title: Association of urinary injury biomarkers with mortality and cardiovascular events.
abstract: Kidney damage is a common sequela of several chronic pathologic conditions. Whether biomarkers of kidney damage are prognostic for more severe outcomes is unknown. We measured three urinary biomarkers (kidney injury molecule-1 [KIM-1], IL-18, and albumin) in 3010 individuals enrolled in the Health, Aging and Body Composition (Health ABC) study and used Cox proportional hazards models to investigate the associations of urinary KIM-1/creatinine (cr), IL-18/cr, and albumin/cr (ACR) with all-cause mortality and cardiovascular disease (CVD). Multivariable models adjusted for demographics, traditional CVD risk factors, and eGFR. Mean age of participants was 74 years, 49% of participants were men, and 41% of participants were black. During the median 12.4 years of follow-up, 1450 deaths and 797 CVD outcomes occurred. Compared with the lowest quartile, successive quartiles had the following adjusted hazard ratios (HRs; 95% confidence intervals [95% CIs]) for mortality: KIM-1/cr: (1.21; 1.03 to 1.41), (1.13; 0.96 to 1.34), and (1.28; 1.08 to 1.52); IL-18/cr: (1.02; 0.88 to 1.19), (1.16; 0.99 to 1.35), and (1.06; 0.90 to 1.25); ACR: (1.08; 0.91 to 1.27), (1.24; 1.06 to 1.46), and (1.63; 1.39 to 1.91). In similar analyses, only ACR quartiles associated with CVD: (1.19; 0.95 to 1.48), (1.35; 1.08 to 1.67), and (1.54; 1.24 to 1.91). Urinary KIM-1 had a modest association with all-cause mortality but did not associate with CVD, and urinary IL-18 did not associate with either outcome. In contrast, albuminuria strongly associated with all-cause mortality and CVD. Future studies should evaluate reasons for these differences in the prognostic importance of individual kidney injury markers.
authors: Division of Nephrology, Tufts Medical Center, Boston, Massachusetts; msarnak@tuftsmedicalcenter.org.
authors: Mark J
authors: MJ
authors: Sarnak
authors: Kidney Research Institute, University of Washington, Seattle, Washington;
authors: Ronit
authors: R
authors: Katz
authors: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania;
authors: Anne
authors: A
authors: Newman
authors: Geriatric Epidemiology Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland;
authors: Tamara
authors: T
authors: Harris
authors: Department of Medicine, University of California and San Francisco Veterans Affairs Medical Center, San Francisco, California;
authors: Carmen A
authors: CA
authors: Peralta
authors: Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio;
authors: Prasad
authors: P
authors: Devarajan
authors: Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio;
authors: Michael R
authors: MR
authors: Bennett
authors: Renal-Electrolyte Division and Renal Section, University of Pittsburgh School of Medicine and Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania;
authors: Linda
authors: L
authors: Fried
authors: Nephrology Section, Veterans Affairs San Diego Healthcare System and Divisions of Nephrology and Preventive Medicine, University of California, San Diego, California;
authors: Joachim H
authors: JH
authors: Ix
authors: Department of Preventive Medicine, University of Tennessee, Memphis, Tennessee;
authors: Suzanne
authors: S
authors: Satterfield
authors: Intramural Research Program, National Institute on Aging, Baltimore, Maryland;
authors: Eleanor M
authors: EM
authors: Simonsick
authors: Section of Nephrology, Department of Medicine and Program of Applied Translational Research, Yale University, New Haven, Connecticut; and.
authors: Chirag R
authors: CR
authors: Parikh
authors: Division of General Internal Medicine, San Francisco Veterans Affairs Medical Center, Departments of Medicine, Epidemiology and Biostatistics, University of California, San Francisco, California.
authors: Michael G
authors: MG
authors: Shlipak
mesh_terms: D000368:Aged; D000419:Albuminuria / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D002318:Cardiovascular Diseases / Q000401:mortality* / Q000652:urine*; D002423:Cause of Death; D005260:Female; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D020382:Interleukin-18 / Q000652:urine*; D008297:Male; D008562:Membrane Glycoproteins / Q000652:urine*; D011991:Receptors, Virus
chemical_list: D015415:Biomarkers; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D020382:Interleukin-18; D008562:Membrane Glycoproteins; D011991:Receptors, Virus