title: Urinary biomarkers of kidney injury are associated with all-cause mortality in the Women's Interagency HIV Study (WIHS).
abstract: OBJECTIVE
  Chronic kidney disease (CKD) is common in HIV-infected individuals, and is associated with mortality in both the HIV-infected and general populations. Urinary markers of tubular injury have been associated with future kidney disease risk, but associations with mortality are unknown.
  
  
  METHODS
  We evaluated the associations of urinary interleukin-18 (IL-18), liver fatty acid binding protein (L-FABP), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) and the albumin-to-creatinine ratio (ACR) with 10-year, all-cause death in 908 HIV-infected women. Serum cystatin C was used to estimate the glomerular filtration rate (eGFRcys).
  
  
  RESULTS
  There were 201 deaths during 9269 person-years of follow-up. After demographic adjustment, compared with the lowest tertile, the highest tertiles of IL-18 [hazard ratio (HR) 2.54; 95% confidence interval (CI) 1.75-3.68], KIM-1 (HR 2.04; 95% CI 1.44-2.89), NGAL (HR 1.50; 95% CI 1.05-2.14) and ACR (HR 1.63; 95% CI 1.13-2.36) were associated with higher mortality. After multivariable adjustment including adjustment for eGFRcys, only the highest tertiles of IL-18 (HR 1.88; 95% CI 1.29-2.74) and ACR (HR 1.46; 95% CI 1.01-2.12) remained independently associated with mortality. Findings for KIM-1 were borderline (HR 1.41; 95% CI 0.99-2.02). We found a J-shaped association between L-FABP and mortality. Compared with persons in the lowest tertile, the HR for the middle tertile of L-FABP was 0.67 (95% CI 0.46-0.98) after adjustment. Associations were stronger when IL-18, ACR and L-FABP were simultaneously included in models.
  
  
  CONCLUSIONS
  Among HIV-infected women, some urinary markers of tubular injury are associated with mortality risk, independently of eGFRcys and ACR. These markers represent potential tools with which to identify early kidney injury in persons with HIV infection.
authors: Department of Medicine, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, CA, USA.
authors: Ca
authors: C
authors: Peralta
authors: R
authors: R
authors: Scherzer
authors: C
authors: C
authors: Grunfeld
authors: A
authors: A
authors: Abraham
authors: Pc
authors: P
authors: Tien
authors: P
authors: P
authors: Devarajan
authors: M
authors: M
authors: Bennett
authors: Aw
authors: A
authors: Butch
authors: K
authors: K
authors: Anastos
authors: Mh
authors: M
authors: Cohen
authors: M
authors: M
authors: Nowicki
authors: A
authors: A
authors: Sharma
authors: Ma
authors: M
authors: Young
authors: Mj
authors: M
authors: Sarnak
authors: Cr
authors: C
authors: Parikh
authors: Mg
authors: M
authors: Shlipak
mesh_terms: D016263:AIDS-Associated Nephropathy / Q000401:mortality / Q000652:urine*; D000209:Acute-Phase Proteins / Q000652:urine; D000328:Adult; D000419:Albuminuria; D015415:Biomarkers / Q000652:urine; D015331:Cohort Studies; D003404:Creatinine / Q000652:urine; D050556:Fatty Acid-Binding Proteins / Q000652:urine; D005260:Female; D015658:HIV Infections / Q000401:mortality / Q000652:urine; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D020382:Interleukin-18 / Q000652:urine; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008562:Membrane Glycoproteins / Q000652:urine; D008875:Middle Aged; D011237:Predictive Value of Tests; D011518:Proto-Oncogene Proteins / Q000652:urine; D011991:Receptors, Virus; D051436:Renal Insufficiency, Chronic / Q000401:mortality*
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C493319:FABP1 protein, human; D050556:Fatty Acid-Binding Proteins; 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
keywords: HIV; interleukin-18; kidney injury molecule-1; liver fatty acid binding protein; neutrophil gelatinase-associated lipocalin; urinary biomarkers