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Cyclosporin A is superior to cyclophosphamide in children with steroid-resistant nephrotic syndrome—a randomized controlled multicentre trial by the Arbeitsgemeinschaft für Pädiatrische Nephrologie

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Abstract

First line immunosuppressive treatment in steroid-resistant nephrotic syndrome in children is still open to discussion. We conducted a controlled multicentre randomized open label trial to test the efficacy and safety of cyclosporin A (CSA) versus cyclophosphamide pulses (CPH) in the initial therapy of children with newly diagnosed primary steroid-resistant nephrotic syndrome and histologically proven minimal change disease, focal segmental glomerulosclerosis or mesangial hypercellularity. Patients in the CSA group (n = 15) were initially treated with 150 mg/m2 CSA orally to achieve trough levels of 120–180 ng/ml, while patients in the CPH group (n = 17) received CPH pulses (500 mg/m2 per month intravenous). All patients were on alternate prednisone therapy. Patients with proteinuria >40 mg/m2 per hour at 12 weeks of therapy were allocated to a non-responder protocol with high-dose CSA therapy or methylprednisolone pulses. At week 12, nine of the 15 (60%) CSA patients showed at least partial remission, evidences by a reduction of proteinuria <40 mg/h per m2. In contrast, three of the 17 (17%) CPH patients responded (p < 0.05, intention-to-treat). Given these results, the study was stopped, in accordance with the protocol. After 24 weeks, complete remission was reached by two of the 15 (13%) CSA and one of the 17 (5%) CPH patients (p = n.s.). Partial remission was achieved by seven of the 15 (46%) CSA and two of the 15 (11%) CPH patients (p <0.05). Five patients in the CSA group and 14 patients in the CPH group were withdrawn from the study, most of them during the non-responder protocol. The number of adverse events was comparable between both groups. We conclude that CSA is more effective than CPH in inducing at least partial remission in steroid-resistant nephrotic syndrome in children.

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Acknowledgements

We thank all the members of the Arbeitsgemeinschaft für Pädiatrische Nephrologie for their help in the design and realization of this project. For their help in coordinating the study, we thank K. Benz, K.-D. Nüsken, B. Geißler and K. Escherich. We very much appreciate the willingness of our patients and their families to participate in this trial. This project was supported in part by a grant of Novartis Pharma, Nuremberg, Germany.

Conflict of interest statement

None to declare.

Members of Protocol committee

W. Rascher, C. Plank (Erlangen, Germany); C. Aufricht (Vienna, Austria); J.H. Ehrich (Hannover, Germany); A. Fuchshuber (Freiburg, Germany); P. Hoyer (Essen); M. Kemper (Hamburg); O. Mehls, K. Schärer, B. Tönshoff (Heidelberg, Germany); U. Querfeld (Berlin, Germany); M. Schwab (Stuttgart, Germany).

List of contributing investigators

Austria: C. Aufricht; K. Arbeiter; T. Müller; A. Grillenberg; M. Mayrhofer; R. Vargha (Vienna, Linz)Germany: U. Querfeld; J. Gellermann; D. Haffner; M. Zimmering; (Berlin), H. Bachmann; N. Matthes (Bremen); G. Kalvoda; B. Mayer; S. Nolte; I. Wülke (Dresden); F. Wegner (Düren); W. Rascher; K. Benz; K. Dittrich; J. Dötsch; K-D. Nüsken; C. Plank (Erlangen); M. Pohl; S. Jacobi; C. von Schnakenburg (Freiburg); J.D. Schwarke; T. Henne (Hamburg); D.E. Müller-Wiefel; M. Kemper; A. Link; K. Zepf; (Hamburg); J.H. Ehrich; D. Franke; J. Strehlau (Hannover); B. Tönshoff; R. Feneberg; R. Himmele (Heidelberg); P. Eggert; D. Roessner (Kiel); R. Beetz (Mainz); G. Klaus; M. Konrad (Marburg); H. Fehrenbach; D. Kleinert (Memmingen); K.G. Pistor; K. Timmermann (Moers); M. Wigger; E. Drückler; I. Franke; J. Muscheites; G. Warncke (Rostock); Mutation Analysis: F. Hildebrandt, B. Hinkes; B. Mucha; R. Ruf (Ann Arbor, USA).

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Authors and Affiliations

  1. Department of Pediatrics, University Erlangen-Nuremberg, Loschgestraße 15, 91054, Erlangen, Germany

    Christian Plank, Veronica Kalb, Bernward Hinkes & Wolfgang Rascher

  2. Department of Pediatrics, University of Michigan, Ann Harbor, MI, USA

    Bernward Hinkes & Friedhelm Hildebrandt

  3. Institute for Medical Informatics, Biometry and Epidemiology, University Erlangen-Nuremberg, Erlangen, Germany

    Olaf Gefeller

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  1. Christian Plank
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Correspondence to Christian Plank.

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Plank, C., Kalb, V., Hinkes, B. et al. Cyclosporin A is superior to cyclophosphamide in children with steroid-resistant nephrotic syndrome—a randomized controlled multicentre trial by the Arbeitsgemeinschaft für Pädiatrische Nephrologie. Pediatr Nephrol 23, 1483–1493 (2008). https://doi.org/10.1007/s00467-008-0794-1

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