Abstract: FR-PO0959
Randomized Clinical Trial Design Considerations for CKD in Pediatric Patients: A Framework Based on the CKD in Children Study
Session Information
- Pediatric Nephrology: Genetic Diseases, Development, Neonatal Nephrology, Glomerular Diseases, and More
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- 1800 Pediatric Nephrology
Authors
- Ng, Derek K., Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States
- Matheson, Matthew, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States
- Hartung, Erum Aftab, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
- Kula, Alexander J., Ann & Robert H Lurie Children's Hospital of Chicago, Chicago, Illinois, United States
- Warady, Bradley A., Children's Mercy Kansas City, Kansas City, Missouri, United States
- Furth, Susan L., The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
Group or Team Name
- CKiD Study Investigators
Background
Randomized clinical trials are urgently needed to evaluate pediatric CKD therapies. We sought to quantify the natural course expected in a placebo arm from the Chronic Kidney Disease in Children (CKiD) Study. We aimed to design and simulate hypothetical trials for effects on eGFR, urine protein:creatinine ratio (UPCr), and a composite of the two based on a risk prediction model.
Methods
A retrospective selection of CKiD participants with an initial U25eGFR between 20 and 80ml/min, and eGFR and proteinuria measured two years later. Simulation evaluated power of treatment effects on eGFR changes (50% less decline; 75% less decline; no decline) and proteinuria changes (no change; a symmetric decrease relative to an increase in placebo; or twice the symmetric decrease) for sample sizes of 50, 75, and 100 per arm (placebo and treatment) and statistical significance at 0.05. Lastly, we estimated power for the composite of both eGFR and UPCr for each combination of treatment effects.
Results
601 nonglomerular (NG) participants were 35% female and average age of 11.6 years; average baseline eGFR was 45 which declined to 41 after two years (-9%); average baseline UPCr was 0.32 mg/mgCr which increased to 0.40 at two years (+25%). 123 glomerular (G) participants were 51% female and average age of 15.7 years; average entry eGFR was 53 which declined to 43 (-19%); average UPCr increased from 0.58 to 0.69 (+19%). In simulations sampling 80% NG and 20% G diagnoses, eGFR declined 11% and UPCR increased 25%. 50 participants/arm was sufficient to detect a twice-symmetrical decrease (e.g., 50% lower UPCr; 97% power) but not for eGFR (>61% power). 75 participants/arm was sufficient only when the treatment halted eGFR decline (82% power) or had at least a symmetric decrease in UPCr (90% power). Smaller treatment effects did not yield power over 82% for 100 participants/arm. The composite outcome yielded some improvement in power, but this was due to strong treatment effects in either eGFR or UPCr.
Conclusion
CKiD provided an expected natural CKD progression course for a placebo group in a hypothetical trial. The composite of eGFR and UPCr rarely yielded improved power, so selecting outcomes should be based on putative therapy mechanisms on eGFR or UPCr. For therapies intended for pediatric CKD, larger sample sizes for a two-year follow-up are likely needed.
Acknowledgment
The CKiD Study is funded by the National Institute of Diabetes and Digestive and Kidney Diseases, with additional funding from the National Institute of Child Health and Human Development, and the National Heart, Lung, and Blood Institute (U01 DK066143, U01 DK066174, U24 DK137522, U24 DK066116).
Funding
- NIDDK Support