Obinutuzumab in Frequently Relapsing and Steroid-Dependent Nephrotic Syndrome in Children.

BACKGROUND: B-cell depletion with rituximab induces sustained remission in children with steroid-dependent or frequently relapsing nephrotic syndrome. However, most patients relapse after B-cell recovery, and some patients do not achieve B-cell depletion. Obinutuzumab is a second-generation anti-CD20 antibody designed to overcome such situations in B-cell malignancies and was recently reported to be safe and effective in other autoimmune diseases affecting the kidneys. METHODS: We retrospectively report 41 children with steroid-dependent or frequently relapsing nephrotic syndrome treated with a single low-dose infusion of obinutuzumab at Robert-Debre Hospital between April 2018 and December 2020. Participants were treated because of rituximab resistance or relapse after rituximab and received a single infusion of 300 mg/1.73 m 2 obinutuzumab with cessation of oral immunosuppressors within 2 months. RESULTS: B-cell depletion was achieved in all participants and lasted a median of 8.3 months (interquartile range, 6.4-11.1), a duration exceeding that for last rituximab treatment. At 12 and 24 months, 92% (38/41) and 68% (28/41) of patients, respectively, were in sustained remission. Mild infusion reactions occurred in five participants (12%) and neutropenia in nine (21%). No significant decrease in IgG level was reported during treatment, and whereas IgM levels decreased in 34 patients (83%), they were normal at last follow-up in 32 (78%). CONCLUSIONS: These results identified low-dose obinituzumab as a promising treatment option in children with steroid-dependent or frequently relapsing nephrotic syndrome, including those resistant to rituximab. The tolerance profile of obinutuzumab was similar to that of rituximab, but hemogram and immunoglobulin levels should be monitored.

Sex and Glomerular Filtration Rate Trajectories in Children.

BACKGROUND AND OBJECTIVES: Differences in CKD progression by sex have been hypothesized to explain disparities in access to kidney transplantation in children. This study aims to identify distinct trajectories of eGFR decline and to investigate the association of sex with eGFR decline. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used data from the CKD in Children study. Latent class mixed models were used to identify eGFR trajectories and patient characteristics were compared between trajectories. Progression was studied to two outcomes: ESKD (dialysis or transplantation) and a combined outcome of ESKD or 50% eGFR decline from baseline, using multivariable parametric failure time models. RESULTS: Among 888 patients, 613 with nonglomerular and 275 with glomerular diseases, we observed four and two distinct GFR trajectories, respectively. Among patients with nonglomerular diseases, there was a higher proportion of males in the group with a low baseline GFR. This group had an increased risk of ESKD or 50% GFR decline, despite a similar absolute decline in GFR. Eight patients with nonglomerular diseases, mostly males with obstructive uropathies, had a more rapid absolute GFR decline. However, the association between male sex and rapid absolute GFR decline was NS after adjustment for age, baseline GFR, and proteinuria. Among patients with glomerular diseases, a subgroup including mostly females with systemic immunologic diseases or crescentic GN had a rapid absolute GFR decline. CONCLUSIONS: This study identifies different trajectories of CKD progression in children and found a faster progression of CKD in females in patients with glomerular diseases, but no significant sex difference in patients with nonglomerular diseases. The differences in progression seem likely explained by sex differences in the underlying primary kidney disease and in baseline GFR rather than by a direct effect of sex on progression.

Asymptomatic bacteriuria in pediatric kidney transplant recipients: to treat or not to treat? A retrospective study.

BACKGROUND: Urinary tract infections (UTI) are common infectious complications in kidney transplant recipients (KTR); asymptomatic bacteriuria (AB) is also frequent. It is unclear whether treatment of AB reduces subsequent UTI in KTR; no guideline is available in pediatric KTR. In this retrospective study, we analyzed the incidence of AB in pediatric KTR and the impact of screening and treating AB on the onset of subsequent UTI. METHODS: Thirty-seven pediatric patients were included. Inclusion criteria were the occurrence of one or more episodes of AB between 2 and 24 months post-renal transplantation. Primary outcome was the cumulative incidence of acute pyelonephritis (APN) or lower urinary tract infections (LUTI) occurring between 2 and 24 months post-renal transplantation. RESULTS: Thirty-seven patients presented 171 AB episodes. One hundred sixty-four AB episodes were untreated (95.9%); among them, 150 episodes (91.5%) were not followed by a clinical infection. Ten episodes (6.1%) led to APN, and 4 (2.4%) to LUTI. There were 53 episodes of APN: 10 (18.9%) after untreated AB and 43 (81.1%) de novo. There were 11 episodes of LUTI: 4 (36.4%) after untreated AB and 7 (63.6%) de novo. Multi-drug resistant bacteria were present in 27% of the patients and in 20% of patients with pre-existing uropathy. CONCLUSIONS: Our results are not in favor of systematic treatment of AB in pediatric KTR. Notably, limitation of antibiotic treatment is an urgent and important health issue in this population, in order to reduce multi-drug resistant bacteria emergence.