Practice variation in the use of steroid-sparing therapies in childhood steroid-sensitive nephrotic syndrome: results from a prospective cohort study

Angie Aguilar-González^{1

2}, Ava Zardynezhad³, Catherine Morgan⁴, Allison Dart⁵, Cherry Mammen⁶, Rulan S Parekh^{1

7}, Pavel Geier⁸, Genevieve Benoit⁹, Guido Filler¹⁰, Janusz Feber⁸, James Tee¹¹, Steven Arora¹², Damien Noone⁴, Silviu Grisaru¹³, Rahul Chanchlani¹², Augustina Okpere¹³, Susan Samuel^{14

15}

Affiliations

¹ Department of Pediatrics, SickKids, University of Toronto, Toronto, ON, Canada.
² Hospital Materno Infantil Juan Pablo II, Universidad Rafael Landivar, Guatemala City, Guatemala.
³ Faculty of Medicine and Dentistry, University of Alberta, Calgary, AB, Canada.
⁴ Division of Pediatric Nephrology, Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
⁵ Department of Pediatrics and Child Health, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada.
⁶ Division of Nephrology, Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
⁷ Women's College Hospital, Toronto, ON, Canada.
⁸ Division of Nephrology, Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada.
⁹ Division of Nephrology, Department of Pediatrics, CHU Sainte-Justine, Université de Montréal, Québec, Canada.
¹⁰ Division of Nephrology and Hypertension, Department of Paediatrics, London Health Sciences Centre, London, ON, Canada.
¹¹ Division of Nephrology, Department of Pediatrics, Dalhousie University, Halifax, NS, Canada.
¹² Division of Pediatric Nephrology, Department of Pediatrics, McMaster University, Hamilton, ON, Canada.
¹³ Division of Pediatric Nephrology, Department of Pediatrics, Cumming School of Medicine, University of Calgary, Alberta, Canada.
¹⁴ Division of Nephrology, Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada. susan.samuel@ubc.ca.
¹⁵ Division of Nephrology, Department of Pediatrics, University of British Columbia, Room V3-337, 938 West 28 Avenue, Vancouver, BC, V6H 3V4, Canada. susan.samuel@ubc.ca.

PMID: 40590957
DOI: 10.1007/s00467-025-06853-8

Observational Study

Practice variation in the use of steroid-sparing therapies in childhood steroid-sensitive nephrotic syndrome: results from a prospective cohort study

Angie Aguilar-González et al. Pediatr Nephrol. 2025 Nov.

. 2025 Nov;40(11):3437-3445.

doi: 10.1007/s00467-025-06853-8. Epub 2025 Jul 1.

Authors

Affiliations

¹ Department of Pediatrics, SickKids, University of Toronto, Toronto, ON, Canada.
² Hospital Materno Infantil Juan Pablo II, Universidad Rafael Landivar, Guatemala City, Guatemala.
³ Faculty of Medicine and Dentistry, University of Alberta, Calgary, AB, Canada.
⁴ Division of Pediatric Nephrology, Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
⁵ Department of Pediatrics and Child Health, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada.
⁶ Division of Nephrology, Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
⁷ Women's College Hospital, Toronto, ON, Canada.
⁸ Division of Nephrology, Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada.
⁹ Division of Nephrology, Department of Pediatrics, CHU Sainte-Justine, Université de Montréal, Québec, Canada.
¹⁰ Division of Nephrology and Hypertension, Department of Paediatrics, London Health Sciences Centre, London, ON, Canada.
¹¹ Division of Nephrology, Department of Pediatrics, Dalhousie University, Halifax, NS, Canada.
¹² Division of Pediatric Nephrology, Department of Pediatrics, McMaster University, Hamilton, ON, Canada.
¹³ Division of Pediatric Nephrology, Department of Pediatrics, Cumming School of Medicine, University of Calgary, Alberta, Canada.
¹⁴ Division of Nephrology, Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada. susan.samuel@ubc.ca.
¹⁵ Division of Nephrology, Department of Pediatrics, University of British Columbia, Room V3-337, 938 West 28 Avenue, Vancouver, BC, V6H 3V4, Canada. susan.samuel@ubc.ca.

PMID: 40590957
DOI: 10.1007/s00467-025-06853-8

Abstract

Background: Steroid-sparing therapies are often used to prolong disease remission while minimizing steroid toxicity in childhood steroid-sensitive nephrotic syndrome (SSNS). This study aims to describe practice variation in the use of steroid-sparing medications for childhood SSNS in Canada.

Methods: Children (1-18 years) with nephrotic syndrome (NS) from eleven pediatric nephrology centers in Canada were enrolled in the Canadian Childhood Nephrotic Syndrome (CHILDNEPH) prospective cohort from 2013-2019. Data, including time to first relapse for children treated with cyclophosphamide, tacrolimus, mycophenolate mofetil, cyclosporine and rituximab were analyzed using summary statistics. Participants who received steroid-sparing therapies prior to enrolment were excluded.

Results: Of the 371 children enrolled, 321 (86.5%) had SSNS and 133 met the study criteria. Median age at enrollment was 3.0 years (IQR: 2.0-6.3). Median follow-up period was 3.0 years (IQR 1.0-4.0). Timing of initiation and choice of steroid-sparing therapy varied across centers. The majority (72.2%) initiated therapies after a median of 3 relapses (IQR: 2-4). Cyclophosphamide and tacrolimus were the most frequently used initial therapies at 39.1% and 23.3%, respectively. Thirty (22.6%) patients switched to a second medication after a median time of 4 months (IQR 0.25-11); of which, 40% switched from either cyclophosphamide or mycophenolate mofetil to tacrolimus. There were no statistically significant differences in time to first relapse with initial therapies (log rank P-value 0.36).

Conclusions: Significant variation in the use of steroid-sparing therapies exists in the treatment of SSNS. A clinical trial is needed to examine the efficacy of these medications to optimize treatment and decrease practice variation.

Keywords: Children; Practice variation; Prospective cohort; Steroid-sensitive nephrotic syndrome; Steroid-sparing medications.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests.

References

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Practice variation in the use of steroid-sparing therapies in childhood steroid-sensitive nephrotic syndrome: results from a prospective cohort study

Affiliations

Practice variation in the use of steroid-sparing therapies in childhood steroid-sensitive nephrotic syndrome: results from a prospective cohort study

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Miscellaneous