title: Tenofovir exposure alters associations of serum bicarbonate with chronic kidney disease risk in HIV-infected veterans.
abstract: OBJECTIVE
  Among HIV-infected persons, tenofovir disoproxil fumarate (TDF) use is associated with higher risk of developing chronic kidney disease (CKD). Because lower serum bicarbonate concentrations may precede CKD onset, this study investigated the associations between TDF use and bicarbonate concentrations, and between bicarbonate with CKD risk among TDF users and nonusers.
  
  
  METHODS
  Retrospective cohort study of 16,070 HIV-infected US veterans who initiated antiretroviral therapy between 1997-2011. The association between TDF use with longitudinal bicarbonate concentrations and associations between bicarbonate with incident CKD stratified by TDF use (never, initial, and later user) were evaluated.
  
  
  RESULTS
  Compared with TDF users, never users had faster declines in bicarbonate concentrations: change in bicarbonate -0.11 mmol/l per year (95% confidence interval -0.16, -0.05), compared with -0.04 mmol/l per year (-0.06, 0.05) in initial users and -0.02 mmol/l per year (-0.05, 0.01) in later users. Low baseline bicarbonate (<22 mmol/l) was significantly associated with CKD risk among TDF never users (1.80; 1.21, 2.68), but not among TDF users (0.98; 0.69, 1.38). Similarly, declining bicarbonate concentrations were associated with higher CKD risk among never users (hazard ratio 1.67 per mmol/l; 1.34, 2.08), but not among TDF users (1.09; 0.98, 1.22). Interactions were highly significant for both analyses (P value = 0.001).
  
  
  CONCLUSIONS
  Despite associations with nephrotoxicity, TDF use was associated with higher serum bicarbonate concentrations longitudinally. Additionally, TDF use obscured the strong associations of bicarbonate with CKD risk in HIV-infected persons. Therefore, the role of bicarbonate concentrations as a tool to monitor kidney health in HIV-infected persons may be limited in the setting of TDF use.
authors.affiliation: San Francisco Veterans Affairs Medical Center, San Francisco, California, USA.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Kim
authors.forename: Rebecca
authors.initials: R
authors.lastname: Scherzer
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Estrella
authors.forename: Joachim H
authors.initials: JH
authors.lastname: Ix
authors.forename: Michael G
authors.initials: MG
authors.lastname: Shlipak
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D001639:Bicarbonates / Q000097:blood*; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000453:epidemiology*; D012189:Retrospective Studies; D018570:Risk Assessment; D044967:Serum / Q000737:chemistry; D000068698:Tenofovir / Q000009:adverse effects* / Q000627:therapeutic use*; D014481:United States / Q000453:epidemiology; D014728:Veterans
chemical_list: D019380:Anti-HIV Agents; D001639:Bicarbonates; D000068698:Tenofovir