Persistent decline in estimated but not measured glomerular filtration rate on tenofovir may reflect tubular rather than glomerular toxicity

AIDS. 2011 Nov 13;25(17):2149-55. doi: 10.1097/QAD.0b013e32834bba87.


Background: Tenofovir disoproxil fumarate (TDF) has been associated with proximal renal tubulopathy and reduction in estimated glomerular filtration rate (eGFR), without accounting for the tubular secretion of creatinine.

Methods: A substudy was performed among 19 participants of a randomized 48-week trial, comparing continuing first-line zidovudine/lamivudine (ZDV/3TC) with switching to TDF/emtricitabine (FTC). GFR was measured with [(125)I]-iothalamate (mGFR) and effective renal plasma flow (ERPF) with [(131)I]-hippuran. eGFR and tubular effects were assessed using plasma and urine samples.

Results: Of the 19 patients, 18 were men, 15 whites, mean (SD) age 46.0 (8.9) years, plasma HIV-1 RNA less than 50 copies/ml in all. After 48 weeks, eGFR using Cockcroft-Gault equation and ERPF, but not mGFR, had significantly decreased, and urinary α1-microglobulin/creatinine and microalbumin/creatinine significantly increased in patients on TDF. Although phosphate metabolism on TDF was affected at week 4, differences between groups disappeared during follow-up.

Conclusion: Replacing ZDV/3TC with TDF/FTC in this limited sample of virologically suppressed HIV-1-infected adults was associated with mild persistent tubular but not glomerular dysfunction over 48 weeks. The observed persistent decrease in Cockcroft-Gault-based eGFR, but not mGFR, rather than being indicative of glomerular dysfunction may be explained by TDF inhibiting tubular creatinine excretion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / adverse effects
  • Adenine / analogs & derivatives*
  • Adult
  • Alpha-Globulins
  • Anti-HIV Agents / adverse effects*
  • Creatinine / metabolism
  • Female
  • Glomerular Filtration Rate / drug effects*
  • HIV Infections / drug therapy*
  • HIV-1*
  • Humans
  • Kidney Glomerulus / drug effects
  • Kidney Tubules / drug effects*
  • Male
  • Middle Aged
  • Organophosphonates / adverse effects*
  • Randomized Controlled Trials as Topic
  • Renal Plasma Flow, Effective / drug effects
  • Serum Albumin / metabolism
  • Tenofovir
  • Time Factors
  • Treatment Outcome


  • Alpha-Globulins
  • Anti-HIV Agents
  • Organophosphonates
  • Serum Albumin
  • alpha-1-microglobulin
  • Tenofovir
  • Creatinine
  • Adenine