A signature of circulating inflammatory proteins and development of end-stage renal disease in diabetes.

Abstract	Chronic inflammation is postulated to be involved in the development of end-stage renal disease in diabetes, but which specific circulating inflammatory proteins contribute to this risk remain unknown. To study this, we examined 194 circulating inflammatory proteins in subjects from three independent cohorts with type 1 and type 2 diabetes. In each cohort, we identified an extremely robust kidney risk inflammatory signature (KRIS), consisting of 17 proteins enriched in tumor necrosis factor-receptor superfamily members, that was associated with a 10-year risk of end-stage renal disease. All these proteins had a systemic, non-kidney source. Our prospective study findings provide strong evidence that KRIS proteins contribute to the inflammatory process underlying end-stage renal disease development in both types of diabetes. These proteins point to new therapeutic targets and new prognostic tests to identify subjects at risk of end-stage renal disease, as well as biomarkers to measure responses to treatment of diabetic kidney disease.
Authors	Monika A Niewczas, Meda E Pavkov, Jan Skupien, Adam Smiles, Zaipul I Md Dom, Jonathan M Wilson, Jihwan Park, Viji Nair, Andrew Schlafly, Pierre-Jean Saulnier, Eiichiro Satake, Christopher A Simeone, Hetal Shah, Chengxiang Qiu, Helen C Looker, Paolo Fiorina, Carl F Ware, Jennifer K Sun, Alessandro Doria, Matthias Kretzler, Katalin Susztak, Kevin L Duffin, Robert G Nelson, Andrzej S Krolewski
Journal	Nature medicine (Nat Med) Vol. 25 Issue 5 Pg. 805-813 (05 2019) ISSN: 1546-170X [Electronic] United States
PMID	31011203 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Biomarkers Blood Proteins Inflammation Mediators Receptors, Tumor Necrosis Factor
Topics	Adult Aged Biomarkers (blood) Blood Proteins (genetics, metabolism) Cohort Studies Diabetes Mellitus, Type 1 (blood, complications, genetics) Diabetes Mellitus, Type 2 (blood, complications, genetics) Diabetic Nephropathies (blood, etiology, genetics) Disease Progression Female Humans Inflammation Mediators (blood) Kidney Failure, Chronic (blood, etiology, genetics) Male Middle Aged Prognosis Prospective Studies Proteomics Receptors, Tumor Necrosis Factor (blood, genetics) Risk Factors

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