A signature of circulating inflammatory proteins and development of end-stage renal disease in diabetes
Open accessAbstract
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.
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With advances in multiplexing, investigators can now measure hundreds of immune proteins and transcripts in various matrices.
“With advances in multiplexing, investigators can now measure hundreds of immune proteins and transcripts in various matrices (105, 106).”
From Connecting aging biology and inflammation in the omics era (2022) · cites this paper as [106]
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Self-citation
- Authors
- Niewczas, M. A., Pavkov, M. E., Skupien, J., Smiles, A., Md Dom, Z. I., Wilson, J. M., Park, J., Nair, V., Schlafly, A., Saulnier, P.-J., Satake, E., Simeone, C. A., Shah, H., Qiu, C., Looker, H. C., Fiorina, P., Ware, C. F., Sun, J. K., Doria, A., Kretzler, M., Susztak, K., Duffin, K. L., Nelson, R. G., & Krolewski, A. S.
- Affiliations
- Joslin Diabetes Center (US)
- Centers for Disease Control and Prevention (US)
- Jagiellonian University (PL)
- Eli Lilly (United States) (US)
- University of Pennsylvania (US)
- University of Michigan (US)
- Inserm (FR)
- National Institute of Diabetes and Digestive and Kidney Diseases (US)
- Boston Children's Hospital (US)
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Corresponding author
- Niewczas, Monika A.
- ORCID
- Niewczas, Monika A.
- Pavkov, Meda E.
- Skupien, Jan
- Wilson, Jonathan M.
- Park, Jihwan
- Nair, Viji
- Schlafly, Andrew
- Saulnier, Pierre-Jean
- Satake, Eiichiro
- Shah, Hetal
- Qiu, Chengxiang
- Looker, Helen C.
- Fiorina, Paolo
- Ware, Carl F.
- Sun, Jennifer K.
- Doria, Alessandro
- Kretzler, Matthias
- Susztak, Katalin
- Duffin, Kevin L.
- Nelson, Robert G.
- Krolewski, Andrzej S.
- Venue
- Nature Medicine
- Published
- 2019-04-22
- Volume
- 25
- Issue
- 5
- Pages
- 805-813
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC6508971
- OpenAlex
- W2939798759
- Cited by
- 432
- References
- 68
- Citations by year
- 2026: 39 · 2025: 58 · 2024: 78 · 2023: 61 · 2022: 58 · 2021: 66 · 2020: 53 · 2019: 18
- FWCI
- 37.66
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Homo Politicus (Academy of Humanities and Economics in Lodz) (submittedVersion, cc-by-nc-nd)
- Jagiellonian University Repository (Jagiellonian University) (submittedVersion, other-oa)
- Funders
- Novo Nordisk Fonden (NNF14OC0013659)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK087635, P30DK081943, DP3DK108220, DP3DK112177, R01DK041526, P30DK036836, R01DK076077)
- Topics
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Nephrology › Dialysis and Renal Disease Management
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- end-stage renal disease, diabetic nephropathy, chronic inflammation, circulating inflammatory proteins, type 1 diabetes, type 2 diabetes, TNF receptor superfamily, prognostic factors, therapeutic target
- MeSH terms
- Adult, Aged, Blood Proteins, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Female, Humans, Kidney Failure, Chronic, Male, Middle Aged, Prognosis, Prospective Studies, Risk Factors, Cohort Studies, Biomarkers, Receptors, Tumor Necrosis Factor, Disease Progression, Inflammation Mediators, Proteomics
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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