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Urinary kidney injury molecule-1 and the risk of cardiovascular mortality in elderly men
Axel C Carlsson1, Anders Larsson2, Johanna Helmersson-Karlqvist2
1Centre 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;
Insights
Higher urinary Kidney Injury Molecule-1 (KIM-1) levels are linked to an increased risk of cardiovascular mortality in men. This association persists even after accounting for traditional cardiovascular risk factors and kidney dysfunction markers.
Area of Science:
- Nephrology
- Cardiology
- Biomarker Research
Background:
- Kidney injury molecule-1 (KIM-1) is a specific biomarker for acute kidney tubular damage.
- Community-based data on urinary KIM-1 and cardiovascular mortality risk are limited.
Purpose of the Study:
- To investigate the association between urinary KIM-1 levels and cardiovascular mortality.
- To determine if KIM-1 is an independent predictor of cardiovascular death.
Main Methods:
- Prospective study of 590 men (mean age 77) from the Uppsala Longitudinal Study of Adult Men.
- Median follow-up of 8.1 years, with adjustment for cardiovascular risk factors and kidney dysfunction markers (eGFR, albuminuria).
Main Results:
- Higher urinary KIM-1/creatinine was associated with increased cardiovascular mortality risk (HR per SD increase, 1.27; P=0.01).
- A combination of high KIM-1, low eGFR, and albuminuria indicated a >8-fold increased risk of cardiovascular mortality (HR, 8.56; P<0.001).
Conclusions:
- Elevated urinary KIM-1 may indicate a predisposition to higher cardiovascular mortality risk.
- KIM-1's predictive value is independent of established cardiovascular risk factors, eGFR, and albuminuria.
- Further research is needed to evaluate KIM-1's clinical utility.
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.
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