Background:  Several case reports and case series indicate that tenofovir disoproxil fumarate (TDF) may be associated with renal failure. A case control study found that TDF use was associated with a low risk of mild renal impairment. We analyzed longitudinal data from a large cohort study to determine the effect of TDF use on renal function.

Methods:  We used medical records of 11,362 HIV-infected persons receiving care in 10 U.S. cities during 2000-2003 from the CDC’s Adult/Adolescent Spectrum of HIV Disease project. Patients without a history of glomerular filtration rate (GFR) <90 were included in the analysis. Logistic regression was used to evaluate the association of TDF prescription with any renal impairment (GFR <90 mL/min), mild renal impairment (GFR 60 to 89 mL/min), moderate renal impairment (GFR 30 to 59 mL/min), and severe renal impairment (GFR <30 mL/min), controlling for sex, age, race, hypertension, anemia, and CD4 count. GFR was estimated from creatinine measurements using the simplified modified diet in renal disease equation, which considers sex, age, race, and serum creatinine.

Results:  Of 11,362 patients, 3986 (35.1%), 724 (6.4%), and 293 (2.6%) experienced mild, moderate, and severe renal impairment, respectively. Persons prescribed a TDF-containing regimen were more likely to have renal insufficiency (adjusted odds ratio [aOR] 1.6, 95%CI 1.5 to 1.8) compared with those not prescribed TDF. When considering the severity of renal impairment in separate, similarly controlled multivariate models, we found that prescribed TDF was associated with mild renal impairment (aOR 1.6, 95%CI 1.5 to 1.8) and with moderate renal impairment (aOR 1.5, 95%CI 1.1 to 1.9), but not with severe renal impairment (aOR 1.3, 95%CI 0.9 to 1.9) renal impairment. Low CD4 count, history of hypertension, and anemia were associated with increased risk of more severe renal impairment. 

Conclusions:  Our findings demonstrate that TDF is associated with mild and moderate renal impairment, after controlling for other important factors associated with decreased renal function. Physicians should monitor patients receiving TDF and consider that mild or moderate renal impairment may be drug-associated. Further research is needed to determine whether changing from TDF to a different antiretroviral agent in the setting of mild or moderate renal impairment is beneficial in terms of progression to severe renal impairment and long-term survival.