SinoXivContemporary Treatment Responses of Recurrent Focal Segmental Glomerulosclerosis or Steroid Resistant Nephrotic Syndrome in Children after Kidney Transplantation: Phase 2 of a Multicenter Electronic Health Record Data Analysis
Abstract
Background Recurrence of focal segmental glomerulosclerosis (rFSGS) remains a major complication and a challenge to study treatment efficacy due to lack of granular data in a sufficient sample size. Aggregated data from electronic health records can provide such data. Methods We applied computational phenotypes to data from 11 large pediatric health systems in the USA, to identify treatments used and remission outcomes in children with rFSGS after renal transplantation. Additional data were collected by chart review. We performed both linear and non-linear multivariable Cox regression analyses with penalized splines to allow for time-varying predictors. Based on effect sizes from the hazard ratios, we then calculated a sample size needed for a future randomized clinical trial. Results Plasmapheresis was used in 101/107 (94%) patients, followed by anti-CD20 agents in 84 (78%), Low-Density-Lipoprotein (LDL)-apheresis in 22 (20%) and CTLA4Igs in 8 (7%). In linear multivariable models, complete remission was associated with more plasmapheresis sessions. In non-linear models, more doses or sessions of all the above treatments were associated with complete remission or any remission (partial or complete). Penalized spline curves for complete or any remission showed greatest yield within 5 doses of anti-CD20 agents but increasing yield with more doses/sessions of CTLA4Igs or LDL-apheresis. Based on observed hazard ratios, a prospective randomized trial of plasmapheresis vs LDL-apheresis would require 155 participants to have 80% power. Conclusions Increased doses/sessions or additional therapies for rFSGS associated with more favorable outcomes. Non-linear modelling identified when further increases did not improve outcomes.
Citation Information
@article{vikasrdharnidharka2026,
title={Contemporary Treatment Responses of Recurrent Focal Segmental Glomerulosclerosis or Steroid Resistant Nephrotic Syndrome in Children after Kidney Transplantation: Phase 2 of a Multicenter Electronic Health Record Data Analysis},
author={Vikas R. Dharnidharka and Asha Moudgil and Priya S. Verghese and Leyat Tal and Rebecca R. Scobell and Mahmoud Kallash and Amy J. Goodwin Davies and Nicole Marchesani and Mitchell G. Maltenfort and Megan Kelton and Margret Bock and Eliza Blanchette and Hillarey K. Stone and Caroline Gluck and Frank Hullekes and Leonardo V. Riella and William E. Smoyer and Mark Mitsnefes and Bradley P. Dixon and Joseph T. Flynn and Michael J.G. Somers and Christopher B. Forrest and Susan Furth and Michelle R. Denburg},
journal={Pediatric Nephrology},
year={2026},
doi={https://doi.org/10.21203/rs.3.rs-9321284/v1}
}
