Background:  Factors associated with renal impairment among patients receiving tenofovir DF (TDF) have not been determined.

Methods:  Between November 2001 and September, 2005, we conducted this observational cohort study of all HIV-infected patients receiving TDF in an urban HIV clinic population. Development of abnormal renal function was defined as an absolute glomerular filtration rate (GFR) ≥90 before initiation of TDF, and <90 at the last creatinine measurement on TDF. We used logistic regression analysis to examine factors associated with abnormal renal function, including ART medications, weight at initiation of TDF, weight change by last measurement on TDF, race, age, gender, CD4 count nadir, HIV-1 RNA level, hepatitis C virus (HCV) antibody, diabetes, and hypertension. We used the Cockcroft-Gault (CG) equation that incorporates body weight to calculate GFR because weight changes are common among HIV-infected patients. We also examined GFR using the modification of diet in renal disease (MDRD) equation.

Results:  Among the 497 patients initiating TDF, 87 patients developed abnormal renal function, which was associated with didanosine (ddI) use (p = 0.009), lower baseline weight (p = 0.001), and older age (p = 0.009) compared with patients with normal renal function. 79 of 87 patients had a moderate decline in GFR (≤60). Of 87 patients, 8 had a severe decline in GFR (>80) that was associated with ritonavir-boosted regimens (p=0.03) containing either amprenavir (p=0.04) or lopinavir (p=0.009), and a trend toward ddI use (38% vs 15%, p = 0.09). After adjusting for other factors, ddI (OR 2.5, p = 0.02), lower baseline weight (OR 0.95/kg, p = 0.001), and increasing age (OR 1.07/year, p <0.002) were significantly associated with abnormal renal function. The results were unchanged when only patients with moderate abnormalities were examined; there were too few patients with severe abnormalities for separate analysis. When GFR was calculated using MDRD, fewer patients had abnormal renal function than when the CG equation was used.

Conclusions:  Increased age, ddI use, and lower baseline weight are significantly associated with risk for renal impairment among patients receiving TDF. GFR results using the MDRD were inconsistent with those calculated using CG which points to the importance of weight in the measurement of GFR among HIV-infected patients. Our findings suggest there may be a moderate and severe category of renal abnormalities associated with TDF and that ritonavir may contribute to severe abnormalities.