Skip to main content
SpringerLink
Log in

Biologika in der Therapie des nephrotischen Syndroms

Biologicals in the treatment of childhood nephrotic syndrome

  • Leitthema
  • Published:
Monatsschrift Kinderheilkunde Aims and scope Submit manuscript

Zusammenfassung

Die Therapie des nephrotischen Syndroms im Kindesalter kann v. a. durch Steroidabhängigkeit und -resistenz kompliziert werden. Selbst der Einsatz von Kalzineurininhibitoren und Alkylanzien bringt mitunter keinen therapeutischen Erfolg oder ist mit schweren (z. B. Nephrotoxizität) bzw. unkalkulierbaren (z. B. Gonadotoxizität) Nebenwirkungen verbunden. Bei einer Reihe von Kindern mit schwer therapierbarem nephrotischem Syndrom und hoher Immunsuppression erlaubt der Einsatz des Anti-CD20-Antikörpers Rituximab die Reduktion weiterer Immunsuppressiva. Nebenwirkungen sind bislang vornehmlich bei anderen Grunderkrankungen beschrieben und umfassen, neben allergischen Reaktionen auf den nicht vollständig humanisierten Antikörper, eine Hypogammaglobulinämie und selten eine äußerst schwer verlaufende progressive multifokale Leukenzephalopathie. Die genaue Rate an Therapieversagern ist beim nephrotischen Syndrom bislang unbekannt. Daher sollte in jedem Fall bis zum Vorliegen konklusiver klinischer Studien Rituximab nur unter Erfassung sämtlicher Daten in Registern verabreicht werden, wie dies in der Gesellschaft für Pädiatrische Nephrologie (GPN) geplant ist.

Abstract

The treatment of childhood nephrotic syndrome can be complicated by steroid dependence or resistance. Even the use of calcineurin inhibitors and alkylating agents does not always lead to sustained remission or is associated with severe (e.g. nephrotoxicity) or incalculable (e.g. gonadotoxicity) risks. A number of children and adolescents with severe nephrotic syndrome receiving intensive immunosuppressive therapy have been treated with the anti-CD20 antibody rituximab, leading to a reduction in immunosuppressive drugs for most patients. Adverse effects – mostly reported in other diseases treated with rituximab – include allergic reactions, hypogammaglobulinaemia, and, rarely, progressive multifocal leukoencephalopathy. The exact percentage of patients with nephrotic syndrome who fail to respond to rituximab is not yet known. Therefore, the use of rituximab should be restricted to clinical studies or, if unavailable, to registries recording side effects and efficacy of treatment, as currently planned by the German Society of Paediatric Nephrology.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2

Literatur

  1. Arbeitsgemeinschaft für Pädiatrische Nephrologie (1982) Effect of cytotoxic drugs in frequently relapsing nephrotic syndrome with and without steroid dependence. N Engl J Med 306:451–454

    Article  Google Scholar 

  2. Bagga A, Hari P, Moudgil A, Nordan SC (2003) Mycophenolate mofetil and prednisolone therapy in children with steroid-dependent nephrotic syndrome. Am J Kidney Dis 42:1114–1120

    Article  PubMed  CAS  Google Scholar 

  3. Bargman JM (1999) Management of minimal lesion glomerulonephritis: evidence-based recommendations. Kidney Int 70:3–16

    Article  Google Scholar 

  4. Benz K, Dötsch J, Rascher W, Stachel D (2004) Change of the course of steroid-dependent nephrotic syndrome after rituximab therapy. Pediatr Nephrol 19:794–797

    Article  PubMed  Google Scholar 

  5. Dallochio IA, Trimoreau F, Feuillard J, Guigonis V (2006) A case of steroid-dependent nephrotic syndrome treated with rituximab (abstract). Pediatr Nephrol 21:1615

    Google Scholar 

  6. Dantal J, Bigot E, Bogers W et al (1994) Effect of plasma protein adsorption on protein excretion in kidney-transplant recipients with recurrent nephrotic syndrome. N Engl J Med 330:7–14

    Article  PubMed  CAS  Google Scholar 

  7. Dörner T, Burmester GR (2008) New approaches of B-cell-directed therapy: beyond rituximab. Curr Opin Rheumatol 20:263–268

    Article  PubMed  Google Scholar 

  8. Dötsch J, Dittrich K, Plank C, Rascher W (2006) Is tacrolimus for childhood steroid-dependent nephrotic syndrome better than ciclosporin A? Nephrol Dial Transplant 21:1761–1763

    Article  PubMed  Google Scholar 

  9. Dötsch J, Müller-Wiefel DE, Kemper MJ (2008) Rituximab: is replacement of cyclophosphamide and calcineurin inhibitors in steroid-dependent nephrotic syndrome possible? Pediatr Nephrol 23:3–7

    Article  PubMed  Google Scholar 

  10. FDA (2007) Rituxan warning. FDA Consum 41:3

    Google Scholar 

  11. Francois H, Daugas E, Bensman A, Ronco P (2007) Unexpected efficacy of rituximab in multirelapsing minimal change nephrotic syndrome in the adult: first case report and pathophysiological considerations. Am J Kidney Dis 49:158–161

    Article  PubMed  CAS  Google Scholar 

  12. Gilbert RD, Hulse E, Rigden S (2006) Rituximab therapy for steroid-dependent minimal change nephrotic syndrome. Pediatr Nephrol 21:1698–1700

    Article  PubMed  Google Scholar 

  13. Gossmann J, Scheuermann EH, Porubsky S et al (2007) Abrogation of nephrotic proteinuria by rituximab treatment in a renal transplant patient with relapsed focal segmental glomerulosclerosis. Transpl Int 20:558–562

    Article  PubMed  Google Scholar 

  14. Guigonis V, Dallocchio A, Baudouin V et al (2008) Rituximab treatment for severe steroid- or cyclosporine-dependent nephrotic syndrome: a multicentric series of 22 cases. Pediatr Nephrol 23:1269–1279

    Article  PubMed  Google Scholar 

  15. Harris HE (2008) Progressive multifocal leucoencephalopathy in a patient with systemic lupus erythematosus treated with rituximab. Rheumatology (Oxford) 47:224–225

    Google Scholar 

  16. Hodson EM, Alexander SI (2008) Evaluation and management of steroid-sensitive nephrotic syndrome. Curr Opin Pediatr 20:145–150

    Article  PubMed  Google Scholar 

  17. Hofstra JM, Deegens JK, Wetzels JF (2007) Rituximab: effective treatment for severe steroid-dependent minimal change nephrotic syndrome? Nephrol Dial Transplant 22(7):2100–2102

    Article  PubMed  Google Scholar 

  18. Hogg RJ, Fitzgibbons L, Buick J et al (2004) Clinical trial of mycophenolate motefil (MMF) for frequent relapsing nephrotic syndrome in children. Pediatr Nephrol 19:C66

    Article  Google Scholar 

  19. Hristea D, Hadaya K, Marangon N et al (2007) Successful treatment of recurrent focal segmental glomerulosclerosis after kidney transplantation by plasmapheresis and rituximab. Transpl Int 20:102–105

    Article  PubMed  CAS  Google Scholar 

  20. Kemper MJ, Meyer-Jark T, Lilova M, Müller-Wiefel DE (2003) Combined T- and B-cell activation in childhood steroid-sensitive nephrotic syndrome. Clin Nephrol 60:242–247

    PubMed  CAS  Google Scholar 

  21. Kemper MJ, Kuwertz-Broeking E, Bulla M et al (2004) Recurrence of severe steroid dependency in cyclosporin A-treated childhood idiopathic nephrotic syndrome. Nephrol Dial Transplant 19:1136–1141

    Article  PubMed  CAS  Google Scholar 

  22. Kemper MJ, Zepf K, Klaassen I et al (2005) Changes of lymphocyte populations in pediatric steroid-sensitive nephrotic syndrome are more pronounced in remission than in relapse. Am J Nephrol 25:132–137

    Article  PubMed  Google Scholar 

  23. Kemper MJ, Möller K, Ludwig K et al (2006) Rituximab in the treatment of refractory steroid-sensitive nephrotic syndrome (abstract). Pediatr Nephrol 21:1528

    Google Scholar 

  24. Kemper MJ, Dittrich K, Billing H et al (2008) Risiko-Register „Steroidsensibles Nephrotisches Syndrom (SSNS)“ der Gesellschaft für Pädiatrische Nephrologie (GPN): Erfahrungen mit Rituximab (RTX). Monatschr Kinderheilkd [Suppl] 1:S109

  25. Kimby E (2005) Tolerability and safety of rituximab (MabThera). Cancer Treat Rev 31:456–473

    Article  PubMed  CAS  Google Scholar 

  26. Lagrue G, Branellec A, Blanc C et al (1975) A vascular permeability factor in lymphocyte culture supernants from patients with nephrotic syndrome. II. Pharmacological and physicochemical properties. Biomedicine 23:73–75

    PubMed  CAS  Google Scholar 

  27. Latta K, Schnakenburg C von, Ehrich JHH (2001) A metaanalysis of cytotoxic treatment of frequently relapsing nephrotic syndrome in children. Pediatr Nephrol 16:271–282

    Article  PubMed  CAS  Google Scholar 

  28. Marks SD, McGraw M (2007) Does rituximab treat recurrent focal segmental glomerulosclerosis post-renal transplantation? Pediatr Nephrol 22:158–160

    Article  PubMed  Google Scholar 

  29. Molloy ES, Calabrese LH (2008) Progressive multifocal leukoencephalopathy in patients with rheumatic diseases: are patients with systemic lupus erythematosus at particular risk? Autoimmun Rev 8(2):144–146

    Article  PubMed  CAS  Google Scholar 

  30. Niaudet P, Habib R (1994) Cyclosporine in the treatment of idiopathic nephrosis. J Am Soc Nephrol 5:1049–1056

    PubMed  CAS  Google Scholar 

  31. NN (1974) Prospective, controlled trial of cyclophosphamide therapy in children with the nephrotic syndrome. International Study of Kidney Disease in Children. Lancet 2:423–427

    Google Scholar 

  32. Nozu K, Iijima K, Fujisawa M et al (2005) Rituximab treatment for posttransplant lymphoproliferative disorder (PTLD) induces complete remission of recurrent nephrotic syndrome. Pediatr Nephrol 20:1660–1663

    Article  PubMed  Google Scholar 

  33. Orman SV, Schechter GP, Whang-Peng J et al (1986) Nephrotic syndrome associated with a clonal T-cell leukemia of large granular lymphocytes with cytotoxic function. Arch Intern Med 146:1827–1829

    Article  PubMed  CAS  Google Scholar 

  34. Pescovitz MD, Book BK, Sidner RA (2006) Resolution of recurrent focal segmental glomerulosclerosis proteinuria after rituximab treatment. N Engl J Med 354:1961–1963

    Article  PubMed  CAS  Google Scholar 

  35. Remuzzi G, Chiurchiu C, Abbate M et al (2002) Rituximab for idiopathic membranous nephropathy. Lancet 360:923–924

    Article  PubMed  CAS  Google Scholar 

  36. Rueth EM, Kemper MJ, Leumann EP et al (2005) Children with steroid-sensitive nephrotic syndrome come of age: long-term outcome. J Pediatr 147:202–207

    Article  Google Scholar 

  37. Smith GC (2007) Is there a role for rituximab in the treatment of idiopathic childhood nephrotic syndrome? Pediatr Nephrol 22(6):893–898

    Article  PubMed  Google Scholar 

  38. Tenbrock K, Muller-Berghaus J, Fuchshuber A et al (1998) Levamisole treatment in steroid-sensitive and steroid-resistant nephrotic syndrome. Pediatr Nephrol 12:459–462

    Article  PubMed  CAS  Google Scholar 

  39. Tumlin JA, Miller D, Near M et al (2006) A prospective, open-label trial of sirolimus in the treatment of focal segmental glomerulosclerosis. Clin J Am Soc Nephrol 1:109–116

    Article  PubMed  CAS  Google Scholar 

  40. Westphal S, Hansson S, Mjörnstedt L et al (2006) Early recurrence of nephrotic syndrome (immunoglobulin M nephropathy) after renal transplantation successfully treated with combinations of plasma exchanges, immunoglobulin, and rituximab. Transplant Proc 38:2659–2560

    Article  PubMed  CAS  Google Scholar 

  41. Yokoyama H, Watanabe T, Maruyama D et al (2008) Progressive multifocal leukoencephalopathy in a patient with B-cell lymphoma during rituximab-containing chemotherapy: case report and review of the literature. Int J Hematol 88(4):443–447

    Article  PubMed  Google Scholar 

Download references

Interessenkonflikt

Der korrespondierende Autor weist auf folgende Beziehung/en hin: Der Erstautor erhält eine Forschungsunterstützung der Fa. Hoffmann-LaRoche für eine durch die Gesellschaft für Pädiatrische Nephrologie gestützte Studie zur Reduktion der Kalzineurininhibitorentoxizität nach Nierentransplantation. Es besteht keine Unterstützung für Studien zum Einsatz von Rituximab.

Author information

Authors and Affiliations

  1. Kinder- und Jugendklinik, Universitätsklinikum Erlangen, Loschgestraße 15, 91054, Erlangen, Deutschland

    J. Dötsch

  2. Pädiatrische Nephrologie, Universitätsklinikum Hamburg, Hamburg, Deutschland

    D.E. Müller-Wiefel & M.J. Kemper

Authors
  1. J. Dötsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D.E. Müller-Wiefel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M.J. Kemper
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. Dötsch.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dötsch, J., Müller-Wiefel, D. & Kemper, M. Biologika in der Therapie des nephrotischen Syndroms. Monatsschr Kinderheilkd 157, 247–253 (2009). https://doi.org/10.1007/s00112-008-1869-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00112-008-1869-6

Schlüsselwörter

Keywords

Search

Navigation