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Clin J Am Soc Nephrol. 2014 Aug 7;9(8):1393-401. doi: 10.2215/CJN.11901113. Epub 2014 Jun 12.

Urinary kidney injury molecule-1 and the risk of cardiovascular mortality in elderly men.

Author information

1
Centre for Family Medicine, Department of Neurobiology, Care Sciences, and Society, Karolinska Institute, Huddinge, Sweden; Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden;
2
Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden;
3
Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden;
4
Department of Clinical Science, Intervention, and Technology, and.
5
Division of Biostatistics, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden; and.
6
Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden; School of Health and Social Studies, Dalarna University, Falun, Sweden johan.arnlov@medsci.uu.se.

Abstract

BACKGROUND AND OBJECTIVES:

Kidney injury molecule-1 (KIM-1) has been suggested as a clinically relevant highly specific biomarker of acute kidney tubular damage. However, community-based data on the association between urinary levels of KIM-1 and the risk for cardiovascular mortality are lacking. This study aimed to investigate the association between urinary KIM-1 and cardiovascular mortality.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:

This was a prospective study, using the community-based Uppsala Longitudinal Study of Adult Men (N=590; mean age 77 years; baseline period, 1997-2001; median follow-up 8.1 years; end of follow-up, 2008).

RESULTS:

During follow-up, 89 participants died of cardiovascular causes (incidence rate, 2.07 per 100 person-years at risk). Models were adjusted for cardiovascular risk factors (age, systolic BP, diabetes, smoking, body mass index, total cholesterol, HDL cholesterol, antihypertensive treatment, lipid-lowering treatment, aspirin treatment, and history of cardiovascular disease) and for markers of kidney dysfunction and damage (cystatin C-based eGFR and urinary albumin/creatinine ratio). Higher urinary KIM-1/creatinine (from 24-hour urine collections) was associated with a higher risk for cardiovascular mortality (hazard ratio per SD increase, 1.27; 95% confidence interval [95% CI], 1.05 to 1.54; P=0.01). Participants with a combination of high KIM-1/creatinine (upper quintile, ≥175 ng/mmol), low eGFR (≤60 ml/min per 1.73 m(2)), and microalbuminuria/macroalbuminuria (albumin/creatinine ratio≥3 g/mol) had a >8-fold increased risk compared with participants with low KIM-1/creatinine (<175 ng/mmol), normal eGFR (>60 ml/min per 1.73 m(2)), and normoalbuminuria (albumin/creatinine ratio<3 g/mol) (hazard ratio, 8.56; 95% CI, 4.17 to 17.56; P<0.001).

CONCLUSIONS:

These findings suggest that higher urinary KIM-1 may predispose to a higher risk of cardiovascular mortality independently of established cardiovascular risk factors, eGFR, and albuminuria. Additional studies are needed to further assess the utility of measuring KIM-1 in the clinical setting.

KEYWORDS:

albuminuria; epidemiology; outcomes; tubule cells

PMID:
24923577
PMCID:
PMC4123404
DOI:
10.2215/CJN.11901113
[Indexed for MEDLINE]
Free PMC Article

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