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.

A signature of circulating inflammatory proteins and development of end-stage renal disease in diabetes / M.A. Niewczas, M.E. Pavkov, J. Skupien, A. Smiles, Z.I. Md Dom, J.M. Wilson, J. Park, V. Nair, A. Schlafly, P.-. Saulnier, E. Satake, C.A. Simeone, H. Shah, C. Qiu, H.C. Looker, P. Fiorina, C.F. Ware, J.K. Sun, A. Doria, M. Kretzler, K. Susztak, K.L. Duffin, R.G. Nelson, A.S. Krolewski. - In: NATURE MEDICINE. - ISSN 1078-8956. - 25:5(2019 May), pp. 805-813.

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

P. Fiorina;
2019

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.
Adult; Aged; Biomarkers; Blood Proteins; Cohort Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Progression; Female; Humans; Inflammation Mediators; Kidney Failure, Chronic; Male; Middle Aged; Prognosis; Prospective Studies; Proteomics; Receptors, Tumor Necrosis Factor; Risk Factors
Settore MED/13 - Endocrinologia
mag-2019
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/667597
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