Strength in numbers: the power of 17 biomarkers for predicting kidney disease progression
The whole is greater than the sum of its parts – this new study combines 17 individual plasma and urine biomarkers to improve predictions for chronic kidney disease progression.
Previous attempts to identify new kidney biomarkers as risk factors for chronic kidney disease (CKD) progression have focused on evaluating implicated proteins individually, which has limited their prognostic value. The National Institute of Diabetes and Digestive and Kidney Diseases’ (NIDDK’s) (MD, USA) CKD Biomarkers Consortium of investigators have overcome this limitation by integrating a set of 17 urine and plasma biomarkers, each previously linked to CKD progression, into their new measure of kidney health. Using Cox proportional hazards models, they assessed the relationships of these biomarkers with CKD progression and mortality. Their research was presented at ASN Kidney Week 2024 (October 23–27; 2024; CA, USA).
CKD is a condition that causes a gradual loss of kidney function, potentially progressing to end-stage kidney failure, which is fatal without dialysis or a kidney transplant. CKD affects over 10% of the global population and is a leading cause of death. Although early diagnosis and management of CKD can help slow progression and prevent end-stage kidney failure, the early stages of CKD are often asymptomatic, so it usually passes by unnoticed. CKD also has numerous causes and a complex interplay of risk factors, which make the disease even more difficult to predict and manage. Because of this, current early detection methods are often inadequate. However, advancements in analytical techniques for kidney biomarkers now offer a promising opportunity to improve the diagnosis and management of CKD progression.
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Using stored samples drawn from 1,256 participants, the research team examined these 17 biomarkers across two cohorts who both had diabetes and CDK. The two cohorts consisted of the NIDDK Chronic Renal Insufficiency Cohort, and REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Three health dimensions containing 10 biomarkers were identified: systemic inflammation and filtration (including biomarkers plasma TNFR-1, TNFR-2, suPAR and SDMA), tubular function (including biomarkers urine EGF, ADMA and SDMA), and tubular damage (including biomarkers urine α1m, KIM-1 and MCP-1).
All three measured health dimensions were linked to either CKD progression or mortality, whilst remaining independent of clinical risk factors and other measures relating to kidney function. One study had discovered that higher tubular damage and lower tubular function scores were connected to an increased risk of CKD progression, while both studies identified higher scores of both systemic inflammation and kidney filtration as predictors of greater mortality risk.
“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,” explained corresponding author Vanessa-Giselle Peschard, a Nephrology Research Fellow at the University of California, San Francisco (CA, USA). “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.”
