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Am J Kidney Dis. 2014 Jul;64(1):49-56. doi: 10.1053/j.ajkd.2014.01.432. Epub 2014 Mar 18.

Urinary kidney injury molecule 1 (KIM-1) and interleukin 18 (IL-18) as risk markers for heart failure in older adults: the Health, Aging, and Body Composition (Health ABC) Study.

Author information

1
School of Medicine, University of California, San Francisco, CA.
2
Collaborative Health Studies Coordinating Center, University of Washington, Seattle, WA.
3
Division of Nephrology and Hypertension, Department of Medicine, University of California, San Diego, CA; Division of Preventive Medicine, Department of Family and Preventive Medicine, University of California, San Diego, CA; Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, CA.
4
Section of Cardiovascular Medicine, Boston University School of Medicine, Boston, MA.
5
Department of Medicine, University of California, San Francisco, San Francisco, CA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA.
6
Section of Nephrology, Department of Medicine, Yale University, New Haven, CT; Program of Applied Translational Research, Yale University, New Haven, CT.
7
Renal Section, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA.
8
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.
9
Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC.
10
Division of Nephrology, Tufts Medical Center, Boston, MA.
11
Department of Medicine, University of California, San Francisco, San Francisco, CA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA; Department of General Internal Medicine, San Francisco Veterans Affairs Medical Center, San Francisco, CA. Electronic address: michael.shlipak@ucsf.edu.

Abstract

BACKGROUND:

Kidney damage and reduced kidney function are potent risk factors for heart failure, but existing studies are limited to assessing albuminuria or estimated glomerular filtration rate (eGFR). We evaluated the associations of levels of urinary biomarkers of kidney tubular injury (interleukin 18 [IL-18] and kidney injury molecule 1 [KIM-1]) with future risk of heart failure.

STUDY DESIGN:

Retrospective cohort study.

SETTING & PARTICIPANTS:

2,917 participants without heart failure in the Health, Aging, and Body Composition (Health ABC) cohort.

PREDICTORS:

Ratios of urine KIM-1, IL-18, and albumin to creatinine (KIM-1:Cr, IL-18:Cr, and ACR, respectively).

OUTCOMES:

Incident heart failure over a median follow-up of 12 years.

RESULTS:

Median values of each marker at baseline were 812 (IQR, 497-1,235)pg/mg for KIM-1:Cr, 31 (IQR, 19-56)pg/mg for IL-18:Cr, and 8 (IQR, 5-19) mg/g for ACR. 596 persons developed heart failure during follow-up. The top quartile of KIM-1:Cr was associated with risk of incident heart failure after adjustment for baseline eGFR, heart failure risk factors, and ACR (HR, 1.32; 95% CI, 1.02-1.70) in adjusted multivariate proportional hazards models. The top quartile of IL-18:Cr also was associated with heart failure in a model adjusted for risk factors and eGFR (HR, 1.35; 95% CI, 1.05-1.73), but was attenuated by adjustment for ACR (HR, 1.15; 95% CI, 0.89-1.48). The top quartile of ACR had a stronger adjusted association with heart failure (HR, 1.96; 95% CI, 1.53-2.51).

LIMITATIONS:

Generalizability to other populations is uncertain.

CONCLUSIONS:

Higher urine KIM-1 concentrations were associated independently with incident heart failure risk, although the associations of higher ACR were of stronger magnitude.

KEYWORDS:

Interleukin 18 (IL-18); albuminuria; cardiovascular disease (CVD); chronic kidney disease (CKD); cystatin C; heart failure; kidney injury molecule 1 (KIM-1); kidney tubular injury; risk marker

PMID:
24656453
PMCID:
PMC4069223
DOI:
10.1053/j.ajkd.2014.01.432
[Indexed for MEDLINE]
Free PMC Article
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