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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Blood Proteins / genetics
  • Blood Proteins / metabolism
  • Cohort Studies
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetic Nephropathies / blood*
  • Diabetic Nephropathies / etiology*
  • Diabetic Nephropathies / genetics
  • Disease Progression
  • Female
  • Humans
  • Inflammation Mediators / blood
  • Kidney Failure, Chronic / blood*
  • Kidney Failure, Chronic / etiology*
  • Kidney Failure, Chronic / genetics
  • Male
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • Proteomics
  • Receptors, Tumor Necrosis Factor / blood
  • Receptors, Tumor Necrosis Factor / genetics
  • Risk Factors


  • Biomarkers
  • Blood Proteins
  • Inflammation Mediators
  • Receptors, Tumor Necrosis Factor