Kidney Week

Abstract: TH-PO0599

Strength of Surrogate End Point Validation in CKD: A Systematic Review

Session Information

• CKD: From Global Burden to Precision Care - Epidemiology, Demographics, Geographies, and Risk Factors
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2201 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

• Garcia Sanchez, Juan Jose, Global Market Access & Pricing, Health Economics and Payer Evidence, AstraZeneca, Barcelona, Spain

Juan Jose Garcia Sanchez, MS

• Ciani, Oriana, SDA Bocconi School of Management, Centre for Research on Health and Social Care Management (CERGAS), Milan, Italy

Oriana Ciani, MSc, PhD

• De Nicola, Luca, University of "L. Vanvitelli", Naples, Italy

Luca De Nicola, MD, PhD

• Buyse, Marc, IDDI, Louvain-la-Neuve, Belgium

Marc Buyse, ScD

• Wanner, Christoph, Division of Nephrology, Wuerzburg University Clinic, Wuerzburg, Germany

Christoph Wanner, MD

• Taylor, Rod, Robertson Centre for Biostatistics & General Practice and Primary Care, School of Health and Wellbeing, University of Glasgow, Glasgow, United Kingdom

Rod Taylor, PhD

• Shi, Jessica, OPEN Health, London, United Kingdom

Jessica Shi, MSc

• Huang, Cici, OPEN Health, Providence, Rhode Island, United States

Cici Huang, ScM

• van Haalen, Heleen, Global Market Access & Pricing, Health Economics and Payer Evidence, AstraZeneca, Gothenburg, Sweden

Heleen van Haalen

• Little, Dustin J., Late-Stage Development, Cardiovascular, Renal and Metabolism (CVRM), Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, United States

Dustin J. Little, MD

• Aranda, Unai, Global Medical Affairs, BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, Maryland, United States

Unai Aranda

• Danelich, Ilya, Global Medical Affairs, BioPharmaceuticals Medical, AstraZeneca, Wilmington, Delaware, United States

Ilya Danelich

• Trapero-Bertran, Marta, Department of Economics and Business, Universidad de Lleida, Lleida, Spain

Marta Trapero-Bertran, DrPH

Background

While in some circumstances, regulators accept eGFR slope and early UACR change as valid surrogate endpoints for final outcomes in CKD,¹ health technology assessment agencies often prefer final clinical outcomes to inform reimbursement.² This systematic literature review evaluated studies validating eGFR and UACR as surrogate endpoints for final outcomes in CKD.

Methods

Level (L)1 evidence is the gold standard for surrogacy validation, showing an association between treatment effect on surrogate endpoint and final outcome (meta-analyses of randomised controlled trials).³ Embase/MEDLINE searches for L1 evidence were conducted on 13Oct25, supplemented by grey literature/conference proceeding searches from 2024/25. Eligible publications reported surrogacy validation in adults with CKD. Surrogate endpoints included eGFR slope and UACR change from baseline; final outcomes included sustained eGFR decline (30–57%), doubling of serum creatinine, and end-stage kidney disease (eGFR <10 or <15 mL/min/1.73m², chronic dialysis or kidney transplant), among others.

Results

A total of 1,546 publications were screened.
In 7 publications reporting surrogacy L1 evidence for eGFR decline using patient-level data (sample size=9,488–186,949),^4–10 strong correlations (R²=0.94–0.97, where available) were found between treatment effects on eGFR total slope and final outcomes. One meta-analysis indicated that 3-year eGFR slope surrogacy performance is consistent across CKD/UACR stages, strengthening its surrogate endpoint validity.⁴
For UACR, 3 publications reported surrogacy evidence. A 2018 study found insufficient evidence to support UACR as a surrogate endpoint;¹⁰ 2 more recent studies reported moderate-to-strong correlations between early UACR change and final outcomes (R²=0.66–0.93).^6,11

Conclusion

We identified L1 evidence for the association of eGFR with final clinical outcomes in CKD, supporting its use in ongoing trials and as a validated surrogate endpoint for future reimbursement and regulatory decisions. Overall, moderate evidence for UACR as a surrogate endpoint for final outcomes was identified, though further evidence is needed.

¹Levey, Am J Kidney Dis 2020;75:84–104; ²Sanchez, Adv Ther 2025;42:5727–41; ³Ciani, Value Health 2017;20:487–95

Acknowledgment

Medical writing: Costello Medical.
The authors acknowledge Prof. Lesley Inker for contributions to the abstract and poster development.

Funding

• Commercial Support – AstraZeneca