Background: Long-term outcomes following multiple rituximab courses among children with frequently-relapsing, steroid-dependent nephrotic syndrome (FRSDNS) are unknown. Methods: A retrospective cohort study at 16 pediatric nephrology centers from 10 countries in Asia, Europe, and North America included children with FRSDNS who received ≥2 rituximab courses. Primary outcomes were relapse-free survival and adverse events. Results: 346 children (age 9.8 years, IQR 6.6-13.5; 73% boys) received 1149 rituximab courses. 145, 83, 50, 28, 22, and 18 children received 2, 3, 4, 5, 6 and ≥7 courses, respectively. Median follow-up was 5.9 years (IQR, 4.3-7.7). Relapse-free survival differed by treatment courses (clustered log-rank test p<0.001). Compared to the first course (10.0 months, 95% CI, 9.0-10.7), relapse-free period and relapse risk progressively improved following subsequent courses (12.0-16.0 months; HRadj, 0.03-0.13; 95% CI, 0.01-0.18; ps<0.001). B-cell depletion duration remained similar with repeated treatments (6.1 months, 95% CI, 6.0-6.3). Adverse events were mostly mild, most commonly hypogammaglobulinemia (50.9%), infection (4.5%), and neutropenia (3.7%). Side effects did not increase with more treatment courses nor higher cumulative dose. Only 78 of the 353 episodes of hypogammaglobulinemia were clinically significant. Younger age at presentation (2.8 vs 3.3 years; p=0.05) and at first rituximab (8.0 y vs 10.0 years; p=0.01) and history of steroid resistance (28% vs 18%; p=0.01) were associated with significant hypogammaglobulinemia. All 53 infective episodes resolved, except one patient with hepatitis B infection and another with EBV infection. There were 42 episodes of neutropenia, associated with history of steroid resistance (30% vs 20%, p=0.04). Upon last follow-up, 332 children (96%) had normal kidney function. Conclusion: Children receiving repeated rituximab for FRSDNS experience an improving clinical response. Side effects appear acceptable but significant complications can occur. These findings support repeated rituximab use in FRSDNS.

IntroductionIdiopathic nephrotic syndrome is the most common glomerular disease in children. The majority of patients respond well to steroids. However, the relapse rate is high and many develop steroid dependency. Although other immunosuppressive medicines are successfully used as steroid-sparing agents, some children still have frequent relapsing episodes. Rituximab (RTX), a chimeric anti-CD20 monoclonal antibody, has shown to be effective in treating difficult frequently relapsing/steroid-dependent nephrotic syndrome (FR/SDNS). Data on the effectiveness and long-term treatment outcomes of repeated courses of RTX are, however, scarce.Material and methodsChildren and young people with FR/SDNS, aged 1–18 years, who received RTX at Great Ormond Street Hospital (GOSH) from 2006 to 2018 were reviewed.ResultsDuring these 12 years, 103 children with FR/SDNS received RTX infusions at GOSH. Among these, 58 cases needed repeated courses of RTX: 2, 3, 4, 5, 6 and 7 repeated courses were given to 21, 21, 7, 5, 1 and 3 patients, respectively. The overall median time to relapse post-RTX was 11 months (range 1–53 months). There was no change in relapse-free interval with subsequent courses of RTX. No difference was found between age groups, genders and ethnicities. No severe side effects were noted.ConclusionsRTX seems to be safe even after several repeated courses. However, long-term follow-up and further studies are needed, with a focus on side-effects in particular.

Background: Anemia is a major complication of pediatric chronic kidney disease (CKD). Iron deficiency is one of the most common causes of anemia. Conventional markers of iron deficiency anemia, transferrin saturation (TSAT) and serum ferritin could be interfered with various factors. in CKD. Reticulocyte hemoglobin equivalent (Ret-He) is useful for assessing iron status among these patients. Methods: A descriptive cross-sectional study enrolling children with CKD stage 3 and above was conducted between April and November 2021. Demographic information was also collected. Correlation of Ret-He, anemia indices and markers of iron status were analyzed. Results: Among 50 participants, we found moderate positive correlations between Hb and Ret-He (r=0.518; p <0.001), Hct and Ret-He (r=0.403; p=0.004), and MCHC and Ret-He (r=0.667; p<0.001); a modest negative correlation between RDW and Ret-He (r=-0.616; p<0.001) and strong correlations between MCV and Ret-He (r=0.747; p<0.001) including MCH and Ret-He (r=0.865; p<0.001). No correlations between TSAT and Ret-He, serum ferritin and Ret-He, TSAT and Hb, or TSAT and Hct were observed. In addition, weak negative correlations between serum ferritin and Hb (r=-0.307; p=0.032) and between serum ferritin and Hct (r=-0.305; p=0.033) were detected. The median RetHe was 28.42 ± 3.37 pg. Twenty-seven participants (54%) met the criteria for iron deficiency anemia (cut-off value <29 pg) of which 2 (4%) had absolute iron deficiency and 9 (18%) had functional iron deficiency defined by conventional markers. Conclusion: Ret-He is a relevant marker of iron status among pediatric patients with CKD and correlates well with anemia indices which could help identify more patients with iron deficiency.

BACKGROUND AND AIMS ANCA-associated vasculitis (AAV) is rare among children but leads to kidney failure (KF) in almost 30% of cases with renal involvement [1]. Kidney transplantation (KT) is the treatment of choice in adults with AAV and KF, while data among children are limited to small case series [2, 3]. We report the outcomes of KT in a multicentre cohort of patients with childhood-onset AAV. METHOD Patients with AAV diagnosed before the age of 18 years who had undergone KT were identified at one Canadian and 20 European centres. We analysed patient and graft survival and the rates of rejection, AAV relapse and infections. Eighteen patients from this cohort had already been reported in previous articles [1, 2]; their follow-up was extended and further relevant data were retrieved. RESULTS We included 55 patients, of whom 38 (69%) had microscopic polyangiitis (MPA) and 17 (31%) granulomatosis with polyangiitis (GPA). Their median age at diagnosis and transplantation was, respectively, 12 (interquartile range, IQR 9–14) and 14 (IQR 12–16) years (Table 1). Living donor transplantation was performed in 20 cases (36%) and deceased donor transplantation in 35 (64%). At the time of transplantation, all patients were in clinical remission and ANCA was positive in 14/54 (26%). As immunosuppressive therapy, 46 patients (84%) received glucocorticoids, tacrolimus and either mycophenolate mofetil or azathioprine. The median follow-up after transplantation was 54 months (IQR 21–91). Acute rejection was reported in 22 patients (40%), 12 of whom experienced it during the first post-transplant year, while chronic rejection was established in two (4%). AAV relapsed in five cases (9%) and involved the graft in 4/5. Positive ANCA at transplantation was significantly associated with relapse (29% versus 2%; P = 0.02). Infections occurred in 34 patients (62%), and were mainly bacterial infections of the urinary tract or viral infections due to CMV (8/34), EBV (5/34) and BK virus (4/34). No patient developed malignancy. At last visit, all patients were alive and 48 (87%) had a functioning graft. Graft function impairment (eGFR &lt;60 mL/min/1.73 m2) developed in 21 patients and seven (13%) of these lost their graft due to acute (6/7) and chronic rejection (1/7). Outcomes and complication rates did not differ significantly between the MPA and the GPA group (Table 1). Graft function impairment was associated with rejection and positive ANCA at transplantation, but not with age at diagnosis and at transplantation, ANCA specificity, the type of donor or the immunosuppressive regimen (Figure. 1). CONCLUSION KT in childhood-onset AAV has a relatively good graft and patient survival, while the rate of complications and the risk of vasculitis relapse appear low. Positive ANCA at the time of transplantation may be a risk factor for both AAV relapse and graft function impairment.