Plasma Biomarkers and Kidney Function Decline in Early and Established Diabetic Kidney Disease.
Pubmed ID: 28476763
Pubmed Central ID: PMC5576932
Journal: Journal of the American Society of Nephrology : JASN
Publication Date: 09/01/2017
Affiliation: Program of Applied Translational Research, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut.
MeSH Terms: Humans, Male, Female, Receptors, Tumor Necrosis Factor, Type II, Aged, Case-Control Studies, Middle Aged, Randomized Controlled Trials as Topic, Disease Progression, Prospective Studies, Prognosis, Diabetic Nephropathies, Predictive Value of Tests, Glomerular Filtration Rate, Diabetes Mellitus, Type 2, Receptors, Tumor Necrosis Factor, Type I, Biomarkers, Hepatitis A Virus Cellular Receptor 1
Grants: UL1 TR000142, K24 DK090203, N01HC95184, Y01 HC001010, Y01 HC009035, N01HC95181, N01HC95179, N01HC95182, N01HC95180, N01HC95178, N01HC95183, P30 DK079310, U01 DK106962, T32 DK007276, R01 DK096549, K23 DK107908, UL1 TR001863
Authors: Coca SG, Parikh CR, Zhang J, Huang Y, Nadkarni GN, Moledina DG, Rao V, Ferket B, Crowley ST, Fried LF
Cite As: Coca SG, Nadkarni GN, Huang Y, Moledina DG, Rao V, Zhang J, Ferket B, Crowley ST, Fried LF, Parikh CR. Plasma Biomarkers and Kidney Function Decline in Early and Established Diabetic Kidney Disease. J Am Soc Nephrol 2017 Sep;28(9):2786-2793. Epub 2017 May 5.
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 (<i>n</i>=190 cases of incident DKD and 190 matched controls) and a prospective cohort study (<i>n</i>=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.