ArticleNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association2026
Novel protein biomarkers for risk stratification and personalized medicine.
Article in Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed.
- Association of Urinary EGF with Kidney Outcomes and Effects of Sodium-Glucose Cotransporter 2 Inhibition.Journal of the American Society of Nephrology : JASN · 2026Trial
- Reconsidering the measurement of urinary proteins in chronic kidney disease: towards a global consensus on albuminuria assessment.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2026Article
- Repurposing a prostate tumor marker: elevated FPSA/TPSA ratio as a novel non-invasive biomarker for declining eGFR in male type 2 diabetes.Frontiers in endocrinology · 2026Article
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Authors and funding
6 authors.
Funding
Abstract
background and hypothesisAlbuminuria is widely used to monitor chronic kidney disease (CKD) and treatment response but is subject to variability and primarily reflects glomerular injury. Urinary clusterin and epidermal growth factor (uEGF) are associated with tubular injury and repair, respectively, and may serve as mechanism-informed pharmacodynamic biomarkers. We investigated responses of urinary clusterin and uEGF to endothelin receptor antagonists (ERAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2i), respectively, in CKD.
methodsWe evaluated changes in urinary clusterin-to-creatinine ratio (uCLU/Cr) and uEGF-to-creatinine ratio (uEGF/Cr) in two randomized CKD trial populations. Effects of ERA on uCLU/Cr and endothelin-1 (ET-1) were assessed during the atrasentan enrichment phase of SONAR (Study of Diabetic Nephropathy with Atrasentan), and effects of SGLT2i on uEGF/Cr were examined in DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) across different CKD etiologies, diabetes status, and glycemic control. Associations between uEGF/Cr and intrarenal EGF messenger RNA (mRNA) expression were examined using kidney biopsy single-cell RNA sequencing data.
resultsAfter 6 weeks of treatment with atrasentan, uCLU/Cr decreased by 46.3% (95% confidence interval [CI]: -57.8 to -37.1), while serum ET-1 increased by 23.4% (95% CI 19.2-27.4). There were no effects on serum clusterin and only a numerical decrease in urinary ET-1. Baseline uCLU/Cr correlated significantly with urinary ET-1 (Pearson r = 0.65, P < .0001). In DAPA-CKD, dapagliflozin attenuated the decline in uEGF/Cr over 1 year, with heterogeneity across CKD etiologies. Relative increases were greatest in diabetic kidney disease and absent in glomerulonephritis and hypertensive nephropathy. Similarly, effects were larger in those with type 2 diabetes and higher baseline HbA1c. Tubular EGF mRNA expression correlated positively with uEGF/Cr.
conclusionsUrinary clusterin and uEGF are mechanism-informed pharmacodynamic biomarkers reflecting distinct intrarenal pathways engaged by ERA and SGLT2i therapy, respectively. These biomarkers complement albuminuria by capturing tubular injury and repair, providing a more comprehensive biological assessment of treatment effects and heterogeneity in CKD.
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