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Published in: Pediatric Nephrology 11/2016

01-11-2016 | Original Article

Mycophenolate mofetil in steroid-dependent idiopathic nephrotic syndrome

Authors: Laurène Dehoux, Julien Hogan, Claire Dossier, Marc Fila, Olivier Niel, Anne Maisin, Marie Alice Macher, Thérésa Kwon, Véronique Baudouin, Georges Deschênes

Published in: Pediatric Nephrology | Issue 11/2016

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Abstract

Background

Prospective studies have established the mycophenolate mofetil (MMF) efficiency in childhood idiopathic nephrotic syndrome (INS) but reports on the long-term outcome are lacking. Moreover, the search for factors influencing its efficiency would be useful to define its place among the other treatments.

Methods

We performed a monocentric retrospective study including 96 children with steroid-dependent INS followed for 4.7 years (median) (IQ 3–6) after the onset of MMF treatment. The characteristics of responder patients (n = 74), as defined by a 50 % decrease of relapse rate and/or a 60 % decrease of steroid dose, and of non-responder patients (n = 22) were compared by univariate analysis and multivariate logistic regression.

Results

Withdrawal of prednisone was achieved in 48/96 patients after a median duration of 18.1 months (IQ 7.8–30.0) of MMF. Only 26/48 patients did not relapse under MMF alone. After MMF was stopped in these patients, only six remained in remission without any treatment at last follow-up. Responders had a shorter time to remission at the first flare (9.5 vs. 15 days, p = 0.02), a shorter disease duration prior to the onset of MMF (22.2 vs. 94.5 months, p = 0.001), and were younger at the MMF initiation (6.7 vs. 10.1 years, p = 0.02) than non-responder patients. The age of MMF initiation was an independent factor associated with efficiency (OR = 0.80, 95 % CI [0.69, 0.93], p < 0.01).

Conclusions

MMF is more efficient in young patients treated early in the disease course. Nevertheless, MMF has no remnant effect while nearly all patients relapsed after withdrawal of the drug.
Literature
1.
go back to reference Deschênes G, Leclerc A (2010) Epidemiology of the idiopathic nephrotic syndrome. Arch Pédiatrie Organe Off Sociéte Fr Pédiatrie 17:622–623. 693X(10)70028-2 Deschênes G, Leclerc A (2010) Epidemiology of the idiopathic nephrotic syndrome. Arch Pédiatrie Organe Off Sociéte Fr Pédiatrie 17:622–623. 693X(10)70028-2
2.
go back to reference 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 124:747–757. doi:10.1542/peds.2008-1559 CrossRefPubMed 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 124:747–757. doi:10.​1542/​peds.​2008-1559 CrossRefPubMed
3.
go back to reference van Husen M, Kemper MJ (2011) New therapies in steroid-sensitive and steroid-resistant idiopathic nephrotic syndrome. Pediatr Nephrol 26:881–892CrossRefPubMed van Husen M, Kemper MJ (2011) New therapies in steroid-sensitive and steroid-resistant idiopathic nephrotic syndrome. Pediatr Nephrol 26:881–892CrossRefPubMed
4.
go back to reference Büscher AK, Kranz B, Büscher R, Hildebrandt F, Dworniczak B, Pennekamp P, Kuwertz-Bröking E, Wingen AM, John U, Kemper M, Monnens L, Hoyer PF, Weber S, Konrad M (2010) Immunosuppression and renal outcome in congenital and pediatric steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol CJASN 5:2075–2084CrossRefPubMed Büscher AK, Kranz B, Büscher R, Hildebrandt F, Dworniczak B, Pennekamp P, Kuwertz-Bröking E, Wingen AM, John U, Kemper M, Monnens L, Hoyer PF, Weber S, Konrad M (2010) Immunosuppression and renal outcome in congenital and pediatric steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol CJASN 5:2075–2084CrossRefPubMed
5.
go back to reference Bagga A, Hari P, Moudgil A, Jordan SC (2003) Mycophenolate mofetil and prednisolone therapy in children with steroid-dependent nephrotic syndrome. Am J Kidney Dis 42:1114–1120CrossRefPubMed Bagga A, Hari P, Moudgil A, Jordan SC (2003) Mycophenolate mofetil and prednisolone therapy in children with steroid-dependent nephrotic syndrome. Am J Kidney Dis 42:1114–1120CrossRefPubMed
6.
go back to reference Mendizábal S, Zamora I, Berbel O, Sanahuja MJ, Fuentes J, Simon J (2005) Mycophenolate mofetil in steroid/cyclosporine-dependent/resistant nephrotic syndrome. Pediatr Nephrol 20:914–919CrossRefPubMed Mendizábal S, Zamora I, Berbel O, Sanahuja MJ, Fuentes J, Simon J (2005) Mycophenolate mofetil in steroid/cyclosporine-dependent/resistant nephrotic syndrome. Pediatr Nephrol 20:914–919CrossRefPubMed
7.
go back to reference Hogg RJ, Fitzgibbons L, Bruick J, Ault B, Baqi N, Trachtman H, Swinford R (2006) Mycophenolate mofetil in children with frequently relapsing nephrotic syndrome: a report from the Southwest Pediatric Nephrology Study Group. Clin J Am Soc Nephrol 1:1173–1178CrossRefPubMed Hogg RJ, Fitzgibbons L, Bruick J, Ault B, Baqi N, Trachtman H, Swinford R (2006) Mycophenolate mofetil in children with frequently relapsing nephrotic syndrome: a report from the Southwest Pediatric Nephrology Study Group. Clin J Am Soc Nephrol 1:1173–1178CrossRefPubMed
8.
go back to reference 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
9.
go back to reference 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
10.
go back to reference Baudouin V, Alberti C, Lapeyraque A-L, Bensman A, André JL, Broux F, Cailliez M, Decramer S, Niaudet P, Deschênes G, Jacqz-Aigrain E, Loirat C (2012) Mycophenolate mofetil for steroid-dependent nephrotic syndrome: a phase II Bayesian trial. Pediatr Nephrol 27:389–396CrossRefPubMed Baudouin V, Alberti C, Lapeyraque A-L, Bensman A, André JL, Broux F, Cailliez M, Decramer S, Niaudet P, Deschênes G, Jacqz-Aigrain E, Loirat C (2012) Mycophenolate mofetil for steroid-dependent nephrotic syndrome: a phase II Bayesian trial. Pediatr Nephrol 27:389–396CrossRefPubMed
11.
go back to reference Bérard E, Broyer M, Dehennault M, Dumas R, Eckart P, Fischbach M, Loirat C, Martinat L, Pediatric Society of Nephrology (2005) Corticosensitive nephrotic syndrome (or nephrosis) in children. Therapeutic guideline proposed by the Pediatric Society of Nephrology. Néphrol Thér 1:150–156CrossRefPubMed Bérard E, Broyer M, Dehennault M, Dumas R, Eckart P, Fischbach M, Loirat C, Martinat L, Pediatric Society of Nephrology (2005) Corticosensitive nephrotic syndrome (or nephrosis) in children. Therapeutic guideline proposed by the Pediatric Society of Nephrology. Néphrol Thér 1:150–156CrossRefPubMed
12.
go back to reference (1984) Minimal change nephrotic syndrome in children: deaths during the first 5 to 15 years’ observation. Report of the International Study of Kidney Disease in Children. Pediatrics 73:497–501 (1984) Minimal change nephrotic syndrome in children: deaths during the first 5 to 15 years’ observation. Report of the International Study of Kidney Disease in Children. Pediatrics 73:497–501
13.
go back to reference Abeyagunawardena AS, Dillon MJ, Rees L, van’t Hoff W, Trompeter RS (2003) The use of steroid-sparing agents in steroid-sensitive nephrotic syndrome. Pediatr Nephrol 18:919–924CrossRefPubMed Abeyagunawardena AS, Dillon MJ, Rees L, van’t Hoff W, Trompeter RS (2003) The use of steroid-sparing agents in steroid-sensitive nephrotic syndrome. Pediatr Nephrol 18:919–924CrossRefPubMed
14.
go back to reference Azib S, Macher MA, Kwon T, Dechartres A, Alberti C, Loirat C, Deschênes G, Baudouin V (2011) Cyclophosphamide in steroid-dependent nephrotic syndrome. Pediatr Nephrol 26:927–932CrossRefPubMed Azib S, Macher MA, Kwon T, Dechartres A, Alberti C, Loirat C, Deschênes G, Baudouin V (2011) Cyclophosphamide in steroid-dependent nephrotic syndrome. Pediatr Nephrol 26:927–932CrossRefPubMed
15.
go back to reference 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 26:178–184CrossRefPubMed 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 26:178–184CrossRefPubMed
16.
go back to reference Zagury A, de Oliveira AL, de Moraes CAP, de Araujo Montalvão JA, Novaes RH, de Sá VM, Monteiro de Carvalho Dde B, Matuck T (2011) Long-term follow-up after cyclophosphamide therapy in steroid-dependent nephrotic syndrome. Pediatr Nephrol 26:915–920CrossRefPubMed Zagury A, de Oliveira AL, de Moraes CAP, de Araujo Montalvão JA, Novaes RH, de Sá VM, Monteiro de Carvalho Dde B, Matuck T (2011) Long-term follow-up after cyclophosphamide therapy in steroid-dependent nephrotic syndrome. Pediatr Nephrol 26:915–920CrossRefPubMed
17.
go back to reference Latta K, von Schnakenburg C, Ehrich JH (2001) A meta-analysis of cytotoxic treatment for frequently relapsing nephrotic syndrome in children. Pediatr Nephrol 16:271–282CrossRefPubMed Latta K, von Schnakenburg C, Ehrich JH (2001) A meta-analysis of cytotoxic treatment for frequently relapsing nephrotic syndrome in children. Pediatr Nephrol 16:271–282CrossRefPubMed
18.
go back to reference Allison AC, Eugui EM (2000) Mycophenolate mofetil and its mechanisms of action. Immunopharmacology 47:85–118CrossRefPubMed Allison AC, Eugui EM (2000) Mycophenolate mofetil and its mechanisms of action. Immunopharmacology 47:85–118CrossRefPubMed
19.
go back to reference Heidt S, Roelen DL, Eijsink C, van Kooten C, Claas FH, Mulder A (2008) Effects of immunosuppressive drugs on purified human B cells: evidence supporting the use of MMF and rapamycin. Transplantation 86:1292–1300CrossRefPubMed Heidt S, Roelen DL, Eijsink C, van Kooten C, Claas FH, Mulder A (2008) Effects of immunosuppressive drugs on purified human B cells: evidence supporting the use of MMF and rapamycin. Transplantation 86:1292–1300CrossRefPubMed
20.
go back to reference Gellermann J, Querfeld U (2004) Frequently relapsing nephrotic syndrome: treatment with mycophenolate mofetil. Pediatr Nephrol 19:101–104CrossRefPubMed Gellermann J, Querfeld U (2004) Frequently relapsing nephrotic syndrome: treatment with mycophenolate mofetil. Pediatr Nephrol 19:101–104CrossRefPubMed
21.
go back to reference 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 24:1689–1697CrossRefPubMedPubMedCentral 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 24:1689–1697CrossRefPubMedPubMedCentral
22.
go back to reference Banerjee S, Pahari A, Sengupta J, Patnaik SK (2013) Outcome of severe steroid-dependent nephrotic syndrome treated with mycophenolate mofetil. Pediatr Nephrol 28:93–97CrossRefPubMed Banerjee S, Pahari A, Sengupta J, Patnaik SK (2013) Outcome of severe steroid-dependent nephrotic syndrome treated with mycophenolate mofetil. Pediatr Nephrol 28:93–97CrossRefPubMed
23.
go back to reference Novak I, Frank R, Vento S, Vergara M, Gauthier B, Trachtman H (2005) Efficacy of mycophenolate mofetil in pediatric patients with steroid-dependent nephrotic syndrome. Pediatr Nephrol B 20:1265–1268CrossRef Novak I, Frank R, Vento S, Vergara M, Gauthier B, Trachtman H (2005) Efficacy of mycophenolate mofetil in pediatric patients with steroid-dependent nephrotic syndrome. Pediatr Nephrol B 20:1265–1268CrossRef
24.
go back to reference Kim J, Patnaik N, Chorny N, Frank R, Infante L, Sethna C (2014) Second-line immunosuppressive treatment of childhood nephrotic syndrome: a single-center experience. Nephron Extra 4:8–17CrossRefPubMedPubMedCentral Kim J, Patnaik N, Chorny N, Frank R, Infante L, Sethna C (2014) Second-line immunosuppressive treatment of childhood nephrotic syndrome: a single-center experience. Nephron Extra 4:8–17CrossRefPubMedPubMedCentral
25.
go back to reference Afzal K, Bagga A, Menon S, Hari P, Jordan SC (2007) Treatment with mycophenolate mofetil and prednisolone for steroid-dependent nephrotic syndrome. Pediatr Nephrol 22:2059–2065CrossRefPubMed Afzal K, Bagga A, Menon S, Hari P, Jordan SC (2007) Treatment with mycophenolate mofetil and prednisolone for steroid-dependent nephrotic syndrome. Pediatr Nephrol 22:2059–2065CrossRefPubMed
26.
go back to reference Frange P, Frey MA, Deschênes G (2005) Immunity and immunosuppression in childhood idiopathic nephrotic syndrome. Arch Pediatr 12:305–315CrossRefPubMed Frange P, Frey MA, Deschênes G (2005) Immunity and immunosuppression in childhood idiopathic nephrotic syndrome. Arch Pediatr 12:305–315CrossRefPubMed
27.
go back to reference Sellier-Leclerc A-L, Macher M-A, Loirat C, Guérin V, Watier H, Peuchmaur M, Baudouin V, Deschênes G (2010) Rituximab efficiency in children with steroid-dependent nephrotic syndrome. Pediatr Nephrol 25:1109–1115CrossRefPubMed Sellier-Leclerc A-L, Macher M-A, Loirat C, Guérin V, Watier H, Peuchmaur M, Baudouin V, Deschênes G (2010) Rituximab efficiency in children with steroid-dependent nephrotic syndrome. Pediatr Nephrol 25:1109–1115CrossRefPubMed
29.
Metadata
Title
Mycophenolate mofetil in steroid-dependent idiopathic nephrotic syndrome
Authors
Laurène Dehoux
Julien Hogan
Claire Dossier
Marc Fila
Olivier Niel
Anne Maisin
Marie Alice Macher
Thérésa Kwon
Véronique Baudouin
Georges Deschênes
Publication date
01-11-2016
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Nephrology / Issue 11/2016
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-016-3400-y

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