Integrating Multiple Protein Markers Predicts Health Outcomes in Chronic Kidney Disease Patients

Previous attempts to discover novel kidney biomarkers as risk factors for chronic kidney disease (CKD) progression have generally focused on evaluating proteins individually, which limits their prognostic capability. Now, a research team has developed and tested new dimensions of kidney health by integrating a combination of 17 urine and plasma biomarkers that have been independently linked to CKD progression.

Investigators at the NIDDK CKD Biomarkers Consortium (Bethesda, MD, USA) evaluated these biomarkers in preserved samples from 1,256 participants across two cohorts: the NIDDK Chronic Renal Insufficiency Cohort (CRIC) and the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. All participants had diabetes and CKD, which was defined as an estimated glomerular filtration rate (eGFR) of less than 60 ml/min/1.73m². The researchers identified three health dimensions comprising ten biomarkers: 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 found to be associated with CKD progression or mortality, independent of clinical risk factors and other indicators of kidney function. Notably, higher scores for tubular damage and lower scores for tubular function correlated with an increased risk of CKD progression in one of the studies, while elevated scores for systemic inflammation and kidney filtration were linked to 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.”

Related Links:
CKD Biomarkers Consortium