title: Fanconi syndrome accompanied by renal function decline with tenofovir disoproxil fumarate: a prospective, case-control study of predictors and resolution in HIV-infected patients.
abstract: OBJECTIVE
  The predictors of Fanconi syndrome (FS) accompanied by renal function decline with use of the antiretroviral tenofovir disoproxil fumarate (TDF) have not been assessed. In addition, the natural history of renal recovery from FS after TDF discontinuation is not well-described.
  
  
  METHODS
  We prospectively enrolled HIV-infected patients receiving TDF with newly identified FS (defined as at least two markers of proximal tubulopathy and either a >25% decline in creatinine clearance (CrCl) from pre-TDF values or a CrCl <60 mL/min in those without a known pre-TDF CrCl) in a multicenter observational study. These case participants were matched 1:2 to controls; characteristics between the two groups were compared. Case participants with known pre-TDF CrCl values were then followed over 48 weeks to assess renal recovery.
  
  
  RESULTS
  Nineteen cases and 37 controls were enrolled. In multivariable analysis, previous or concurrent use of lopinavir/ritonavir [OR 16.37, 95% CI (2.28, 117.68); P = 0.006] and reduced creatinine clearance prior to initiation of TDF [OR 1.44 for every 5 mL/min reduction, 95% CI (1.09, 1.92); P = 0.012; OR 19.77 for pre-TDF CrCl lower than 83 mL/min, 95% CI (2.24, 174.67); P = 0.007] were significantly associated with FS. Of the 14 cases followed for resolution, 7 (50%) achieved at least partial resolution (defined as recovering CrCl >70% of pre-TDF values) although most participants had full normalization of proximal tubulopathy markers within two months of TDF discontinuation.
  
  
  CONCLUSIONS
  FS, defined by specific CrCl decreases and markers of tubulopathy, is more likely in those who have received or are currently receiving concomitant lopinavir/ritonavir or who had lower CrCl prior to TDF initiation. Half of those with protocol-defined FS had CrCl recover to near pre-TDF values during the first year after TDF discontinuation.
authors.affiliation: Division of Infectious Diseases, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Samir K
authors.initials: SK
authors.lastname: Gupta
authors.affiliation: Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Albert M
authors.initials: AM
authors.lastname: Anderson
authors.affiliation: Gilead Sciences, Inc., Foster City, California, United States of America.
authors.forename: Ramin
authors.initials: R
authors.lastname: Ebrahimi
authors.affiliation: Gilead Sciences, Inc., Foster City, California, United States of America.
authors.forename: Todd
authors.initials: T
authors.lastname: Fralich
authors.affiliation: Gilead Sciences, Inc., Foster City, California, United States of America.
authors.forename: Hiba
authors.initials: H
authors.lastname: Graham
authors.affiliation: Gilead Sciences, Inc., Foster City, California, United States of America.
authors.forename: Valeska
authors.initials: V
authors.lastname: Scharen-Guivel
authors.affiliation: Gilead Sciences, Inc., Foster City, California, United States of America.
authors.forename: John F
authors.initials: JF
authors.lastname: Flaherty
authors.affiliation: Hôpital Notre Dame of Montreal University Medical Center, Montreal, Canada.
authors.forename: Claude
authors.initials: C
authors.lastname: Fortin
authors.affiliation: Division of Infectious Diseases, Metrohealth Medical Center, Cleveland, Ohio, United States of America.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kalayjian
authors.affiliation: Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
authors.forename: Anita
authors.initials: A
authors.lastname: Rachlis
authors.affiliation: Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Wyatt
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D016022:Case-Control Studies; D003404:Creatinine / Q000652:urine; D005198:Fanconi Syndrome / Q000150:complications*; D005260:Female; D005919:Glomerular Filtration Rate; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced* / Q000503:physiopathology*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000009:adverse effects* / Q000627:therapeutic use; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D000068698:Tenofovir
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D000068698:Tenofovir; D003404:Creatinine; D000225:Adenine