title: Rituximab is a safe and effective long-term treatment for children with steroid and calcineurin inhibitor-dependent idiopathic nephrotic syndrome.
abstract: In children with idiopathic nephrotic syndrome, rituximab can maintain short-term remission with withdrawal of prednisone and calcineurin inhibitors. Long-term effects including the number of repeated infusions to maintain remission are unknown. To test this, we treated 46 consecutive children with idiopathic nephrotic syndrome lasting for at least 1 year (mean 6.3 years), maintained in remission with oral prednisone and calcineurin inhibitors. They received 1-5 rituximab courses during a median follow-up of 3 years. Oral agents were tapered after each infusion, and completely withdrawn within 45 days. Rituximab was well tolerated. Six-month probabilities of remission were 48% after the first infusion and 37% after subsequent infusions. One- and 2-year-remission probabilities were, respectively, 20 and 10%. Median time intervals between complete oral-agent withdrawal and relapse were 5.6 and 8.5 months, respectively, following the first and subsequent courses. The time to reconstitution of CD20 cells correlated with the duration of remission, but was not associated with variation in FcyR, CD20, or SMPDL-3B polymorphisms. Podocyte Src phosphorylation was normal. Thus, rituximab can be safely and repeatedly used as a prednisone and calcineurin inhibitor-sparing therapy in a considerable proportion of children with dependent forms of idiopathic nephrotic syndrome. Further study is needed to identify patients who will benefit most from rituximab therapy.
authors.affiliation: Division of Nephrology, Department of Medicine, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Pietro
authors.initials: P
authors.lastname: Ravani
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ponticelli
authors.forename: Chiara
authors.initials: C
authors.lastname: Siciliano
authors.forename: Alessia
authors.initials: A
authors.lastname: Fornoni
authors.forename: Alberto
authors.initials: A
authors.lastname: Magnasco
authors.forename: Felice
authors.initials: F
authors.lastname: Sica
authors.forename: Monica
authors.initials: M
authors.lastname: Bodria
authors.forename: Gianluca
authors.initials: G
authors.lastname: Caridi
authors.forename: Changli
authors.initials: C
authors.lastname: Wei
authors.forename: Mirco
authors.initials: M
authors.lastname: Belingheri
authors.forename: Luciana
authors.initials: L
authors.lastname: Ghio
authors.forename: Sandra
authors.initials: S
authors.lastname: Merscher-Gomez
authors.forename: Alberto
authors.initials: A
authors.lastname: Edefonti
authors.forename: Andrea
authors.initials: A
authors.lastname: Pasini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Montini
authors.forename: Corrado
authors.initials: C
authors.lastname: Murtas
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Wang
authors.forename: Daniel
authors.initials: D
authors.lastname: Muruve
authors.forename: Augusto
authors.initials: A
authors.lastname: Vaglio
authors.forename: Davide
authors.initials: D
authors.lastname: Martorana
authors.forename: Antonello
authors.initials: A
authors.lastname: Pani
authors.forename: Francesco
authors.initials: F
authors.lastname: Scolari
authors.forename: Jochen
authors.initials: J
authors.lastname: Reiser
authors.forename: Gian M
authors.initials: GM
authors.lastname: Ghiggeri
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000367:Age Factors; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018951:Antigens, CD20 / Q000235:genetics / Q000378:metabolism; D019703:Calcineurin / Q000378:metabolism; D065095:Calcineurin Inhibitors; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D009404:Nephrotic Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D010766:Phosphorylation; D050199:Podocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D011110:Polymorphism, Genetic; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D017452:Receptors, IgG / Q000235:genetics; D012008:Recurrence; D012074:Remission Induction; D012307:Risk Factors; D000069283:Rituximab; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics; D013997:Time Factors; D016896:Treatment Outcome; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D065095:Calcineurin Inhibitors; C499173:FCGR2B protein, human; C496124:FCGR3A protein, human; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D017452:Receptors, IgG; D000069283:Rituximab; D019061:src-Family Kinases; D019703:Calcineurin; C508196:SMPDL3B protein, human; D013108:Sphingomyelin Phosphodiesterase; D011241:Prednisone