Blood Protein Signature Reported for Diabetic Kidney Disease

Diabetic nephropathy or diabetic kidney disease (DKD), is a result of vascular abnormalities that accompany diabetes and increases mortality risk. Furthermore, diabetes mellitus is a main risk factor for end-stage renal disease, the most advanced stage of kidney disease.

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. End-stage renal disease (ESRD) in diabetes is a life threatening complication resulting in a poor prognosis for patients as well as high medical costs.

An international team of scientists led by the Harvard Medical School (Boston, MA, USA) examined 194 circulating inflammatory proteins in subjects from three independent cohorts with type 1 and type 2 diabetes. In each cohort, they 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.

The type 1 diabetes group included 108 individuals who developed end-stage renal disease during the study's follow up time, while 35 of the individuals with type 2 diabetes had kidney disease that advanced to that point. Half a dozen of the proteins came from tumor necrosis factor receptor super-families, while the remaining proteins represented receptor or secreted proteins. The team used a custom SOMAscan array (SomaLogic, Boulder, CO, USA), and assessed 194 circulating proteins, focusing on inflammatory proteins and proteins previously implicated in diabetic kidney disease, in blood samples from 219 individuals with type 1 diabetes and a validation group of 144 type 2 diabetes patients, all with some level of kidney impairment.

The authors concluded that 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. Andrzej S. Krolewski, MD, PhD, the senior author of the study, said, “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.” The study was published on April 22, 2019, in the journal Nature Medicine.

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