The association between hypogammaglobulinemia severity and infection risk in rituximab-treated patients with childhood-onset idiopathic nephrotic syndrome

Rituximab-associated hypogammaglobulinemia in children with idiopathic nephrotic syndrome: results of an ESPN survey

“…Repeated courses of RTX, malignancies, concomitant steroid/IMS treatment, and pretreatment low IgG levels have been implicated as risk factors for significant HGG and severe infections [14,15,17,18,22,29]. In a recent single-center Japanese study, the severity of HGG was not significantly associated with the risk of infection in nephrotic children [23].…”

“…The causes of pretreatment HGG have been related to previous IMS/ steroid treatment, a previously undiagnosed primary common variable immunodeficiency or urinary loss of immunoglobulins [15,16,18]. Both primary and secondary causes of HGG have been recognized as risk factors for the severity of RTX-associated HGG and its related infectious complications [16,17,19,22,23,29]. The increased rate of infectious complications in RTX-treated adults with rheumatoid arthritis led to the publication of a consensus statement for the pretreatment assessment of Ig in this disease population [30,31].…”

“…Furthermore, the causal relationship of severe infections and RTX use is probably complex and additional factors may play a role including, but not limited to, previous or concomitant IMS drugs, pre-existing low IgG levels, or RTX dosage. The high frequency of HGG in subjects with severe infections (80%) is highly suggestive that low serum IgG contributes to the development of severe infections in a subset of nephrotic children, though most children with HGG seem to fare well [19,23].…”

“…The reported incidence in adults is relatively low, ranging from 14-20% in adults with malignancies to 3.5-4.2% in subjects with autoimmune diseases [18,[20][21][22]. The clinical significance of this acquired HGG is not fully known but recent publications have shown an increased risk of infections following its use in adults and children [18,19,23]. Due to the paucity of data on the incidence of HGG and its consequences in RTX-treated children with INS, a survey was undertaken by the Glomerulonephritis Working Group (WG) of the European Society Pediatric Nephrology (ESPN) addressing the screening and management practices in place in pediatric nephrology centers for the recognition and treatment of this complication and its potential association with severe infections.…”

Efficacy of rituximab and risk factors for poor prognosis in patients with childhood-onset refractory steroid-resistant nephrotic syndrome: a multicenter study

“…In the present study cohort, 20%, 11%, and 16% of the patients experienced hypogammaglobulinemia, neutropenia, and infectious episodes related to these adverse events, respectively. In a previous observational study of 140 patients treated with rituximab for idiopathic nephrotic syndrome, we found that the incidence of infections in patients with normal, mildly low, and severely low IgG levels were 0.028, 0.071, and 0.096 per person-years, respectively, suggesting that the incidence of infections was relatively low even in patients with severe hypogammaglobulinemia [22]. In another study including 213 rituximab administrations given to114 patients with refractory nephrotic syndrome, we reported neutropenia in 9.6% of all patients and 5.2% of all rituximab infusions [23].…”