inhibitor (PI) use, efavirenz without PI, TDF, ritonavir, TMP-SMX, calcineurin inhibitor (CI) trough, rejection in the prior 3 months and time. Data on duration of TDF use pre-TX and discontinuation reason were not collected. Results: 125 LT (including 9 LT/KT) and 150 KT recipients were followed for a median of 2.3 yrs [IQR 1.0, 3.7] and 2.7 yrs [IQR 1.8, 4.0], respectively. TDF was used pre-TX in 43/150 (29%) KT and 74/125 (59%) LT, with any post-TX TDF use in 52 (35%) KT and 97 (78%) LT. 3 K and 28 L were HBV+. TDF was discontinued in 15 (29%) KT and 27 (28%) LT (3 HBV+). In KT, there was no significant association between TDF and post-TX Cr in a UV model (p=0.58). Male sex, non-white race, rejection, cyclosporine (CsA) trough and time were associated with increased Cr in the MV model. In LT, TDF was marginally associated (p=0.06) with decreased Cr in a UV model but lost significance in the MV model. Higher baseline Cr, CsA trough and time were associated, and age was marginally associated, with increased Cr in the final model. Conclusions: TDF was used more often in LT than KT but was discontinued in over 25% of both. It is not known if TDF was discontinued due to TDF-associated toxicity, nor if continued use would be associated with renal dysfunction in MV models. With careful monitoring and clinical management, TDF appears to be a safe drug to continue or initiate in HIV+ TX recipients. Ongoing follow-up is required to determine the impact of long-term post-TX TDF use.