Kidney Week

Abstract: SA-PO1184

Influence of Enrichment Criteria on eGFR Slope: Implications for CKD Trial Design

Session Information

• CKD: Biomarkers and Emerging Tools for Diagnosis and Monitoring
  November 08, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

• Mc Causland, Finnian R., Brigham and Women's Hospital, Boston, Massachusetts, United States

Finnian R. Mc Causland, MBChB, MS, FASN

• Claggett, Brian, Brigham and Women's Hospital, Boston, Massachusetts, United States

Brian Claggett, MS, PhD

• Chertow, Glenn M., Stanford University, Stanford, California, United States

Glenn M. Chertow, MD, MPH, FASN

• Heerspink, Hiddo Jan L., Rijksuniversiteit Groningen, Groningen, GR, Netherlands

Hiddo Jan L. Heerspink, PhD

Background

Change in eGFR slope is increasingly used as an intermediate outcome for trials testing therapies to slow CKD progression. Enrichment criteria can be used to select patients with faster eGFR decline, enhancing the ability to detect treatment effects. Herein, we explore the relative contribution of enrichment criteria among patients with CKD.

Methods

Using data from patients with at least 3 eGFR values from CRIC (n=5,348), we used mixed effects regression to explore the association of common enrichment criteria (baseline eGFR, 24-hour urine protein excretion (UPE), systolic blood pressure (SBP), and diabetes) with the subsequent annualized decline in eGFR.

Results

Mean baseline was eGFR 47±16 mL/min/1.73m², median UPE 0.2 [0.1, 0.8] g/day, mean SBP 128±21 mmHg, and 50% had diabetes. Over a median 6.9-year follow-up, eGFR changed by -0.87 (-0.94, -0.80) mL/min/1.73m²/year. Higher eGFR, log-UPE, SBP, and diabetes were each associated with a more rapid eGFR decline (Table 1). Mean slopes for those with eGFR <45 and ≥45 were -0.7 and -1.0 mL/min/1.73m²/year, respectively; UPE ≤0.3g and >0.3g were -0.3 and -1.6 mL/min/1.73m²/year, respectively; SBP <130 and ≥130 mmHg were -0.5 and -1.4 mL/min/1.73m²/year, respectively; for no diabetes and diabetes were -0.4 and -1.4, respectively (P-diff all <0.001; Fig.1).

Conclusion

For trials considering eGFR slope as a primary outcome, higher albuminuria appears to be the most potent predictor of more rapid eGFR decline. Higher (not lower) baseline eGFR was associated with more rapid eGFR decline. For patients with established CKD at baseline, threshold-based decline in eGFR (e.g., 40-57%) or a hierarchical composite endpoint might better capture treatment effects, relative to eGFR slope.

Funding

• NIDDK Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025jgnhkd03