Skip to main content
Erschienen in: Pediatric Nephrology 3/2015

01.03.2015 | Original Article

Morbidity in children with frequently relapsing nephrosis: 10-year follow-up of a randomized controlled trial

verfasst von: Kenji Ishikura, Norishige Yoshikawa, Hitoshi Nakazato, Satoshi Sasaki, Koichi Nakanishi, Takeshi Matsuyama, Shuichi Ito, Yuko Hamasaki, Nahoko Yata, Takashi Ando, Kazumoto Iijima, Masataka Honda, for Japanese Study Group of Renal Disease in Children

Erschienen in: Pediatric Nephrology | Ausgabe 3/2015

Einloggen, um Zugang zu erhalten

Abstract

Background

To investigate the long-term outcome in children with frequently relapsing nephrotic syndrome (FRNS) we conducted a follow-up of a previous randomized controlled trial (RCT) 10 years after the initiation of the treatment protocol.

Methods

We previously conducted an RCT on the efficacy of cyclosporine for treating children with FRNS. After 2 years of treatment, a recommended a management protocol of steroids, and immunosuppressants was provided.

Results

Valid information was available for 46 of the 56 patients (82.1 %) enrolled in the original RCT. The median follow-up period was 10.3 years from the start of protocol treatment with cyclosporine. At last follow-up (mean age 18.7 years), only ten patients (21.7 %) showed disease-free remission (no relapse for at least 2 years). In contrast, 23 (50.0 %) continued to relapse frequently or were on immunosuppressants, eight patients (17.4 %) had infrequent relapses without immunosuppressants. Adverse effects attributable to treatment included short stature (6 patients), osteoporosis (six patients), obesity (4 patients), cataracts (3 patients) and hypertension (3 patients). No lethal event or renal dysfunction occurred during follow-up.

Conclusions

This 10-year follow-up study shows that most children with FRNS experience relapses after 2 years of cyclosporine treatment, in adolescence and into adulthood. Outcomes in terms of life expectancy and renal function are favorable.
Literatur
1.
Zurück zum Zitat Pravitsitthikul N, Willis NS, Hodson EM, Craig JC (2013) Non-corticosteroid immunosuppressive medications for steroid-sensitive nephrotic syndrome in children. Cochrane Database Syst Rev 10:CD002290PubMed Pravitsitthikul N, Willis NS, Hodson EM, Craig JC (2013) Non-corticosteroid immunosuppressive medications for steroid-sensitive nephrotic syndrome in children. Cochrane Database Syst Rev 10:CD002290PubMed
2.
Zurück zum Zitat Latta K, von Schnakenburg C, Ehrich JH (2001) A meta-analysis of cytotoxic treatment for frequently relapsing nephrotic syndrome in children. Pediatr Nephrol 16:271–282PubMedCrossRef Latta K, von Schnakenburg C, Ehrich JH (2001) A meta-analysis of cytotoxic treatment for frequently relapsing nephrotic syndrome in children. Pediatr Nephrol 16:271–282PubMedCrossRef
3.
Zurück zum Zitat van Husen M, Kemper MJ (2011) New therapies in steroid-sensitive and steroid-resistant idiopathic nephrotic syndrome. Pediatr Nephrol 26:881–892PubMedCrossRef van Husen M, Kemper MJ (2011) New therapies in steroid-sensitive and steroid-resistant idiopathic nephrotic syndrome. Pediatr Nephrol 26:881–892PubMedCrossRef
4.
Zurück zum Zitat Lombel RM, Gipson DS, Hodson EM (2013) Treatment of steroid-sensitive nephrotic syndrome: new guidelines from KDIGO. Pediatr Nephrol 28:415–426PubMedCrossRef Lombel RM, Gipson DS, Hodson EM (2013) Treatment of steroid-sensitive nephrotic syndrome: new guidelines from KDIGO. Pediatr Nephrol 28:415–426PubMedCrossRef
5.
Zurück zum Zitat Gipson DS, Massengill SF, Yao L, Nagaraj S, Smoyer WE, Mahan JD, Wigfall D, Miles P, Powell L, Lin JJ, Trachtman H, Greenbaum LA (2009) Management of childhood onset nephrotic syndrome. Pediatrics 124:747–757PubMedCrossRef Gipson DS, Massengill SF, Yao L, Nagaraj S, Smoyer WE, Mahan JD, Wigfall D, Miles P, Powell L, Lin JJ, Trachtman H, Greenbaum LA (2009) Management of childhood onset nephrotic syndrome. Pediatrics 124:747–757PubMedCrossRef
6.
Zurück zum Zitat Fakhouri F, Bocquet N, Taupin P, Presne C, Gagnadoux MF, Landais P, Lesavre P, Chauveau D, Knebelmann B, Broyer M, Grunfeld JP, Niaudet P (2003) Steroid-sensitive nephrotic syndrome: from childhood to adulthood. Am J Kidney Dis 41:550–557PubMedCrossRef Fakhouri F, Bocquet N, Taupin P, Presne C, Gagnadoux MF, Landais P, Lesavre P, Chauveau D, Knebelmann B, Broyer M, Grunfeld JP, Niaudet P (2003) Steroid-sensitive nephrotic syndrome: from childhood to adulthood. Am J Kidney Dis 41:550–557PubMedCrossRef
7.
Zurück zum Zitat Ruth EM, Kemper MJ, Leumann EP, Laube GF, Neuhaus TJ (2005) Children with steroid-sensitive nephrotic syndrome come of age: long-term outcome. J Pediatr 147:202–207PubMedCrossRef Ruth EM, Kemper MJ, Leumann EP, Laube GF, Neuhaus TJ (2005) Children with steroid-sensitive nephrotic syndrome come of age: long-term outcome. J Pediatr 147:202–207PubMedCrossRef
8.
Zurück zum Zitat Kyrieleis HA, Levtchenko EN, Wetzels JF (2007) Long-term outcome after cyclophosphamide treatment in children with steroid-dependent and frequently relapsing minimal change nephrotic syndrome. Am J Kidney Dis 49:592–597PubMedCrossRef Kyrieleis HA, Levtchenko EN, Wetzels JF (2007) Long-term outcome after cyclophosphamide treatment in children with steroid-dependent and frequently relapsing minimal change nephrotic syndrome. Am J Kidney Dis 49:592–597PubMedCrossRef
9.
Zurück zum Zitat Trompeter RS, Lloyd BW, Hicks J, White RH, Cameron JS (1985) Long-term outcome for children with minimal-change nephrotic syndrome. Lancet 1:368–370PubMedCrossRef Trompeter RS, Lloyd BW, Hicks J, White RH, Cameron JS (1985) Long-term outcome for children with minimal-change nephrotic syndrome. Lancet 1:368–370PubMedCrossRef
10.
Zurück zum Zitat Ishikura K, Ikeda M, Hattori S, Yoshikawa N, Sasaki S, Iijima K, Nakanishi K, Yata N, Honda M (2008) Effective and safe treatment with cyclosporine in nephrotic children: a prospective, randomized multicenter trial. Kidney Int 73:1167–1173PubMedCrossRef Ishikura K, Ikeda M, Hattori S, Yoshikawa N, Sasaki S, Iijima K, Nakanishi K, Yata N, Honda M (2008) Effective and safe treatment with cyclosporine in nephrotic children: a prospective, randomized multicenter trial. Kidney Int 73:1167–1173PubMedCrossRef
11.
Zurück zum Zitat Anonymous (1982) Early identification of frequent relapsers among children with minimal change nephrotic syndrome. A report of the International Study of Kidney Disease in Children. J Pediatr 101:514–518 Anonymous (1982) Early identification of frequent relapsers among children with minimal change nephrotic syndrome. A report of the International Study of Kidney Disease in Children. J Pediatr 101:514–518
12.
Zurück zum Zitat Nishiyama S, Kiwaki K, Inomoto T, Seino T (1993) Bone mineral density of the lumber spine and total body mass in Japanese children and adolescents. J Jpn Pediatr Soc 103:1131–1138 Nishiyama S, Kiwaki K, Inomoto T, Seino T (1993) Bone mineral density of the lumber spine and total body mass in Japanese children and adolescents. J Jpn Pediatr Soc 103:1131–1138
13.
Zurück zum Zitat Schwartz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637PubMedCentralPubMedCrossRef Schwartz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637PubMedCentralPubMedCrossRef
14.
Zurück zum Zitat Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, Yamagata K, Tomino Y, Yokoyama H, Hishida A (2009) Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis 53:982–992PubMedCrossRef Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, Yamagata K, Tomino Y, Yokoyama H, Hishida A (2009) Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis 53:982–992PubMedCrossRef
15.
Zurück zum Zitat McCullagh P (1980) Regression models for ordinal data. J R Stat Soc 42:109–142 McCullagh P (1980) Regression models for ordinal data. J R Stat Soc 42:109–142
16.
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 7:1576–1583PubMedCentralPubMedCrossRef 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 7:1576–1583PubMedCentralPubMedCrossRef
17.
Zurück zum Zitat Kabuki N, Okugawa T, Hayakawa H, Tomizawa S, Kasahara T, Uchiyama M (1998) Influence of age at onset on the outcome of steroid-sensitive nephrotic syndrome. Pediatr Nephrol 12:467–470PubMedCrossRef Kabuki N, Okugawa T, Hayakawa H, Tomizawa S, Kasahara T, Uchiyama M (1998) Influence of age at onset on the outcome of steroid-sensitive nephrotic syndrome. Pediatr Nephrol 12:467–470PubMedCrossRef
18.
Zurück zum Zitat Lewis MA, Baildom EM, Davis N, Houston IB, Postlethwaite RJ (1989) Nephrotic syndrome: from toddlers to twenties. Lancet 1:255–259PubMedCrossRef Lewis MA, Baildom EM, Davis N, Houston IB, Postlethwaite RJ (1989) Nephrotic syndrome: from toddlers to twenties. Lancet 1:255–259PubMedCrossRef
19.
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 25:3956–3962PubMedCrossRef 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 25:3956–3962PubMedCrossRef
20.
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 9:271–278PubMedCrossRef 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 9:271–278PubMedCrossRef
21.
Zurück zum Zitat Zagury A, de Oliveira AL, de Moraes CA, de Araujo Montalvao JA, Novaes RH, de Sa VM, de Carvalho M, Dde B, Matuck T (2011) Long-term follow-up after cyclophosphamide therapy in steroid-dependent nephrotic syndrome. Pediatr Nephrol 26:915–920PubMedCrossRef Zagury A, de Oliveira AL, de Moraes CA, de Araujo Montalvao JA, Novaes RH, de Sa VM, de Carvalho M, Dde B, Matuck T (2011) Long-term follow-up after cyclophosphamide therapy in steroid-dependent nephrotic syndrome. Pediatr Nephrol 26:915–920PubMedCrossRef
22.
Zurück zum Zitat Cammas B, Harambat J, Bertholet-Thomas A, Bouissou F, Morin D, Guigonis V, Bendeddouche S, Afroukh-Hacini N, Cochat P, Llanas B, Decramer S, Ranchin B (2011) Long-term effects of cyclophosphamide therapy in steroid-dependent or frequently relapsing idiopathic nephrotic syndrome. Nephrol Dial Transplant 26:178–184PubMedCrossRef Cammas B, Harambat J, Bertholet-Thomas A, Bouissou F, Morin D, Guigonis V, Bendeddouche S, Afroukh-Hacini N, Cochat P, Llanas B, Decramer S, Ranchin B (2011) Long-term effects of cyclophosphamide therapy in steroid-dependent or frequently relapsing idiopathic nephrotic syndrome. Nephrol Dial Transplant 26:178–184PubMedCrossRef
23.
Zurück zum Zitat Kemper MJ, Gellermann J, Habbig S, Krmar RT, Dittrich K, Jungraithmayr T, Pape L, Patzer L, Billing H, Weber L, Pohl M, Rosenthal K, Rosahl A, Mueller-Wiefel DE, Dotsch J (2012) Long-term follow-up after rituximab for steroid-dependent idiopathic nephrotic syndrome. Nephrol Dial Transplant 27:1910–1915PubMedCrossRef Kemper MJ, Gellermann J, Habbig S, Krmar RT, Dittrich K, Jungraithmayr T, Pape L, Patzer L, Billing H, Weber L, Pohl M, Rosenthal K, Rosahl A, Mueller-Wiefel DE, Dotsch J (2012) Long-term follow-up after rituximab for steroid-dependent idiopathic nephrotic syndrome. Nephrol Dial Transplant 27:1910–1915PubMedCrossRef
24.
Zurück zum Zitat Kamei K, Ito S, Nozu K, Fujinaga S, Nakayama M, Sako M, Saito M, Yoneko M, Iijima K (2009) Single dose of rituximab for refractory steroid-dependent nephrotic syndrome in children. Pediatr Nephrol 24:1321–1328PubMedCrossRef Kamei K, Ito S, Nozu K, Fujinaga S, Nakayama M, Sako M, Saito M, Yoneko M, Iijima K (2009) Single dose of rituximab for refractory steroid-dependent nephrotic syndrome in children. Pediatr Nephrol 24:1321–1328PubMedCrossRef
25.
Zurück zum Zitat Goto M, Ikeda M, Hataya H, Ishikura K, Hamasaki Y, Honda M (2006) Beneficial and adverse effects of high-dosage MZR therapy in the management of children with frequently relapsing nephrotic syndrome. Nihon Jinzo Gakkai Shi 48:365–370PubMed Goto M, Ikeda M, Hataya H, Ishikura K, Hamasaki Y, Honda M (2006) Beneficial and adverse effects of high-dosage MZR therapy in the management of children with frequently relapsing nephrotic syndrome. Nihon Jinzo Gakkai Shi 48:365–370PubMed
26.
Zurück zum Zitat Kawasaki Y, Hosoya M, Kobayashi S, Ohara S, Onishi N, Takahashi A, Isome M, Suzuki H (2005) Oral mizoribine pulse therapy for patients with steroid-resistant and frequently relapsing steroid-dependent nephrotic syndrome. Nephrol Dial Transplant 20:2243–2247PubMedCrossRef Kawasaki Y, Hosoya M, Kobayashi S, Ohara S, Onishi N, Takahashi A, Isome M, Suzuki H (2005) Oral mizoribine pulse therapy for patients with steroid-resistant and frequently relapsing steroid-dependent nephrotic syndrome. Nephrol Dial Transplant 20:2243–2247PubMedCrossRef
Metadaten
Titel
Morbidity in children with frequently relapsing nephrosis: 10-year follow-up of a randomized controlled trial
verfasst von
Kenji Ishikura
Norishige Yoshikawa
Hitoshi Nakazato
Satoshi Sasaki
Koichi Nakanishi
Takeshi Matsuyama
Shuichi Ito
Yuko Hamasaki
Nahoko Yata
Takashi Ando
Kazumoto Iijima
Masataka Honda
for Japanese Study Group of Renal Disease in Children
Publikationsdatum
01.03.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
Pediatric Nephrology / Ausgabe 3/2015
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-014-2955-8

Weitere Artikel der Ausgabe 3/2015

Pediatric Nephrology 3/2015 Zur Ausgabe

Darf man die Behandlung eines Neonazis ablehnen?

08.05.2024 Gesellschaft Nachrichten

In einer Leseranfrage in der Zeitschrift Journal of the American Academy of Dermatology möchte ein anonymer Dermatologe bzw. eine anonyme Dermatologin wissen, ob er oder sie einen Patienten behandeln muss, der eine rassistische Tätowierung trägt.

Ein Drittel der jungen Ärztinnen und Ärzte erwägt abzuwandern

07.05.2024 Klinik aktuell Nachrichten

Extreme Arbeitsverdichtung und kaum Supervision: Dr. Andrea Martini, Sprecherin des Bündnisses Junge Ärztinnen und Ärzte (BJÄ) über den Frust des ärztlichen Nachwuchses und die Vorteile des Rucksack-Modells.

Häufigste Gründe für Brustschmerzen bei Kindern

06.05.2024 Pädiatrische Diagnostik Nachrichten

Akute Brustschmerzen sind ein Alarmsymptom par exellence, schließlich sind manche Auslöser lebensbedrohlich. Auch Kinder klagen oft über Schmerzen in der Brust. Ein Studienteam ist den Ursachen nachgegangen.

Endlich: Zi zeigt, mit welchen PVS Praxen zufrieden sind

IT für Ärzte Nachrichten

Darauf haben viele Praxen gewartet: Das Zi hat eine Liste von Praxisverwaltungssystemen veröffentlicht, die von Nutzern positiv bewertet werden. Eine gute Grundlage für wechselwillige Ärztinnen und Psychotherapeuten.

Update Pädiatrie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.