Kidney Week

Abstract: FR-PO720

Comparative Effectiveness of Cyclophosphamide and Calcineurin Inhibitors in Childhood Nephrotic Syndrome

Session Information

• Pediatric Nephrology - 1
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

• 1900 Pediatric Nephrology

Authors

• Robinson, Cal, The Hospital for Sick Children, Toronto, Ontario, Canada

Cal Robinson, MBChB

• Brooke, Josefina A., The Hospital for Sick Children, Toronto, Ontario, Canada

Josefina A. Brooke, RN

• Chanchlani, Rahul, McMaster Children's Hospital, Hamilton, Ontario, Canada

Rahul Chanchlani, MD, MBBS, MS, FASN

• Cuthbertson, Brian H., Sunnybrook Research Institute, Toronto, Ontario, Canada

Brian H. Cuthbertson, MD

• Dhillon, Vaneet, The Hospital for Sick Children, Toronto, Ontario, Canada

Vaneet Dhillon, NP, RN

• Fan, Eddy, University of Toronto, Toronto, Ontario, Canada

Eddy Fan, MD, PhD

• Licht, Christoph, The Hospital for Sick Children, Toronto, Ontario, Canada

Christoph Licht, MD, FASN

• McKay, Ashlene Maree, The Hospital for Sick Children, Toronto, Ontario, Canada

Ashlene Maree McKay, MD

• Noone, Damien Gerard, The Hospital for Sick Children, Toronto, Ontario, Canada

Damien Gerard Noone, MD

• Pearl, Rachel Jane, The Hospital for Sick Children, Toronto, Ontario, Canada

Rachel Jane Pearl, MD

• Radhakrishnan, Seetha, The Hospital for Sick Children, Toronto, Ontario, Canada

Seetha Radhakrishnan, MD

• Rowley, Veronique, The Hospital for Sick Children, Toronto, Ontario, Canada

Veronique Rowley, MSc

• Teoh, Chia Wei, The Hospital for Sick Children, Toronto, Ontario, Canada

Chia Wei Teoh, MBChB, MSc

• Vasilevska-Ristovska, Jovanka, The Hospital for Sick Children, Toronto, Ontario, Canada

Jovanka Vasilevska-Ristovska, MD

• Parekh, Rulan S., Women's College Hospital, Toronto, Ontario, Canada

Rulan S. Parekh, MD, MS, FASN

Background

Nephrotic syndrome is a common pediatric kidney disease with high morbidity. Cyclophosphamide and calcineurin inhibitors are the most used second-line medications, but their comparative effectiveness is unknown.

Methods

Using target trial methods, we emulated a pragmatic, open-label clinical trial using Insight into Nephrotic Syndrome: Investigating Genes, Health, and Therapeutics study data. We included children (1-18yr) diagnosed with nephrotic syndrome from 1996-2019 in Toronto, Canada that initiated cyclophosphamide or calcineurin inhibitors. Randomization was emulated by propensity score overlap weighting. The primary outcome was time-to-relapse, analyzed by weighted Cox proportional hazards models.

Results

Of 578 children, 252 started cyclophosphamide and 131 calcineurin inhibitors. Baseline characteristics were balanced after propensity score weighting. During median 5.5-year (IQR 2.5-9.2) follow-up, there was no difference in relapses after calcineurin inhibitor vs. cyclophosphamide (HR 1.25, 95%CI 0.84-1.87). There were also no differences in relapses by 1, 2, or 5-years, hypertension, or chronic kidney disease. Calcineurin inhibitor use was associated with hospitalization (HR 1.83, 95%CI 1.14-2.92) and intravenous albumin use (HR 2.81, 95%CI 1.65-4.81).

Conclusion

There was no difference in risk of relapse after cyclophosphamide vs. calcineurin inhibitor treatment in childhood nephrotic syndrome. Cyclophosphamide treatment is shorter in duration and more accessible in low-to-middle income countries.

Figure. Weighted relapse-free survival after cyclophosphamide vs. calcineurin inhibitor initiation

Funding

• Government Support – Non-U.S.