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Erschienen in: Pediatric Nephrology 4/2015

01.04.2015 | Brief Report

Positive role of rituximab in switching from cyclosporine to mycophenolate mofetil for children with high-dose steroid-dependent nephrotic syndrome

verfasst von: Shuichiro Fujinaga, Koji Sakuraya, Akifumi Yamada, Yasuko Urushihara, Yoshiyuki Ohtomo, Toshiaki Shimizu

Erschienen in: Pediatric Nephrology | Ausgabe 4/2015

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Abstract

Background

Recent randomized studies indicate that mycophenolate mofetil (MMF) is inferior to cyclosporine (CsA) in preventing relapses of nephrotic syndrome (NS). During the last decade, rituximab (RTX) has emerged as a rescue therapy in patients with complicated, frequently relapsing, or steroid-dependent NS.

Case-Diagnosis/Treatment

After introducing RTX in our single center, we analyzed 26 patients with steroid-dependent NS who had relapses while receiving long-term CsA and who were subsequently switched to MMF. MMF was adjusted to maintain a targeted predose mycophenolic acid (MPA) level of 2–5 μg/ml. Moreover, for patients who required MMF and high-dose prednisolone (PSL) to maintain remission, a single infusion of RTX (375 mg/m2) was added. The primary endpoint was the probability of achieving PSL-free remission for >1 year. At a mean follow-up of 28.8 ± 9.9 months, 11 of 26 patients (42 %) required RTX treatment, and 22 of those patients (85 %) achieved PSL-free sustained remission. The mean predose MPA levels for patients who achieved PSL-free sustained remission were significantly higher compared with those for patients who did not (3.1 μg/ml vs. 1.7 μg/ml, p < 0.05).

Conclusions

After RTX introduction, most patients were able to switch from CsA to MMF and achieve sustained PSL-free remission.
Literatur
1.
Zurück zum Zitat Ishikura K, Yoshikawa N, Hattori S, Sasaki S, Iijima K, Nakanishi K, Matsuyama T, Yata N, Ando T, Honda M (2010) Treatment with microemulsified cyclosporine in children with frequently relapsing nephrotic syndrome. Nephrol Dial Transplant 25:3956–3962CrossRefPubMed Ishikura K, Yoshikawa N, Hattori S, Sasaki S, Iijima K, Nakanishi K, Matsuyama T, Yata N, Ando T, Honda M (2010) Treatment with microemulsified cyclosporine in children with frequently relapsing nephrotic syndrome. Nephrol Dial Transplant 25:3956–3962CrossRefPubMed
2.
Zurück zum Zitat Iijima K, Sako M, Oba MS, Ito S, Hataya H, Tanaka R, Ohwada Y, Kamei K, Ishikura K, Yata N, Nozu K, Honda M, Nakamura H, Nagata M, Ohashi Y, Nakanishi K, Yoshikawa N (2014) Cyclosporine C2 monitoring for the treatment of frequently relapsing nephrotic syndrome in children: a multicenter randomized phase II trial. Clin J Am Soc Nephrol 9:271–278CrossRefPubMedCentralPubMed Iijima K, Sako M, Oba MS, Ito S, Hataya H, Tanaka R, Ohwada Y, Kamei K, Ishikura K, Yata N, Nozu K, Honda M, Nakamura H, Nagata M, Ohashi Y, Nakanishi K, Yoshikawa N (2014) Cyclosporine C2 monitoring for the treatment of frequently relapsing nephrotic syndrome in children: a multicenter randomized phase II trial. Clin J Am Soc Nephrol 9:271–278CrossRefPubMedCentralPubMed
3.
Zurück zum Zitat Iijima K, Hamahira K, Tanaka R, Kobayashi A, Nozu K, Nakamura H, Yoshikawa N (2002) Risk factors for cyclosporine-induced tubulointerstitial lesions in children with minimal change nephrotic syndrome. Kidney Int 61:1801–1805CrossRefPubMed Iijima K, Hamahira K, Tanaka R, Kobayashi A, Nozu K, Nakamura H, Yoshikawa N (2002) Risk factors for cyclosporine-induced tubulointerstitial lesions in children with minimal change nephrotic syndrome. Kidney Int 61:1801–1805CrossRefPubMed
4.
Zurück zum Zitat Fujinaga S, Kaneko K, Muto T, Ohtomo Y, Murakami H, Yamashiro Y (2006) Independent risk factors for chronic cyclosporine induced nephropathy in children with nephrotic syndrome. Arch Dis Child 91:666–670CrossRefPubMedCentralPubMed Fujinaga S, Kaneko K, Muto T, Ohtomo Y, Murakami H, Yamashiro Y (2006) Independent risk factors for chronic cyclosporine induced nephropathy in children with nephrotic syndrome. Arch Dis Child 91:666–670CrossRefPubMedCentralPubMed
5.
Zurück zum Zitat Kemper MJ, Kuwertz-Broeking E, Bulla M, Mueller-Wiefel DE, Neuhaus TJ (2004) Recurrence of severe steroid dependency in cyclosporin A-treated childhood idiopathic nephrotic syndrome. Nephrol Dial Transplant 19:1136–1141CrossRefPubMed Kemper MJ, Kuwertz-Broeking E, Bulla M, Mueller-Wiefel DE, Neuhaus TJ (2004) Recurrence of severe steroid dependency in cyclosporin A-treated childhood idiopathic nephrotic syndrome. Nephrol Dial Transplant 19:1136–1141CrossRefPubMed
6.
Zurück zum Zitat Fujinaga S, Ohtomo Y, Umino D, Takemoto M, Shimizu T, Yamashiro Y, Kaneko K (2007) A prospective study on the use of mycophenolate mofetil in children with cyclosporine-dependent nephrotic syndrome. Pediatr Nephrol 22:71–76CrossRefPubMed Fujinaga S, Ohtomo Y, Umino D, Takemoto M, Shimizu T, Yamashiro Y, Kaneko K (2007) A prospective study on the use of mycophenolate mofetil in children with cyclosporine-dependent nephrotic syndrome. Pediatr Nephrol 22:71–76CrossRefPubMed
7.
Zurück zum Zitat Fujinaga S, Ohtomo Y, Hirano D, Nishizaki N, Someya T, Ohtsuka Y, Kaneko K, Shimizu T (2009) Mycophenolate mofetil therapy for childhood-onset steroid dependent nephrotic syndrome after long-term cyclosporine: extended experience in a single center. Clin Nephrol 72:268–273PubMed Fujinaga S, Ohtomo Y, Hirano D, Nishizaki N, Someya T, Ohtsuka Y, Kaneko K, Shimizu T (2009) Mycophenolate mofetil therapy for childhood-onset steroid dependent nephrotic syndrome after long-term cyclosporine: extended experience in a single center. Clin Nephrol 72:268–273PubMed
8.
Zurück zum Zitat Dorresteijn EM, Kist-van Holthe JE, Levtchenko EN, Nauta J, Hop WC, van der Heijden AJ (2008) Mycophenolate mofetil versus cyclosporine for remission maintenance in nephrotic syndrome. Pediatr Nephrol 23:2013–2020CrossRefPubMed Dorresteijn EM, Kist-van Holthe JE, Levtchenko EN, Nauta J, Hop WC, van der Heijden AJ (2008) Mycophenolate mofetil versus cyclosporine for remission maintenance in nephrotic syndrome. Pediatr Nephrol 23:2013–2020CrossRefPubMed
9.
Zurück zum Zitat Gellermann J, Weber L, Pape L, Tönshoff B, Hoyer P, Querfeld U (2013) Mycophenolate mofetil versus cyclosporin A in children with frequently relapsing nephrotic syndrome. J Am Soc Nephrol 24:1689–1697CrossRefPubMedCentralPubMed Gellermann J, Weber L, Pape L, Tönshoff B, Hoyer P, Querfeld U (2013) Mycophenolate mofetil versus cyclosporin A in children with frequently relapsing nephrotic syndrome. J Am Soc Nephrol 24:1689–1697CrossRefPubMedCentralPubMed
10.
Zurück zum Zitat Fujinaga S, Hirano D, Nishizaki N, Kamei K, Ito S, Ohtomo Y, Shimizu T, Kaneko K (2010) Single infusion of rituximab for persistent steroid-dependent minimal-change nephrotic syndrome after long-term cyclosporine. Pediatr Nephrol 25:539–544CrossRefPubMed Fujinaga S, Hirano D, Nishizaki N, Kamei K, Ito S, Ohtomo Y, Shimizu T, Kaneko K (2010) Single infusion of rituximab for persistent steroid-dependent minimal-change nephrotic syndrome after long-term cyclosporine. Pediatr Nephrol 25:539–544CrossRefPubMed
11.
Zurück zum Zitat Ito S, Kamei K, Ogura M, Sato M, Fujimaru T, Ishikawa T, Udagawa T, Iijima K (2011) Maintenance therapy with mycophenolate mofetil after rituximab in pediatric patients with steroid-dependent nephrotic syndrome. Pediatr Nephrol 26:1823–1828CrossRefPubMed Ito S, Kamei K, Ogura M, Sato M, Fujimaru T, Ishikawa T, Udagawa T, Iijima K (2011) Maintenance therapy with mycophenolate mofetil after rituximab in pediatric patients with steroid-dependent nephrotic syndrome. Pediatr Nephrol 26:1823–1828CrossRefPubMed
12.
Zurück zum Zitat Tellier S, Brochard K, Garnier A, Bandin F, Llanas B, Guigonis V, Cailliez M, Pietrement C, Dunand O, Nathanson S, Bertholet-Thomas A, Ichay L, Decramer S (2013) Long-term outcome of children treated with rituximab for idiopathic nephrotic syndrome. Pediatr Nephrol 28:911–918CrossRefPubMed Tellier S, Brochard K, Garnier A, Bandin F, Llanas B, Guigonis V, Cailliez M, Pietrement C, Dunand O, Nathanson S, Bertholet-Thomas A, Ichay L, Decramer S (2013) Long-term outcome of children treated with rituximab for idiopathic nephrotic syndrome. Pediatr Nephrol 28:911–918CrossRefPubMed
13.
Zurück zum Zitat Chaumais MC, Garnier A, Chalard F, Peuchmaur M, Dauger S, Jacqz-Agrain E, Deschênes G (2009) Fatal pulmonary fibrosis after rituximab administration. Pediatr Nephrol 24:1753–1755CrossRefPubMed Chaumais MC, Garnier A, Chalard F, Peuchmaur M, Dauger S, Jacqz-Agrain E, Deschênes G (2009) Fatal pulmonary fibrosis after rituximab administration. Pediatr Nephrol 24:1753–1755CrossRefPubMed
14.
Zurück zum Zitat Sellier-Leclerc AL, Belli E, Guérin V, Dorfmüller P, Deschênes G (2013) Fulminant viral myocarditis after rituximab therapy in pediatric nephrotic syndrome. Pediatr Nephrol 28:1875–1879CrossRefPubMed Sellier-Leclerc AL, Belli E, Guérin V, Dorfmüller P, Deschênes G (2013) Fulminant viral myocarditis after rituximab therapy in pediatric nephrotic syndrome. Pediatr Nephrol 28:1875–1879CrossRefPubMed
15.
Zurück zum Zitat Ishikura K, Yoshikawa N, Nakazato H, Sasaki S, Iijima K, Nakanishi K, Matsuyama T, Ito S, Yata N, Ando T, Honda M (2012) Two-year follow-up of a prospective clinical trial of cyclosporine for frequently relapsing nephrotic syndrome in children. Clin J Am Soc Nephrol 7:1576–1583CrossRefPubMedCentralPubMed Ishikura K, Yoshikawa N, Nakazato H, Sasaki S, Iijima K, Nakanishi K, Matsuyama T, Ito S, Yata N, Ando T, Honda M (2012) Two-year follow-up of a prospective clinical trial of cyclosporine for frequently relapsing nephrotic syndrome in children. Clin J Am Soc Nephrol 7:1576–1583CrossRefPubMedCentralPubMed
16.
Zurück zum Zitat Fujinaga S, Hirano D (2014) Risk factors for early relapse during maintenance therapy after a single infusion of rituximab in children with steroid-dependent nephrotic syndrome. Pediatr Nephrol 29:491–492CrossRefPubMed Fujinaga S, Hirano D (2014) Risk factors for early relapse during maintenance therapy after a single infusion of rituximab in children with steroid-dependent nephrotic syndrome. Pediatr Nephrol 29:491–492CrossRefPubMed
17.
Zurück zum Zitat Trujillo JE, Bosque M, Asensio O, Ranera A, Rojo JC, Vilella M, Guijarro E, Domingo X, Valdesoiro L, Larramona H (2014) PD42 - Is rituximab a trigger for persistent hypogammaglobulinemia in idiopathic nephrotic syndrome? Clin Transl Allergy 28:4 Trujillo JE, Bosque M, Asensio O, Ranera A, Rojo JC, Vilella M, Guijarro E, Domingo X, Valdesoiro L, Larramona H (2014) PD42 - Is rituximab a trigger for persistent hypogammaglobulinemia in idiopathic nephrotic syndrome? Clin Transl Allergy 28:4
18.
Zurück zum Zitat Boyer O, Niaudet P (2013) Rituximab in childhood steroid-dependent nephrotic syndrome. Nat Rev Nephrol 9:562–563CrossRefPubMed Boyer O, Niaudet P (2013) Rituximab in childhood steroid-dependent nephrotic syndrome. Nat Rev Nephrol 9:562–563CrossRefPubMed
Metadaten
Titel
Positive role of rituximab in switching from cyclosporine to mycophenolate mofetil for children with high-dose steroid-dependent nephrotic syndrome
verfasst von
Shuichiro Fujinaga
Koji Sakuraya
Akifumi Yamada
Yasuko Urushihara
Yoshiyuki Ohtomo
Toshiaki Shimizu
Publikationsdatum
01.04.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
Pediatric Nephrology / Ausgabe 4/2015
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-014-3034-x

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