Combined methylmalonic acidemia (MMA) and homocysteinemia are a group of autosomal recessive disorders caused by inborn errors of cobalamin metabolism, including CblC, D, F, and J, with cblC being the most common subtype. The clinical manifestations of combined MMA and homocysteinemia vary, but typically include neurologic, developmental and hematologic abnormalities. We report 4 children with combined MMA and homocysteinemia who presented predominantly with late-onset diffuse lung diseases (DLD). Of these, 3 accompanied by pulmonary arterial hypertension (PAH), 1 accompanied by hypertension, and 2 accompanied by renal thrombotic microangiopathy (TMA), which was confirmed by renal biopsy. This confirms combined MMA and homocysteinemia should be considered in the differential diagnosis of DLD with or without PAH or renal TMA.

Background: B-cell-deleted therapy has been successfully used for children with idiopathic nephrotic syndrome (INS), suggesting that B cells may be involved in the pathogenesis of INS. B cells are a heterogenous population comprised of subpopulations distinguished by their phenotypes. However, few studies have focused on the alteration of B-cell homeostasis in INS. Methods: We measured the levels of B-cell subsets in the blood of 87 INS children via flow cytometry, prior to treatment with steroids. INS patients were divided into steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS) groups based on their sensitivities to steroids after a one-month follow-up. Subsequently, we compared these INS patients with age- and sex-matched patients with relapse (n = 35) and remissions (n = 32), as well as healthy controls (n = 75). Results: We found that 65 SSNS patients exhibited an altered peripheral-blood B-cell-subset distribution, with increased levels of total, transitional, memory, IgM (immunoglobulin M) memory and switched-memory B cells compared to 22 SRNS patients. The proportion of total B cells was significantly higher in the SSNS group (22.1 ± 6.7% L, p < 0.001) than in the SRNS, remission, and control groups. In contrast, the levels of B-cell subsets in SRNS patients were generally the same as those in remission patients and healthy controls. Patients in relapse presented elevated memory B cells compared to those in other groups. The area under the ROC (receiver operating characteristic) curve of transition B cells at initial onset for the prediction of SSNS was 0.907 (95% confidence interval, 0.835–0.979). The analysis rendered an optimal cut-off value of 2.05 (% Lymphocyte) corresponding to 79.1% sensitivity and 90.9% specificity. Conclusions: We observed and verified that B-cell subsets are significantly altered in children with SSNS. We propose that elevated transitional B cells may be a promising marker for predicting successful immunosuppressive therapy during the initial onset of INS. Further research is needed to determine the function of memory B cells in INS.

The Oxford Classification was proposed as an independent prognostic indicator in IgA nephropathy (IgAN). However, most studies on the subject focus on adults instead of children. Using a meta-analysis to appraise the predictive roles of the Oxford classification for the prognosis of pediatric patients with IgAN. All cohort studies regarding the analysis of the association between poor kidney-related prognosis (GFR categories G2-G5) according to the Kidney Disease Improving Global Outcomes (KDIGO) Guideline in pediatric patients with IgAN and five pathologic lesions in the Oxford Classification were included. Hazard ratios (HRs) regarding the association between the Oxford classification and prognosis of pediatric patients with IgAN were synthesized using random effect models. The risk of bias in studies was assessed based on the Newcastle-Ottawa scale. Fourteen articles were included with 5679 IgAN patients and 710 endpoint outcome events occurred. M1 was associated with a higher risk of poor kidney-related prognosis compared with M0, pooled HR (1.79; 95%CI, 1.46–2.19; p < 0.001, random effect model). S1 and T1 or T2 increased the risk of poor kidney-related prognosis (pooled HR, 2.13; 95%CI, 1.68–2.70; p < 0.001; pooled HR, 2.64; 95%CI, 1.81–3.86; p < 0.001, respectively, estimated by random effect model). Compared with C0, C1, or C2 was also associated with an increased risk of poor kidney-related prognosis in the subgroup analysis of Asian and other populations. Evidence to indicate that E1 increased the risk of poor kidney-related prognosis was marginal.

This study retrospectively evaluated telitacicept in ten pediatric IgA nephropathy patients with proteinuria (24-hour urinary protein: 23.97 ± 26.63 mg/kg). All patients received steroid therapy, and half received combined immunosuppressants. After a median follow-up of 3.75 months, eight patients achieved proteinuria remission (four complete, four partial). Steroid reduction (33.3–92%) occurred in six patients, and four discontinued steroids entirely. Key clinical outcomes included improvements in protein excretion. Adverse events were mild, including injection-site reactions (2 cases), upper respiratory infection (1 case), rash (1 case), and leukopenia (1 case), with no severe events reported. Telitacicept appears effective and safe for reducing proteinuria and steroid use in pediatric IgAN.

Background: Rituximab has been shown efficacy in reducing relapses among patients with steroid-dependent or frequently relapsing nephrotic syndrome (SDNS/FRNS), primarily due to minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS). However, whether its efficacy differs between these two histological subtypes remains unclear. Methods: A retrospective cohort study included 42 pediatric SDNS/FRNS patients with biopsy-proven MCD or FSGS. Clinical outcomes, including remission rates and relapse frequency were assessed. Results: The median age at diagnosis of the 42 patients was 5.1 years (IQR: 2.9–7.4), and 28 (67%) patients were male during the 6-year follow-up. Each patient received a median of 4 (IQR: 3–5) infusions. All patients achieved clinical remission, with 90.5% attaining complete remission. Relapse times decreased to 35.7% within 1 year after the first rituximab treatment, from a median of 2 relapses to 0. No significant difference in relapse rates was observed between patients receiving 3–4 doses versus 1–2 doses during the initial course. Histologically, 36 patients (85.7%) had MCD and 6 (14.3%) had FSGS. In the FSGS group, the 96-month relapse-free survival was higher compared to MCD controls (2/6 [33.3%] vs. 15/36 [41.7%]; p < 0.01; HR, 0.13; 95% CI, 0.05–0.35). Rituximab was well tolerated. Conclusion: Rituximab is effective for SDNS/FRNS children, whatever MCD or FSGS. These findings support repeated rituximab use in SDNS/FRNS. However, given the small sample size of the FSGS subgroup, these findings should be interpreted with caution and require validation in larger, multicenter studies.