---
title: "Urinary Clusterin and uEGF as Protein Biomarkers for Risk Stratification in CKD"
id: "pubmed-41874429"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-41874429"
content_type: "clinical_feed_article"
specialty: "Nephrology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/41874429/"
doi: "10.1093/ndt/gfag068"
published_at: "2026-08-25T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Urinary Clusterin and uEGF as Protein Biomarkers for Risk Stratification in CKD
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-41874429
- **Specialty:** [Nephrology](https://medichelpline.com/clinical-feed/nephrology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/41874429/)
- **DOI:** [10.1093/ndt/gfag068](https://doi.org/10.1093%2Fndt%2Fgfag068)
- **Published At:** 2026-08-25T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- The article evaluates **urinary clusterin** (uCLU/Cr) and **urinary epidermal growth factor** (uEGF/Cr) as mechanism-informed pharmacodynamic biomarkers in chronic kidney disease (CKD). - Albuminuria is the current standard for monitoring CKD and treatment response but has limitations: variability and predominant reflection of glomerular injury. - uCLU/Cr is associated with **tubular injury**, while **uEGF/Cr** reflects tubular repair processes; both may complement albuminuria by capturing intrarenal pathways. - Two randomized trial populations were analyzed: the atrasentan enrichment phase of SONAR for effects of endothelin receptor antagonists (ERA) on uCLU/Cr, and DAPA-CKD for effects of SGLT2 inhibitors (SGLT2i; dapagliflozin) on uEGF/Cr across CKD etiologies and diabetes status. - In SONAR, 6 weeks of atrasentan reduced uCLU/Cr by 46.3% (95% CI -57.8 to -37.1) and increased serum ET-1 by 23.4% (95% CI 19.2-27.4); baseline uCLU/Cr correlated with urinary ET-1 (Pearson r = 0.65, P < .0001). - There were no effects of atrasentan on serum clusterin and only a numerical decrease in urinary ET-1 reported. - In DAPA-CKD, dapagliflozin attenuated the decline in uEGF/Cr over 1 year, with heterogeneity by CKD etiology: largest relative increases in diabetic kidney disease, absent effects in glomerulonephritis and hypertensive nephropathy. - SGLT2i effects on uEGF/Cr were greater in participants with type 2 diabetes and higher baseline HbA1c. - Intrarenal EGF mRNA expression from kidney biopsy single-cell RNA sequencing correlated positively with uEGF/Cr, supporting a mechanistic link between urinary biomarker and tissue expression. - Authors conclude that **urinary clusterin** and **uEGF** reflect distinct intrarenal pathways engaged by ERA and SGLT2i therapies and can provide a more comprehensive biological assessment than albuminuria alone. - The article does not report additional methodological details beyond the trial populations, nor does it provide long-term outcome data or full assay characteristics in this abstract.
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Affiliations Expand ### Affiliations * 1 Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. * 2 Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA. * 3 Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA. * PMID: **41874429** * DOI: [ 10.1093/ndt/gfag068 ](https://doi.org/10.1093/ndt/gfag068) Free article Item in Clipboard Randomized Controlled Trial # Novel protein biomarkers for risk stratification and personalized medicine Erik Moedt et al. Nephrol Dial Transplant. 2026. Free article Show details Display options Display options Format Abstract PubMed PMID Nephrol Dial Transplant Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Nephrol+Dial+Transplant%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Nephrol+Dial+Transplant%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/41874429/) . 2026 Aug 25;41(Supplement_2):ii50-ii58. doi: 10.1093/ndt/gfag068. ### Authors [Erik Moedt](https://pubmed.ncbi.nlm.nih.gov/?term=Moedt+E&cauthor_id=41874429)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/41874429/#short-view-affiliation-1 "Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands."), [Wenjun Ju](https://pubmed.ncbi.nlm.nih.gov/?term=Ju+W&cauthor_id=41874429)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/41874429/#short-view-affiliation-2 "Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA."), [Viji Nair](https://pubmed.ncbi.nlm.nih.gov/?term=Nair+V&cauthor_id=41874429)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/41874429/#short-view-affiliation-2 "Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA."), [Petter Bjornstad](https://pubmed.ncbi.nlm.nih.gov/?term=Bjornstad+P&cauthor_id=41874429)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/41874429/#short-view-affiliation-3 "Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA."), [Matthias Kretzler](https://pubmed.ncbi.nlm.nih.gov/?term=Kretzler+M&cauthor_id=41874429)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/41874429/#short-view-affiliation-2 "Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA."), [Hiddo J L Heerspink](https://pubmed.ncbi.nlm.nih.gov/?term=Heerspink+HJL&cauthor_id=41874429)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/41874429/#short-view-affiliation-1 "Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.") ### Affiliations * 1 Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. * 2 Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA. * 3 Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA. * PMID: **41874429** * DOI: [ 10.1093/ndt/gfag068 ](https://doi.org/10.1093/ndt/gfag068) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract **Background and hypothesis:** Albuminuria 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. **Methods:** We 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. **Results:** After 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. **Conclusions:** Urinary 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. **Keywords:** albuminuria; chronic kidney disease; clusterin; endothelin; epidermal growth factor. © The Author(s) 2026. Published by Oxford University Press on behalf of the ERA. 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