Influence of Enrichment Criteria on eGFR Slope: Implications for Clinical Trial Design in CKD
7 affiliations
- 1Renal Division, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA
- 2Harvard Medical School, Boston, Massachusetts, USA
- 3Cardiology Division, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA
- 4Department of Medicine, Stanford University School of Medicine, Stanford, California, USA
- 5Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, California, USA
- 6Department of Health Policy, Stanford University School of Medicine, Stanford, California, USA
- 7Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
Abstract
Introduction: Estimated glomerular filtration rate (eGFR) slope is increasingly employed as an intermediate endpoint in clinical trials, which are often enriched to select those at risk of more rapid eGFR decline. Herein, we explored the relative contribution of enrichment criteria to eGFR slope among patients with established chronic kidney disease (CKD).
Methods: Using data from patients with at least 3 eGFR values from the Chronic Renal Insufficiency Cohort (CRIC) study (n = 4563), we used mixed effects regression to explore the association of baseline eGFR, 24-hour urine protein excretion (UPE), systolic blood pressure (SBP), and diabetes with annualized eGFR slope.
Results: Mean baseline eGFR was 48 ± 16 ml/min per 1.73 m2, median UPE was 0.18 [25th, 75th percentile; 0.07, 0.70] g/d, mean SBP was 127 ± 20 mm Hg, and 49% had diabetes. Over a median follow-up of 7.1-year, eGFR changed by −1.30 (−1.36 to −1.24) ml/min per 1.73 m2 per year. In unadjusted models, higher UPE, SBP, and diabetes were associated with more rapid eGFR decline. Mean rates of decline with baseline eGFR < 45 and ≥ 45 ml/min per 1.73 m2 were −1.4 and −1.3 ml/min per 1.73 m2 per year, respectively (P = 0.42); UPE ≤ 0.3 g and > 0.3 g were −0.5 and −2.8 ml/min per 1.73 m2 per year, respectively; SBP < 130 and ≥ 130 mm Hg were −0.9 and −2.1 ml/min per 1.73 m2 per year, respectively; and for no diabetes and diabetes were −0.8 and −1.8, respectively (all P < 0.001).
Conclusion: Higher albuminuria appears to be the most potent predictor of more rapid eGFR decline. As higher (rather than lower) baseline eGFR predicts steeper subsequent eGFR decline, for patients with moderate to advanced CKD, a threshold-based decline in eGFR (e.g., 40, 50, or 57%) or a hierarchical composite endpoint might better capture treatment effects, rather than eGFR slope.
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BibTeX
@article{causland2026influence,
title = {{Influence of Enrichment Criteria on eGFR Slope: Implications for Clinical Trial Design in CKD}},
author = {Finnian R. Mc Causland and Brian L. Claggett and Glenn M. Chertow and Hiddo J.L. Heerspink},
journal = {Kidney International Reports},
year = {2026},
month = sep,
doi = {10.1016/j.ekir.2026.107080},
url = {https://doi.org/10.1016/j.ekir.2026.107080},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Influence of Enrichment Criteria on eGFR Slope: Implications for Clinical Trial Design in CKD
AU - Finnian R. Mc Causland
AU - Brian L. Claggett
AU - Glenn M. Chertow
AU - Hiddo J.L. Heerspink
PY - 2026
DA - 2026/09/17
JO - Kidney International Reports
DO - 10.1016/j.ekir.2026.107080
UR - https://doi.org/10.1016/j.ekir.2026.107080
AB - Introduction: Estimated glomerular filtration rate (eGFR) slope is increasingly employed as an intermediate endpoint in clinical trials, which are often enriched to select those at risk of more rapid eGFR decline. Herein, we explored the relative contribution of enrichment criteria to eGFR slope among patients with established chronic kidney disease (CKD). Methods: Using data from patients with at least 3 eGFR values from the Chronic Renal Insufficiency Cohort (CRIC) study (n = 4563), we used mixed effects regression to explore the association of baseline eGFR, 24-hour urine protein excretion (UPE), systolic blood pressure (SBP), and diabetes with annualized eGFR slope. Results: Mean baseline eGFR was 48 ± 16 ml/min per 1.73 m2, median UPE was 0.18 [25th, 75th percentile; 0.07, 0.70] g/d, mean SBP was 127 ± 20 mm Hg, and 49% had diabetes. Over a median follow-up of 7.1-year, eGFR changed by −1.30 (−1.36 to −1.24) ml/min per 1.73 m2 per year. In unadjusted models, higher UPE, SBP, and diabetes were associated with more rapid eGFR decline. Mean rates of decline with baseline eGFR < 45 and ≥ 45 ml/min per 1.73 m2 were −1.4 and −1.3 ml/min per 1.73 m2 per year, respectively (P = 0.42); UPE ≤ 0.3 g and > 0.3 g were −0.5 and −2.8 ml/min per 1.73 m2 per year, respectively; SBP < 130 and ≥ 130 mm Hg were −0.9 and −2.1 ml/min per 1.73 m2 per year, respectively; and for no diabetes and diabetes were −0.8 and −1.8, respectively (all P < 0.001). Conclusion: Higher albuminuria appears to be the most potent predictor of more rapid eGFR decline. As higher (rather than lower) baseline eGFR predicts steeper subsequent eGFR decline, for patients with moderate to advanced CKD, a threshold-based decline in eGFR (e.g., 40, 50, or 57%) or a hierarchical composite endpoint might better capture treatment effects, rather than eGFR slope.
SN - 2468-0249
ER -