A multicenter retrospective study of calcineurin inhibitors in nephrotic syndrome secondary to podocyte gene variants

CNI in Monogenic SRNS Study Investigators, Georgia Malakasioti*, Daniela Iancu, Anastasiia Milovanova, Alexey Tsygin, Tomoko Horinouchi, China Nagano, Kandai Nozu, Koichi Kamei, Shuichiro Fujinaga, Kazumoto Iijima, Rajiv Sinha, Biswanath Basu, William Morello, Giovanni Montini, Aoife Waters, Olivia Boyer, Zeynep Yürük Yıldırım, Sibel Yel, İsmail DursunHugh J. McCarthy, Marina Vivarelli, Larisa Prikhodina, Martine T.P. Besouw, Eugene Yu hin Chan, Wenyan Huang, Markus J. Kemper, Sebastian Loos, Chanel Prestidge, William Wong, Galia Zlatanova, Rasmus Ehren, Lutz T. Weber, Hassib Chehade, Nakysa Hooman, Marcin Tkaczyk, Małgorzata Stańczyk, Michael Miligkos, Kjell Tullus

*Bijbehorende auteur voor dit werk

    OnderzoeksoutputAcademicpeer review

    6 Citaten (Scopus)
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    While 44-83% of children with steroid-resistant nephrotic syndrome (SRNS) without a proven genetic cause respond to treatment with a calcineurin inhibitor (CNI), current guidelines recommend against the use of immunosuppression in monogenic SRNS. This is despite existing evidence suggesting that remission with CNI treatment is possible and can improve prognosis in some cases of monogenic SRNS. Herein, our retrospective study assessed response frequency, predictors of response and kidney function outcomes among children with monogenic SRNS treated with a CNI for at least three months. Data from 203 cases (age 0-18 years) were collected from 37 pediatric nephrology centers. Variant pathogenicity was reviewed by a geneticist, and 122 patients with a pathogenic and 19 with a possible pathogenic genotype were included in the analysis. After six months of treatment and at last visit, 27.6% and 22.5% of all patients respectively, demonstrated partial or full response. Achievement of at least partial response at six months of treatment conferred a significant reduction in kidney failure risk at last follow-up compared to no response (hazard ratio [95% confidence interval] 0.25, [0.10-0.62]). Moreover, risk of kidney failure was significantly lower when only those with a follow-up longer than two years were considered (hazard ratio 0.35, [0.14-0.91]). Higher serum albumin level at CNI initiation was the only factor related to increased likelihood of significant remission at six months (odds ratio [95% confidence interval] 1.16, [1.08-1.24]). Thus, our findings justify a treatment trial with a CNI also in children with monogenic SRNS.

    Originele taal-2English
    Pagina's (van-tot)962-972
    Aantal pagina's11
    TijdschriftKidney International
    Nummer van het tijdschrift5
    Vroegere onlinedatum8-mrt.-2023
    StatusPublished - mei-2023

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