title: Urinary markers of kidney injury and kidney function decline in HIV-infected women.
abstract: OBJECTIVE
  HIV-infected persons have substantially higher risk of kidney failure than persons without HIV, but serum creatinine levels are insensitive for detecting declining kidney function. We hypothesized that urine markers of kidney injury would be associated with declining kidney function among HIV-infected women.
  
  
  METHODS
  In the Women's Interagency HIV Study, we measured concentrations of albumin-to-creatinine ratio, interleukin-18 (IL-18), kidney injury marker-1 (KIM-1), and neutrophil gelatinase-associated lipocalin from stored urine among 908 HIV-infected and 289 HIV-uninfected participants. Primary analyses used cystatin C-based estimated glomerular filtration rate (CKD-EPI eGFRcys) as the outcome, measured at baseline and 2 follow-up visits over 8 years; secondary analyses used creatinine (CKD-EPI eGFRcr). Each urine biomarker was categorized into tertiles, and kidney decline was modeled with both continuous and dichotomized outcomes.
  
  
  RESULTS
  Compared with the lowest tertiles, the highest tertiles of albumin-to-creatinine ratio (-0.15 mL/min per 1.73 m, P < 0.0001), IL-18 (-0.09 mL/min per 1.73 m, P < 0.0001) and KIM-1 (-0.06 mL/min per 1.73 m, P < 0.001) were independently associated with faster eGFRcys decline after multivariate adjustment including all 3 biomarkers among HIV-infected women. Among these biomarkers, only IL-18 was associated with each dichotomized eGFRcys outcome: ≥3% (relative risk = 1.40; 95% confidence interval: 1.04 to 1.89); ≥5% (1.88; 1.30 to 2.71); and ≥10% (2.16; 1.20 to 3.88) for the highest versus lowest tertile. In alternative models using eGFRcr, the high tertile of KIM-1 had independent associations with 5% (1.71; 1.25 to 2.33) and 10% (1.78; 1.07 to 2.96) decline, and the high IL-18 tertile with 10% decline (1.97; 1.00 to 3.87).
  
  
  CONCLUSIONS
  Among HIV-infected women in the Women's Interagency HIV Study cohort, novel urine markers of kidney injury detect risk for subsequent declines in kidney function.
authors.affiliation: Department of Medicine, San Francisco VA Medical Center, San Francisco, CA 94121, USA. michael.shlipak@ucsf.edu
authors.forename: Michael G
authors.initials: MG
authors.lastname: Shlipak
authors.forename: Rebecca
authors.initials: R
authors.lastname: Scherzer
authors.forename: Alison
authors.initials: A
authors.lastname: Abraham
authors.forename: Phyllis C
authors.initials: PC
authors.lastname: Tien
authors.forename: Carl
authors.initials: C
authors.lastname: Grunfeld
authors.forename: Carmen A
authors.initials: CA
authors.lastname: Peralta
authors.forename: Prasad
authors.initials: P
authors.lastname: Devarajan
authors.forename: Michael
authors.initials: M
authors.lastname: Bennett
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Butch
authors.forename: Kathryn
authors.initials: K
authors.lastname: Anastos
authors.forename: Mardge H
authors.initials: MH
authors.lastname: Cohen
authors.forename: Marek
authors.initials: M
authors.lastname: Nowicki
authors.forename: Anjali
authors.initials: A
authors.lastname: Sharma
authors.forename: Mary A
authors.initials: MA
authors.lastname: Young
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Sarnak
authors.forename: Chirag R
authors.initials: CR
authors.lastname: Parikh
mesh_terms: D016263:AIDS-Associated Nephropathy / Q000209:etiology / Q000503:physiopathology* / Q000652:urine*; D000209:Acute-Phase Proteins / Q000652:urine; D000328:Adult; D000419:Albuminuria / Q000652:urine; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D003404:Creatinine / Q000652:urine; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D015658:HIV Infections / Q000503:physiopathology* / Q000652:urine*; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D020382:Interleukin-18 / Q000652:urine; D007668:Kidney / Q000293:injuries* / Q000503:physiopathology*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008562:Membrane Glycoproteins / Q000652:urine; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000652:urine; D011991:Receptors, Virus; D012307:Risk Factors
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D020382:Interleukin-18; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D011991:Receptors, Virus; D003404:Creatinine