Associations between urinary kidney injury biomarkers and cardiovascular mortality risk in elderly men with diabetes

Abstract

Aim: Three urinary biomarkers, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and cystatin C, have been suggested as clinically relevant highly specific biomarkers of acute kidney tubular damage. Yet, the utility of these biomarkers in the prognostication of diabetic nephropathy has been less studied. Therefore, we aimed to investigate the longitudinal association between these urinary biomarkers and cardiovascular mortality in patients with diabetes.

Methods: The study sample consisted of participants with diabetes in the community-based Uppsala Longitudinal Study of Adult Men (n = 91; mean age 77.8 years). During follow-up (median 8.3 years, interval 0.7–13.4 years), 33 participants died of cardiovascular causes.

Results: In a multivariable Cox regression model adjusting for age, glomerular filtration rate, and urinary albumin/creatinine ratio, higher urinary KIM-1/creatinine was associated with an increased risk for cardiovascular mortality (HR per SD increase 1.51, 95% confidence intervals 1.03–2.24, P = 0.03). Neither urinary NGAL/creatinine nor urinary cystatin C/creatinine were independently associated with an increased cardiovascular mortality risk.

Conclusion: In elderly men with diabetes, higher urinary KIM-1/creatinine was associated with an increased long-term risk of cardiovascular mortality independently of established markers of diabetic nephropathy. Our data provide support for kidney tubular damage as an important aspect of diabetic nephropathy that merits further investigation.

Key words:

• Biomarkers
• diabetes
• epidemiology
• kidney
• KIM-1

Acknowledgements

Aleksandra Tonkonogi and Axel C. Carlsson contributed equally to the writing of this paper.

Disclosure statement

The authors report no conflicts of interest.

Funding information

This study was supported by The Swedish Research Council, Swedish Heart-Lung foundation, the Marianne and Marcus Wallenberg Foundation, Dalarna University and Uppsala University. The funding sources did not play any role in the design and conduct of the study collection, management, analysis, and interpretation of the data and preparation, review, or approval of the manuscript. Dr Ärnlöv is the guarantor of this work, had full access to all the data, and takes full responsibility for the integrity of data and the accuracy of data analysis.