Background:  Since its release in 2001, tenofovir (TFV) has been variably associated with renal complications. Most reported cases return to baseline laboratory values after discontinuation of TFV. This study was performed to identify patients who have experienced nephrotoxicity while receiving a TFV-containing ART regimen and to identify potential risk factors for the development of nephrotoxicity.

Methods:  At the Atlanta VA Medical Center, 222 patients who had baseline and follow-up serum creatinine and phosphates were analyzed. Follow-up determinations were made during routine clinical follow-up at 6 weeks, and 3-, 6-, 9-, and 12-month intervals after initiation of TFV. Data on co-morbid conditions and concomitant medications was collected to determine risk factors associated with nephrotoxicity. Renal insufficiency was defined as a ³50% decline in calculated creatinine clearance from baseline. Hypophosphatemia was defined as a single serum phosphate <2.0 mg/dL during the treatment period. Additionally, a composite of nephrotoxicity including both groups was analyzed, as was time to each endpoint.

Results:  At baseline, patients had normal renal functioning (mean baseline SrCr 0.99 (±0.31) mg/dL, mean baseline creatinine clearance 99 (±31.15) mL/min), were highly treatment experienced (only 8 treatment naive (4%)), and had an AIDS diagnosis (188 patients (84.6%)). During the first year of therapy, 38 patients (17.12%) developed nephrotoxicity with 9 (4%) specifically developing renal insufficiency and 29 (13%) hypophosphatemia. Renal insufficiency appeared to be a cumulative toxicity with 56% of these patients experiencing it after >6 months of TFV exposure. Hypophosphatemia appeared to be more of an acute issue with 66% of these patients experiencing this during the first 6 months of TFV. Treatment naïve patients and those with a prior history of amphotericin B exposure were >3 times more likely to develop the composite endpoint of nephrotoxicity (p <0.03, for each). Injecting drug users (RR 3.94 [1.05 to 14.778], p = 0.0329) and treatment naïve patients (RR 11.78 [3.49 to 39.69] p <0.0001) were more likely to specifically develop renal insufficiency (p = 0.0329).

Conclusions:  The incidence of nephrotoxicity in our cohort during the first year of therapy was higher than previously reported in other cohorts. Treatment naïve patients, injecting drug users, and patients with previous exposure to amphotericin B were all at increased risk for renal complications.