Journal
AMERICAN JOURNAL OF KIDNEY DISEASES
Volume 64, Issue 1, Pages 49-56Publisher
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1053/j.ajkd.2014.01.432
Keywords
Interleukin 18 (IL-18); kidney injury molecule 1 (KIM-1); cystatin C; heart failure; chronic kidney disease (CKD); risk marker; cardiovascular disease (CVD); albuminuria; kidney tubular injury
Categories
Funding
- NIA [5R01AG027002-07, N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050]
- UCSF-CTSI [TL1 TR000144]
- National Institute of Nursing Research [R01-NR012459]
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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. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use.
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