Plasma Biomarkers and Kidney Function Decline in Early and Established Diabetic Kidney Disease

Biomarkers of diverse pathophysiologic mechanisms may improve risk stratification for incident or progressive diabetic kidney disease (DKD) in persons with type 2 diabetes. To evaluate such biomarkers, we performed a nested case-control study ( =190 cases of incident DKD and 190 matched controls) an...

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Published in:	Journal of the American Society of Nephrology 2017-09, Vol.28 (9), p.2786-2793
Main Authors:	Coca, Steven G, Nadkarni, Girish N, Huang, Yuan, Moledina, Dennis G, Rao, Veena, Zhang, Jane, Ferket, Bart, Crowley, Susan T, Fried, Linda F, Parikh, Chirag R
Format:	Article
Language:	eng
Subjects:	Aged Biomarkers - blood Case-Control Studies Clinical Research Diabetes Mellitus, Type 2 - complications Diabetic Nephropathies - blood Diabetic Nephropathies - etiology Diabetic Nephropathies - physiopathology Disease Progression Female Glomerular Filtration Rate Hepatitis A Virus Cellular Receptor 1 - blood Humans Male Middle Aged Predictive Value of Tests Prognosis Prospective Studies Randomized Controlled Trials as Topic Receptors, Tumor Necrosis Factor, Type I - blood Receptors, Tumor Necrosis Factor, Type II - blood
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Summary:	Biomarkers of diverse pathophysiologic mechanisms may improve risk stratification for incident or progressive diabetic kidney disease (DKD) in persons with type 2 diabetes. To evaluate such biomarkers, we performed a nested case-control study ( =190 cases of incident DKD and 190 matched controls) and a prospective cohort study ( =1156) using banked baseline plasma samples from participants of randomized, controlled trials of early (ACCORD) and advanced (VA NEPHRON-D) DKD. We assessed the association and discrimination obtained with baseline levels of plasma TNF receptor-1 (TNFR-1), TNFR-2, and kidney injury molecule-1 (KIM-1) for the outcomes of incident DKD (ACCORD) and progressive DKD (VA-NEPHRON-D). At baseline, median concentrations of TNFR-1, TNFR-2, and KIM-1 were roughly two-fold higher in the advanced DKD population (NEPHRON-D) than in the early DKD population (ACCORD). In both cohorts, patients who reached the renal outcome had higher baseline levels than those who did not reach the outcome. Associations between doubling in TNFR-1, TNFR-2, and KIM-1 levels and risk of the renal outcomes were significant for both cohorts. Inclusion of these biomarkers in clinical models increased the area under the curve (SEM) for predicting the renal outcome from 0.68 (0.02) to 0.75 (0.02) in NEPHRON-D. Systematic review of the literature illustrated high consistency in the association between these biomarkers of inflammation and renal outcomes in DKD. In conclusion, TNFR-1, TNFR-2, and KIM-1 independently associated with higher risk of eGFR decline in persons with early or advanced DKD. Moreover, addition of these biomarkers to clinical prognostic models significantly improved discrimination for the renal outcome.
ISSN:	1046-6673 1533-3450