A signature of circulating inflammatory proteins and development of end-stage renal disease in diabetes
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 independen...
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| Published in | Nature medicine Vol. 25; no. 5; pp. 805 - 813 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
New York
Nature Publishing Group US
01.05.2019
Nature Publishing Group |
| Subjects | |
| Online Access | Get full text |
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| Summary: | 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 robust signature of circulating inflammatory proteins is causally associated with 10-year risk of progression to end-stage renal disease in diabetic patients |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Author Contributions: M.A.N. contributed to the design of the study, supervised proteomics data collection, conducted the data analysis, interpreted the results and wrote the manuscript. J.K.S, A.S. A.S., E.S. and C.A.S. were involved in data collection, data management of the Joslin Kidney Study, performed preliminary data analyses and reviewed the manuscript. A.D., Z.I.M.D, H.S. and J.K.S. designed the Joslin study on retinopathy, contributed to eye data collection and analysis, edited and reviewed the manuscript. R.G.N., M.E.P., P.-J.S. and H.C.L. were responsible for design and implementation of the Pima Indian Study, contributed to the proteomic data collection in the Pima Indian Study, performed preliminary data analysis, and reviewed and edited the manuscript. M.K., V.N. and R.G.N. designed the expression study in Pima Indians, provided data analysis, reviewed the manuscript. J.P., C.Q. and K.S. designed the expression study (1KGP) to be used in the current study, performed the data analyses and interpreted the results and edited the manuscript. P.F. and C.F.W. were involved in the interpretation of the results of the study and edited the manuscript. K.L.D. and J.M.W. provided the samples from the baricitinib study, facilitated measurements on the Olink platform, reviewed the analysis, reviewed and edited the manuscript. A.S.K designed the whole study, supervised all aspects of the study implementation, planned and contributed the data analysis, interpreted the data, and contributed to the manuscript writing. M.A.N. and A.S.K. are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of data and the accuracy of the data analysis. |
| ISSN: | 1078-8956 1546-170X 1546-170X |
| DOI: | 10.1038/s41591-019-0415-5 |