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

Aleksandra  Tonkonogi; Axel C.  Carlsson; Johanna  Helmersson-Karlqvist; Anders  Larsson; Johan  Ärnlöv

doi:10.1080/03009734.2016.1192704

Aleksandra Tonkonogi Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden
Axel C. Carlsson Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden; and Division of Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden
Johanna Helmersson-Karlqvist Department of Medical Sciences, Biochemical Structure and Function, Uppsala University, Uppsala, Sweden
Anders Larsson Department of Medical Sciences, Biochemical Structure and Function, Uppsala University, Uppsala, Sweden
Johan Ärnlöv Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden; and School of Health and Social Studies, Dalarna University, Falun, Sweden

DOI: https://doi.org/10.1080/03009734.2016.1192704

Keywords: Biomarkers, diabetes, epidemiology, kidney, KIM-1

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.

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