期刊
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
卷 28, 期 9, 页码 2786-2793出版社
AMER SOC NEPHROLOGY
DOI: 10.1681/ASN.2016101101
关键词
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资金
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01DK096549]
- National Institutes of Health (NIH) [K23DK107908]
- NIH [K24-DK090203]
- O'Brien Center grant [P30-DK079310-07]
- Chronic Kidney Disease Biomarker Consortium [1U01DK106962-01]
- Clinical and Translational Science Award from the National Center for Advancing Translational Science, a component of the NIH [UL1 TR000142]
- American Heart Association [16MCPRP31030016]
- National Heart, Lung, and Blood Institute [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]
- NIDDK
- National Institute on Aging
- National Eye Institute
- Centers for Disease Control and Prevention
- General Clinical Research Centers
- Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development, VA-NEPHRON-D
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.
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