Skip to main content
Erschienen in: Pediatric Nephrology 3/2020

08.11.2019 | Original Article

Immunoglobulin serum levels in rituximab-treated patients with steroid-dependent nephrotic syndrome

verfasst von: Cyrielle Parmentier, Jean-Daniel Delbet, Stéphane Decramer, Olivia Boyer, Julien Hogan, Tim Ulinski

Erschienen in: Pediatric Nephrology | Ausgabe 3/2020

Einloggen, um Zugang zu erhalten

Abstract

Background

Rituximab (RTX) is efficient in steroid-dependent nephrotic syndrome (SDNS) in pediatric and adult patients. The aim of this study is to describe hypogammaglobulinemia as a side effect of RTX treatment.

Methods

All pediatric patients (< 18 years old) of four French pediatric nephrology centers who received RTX for SDNS between 2010 and 2015 have been included. Clinical and biological data have been analyzed retrospectively before, during, and after RTX treatment. Hypogammaglobulinemia was defined as an IgG level < − 2 standard deviations for patient age.

Results

A total of 107 pediatric patients have been included, 65.9% were boys, median age at nephrotic syndrome diagnosis was 3.1 interquartile range [IQ 2.24–5.45] years and age at RTX introduction was 11.7 [IQ 8.6–14.2] years. Twenty-one patients had hypogammaglobulinemia before the initiation of RTX. Of the patients, 25/86 had at least one hypogammaglobulinemia during B cell depletion or after B cell recovery while IgG levels at initiation were normal with a persisting hypogammaglobulinemia for 13 patients 1 year after B cell recovery. Patients who developed hypogammaglobulinemia were younger at RTX initiation with a median age of 8.2 years [IQ 6.3–12.4]. Among all the 46 patients with hypogammaglobulinemia during follow-up, 13 had a concomitant infection.

Conclusions

Hypogammaglobulinemia is a frequent complication of RTX treatment in younger children treated for SDNS. The use of RTX in children has to be carefully evaluated and their clinical and biological follow-up should be adapted to the age-dependent risk profile for hypogammaglobulinemia.
Literatur
1.
Zurück zum Zitat Sellier-Leclerc A-L, Baudouin V, Kwon T, Macher M-A, Guérin V, Lapillonne H, Deschênes G, Ulinski T (2012) Rituximab in steroid-dependent idiopathic nephrotic syndrome in childhood--follow-up after CD19 recovery. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc - Eur Ren Assoc 27:1083–1089 Sellier-Leclerc A-L, Baudouin V, Kwon T, Macher M-A, Guérin V, Lapillonne H, Deschênes G, Ulinski T (2012) Rituximab in steroid-dependent idiopathic nephrotic syndrome in childhood--follow-up after CD19 recovery. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc - Eur Ren Assoc 27:1083–1089
2.
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 Berl Ger 25:539–544CrossRef 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 Berl Ger 25:539–544CrossRef
3.
Zurück zum Zitat Colucci M, Carsetti R, Cascioli S, Casiraghi F, Perna A, Ravà L, Ruggiero B, Emma F, Vivarelli M (2016) B Cell Reconstitution after Rituximab Treatment in Idiopathic Nephrotic Syndrome. J Am Soc Nephrol JASN 27:1811–1822CrossRef Colucci M, Carsetti R, Cascioli S, Casiraghi F, Perna A, Ravà L, Ruggiero B, Emma F, Vivarelli M (2016) B Cell Reconstitution after Rituximab Treatment in Idiopathic Nephrotic Syndrome. J Am Soc Nephrol JASN 27:1811–1822CrossRef
4.
Zurück zum Zitat Guigonis V, Dallocchio A, Baudouin V, Dehennault M, Hachon-Le Camus C, Afanetti M, Groothoff J, Llanas B, Niaudet P, Nivet H, Raynaud N, Taque S, Ronco P, Bouissou F (2008) Rituximab treatment for severe steroid- or cyclosporine-dependent nephrotic syndrome: a multicentric series of 22 cases. Pediatr Nephrol Berl Ger 23:1269–1279CrossRef Guigonis V, Dallocchio A, Baudouin V, Dehennault M, Hachon-Le Camus C, Afanetti M, Groothoff J, Llanas B, Niaudet P, Nivet H, Raynaud N, Taque S, Ronco P, Bouissou F (2008) Rituximab treatment for severe steroid- or cyclosporine-dependent nephrotic syndrome: a multicentric series of 22 cases. Pediatr Nephrol Berl Ger 23:1269–1279CrossRef
5.
Zurück zum Zitat 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 Berl Ger 25:1109–1115CrossRef 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 Berl Ger 25:1109–1115CrossRef
6.
Zurück zum Zitat Kimata T, Hasui M, Kino J, Kitao T, Yamanouchi S, Tsuji S, Kaneko K (2013) Novel use of rituximab for steroid-dependent nephrotic syndrome in children. Am J Nephrol 38:483–488CrossRef Kimata T, Hasui M, Kino J, Kitao T, Yamanouchi S, Tsuji S, Kaneko K (2013) Novel use of rituximab for steroid-dependent nephrotic syndrome in children. Am J Nephrol 38:483–488CrossRef
7.
Zurück zum Zitat Trujillo JE, Bosque M, Asensio Ò, 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 4:P42CrossRef Trujillo JE, Bosque M, Asensio Ò, 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 4:P42CrossRef
8.
Zurück zum Zitat Barmettler S, Ong M-S, Farmer JR, Choi H, Walter J (2018) Association of Immunoglobulin Levels, Infectious Risk, and Mortality With Rituximab and Hypogammaglobulinemia. JAMA Netw Open 1:e184169CrossRef Barmettler S, Ong M-S, Farmer JR, Choi H, Walter J (2018) Association of Immunoglobulin Levels, Infectious Risk, and Mortality With Rituximab and Hypogammaglobulinemia. JAMA Netw Open 1:e184169CrossRef
9.
Zurück zum Zitat Roberts DM, Jones RB, Smith RM, Alberici F, Kumaratne DS, Burns S, Jayne DRW (2015) Rituximab-associated hypogammaglobulinemia: incidence, predictors and outcomes in patients with multi-system autoimmune disease. J Autoimmun 57:60–65CrossRef Roberts DM, Jones RB, Smith RM, Alberici F, Kumaratne DS, Burns S, Jayne DRW (2015) Rituximab-associated hypogammaglobulinemia: incidence, predictors and outcomes in patients with multi-system autoimmune disease. J Autoimmun 57:60–65CrossRef
10.
Zurück zum Zitat Besada E, Koldingsnes W, Nossent JC (2014) Serum immunoglobulin levels and risk factors for hypogammaglobulinaemia during long-term maintenance therapy with rituximab in patients with granulomatosis with polyangiitis. Rheumatol Oxf Engl 53:1818–1824CrossRef Besada E, Koldingsnes W, Nossent JC (2014) Serum immunoglobulin levels and risk factors for hypogammaglobulinaemia during long-term maintenance therapy with rituximab in patients with granulomatosis with polyangiitis. Rheumatol Oxf Engl 53:1818–1824CrossRef
11.
Zurück zum Zitat Delbe-Bertin L, Aoun B, Tudorache E, Lapillone H, Ulinski T (2013) Does rituximab induce hypogammaglobulinemia in patients with pediatric idiopathic nephrotic syndrome? Pediatr Nephrol Berl Ger 28:447–451CrossRef Delbe-Bertin L, Aoun B, Tudorache E, Lapillone H, Ulinski T (2013) Does rituximab induce hypogammaglobulinemia in patients with pediatric idiopathic nephrotic syndrome? Pediatr Nephrol Berl Ger 28:447–451CrossRef
12.
Zurück zum Zitat Fujinaga S, Ozawa K, Sakuraya K, Yamada A, Shimizu T (2016) Late-onset adverse events after a single dose of rituximab in children with complicated steroid-dependent nephrotic syndrome. Clin Nephrol 85:340–345CrossRef Fujinaga S, Ozawa K, Sakuraya K, Yamada A, Shimizu T (2016) Late-onset adverse events after a single dose of rituximab in children with complicated steroid-dependent nephrotic syndrome. Clin Nephrol 85:340–345CrossRef
13.
Zurück zum Zitat Jolliff CR, Cost KM, Stivrins PC, Grossman PP, Nolte CR, Franco SM, Fijan KJ, Fletcher LL, Shriner HC (1982) Reference intervals for serum IgG, IgA, IgM, C3, and C4 as determined by rate nephelometry. Clin Chem 28:126–128CrossRef Jolliff CR, Cost KM, Stivrins PC, Grossman PP, Nolte CR, Franco SM, Fijan KJ, Fletcher LL, Shriner HC (1982) Reference intervals for serum IgG, IgA, IgM, C3, and C4 as determined by rate nephelometry. Clin Chem 28:126–128CrossRef
14.
Zurück zum Zitat Agarwal S, Cunningham-Rundles C (2007) Assessment and clinical interpretation of reduced IgG values. Ann Allergy Asthma Immunol Off Publ Am Coll Allergy Asthma Immunol 99:281–283CrossRef Agarwal S, Cunningham-Rundles C (2007) Assessment and clinical interpretation of reduced IgG values. Ann Allergy Asthma Immunol Off Publ Am Coll Allergy Asthma Immunol 99:281–283CrossRef
15.
Zurück zum Zitat Sellier-Leclerc A-L, Belli E, Guérin V, Dorfmüller P, Deschênes G (2013) Fulminant viral myocarditis after rituximab therapy in pediatric nephrotic syndrome. Pediatr Nephrol Berl Ger 28:1875–1879CrossRef Sellier-Leclerc A-L, Belli E, Guérin V, Dorfmüller P, Deschênes G (2013) Fulminant viral myocarditis after rituximab therapy in pediatric nephrotic syndrome. Pediatr Nephrol Berl Ger 28:1875–1879CrossRef
16.
Zurück zum Zitat Fujinaga S, Nishino T, Umeda C, Tomii Y, Watanabe Y, Sakuraya K (2019) Long-term outcomes after early treatment with rituximab for Japanese children with cyclosporine- and steroid-resistant nephrotic syndrome. Pediatr Nephrol Berl Ger 34:353–357CrossRef Fujinaga S, Nishino T, Umeda C, Tomii Y, Watanabe Y, Sakuraya K (2019) Long-term outcomes after early treatment with rituximab for Japanese children with cyclosporine- and steroid-resistant nephrotic syndrome. Pediatr Nephrol Berl Ger 34:353–357CrossRef
17.
Zurück zum Zitat Christou EAA, Giardino G, Worth A, Ladomenou F (2017) Risk factors predisposing to the development of hypogammaglobulinemia and infections post-Rituximab. Int Rev Immunol 36:352–359CrossRef Christou EAA, Giardino G, Worth A, Ladomenou F (2017) Risk factors predisposing to the development of hypogammaglobulinemia and infections post-Rituximab. Int Rev Immunol 36:352–359CrossRef
18.
Zurück zum Zitat Mariette X, Gottenberg J-E, Ravaud P, Combe B (2011) Registries in rheumatoid arthritis and autoimmune diseases: data from the French registries. Rheumatol Oxf Engl 50:222–229CrossRef Mariette X, Gottenberg J-E, Ravaud P, Combe B (2011) Registries in rheumatoid arthritis and autoimmune diseases: data from the French registries. Rheumatol Oxf Engl 50:222–229CrossRef
19.
Zurück zum Zitat Hogan J, Dossier C, Kwon T, Macher M-A, Maisin A, Couderc A, Niel O, Baudouin V, Deschênes G (2019) Effect of different rituximab regimens on B cell depletion and time to relapse in children with steroid-dependent nephrotic syndrome. Pediatr Nephrol Berl Ger 34:253–259CrossRef Hogan J, Dossier C, Kwon T, Macher M-A, Maisin A, Couderc A, Niel O, Baudouin V, Deschênes G (2019) Effect of different rituximab regimens on B cell depletion and time to relapse in children with steroid-dependent nephrotic syndrome. Pediatr Nephrol Berl Ger 34:253–259CrossRef
20.
Zurück zum Zitat Kavcic M, Fisher BT, Seif AE, Li Y, Huang Y-S, Walker D, Aplenc R (2013) Leveraging administrative data to monitor rituximab use in 2875 patients at 42 freestanding children’s hospitals across the United States. J Pediatr 162:1252–1258 1258.e1CrossRef Kavcic M, Fisher BT, Seif AE, Li Y, Huang Y-S, Walker D, Aplenc R (2013) Leveraging administrative data to monitor rituximab use in 2875 patients at 42 freestanding children’s hospitals across the United States. J Pediatr 162:1252–1258 1258.e1CrossRef
21.
Zurück zum Zitat Michelow IC, Olsen K, Lozano J, Rollins NK, Duffy LB, Ziegler T, Kauppila J, Leinonen M, McCracken GH (2004) Epidemiology and clinical characteristics of community-acquired pneumonia in hospitalized children. Pediatrics 113:701–707CrossRef Michelow IC, Olsen K, Lozano J, Rollins NK, Duffy LB, Ziegler T, Kauppila J, Leinonen M, McCracken GH (2004) Epidemiology and clinical characteristics of community-acquired pneumonia in hospitalized children. Pediatrics 113:701–707CrossRef
22.
Zurück zum Zitat Barmettler S, Price C (2015) Continuing IgG replacement therapy for hypogammaglobulinemia after rituximab--for how long? J Allergy Clin Immunol 136:1407–1409CrossRef Barmettler S, Price C (2015) Continuing IgG replacement therapy for hypogammaglobulinemia after rituximab--for how long? J Allergy Clin Immunol 136:1407–1409CrossRef
Metadaten
Titel
Immunoglobulin serum levels in rituximab-treated patients with steroid-dependent nephrotic syndrome
verfasst von
Cyrielle Parmentier
Jean-Daniel Delbet
Stéphane Decramer
Olivia Boyer
Julien Hogan
Tim Ulinski
Publikationsdatum
08.11.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
Pediatric Nephrology / Ausgabe 3/2020
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-019-04398-1

Weitere Artikel der Ausgabe 3/2020

Pediatric Nephrology 3/2020 Zur Ausgabe

Update Pädiatrie

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