Journal article
Plasma Biomarkers and Kidney Function Decline in Early and Established Diabetic Kidney Disease
Journal of the American Society of Nephrology, Vol.28(9), pp.2786-2793
09/01/2017
DOI: 10.1681/ASN.2016101101
PMCID: PMC5576932
PMID: 28476763
Abstract
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 (n=190 cases of incident DKD and 190 matched controls) and a prospective cohort study (n=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-1were roughly two-fold higher in the advancedDKD population (NEPHRON-D) than in the earlyDKDpopulation (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.
Details
- Title: Subtitle
- Plasma Biomarkers and Kidney Function Decline in Early and Established Diabetic Kidney Disease
- Creators
- Steven G. Coca - Icahn School of Medicine at Mount SinaiGirish N. Nadkarni - Icahn School of Medicine at Mount SinaiYuan Huang - Yale UniversityDennis G. Moledina - Yale UniversityVeena Rao - Yale UniversityJane Zhang - Veterans Health AdministrationBart Ferket - Icahn School of Medicine at Mount SinaiSusan T. Crowley - Veterans Health AdministrationLinda F. Fried - Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USAChirag R. Parikh - Veterans Health Administration
- Resource Type
- Journal article
- Publication Details
- Journal of the American Society of Nephrology, Vol.28(9), pp.2786-2793
- Publisher
- Amer Soc Nephrology
- DOI
- 10.1681/ASN.2016101101
- PMID
- 28476763
- PMCID
- PMC5576932
- ISSN
- 1046-6673
- eISSN
- 1533-3450
- Number of pages
- 8
- Grant note
- Centers for Disease Control and Prevention; United States Department of Health & Human Services; Centers for Disease Control & Prevention - USA UL1TR000142 / NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS) N01-HC-95178; N01-HC-95179; N01-HC95180; N01-HC-95181; N01-HC-95182; N01-HC-95183; N01-HC95184; IAA-Y1-HC-9035; IAA-Y1-HC-1010 / National Heart, Lung, and Blood Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) General Clinical Research Centers; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) NIDDK; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) K24-DK090203 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R43HL095181 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) P30-DK079310-07 / O'Brien Center grant National Eye Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI) 16MCPRP31030016 / American Heart Association National Institute on Aging; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) R01DK096549 / National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) 1U01DK106962-01 / Chronic Kidney Disease Biomarker Consortium UL1 TR000142 / Clinical and Translational Science Award from the National Center for Advancing Translational Science, a component of the NIH Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development, VA-NEPHRON-D K23DK107908 / National Institutes of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA K23DK107908 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)
- Language
- English
- Date published
- 09/01/2017
- Academic Unit
- Biostatistics
- Record Identifier
- 9984364407002771
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