Rituximab-associated agranulocytosis in children with refractory idiopathic nephrotic syndrome: case series and review of literature

Kamei, Koichi; Takahashi, Masaki; Fuyama, Masaki; Saida, Ken; Machida, Haruhiko; Mai, Sabine; Ogura, Masao; Ito, Shuichi

doi:10.1093/ndt/gfu258

Cited by 50 publications

(27 citation statements)

References 32 publications

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“…15 While more doses may prolong drug-free remission, this may increase the risk of adverse events, such as neutropenia. 18 In the Japanese trial, for example, lymphocytopenia and neutropenia occurred in 17% and 8% of the children, respectively. 14 Results from our study suggest that oral drug-free remission may be up to three times as long in children with a relatively recent diagnosis of SDNS who are maintained in complete remission with steroids alone.…”

Section: Discussionmentioning

confidence: 99%

Rituximab in Children with Steroid-Dependent Nephrotic Syndrome

Ravani

Rossi

Bonanni

et al. 2015

Journal of the American Society of Nephrology

164

142

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Steroid-dependent nephrotic syndrome (SDNS) carries a high risk of toxicity from steroids or steroid-sparing agents. This open-label, noninferiority, randomized controlled trial at four sites in Italy tested whether rituximab is noninferior to steroids in maintaining remission in juvenile SDNS. We enrolled children age 1-16 years who had developed SDNS in the previous 6-12 months and were maintained in remission with high prednisone doses ($0.7 mg/kg per day). We randomly assigned participants to continue prednisone alone for 1 month (control) or to add a single intravenous infusion of rituximab (375 mg/m 2 ; intervention). Prednisone was tapered in both groups after 1 month. For noninferiority, rituximab had to permit steroid withdrawal and maintain 3-month proteinuria (mg/m 2 per day) within a prespecified noninferiority margin of three times the levels among controls (primary outcome). We followed participants for $1 year to compare risk of relapse (secondary outcome). Fifteen children per group (21 boys; mean age, 7 years [range, 2.6-13.5 years]) were enrolled and followed for #60 months (median, 22 months). Three-month proteinuria was 42% lower in the rituximab group (geometric mean ratio, 0.58; 95% confidence interval, 0.18 to 1.95 [i.e., within the noninferiority margin of three times the levels in controls]). All but one child in the control group relapsed within 6 months; median time to relapse in the rituximab group was 18 months (95% confidence interval, 9 to 32 months). In the rituximab group, nausea and skin rash during infusion were common; transient acute arthritis occurred in one child. In conclusion, rituximab was noninferior to steroids for the treatment of juvenile SDNS.

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Section: Discussionmentioning

confidence: 99%

Rituximab in Children with Steroid-Dependent Nephrotic Syndrome

Ravani

Rossi

Bonanni

et al. 2015

Journal of the American Society of Nephrology

164

142

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“…Rituximab is also associated with serious adverse events in children with complicated FRNS/SDNS, including pulmonary fibrosis [28], fulminant myocarditis [29], pneumocystis pneumonia [16], immune-mediated ulcerative colitis [30] and agranulocytosis [31]. After rituximab treatment, hypogammaglobulinemia persists in most patients with decreased immunoglobulin G (IgG) levels before treatment [32].…”

Section: Adverse Events Of Rituximab In Ssns In Childrenmentioning

confidence: 99%

Rituximab in steroid-sensitive nephrotic syndrome: lessons from clinical trials

et al. 2017

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Idiopathic nephrotic syndrome is the most common chronic glomerular disease in children. A total of 80–90% of patients with childhood idiopathic nephrotic syndrome achieve remission with steroid therapy [steroid-sensitive nephrotic syndrome (SSNS)]. However, approximately 50% of children with SSNS develop frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS). Children with FRNS or SDNS are usually treated with immunosuppressive agents, but 10–20% of children receiving immunosuppressive agents still show frequent relapses or steroid dependence during or after treatment, defined as complicated FRNS or SDNS. Rituximab, a chimeric anti-CD20 monoclonal antibody that was originally developed to treat patients with B-cell non-Hodgkin’s lymphoma, is currently used for treating SSNS. In this review we highlight recent studies, mainly randomized controlled trials of rituximab for SSNS, including complicated and uncomplicated forms of FRNS or SDNS in children. We also discuss the effects of these studies on the management of patients suffering from these conditions.

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“…In addition, agranulocytosis has been reported as a delayed onset complication of rituximab, a treatment strategy for patients with complicated steroid‐dependent NS. Kamei et al studied 114 refractory NS cases treated with rituximab and reported that 11 patients (9.6%) had episodes of agranulocytosis at a median age of 6.4 years. The exact reason why agranulocytosis develops in this context still needs to be explained, but the use of rituximab requires caution since the risk of life‐threatening infections such as sepsis accompanies agranulocytosis.…”

Section: Major Infectionsmentioning

confidence: 99%

Review on long‐term non‐renal complications of childhood nephrotic syndrome

et al. 2019

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Background Nephrotic syndrome (NS) is the most common glomerular childhood disease. A body of literature has described the long‐term renal prognosis of childhood‐onset idiopathic NS. However, the nonrenal outcomes have not been studied as much. Aim We aimed to discuss the long‐term non‐renal outcomes of childhood NS, highlighting studies with a follow‐up period of more than 10 years. Results We reviewed the literature and found that a number of immunosuppressive agents have stopped inflammation, stabilised the podocyte cytoskeleton and reduce proteinuria. However, prolonged treatment has frequently been associated with a high risk of renal and non‐renal complications in patients with a complicated disease course, defined as frequent relapses or steroid dependency. Non‐renal complications may include impaired longitudinal growth and pubertal development, undesirable fertility outcomes, ocular complications, bone mineral diseases and potential malignancies. Conclusion This review discusses and summarises the non‐renal outcomes of idiopathic childhood NS.

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Rituximab-associated agranulocytosis in children with refractory idiopathic nephrotic syndrome: case series and review of literature

Abstract: It is important to pay extra attention to this clinically serious delayed-onset complication as it may be accompanied by life-threatening infections such as sepsis. Further clinical studies are needed to clarify its pathogenesis.

Cited by 50 publications

References 32 publications

Rituximab in Children with Steroid-Dependent Nephrotic Syndrome

Rituximab in Children with Steroid-Dependent Nephrotic Syndrome

Rituximab in steroid-sensitive nephrotic syndrome: lessons from clinical trials

Review on long‐term non‐renal complications of childhood nephrotic syndrome

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