Researchers integrate multiple protein markers to predict health outcomes in individuals with chronic kidney disease

Prior efforts to identify novel kidney biomarkers as risk factors for chronic kidney disease (CKD) progression have typically evaluated proteins individually, which limits their prognostic power.

The National Institute of Diabetes and Digestive and Kidney Diseases’ (NIDDK’s) CKD Biomarkers Consortium of investigators recently developed and tested novel dimensions of kidney health by combining a set of 17 urine and plasma biomarkers that had been individually associated with CKD progression.

The research was presented at ASN Kidney Week 2024 October 23–27.

The team tested these biomarkers in stored samples taken from 1,256 participants across two cohorts—the NIDDK Chronic Renal Insufficiency Cohort (CRIC), and REasons for Geographic And Racial Differences in Stroke (REGARDS) study—who had diabetes and CKD (defined as an estimated glomerular filtration rate < 60 ml/min/1.73m²).

Three health dimensions comprising 10 biomarkers were derived: systemic inflammation and filtration (plasma TNFR-1, TNFR-2, suPAR, SDMA), tubular function (urine EGF, ADMA, SDMA), and tubular damage (urine α1m, KIM-1, MCP-1).

Each of these health dimensions was associated with CKD progression or mortality, independent of clinical risk factors and other measures of kidney function. Notably, higher tubular damage and lower tubular function scores were associated with higher risk of CKD progression in only one study, while higher systemic inflammation and kidney filtration scores were associated with a higher mortality risk in both studies.

“These findings suggest that a multi-biomarker approach could help clarify the wide variation in CKD progression trajectories among persons with diabetes by simultaneously capturing information on glomerular and tubulointerstitial compartments of the kidney,” said corresponding author Vanessa-Giselle Peschard, MD, of UCSF.

“Further research will be needed to determine whether these kidney health dimensions could offer prognostic value for individual patients or could be used to monitor the response to medications that impact kidney health.”