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 microg/liter at baseline to 555 microg/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 0.64 mg/dl to 0.74 mg/dl at week 96 (p = 0.02). The GFR level declined minimally but significantly in TDF-receiving patients (-17 ml/min/1.73 m(2)), whereas it did not change in other NRTI-receiving patients [+ 3 ml/min/1.73 m(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 microg/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 microg/liter and %TRP values <80% are observed, discontinuing TDF may be beneficial.
Department of Hematology, Ogikubo Hospital , Tokyo, Japan 167-8515. ekinai@mui.biglobe.ne.jp
Ei
E
Kinai
Hideji
H
Hanabusa
D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005919:Glomerular Filtration Rate / Q000187:drug effects; D015658:HIV Infections / Q000188:drug therapy* / Q000652:urine / Q000821:virology; D015497:HIV-1; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced*; D007687:Kidney Tubules, Proximal / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000068698:Tenofovir; D013997:Time Factors; D016482:Urinalysis; D055815:Young Adult
D019380:Anti-HIV Agents; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D000225:Adenine