RESEARCHERS have identified two urinary protein biomarkers that could improve risk stratification and support personalised treatment approaches in chronic kidney disease (CKD), addressing key limitations of the widely used marker albuminuria.
Novel Urinary Biomarkers Target Tubular Injury and Repair
Albuminuria is routinely used to monitor CKD progression and response to therapy, but it is variable and primarily reflects glomerular injury. In contrast, the newly studied biomarkers, urinary clusterin (uCLU) and urinary epidermal growth factor (uEGF), capture distinct aspects of kidney biology, specifically tubular injury and repair.
In this study, researchers analysed data from two major randomised CKD trials to evaluate how these biomarkers respond to different therapeutic interventions. The effects of the endothelin receptor antagonist (ERA) atrasentan were assessed using data from the SONAR trial, while the sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin was evaluated in the DAPA-CKD trial.
After six weeks of atrasentan treatment, the urinary clusterin-to-creatinine ratio (uCLU/Cr) decreased by 46.3%, indicating a marked reduction in tubular injury. This change occurred alongside a rise in circulating endothelin-1 levels, suggesting engagement of the endothelin pathway. Importantly, baseline uCLU/Cr showed a strong correlation with urinary endothelin-1, supporting its role as a mechanistically relevant biomarker.
In contrast, dapagliflozin influenced uEGF, a marker associated with tubular repair. Over one year, treatment attenuated the decline in the uEGF-to-creatinine ratio (uEGF/Cr), although responses varied across patient subgroups. The greatest increases were observed in individuals with diabetic kidney disease, particularly those with type 2 diabetes and higher baseline HbA1c levels. No significant effect was seen in patients with glomerulonephritis or hypertensive nephropathy.
Further supporting its biological relevance, uEGF/Cr levels were positively correlated with intrarenal EGF gene expression derived from kidney biopsy data.
Future Role of Biomarkers in CKD Treatment Optimisation
Together, these findings suggest that uCLU and uEGF act as mechanism-informed pharmacodynamic biomarkers, reflecting different therapeutic pathways targeted by ERA and SGLT2 inhibitors. By complementing albuminuria, these markers offer a more comprehensive assessment of kidney injury and repair.
The authors conclude that incorporating such biomarkers into clinical practice could enhance patient stratification, improve monitoring of treatment response, and advance precision medicine in CKD.
Reference
Moedt E et al. Novel protein biomarkers for risk stratification and personalized medicine. NDT. 2026;doi: 10.1093/ndt/gfag068.
Featured image: Csaba Deli on Adobe Stock
