Efficacy of Calcineurin Inhibition in Children With Steroid-Resistant Nephrotic Syndrome

Trautmann A. Hofstetter J. Lipska-Ziętkiewicz B. Tsygin A. Ogarek I. Saeed B. Szczepanska M. Azocar M. Emma F. Ozaltin F. Caliskan S. Bodria M. Paripovic D. Tkaczyk M. Oh J. Boutaba M. Jardim H. Yilmaz A. Csaicsich D. Ranchin B. Jankauskiene A. Pasini A. Bitzan M. Nigmatullina N. Tory K. Zieg J. Camilla R. Hooman N. Schaefer F.
October 2025 Elsevier Inc.

Kidney International Reports
2025 #10 Issue 10 3535 - 3548 pp.

Introduction: We aimed to provide evidence for the efficacy of calcineurin inhibitor (CNI) treatment in children with steroid-resistant nephrotic syndrome (SRNS). Methods: In 278 SRNS children receiving first-line CNI treatment, cumulative remission and kidney failure incidence were estimated using competing risk analysis. Kaplan-Meier and Cox regression analyses were performed to analyze kidney survival, identify predictors of CNI responsiveness and estimate the cumulative incidence of breakthrough proteinuria episodes on or off CNI treatment. The impact of CNI dosage and trough levels on proteinuria was assessed using multivariable linear-mixed effects modeling. Results: Within 6 months of CNI administration, proteinuria was reduced by 84% (interquartile range: 80%–87%) in 219 nongenetic SRNS cases and by 58% (42%–70%) in 59 genetic SRNS cases but returned to pretreatment level in the latter group within 9 to 12 months. Whereas complete remission was observed in 91 of 219 nongenetic SRNS cases (42%) and 6 of 59 genetic SRNS cases (10%), remission was sustained in 53 nongenetic (24%) and 2 genetic (3%) cases only. Proteinuria reduction, but not attainment of complete remission, was associated with the use of higher CNI doses. The cumulative risk of breakthrough proteinuria on CNI treatment was 51% (40%–62%) and 65% (54%–75%) after 12 and 24 months, respectively, in nongenetic SRNS. The postdiscontinuation relapse risk in patients with complete remission was 40% (22%–59%) and 50% (30%–69%) after 12 and 24 months, respectively. Kidney survival in nongenetic SRNS was superior in CNI-responsive children (92% vs. 42% at 15 years), independent of breakthrough proteinuria episodes. Conclusion: Our study provides real-world evidence regarding the extent, dynamics, dose-response relationship, and long-term functional impact of CNI therapy in nongenetic and genetic forms of SRNS.

calcineurin inhibitor , genetic kidney disease , nephrotic syndrome , steroid resistance

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Division of Pediatric Nephrology, University Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany
Rare Diseases Centre and Clinical Genetics Unit, Department of Biology and Medical Genetics, Medical University of Gdansk, Gdansk, Poland
Department of Pediatric Nephrology, National Medical and Research Center for Childrens Health, Moscow, Russian Federation
Department of Pediatric Nephrology, Jagiellonian University Medical College, Krakow, Poland
Farah Association for Child with Kidney Disease, Damascus, Syrian Arab Republic
Department of Pediatrics, School of Medicine with the Division of Dentistry, Zabrze, Poland
Department of Pediatric Nephrology, Hospital Luis Calvo Mackenna-Facultad de Medicina Universidad de Chile, Santiago de Chile, Chile
Department of Pediatric Subspecialties, Nephrology and Dialysis Unit, Childrens Hospital Bambino Gesù, IRCCS, Rome, Italy
Department of Pediatric Nephrology, Nephrogenetics Laboratory, Center for Biobanking and Genomics, Hacettepe University, Ankara, Turkey
Department of Bioinformatics, Nephrogenetics Laboratory, Center for Biobanking and Genomics, Hacettepe University, Ankara, Turkey
Pediatric Nephrology Departement, Cerrahpaşa Medical Faculty, Istanbul University-Cerrahpasa, Turkey
Dipartimento di Medicina Clinica e Sperimentale, University of Studies of Parma, Parma, Italy
Division of Nephrology, Dialysis and Transplantation, IRCCS Giannina Gaslini, Genoa, Italy
Department of Pediatric Nephrology, University Childrens Hospital, Belgrade, Serbia
Department of Pediatrics, Immunology and Nephrology, Polish Mothers Memorial Hospital Research Institute, Lodz, Poland
Department of Pediatric Nephrology, University Childrens Hospital, Hamburg, Germany
Department of Pediatric Nephrology, Nefissa Hammond (ex Parnet) Hospital, Algers, Algeria
Department of Pediatric Nephrology, Centre Hospitalar, Porto, Portugal
Department of Pediatric Nephrology, Istanbul Medical Faculty, Istanbul, Turkey
Department of Pediatrics, Medical University Vienna, Vienna, Austria
Pediatric Nephrology Unit, Hôpital Femme Mere Enfant, Hospices Civils de Lyon, France
Pediatric Center, Institute of Clinical Medicine, Vilnius University, Lithuania
Pediatric Nephrology and Dialysis Unit, S.Orsola-Malpighi Hospital, Bologna, Italy
Kidney Center of Excellence, Dubai Al Jalila Childrens Hospital, Dubai, United Arab Emirates
Department of Nephrology, Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan
First Department of Pediatrics, Semmelweis University, Budapest, Hungary
Department of Pediatics, University Hospital Motol, Prague, Czech Republic
Pediatric Nephrology, Dialysis, Transplantation Unit, Regina Margherita Children Hospital, Torino, Italy
Department of Pediatrics, School of Medicine, Aliasghar Clinical Research Development Center, Iran University of Medical Sciences, Tehran, Iran

Division of Pediatric Nephrology
Rare Diseases Centre and Clinical Genetics Unit
Department of Pediatric Nephrology
Department of Pediatric Nephrology
Farah Association for Child with Kidney Disease
Department of Pediatrics
Department of Pediatric Nephrology
Department of Pediatric Subspecialties
Department of Pediatric Nephrology
Department of Bioinformatics
Pediatric Nephrology Departement
Dipartimento di Medicina Clinica e Sperimentale
Division of Nephrology
Department of Pediatric Nephrology
Department of Pediatrics
Department of Pediatric Nephrology
Department of Pediatric Nephrology
Department of Pediatric Nephrology
Department of Pediatric Nephrology
Department of Pediatrics
Pediatric Nephrology Unit
Pediatric Center
Pediatric Nephrology and Dialysis Unit
Kidney Center of Excellence
Department of Nephrology
First Department of Pediatrics
Department of Pediatics
Pediatric Nephrology
Department of Pediatrics

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