Format

Send to

Choose Destination
Nat Med. 2019 May;25(5):805-813. doi: 10.1038/s41591-019-0415-5. Epub 2019 Apr 22.

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

Author information

1
Research Division, Joslin Diabetes Center, Boston, MA, USA. Monika.Niewczas@joslin.harvard.edu.
2
Department of Medicine, Harvard Medical School, Boston, MA, USA. Monika.Niewczas@joslin.harvard.edu.
3
Division of Diabetes Translation, Centers for Disease Control and Prevention, Atlanta, GA, USA.
4
Research Division, Joslin Diabetes Center, Boston, MA, USA.
5
Department of Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland.
6
Department of Medicine, Harvard Medical School, Boston, MA, USA.
7
Diabetes and Complications Department, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.
8
Renal Electrolyte and Hypertension Division, Department of Medicine, Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
9
Nephrology/Internal Medicine and Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
10
Chronic Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, USA.
11
CHU Poitiers, University of Poitiers, Inserm, Clinical Investigation Center CIC1402, Poitiers, France.
12
Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
13
Romeo ed Enrica Invernizzi Pediatric Center, Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy.
14
Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
15
Research Division, Joslin Diabetes Center, Boston, MA, USA. Andrzej.Krolewski@joslin.harvard.edu.
16
Department of Medicine, Harvard Medical School, Boston, MA, USA. Andrzej.Krolewski@joslin.harvard.edu.

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.

PMID:
31011203
PMCID:
PMC6508971
[Available on 2019-10-22]
DOI:
10.1038/s41591-019-0415-5

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center