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


CONCLUSIONS
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.
a Department of Medical Sciences , Cardiovascular Epidemiology, Uppsala University , Uppsala , Sweden ;
Aleksandra
A
Tonkonogi
a Department of Medical Sciences , Cardiovascular Epidemiology, Uppsala University , Uppsala , Sweden ;|b Division of Family Medicine, Department of Neurobiology, Care Sciences and Society , Karolinska Institutet , Huddinge , Sweden ;
Axel C
AC
Carlsson
c Department of Medical Sciences, Biochemical Structure and Function , Uppsala University , Uppsala , Sweden ;
Johanna
J
Helmersson-Karlqvist
c Department of Medical Sciences, Biochemical Structure and Function , Uppsala University , Uppsala , Sweden ;
Anders
A
Larsson
a Department of Medical Sciences , Cardiovascular Epidemiology, Uppsala University , Uppsala , Sweden ;|d School of Health and Social Studies , Dalarna University , Falun , Sweden.
Johan
J
Ärnlöv
D058186:Acute Kidney Injury / Q000652:urine; D000368:Aged; D015415:Biomarkers / Q000652:urine*; D002318:Cardiovascular Diseases / Q000150:complications / Q000401:mortality / Q000652:urine*; D055316:Cystatin C / Q000652:urine; D048909:Diabetes Complications / Q000401:mortality / Q000652:urine; D003920:Diabetes Mellitus / Q000401:mortality / Q000652:urine*; D003928:Diabetic Nephropathies / Q000652:urine; D000072596:Hepatitis A Virus Cellular Receptor 1 / Q000032:analysis; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism; D000071068:Lipocalin-2 / Q000652:urine; D008137:Longitudinal Studies; D008297:Male; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors
D015415:Biomarkers; D055316:Cystatin C; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; C489506:LCN2 protein, human; D000071068:Lipocalin-2
Biomarkers; KIM-1; diabetes; epidemiology; kidney