A multi-national study examined the response sustainability to calcineurin inhibitors and long-term kidney survivals in children with genetic podocytopathies
- Posted27 July 2026
- PMID42508611
AuthorsGeorgia Malakasioti, Daniela Iancu, Chun Ting Au, Dongyang Zhou, Anastasiia Milovanova, Alexey Tsygin, Tomoko Horinouchi, China Nagano, Kandai Nozu, Koichi Kamei, Shuichiro Fujinaga, Kazumoto Iijima, Hee Gyung Kang, Seon Hee Lim, Rajiv Sinha, Biswanath Basu, William Morello, Giovanni Montini, Aoife Waters, Olivia Boyer, Zeynep Y Yildirim, Sibel Yel, Ismail Dursun, Hugh J McCarthy, Laura Massella, Marina Vivarelli, Larisa Prikhodina, Martine TP Besouw, Wenyan Huang, Markus J Kemper, Sebastian Loos, Chanel Prestidge, Galia Zlatanova, Rasmus Ehren, Lutz T Weber, Hassib Chehade, Nakysa Hooman, Marcin Tkaczyk, Małgorzata Stańczyk, Howard Trachtman, Eugene Yu-Hin Chan, Kjell Tullus, CNI in Monogenic SRNS Study Investigators
Periodical/sKidney International
Overview
Abstract
Introduction: While calcineurin inhibitors (CNI) reduce proteinuria in a subgroup of children with genetic podocytopathies, previous reports suggest that the response is short-lived and of no benefit to long-term outcomes. Here, we assess CNI response sustainability and the association between different patterns of response preservation and kidney survival.
Methods: We performed a retrospective cohort study of patients aged 0-18 years with genetic podocytopathies treated with CNI for at least three months from 34 pediatric nephrology centers worldwide. Response status was defined in accordance with International Pediatric Nephrology Association Clinical Practice Recommendations.
Results: We analyzed 136 patients with genetic podocytopathies over a median follow-up period of 42.1 months (between CNI initiation and last follow-up or commencement of kidney replacement therapy, whichever occurred first). At least partial response was attained in 28% and 22% of patients at six months post-CNI initiation and last follow-up, respectively. Compared to non-response group, patients with at least partial response at six months had significantly lower urine protein-to-creatinine ratios across various timepoints post-CNI. 71%, 11% and 18% exhibited no response, non-sustained and sustained response, respectively, throughout the observation period. Both sustained and non-sustained responses were significantly associated with superior kidney survival compared to no response. Importantly, no patients with sustained response developed kidney failure over a follow-up period of 42 (inter quartile range 19-62) months. Patients with non-sustained response had a 92% lower risk of kidney failure, compared to non-responders.
Conclusion: A subset of children with genetic podocytopathies experienced a sustained response to CNI, and none developed kidney failure. Children with non-sustained response still demonstrated superior kidney survival compared to non-responders. Our findings may support a trial of CNI in genetic podocytopathies, and continuing therapy among those showing clinical response.