Management des steroidsensiblen nephrotischen Syndroms im Kindes- und Jugendalter

Zusammenfassung

Das nephrotische Syndrom im Kindesalter erfüllt die Kriterien einer seltenen Erkrankung und doch ist es die häufigste Glomerulopathie in dieser Altersgruppe. Gleichzeitig ist es eine heterogene Erkrankung, die durch die Kategorien Alter bei Erstmanifestation, Ätiologie, Histologie und Ansprechen auf eine Standardtherapie mit Glukokortikoiden eingeteilt werden kann. Wichtigster Prognosefaktor ist das primäre Ansprechen auf eine Standardtherapie mit Glukokortikoiden und differenziert zwischen steroidsensiblem (SSNS) und steroidresistentem nephrotischem Syndrom (SRNS). Eine hohe kumulative Dosis an Glukokortikoiden oder die verlängerte Gabe bei Behandlung der Erstmanifestation scheinen das Rezidivrisiko nicht zu beeinflussen. Trotz der kurz- und langfristigen Nebenwirkungen der Glukokortikoide, die die primäre Therapiesäule des nephrotischen Syndroms darstellen, ist die Bewertung der medikamentösen Alternativen bei Patienten mit häufigen Rezidiven eines SSNS eine ständige differenzialtherapeutische Herausforderung. Dies gilt ebenso für die Therapie des SRNS. Beim SRNS ist eine molekulargenetische Abklärung dringend zu empfehlen. Der vorliegende Text gibt eine Übersicht zur Therapie des SSNS.

Summary

Despite being an orphan disease, idiopathic nephrotic syndrome in children is the most frequent glomerular disease in this age group. Nephrotic syndrome in children is a heterogeneous disease and in order to assess the individual facets of the disease a classification using the following criteria is helpful: etiology, age at onset, histology, and responsiveness to initial standard treatment with glucocorticoids. As for prognosis the differentiation between steroid-sensitive (SSNS) and steroid-resistant nephrotic syndrome (SRNS) is most important, because SRNS is a risk factor for developing end-stage renal disease. High cumulative dosages of glucocorticoids or prolonged initial therapy do not seem to influence risk of relapse. In order to avoid short- and long-term glucocorticoid-associated side effects alternative treatment options should be kept in mind planning individual treatment of patients with frequently relapsing disease. Genetic diagnostic is highly advisable in patients with SRNS. The following manuscript gives an overview on the management of SSNS.

Schlüsselwörter

Steroidresistentes nephrotisches Syndrom - Therapie - Glukokortikoide - Komplikationen - Alternativtherapie

Keywords

Steroid-sensitive nephrotic syndrome - steroid-resistant nephrotic syndrome - treatment - glucocorticoids

• Literatur

• 1 Sahali D, Sendeyo K, Mangier M. et al. Immunopathogenesis of idiopathic nephrotic syndrome with relapse. Semin Immunopathol. 2014; 36: 421-429.
• 2 Lombel RM, Gipson DS, Hodson EM. Kidney Disease: Improving Global O. Treatment of steroidsensitive nephrotic syndrome: new guidelines from KDIGO. Pediatr Nephrol 2013; 28: 415-426.
• 3 Gipson DS, Massengill SF, Yao L. et al. Management of childhood onset nephrotic syndrome. Pediatrics 2009; 124: 747-757.
• 4 Brodehl J. The treatment of minimal change nephrotic syndrome: lessons learned from multicentre co-operative studies. Eur J Pediatr 1991; 150: 380-387.
• 5 Hodson EM, Willis NS, Craig JC. Corticosteroid therapy for nephrotic syndrome in children. Cochrane Database Syst Rev 2007; CD001533.
• 6 Teeninga N, Kist-van Holthe JE, van Rijswijk N. et al. Extending prednisolone treatment does not reduce relapses in childhood nephrotic syndrome. J Am Soc Nephrol 2013; 24: 149-159.
• 7 Yoshikawa N, Nakanishi K, Sako M. et al. A multicenter randomized trial indicates initial prednisolone treatment for childhood nephrotic syndrome for two months is not inferior to six-month treatment. Kidney Int 2015; 87: 225-232.
• 8 Sinha A, Saha A, Kumar M. et al. Extending initial prednisolone treatment in a randomized control trial from 3 to 6 months did not significantly influence the course of illness in children with steroid-sensitive nephrotic syndrome. Kidney Int 2015; 87: 217-224.
• 9 Hahn D, Hodson EM, Willis NS, Craig JC. Corticosteroid therapy for nephrotic syndrome in children. Cochrane Database Syst Rev 2015; 3: CD001533.
• 10 Dorresteijn EM, Kist-van Holthe JE, Levtchenko EN. et al. Mycophenolate mofetil versus cyclosporine for remission maintenance in nephrotic syndrome. Pediatr Nephrol 2008; 23: 2013-2020.
• 11 Fujinaga S, Ohtomo Y, Hirano D. et al. Mycophenolate mofetil therapy for childhood-onset steroid dependent nephrotic syndrome after long-term cyclosporine: extended experience in a single center. Clin Nephrol 2009; 72: 268-273.
• 12 Gellermann J, Weber L, Pape L. et al. Mycophenolate mofetil versus cyclosporin A in children with frequently relapsing nephrotic syndrome. J Am Soc Nephrol 2013; 24: 1689-1697.
• 13 Kwiterovich PO. Clinical and laboratory assessment of cardiovascular risk in children: Guidelines for screening, evaluation, and treatment. J Clin Lipidol 2008; 2: 248-266.
• 14 Nakamura A, Niimi R, Kurosaki K. et al. Factors influencing cardiovascular risk following termination of glucocorticoid therapy for nephrotic syndrome. Clin Exp Nephrol 2010; 14: 457-462.
• 15 Skrzypczyk P, Panczyk-Tomaszewska M, Roszkowska-Blaim M. et al. Long-term outcomes in idiopathic nephrotic syndrome: from childhood to adulthood. Clin Nephrol 2014; 81: 166-173.
• 16 Abeyagunawardena AS, Trompeter RS. Increasing the dose of prednisolone during viral infections reduces the risk of relapse in nephrotic syndrome: a randomised controlled trial. Arch Dis Child 2008; 93: 226-228.
• 17 Mattoo TK, Mahmoud MA. Increased maintenance corticosteroids during upper respiratory infection decrease the risk of relapse in nephrotic syndrome. Nephron 2000; 85: 343-345.
• 18 Gulati A, Sinha A, Sreenivas V. et al. Daily corticosteroids reduce infection-associated relapses in frequently relapsing nephrotic syndrome: a randomized controlled trial. Clin J Am Soc Nephrol 2011; 6: 63-69.
• 19 Webb NJ, Frew E, Brettell EA. et al. Short course daily prednisolone therapy during an upper respiratory tract infection in children with relapsing steroid-sensitive nephrotic syndrome (PREDNOS 2): protocol for a randomised controlled trial. Trials 2014; 15: 147.
• 20 Benz MR TB, Weber LT. Treatment of children with frequent relapsing steroid-sensitive nephrotic syndrome: recent trial results. Clin Invest (Lond) 2014; 4: 1043-1054.
• 21 van Husen M, Kemper MJ. New therapies in steroid-sensitive and steroid-resistant idiopathic nephrotic syndrome. Pediatr Nephrol 2011; 26: 881-892.
• 22 Cammas B, Harambat J, Bertholet-Thomas A. et al. Long-term effects of cyclophosphamide therapy in steroid-dependent or frequently relapsing idiopathic nephrotic syndrome. Nephrol Dial Transplant 2011; 26: 178-184.
• 23 Fujinaga S, Endo A, Ohtomo Y. et al. Uncertainty in management of childhood-onset idiopathic nephrotic syndrome: is the long-term prognosis really favorable?. Pediatr Nephrol 2013; 28: 2235-2238.
• 24 Latta K, von Schnakenburg C, Ehrich JH. A metaanalysis of cytotoxic treatment for frequently relapsing nephrotic syndrome in children. Pediatr Nephrol 2001; 16: 271-282.
• 25 Kemper MJ LA, Zawischa A, Oh J. Is rituximab effective in childhood nephrotic syndrome? Yes and no. Pediatric nephrology 2014; 29: 1305-1311.
• 26 Iijima K, Sako M, Nozu K. et al. Rituximab for childhood-onset, complicated, frequently relapsing nephrotic syndrome or steroid-dependent nephrotic syndrome: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet 2014; 384: 1273-1281.
• 27 Ravani P, Rossi R, Bonanni A. et al. Rituximab in Children with Steroid-Dependent Nephrotic Syndrome: A Multicenter, Open-Label, Noninferiority, Randomized Controlled Trial. Journal of the American Society of Nephrology: JASN. 2015
• 28 Ishikura K IM, Hattori S, Yoshikawa N. et al. Effective and safe treatment with cyclosporine in nephrotic children: a prospective, randomized multicenter trial. Kidney Int 2008; 73: 1167-1673.
• 29 Wang W, Xia Y. Mao et al. Treatment of tacrolimus or cyclosporine A in children with idiopathic nephrotic syndrome. Pediatric nephrology 2012; 27: 2073-2079.
• 30 Bock ME, Cohn RA, Ali FN. Treatment of childhood nephrotic syndrome with long-term, low-dose tacrolimus. Clin Nephrol 2013; 79: 432-438.
• 31 Citak A, Emre S, Sairin A. et al. Hemostatic problems and thromboembolic complications in nephrotic children. Pediatr Nephrol 2000; 14: 138-142.
• 32 Limperger V, Franke A, Kenet G. et al. Clinical and laboratory characteristics of paediatric and adolescent index cases with venous thromboembolism and antithrombin deficiency. An observational multicentre cohort study. Thromb Haemost 2014; 112: 478-485.
• 33 Suri D, Ahluwalia J, Saxena AK. et al. Thromboembolic complications in childhood nephrotic syndrome: a clinical profile. Clin Exp Nephrol 2014; 18: 803-813.
• 34 Kapur G, Valentini RP, Imam AA, Mattoo TK. Treatment of severe edema in children with nephrotic syndrome with diuretics alone – a prospective study. Clin J Am Soc Nephrol. 2009; 4: 907-913.
• 35 Afroz S, Khan AH, Roy DK. Thyroid function in children with nephrotic syndrome. Mymensingh Med J 2011; 20: 407-411.
• 36 Dagan A, Cleper R, Krause I. et al. Hypothyroidism in children with steroid-resistant nephrotic syndrome. Nephrol Dial Transplant 2012; 27: 2171-2175.
• 37 Wetzsteon RJ, Shults J, Zemel BS. et al. Divergent effects of glucocorticoids on cortical and trabecular compartment BMD in childhood nephrotic syndrome. Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 2009; 24: 503-513.
• 38 Emma F, Sesto A, Rizzoni G. Long-term linear growth of children with severe steroid-responsive nephrotic syndrome. Pediatr Nephrol 2003; 18: 783-788.