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. 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

Todd H Driver  1 , Ronit Katz  2 , Joachim H Ix  3 , Jared W Magnani  4 , Carmen A Peralta  5 , Chirag R Parikh  6 , Linda Fried  7 , Anne B Newman  8 , Stephen B Kritchevsky  9 , Mark J Sarnak  10 , Michael G Shlipak  11 ; Health ABC Study
Collaborators, Affiliations

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

Todd H Driver et al. Am J Kidney Dis. 2014 Jul.

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.

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Figures

Figure 1
Figure 1
Association of baseline KIM-1/Cr, IL-18/Cr, and ACR with incident heart failure. Solid lines denote the HR of incident heart failure (with dotted 95% CI bounds) calculated from unadjusted generalized additive models. Each line on the x-axis represents one study participant. The lowest and highest 2.5% of urine biomarker concentrations are truncated.
See this image and copyright information in PMC

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