Progressive Renal Tubular Dysfunction Associated with Long-Term Use of Tenofovir DF

It became evident that tenofovir DF (TDF) causes a modest and gradual decline in GFR, however, the impact of long-term use of TDF on tubular function has not been fully evaluated. In 40 patients treated with TDF and 23 patients treated with other NRTIs, urine beta(2)-microglobulin (U-BMG), percentage tubular reabsorption of phosphate (%TRP), alkaline phosphatase (ALP), serum creatinine, and calculated GFR were prospectively measured for 96 weeks. In patients receiving TDF, median U-BMG rose from 188 mu g=liter at baseline to 555 mu g=liter at week 96 (p=0.02), median % TRP declined from 94% at baseline to 90% at week 96 (p=0.002), median ALP ratio compared with baseline persistently increased from 1 to 1.278 at week 96 (p=0.001), and serum creatinine showed significant but minimal change from 0.64mg=dl to 0.74mg=dl at week 96 (p=0.02). The GFR level declined minimally but significantly in TDF-receiving patients (-17 ml=min=1.73m(2)), whereas it did not change in other NRTI-receiving patients [+ 3ml=min=1.73m(2); mixed models analysis of variance (MMANOVA) p=0.03 for overall change from baseline to week 96]. U-BMG, % TRP, ALP, or serum creatinine did not change significantly in other NRTI-receiving patients during the observation period. In five patients with marked changes in U-BMG (>10,000 mu g=liter) and % TRP (<80%), both U-BMG and % TRP immediately recovered in all patients after discontinuing TDF, whereas GFR levels did not fully recover for 6 months in three patients. Prolonged treatment with TDF caused progressive renal tubular dysfunction as well as a modest decline in GFR. If U-BMG levels >10,000 mu g=liter and % TRP values <80% are observed, discontinuing TDF may be beneficial.