title: Persistent decline in estimated but not measured glomerular filtration rate on tenofovir may reflect tubular rather than glomerular toxicity.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Global Health, Amsterdam Institute for Global Health and Development, Center for Infection and Immunity, Amsterdam, The Netherlands. s.m.vrouenraets@amc.uva.nl
authors.forename: Saskia M E
authors.initials: SM
authors.lastname: Vrouenraets
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Fux
authors.forename: Ferdinand W N M
authors.initials: FW
authors.lastname: Wit
authors.forename: Evian Fernandez
authors.initials: EF
authors.lastname: Garcia
authors.forename: Hansjakob
authors.initials: H
authors.lastname: Furrer
authors.forename: Kees
authors.initials: K
authors.lastname: Brinkman
authors.forename: Frans J
authors.initials: FJ
authors.lastname: Hoek
authors.forename: Nico G G M
authors.initials: NG
authors.lastname: Abeling
authors.forename: Ray T
authors.initials: RT
authors.lastname: Krediet
authors.forename: Peter
authors.initials: P
authors.lastname: Reiss
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives*; D000328:Adult; D000510:Alpha-Globulins; D019380:Anti-HIV Agents / Q000009:adverse effects*; D003404:Creatinine / Q000378:metabolism; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D007678:Kidney Glomerulus / Q000187:drug effects; D007684:Kidney Tubules / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic; D017596:Renal Plasma Flow, Effective / Q000187:drug effects; D012709:Serum Albumin / Q000378:metabolism; D000068698:Tenofovir; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000510:Alpha-Globulins; D019380:Anti-HIV Agents; D063065:Organophosphonates; D012709:Serum Albumin; C016001:alpha-1-microglobulin; D000068698:Tenofovir; D003404:Creatinine; D000225:Adenine