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

BACKGROUND: The efficacy of rituximab in steroid-resistant nephrotic syndrome (SRNS) is controversial. We previously reported that rituximab in combination with methylprednisolone pulse therapy (MPT) and immunosuppressants was associated with favorable outcomes. We determined risk factors for poor response following rituximab treatment, which remains unknown. METHODS: This retrospective study included 45 patients with childhood-onset SRNS treated with rituximab across four pediatric kidney facilities. Treatment effects were categorized as complete remission (CR), partial remission (PR), and no remission (NR) at one year after rituximab treatment. The primary outcome was the rate of CR, PR, and NR. Risk factors for non-CR were calculated with multivariate logistic regression. Adverse events and the relationship between disease status at one year and long-term prognosis were also evaluated. RESULTS: The rates of CR, PR, and NR at one year were 69%, 24%, and 7%, respectively. The median time from rituximab administration to CR was 90 days. The median follow-up period after rituximab administration was 7.4 years. In multivariate analysis, significant risk factors for poor response were the pathologic finding of focal segmental glomerular sclerosis and a long interval between SRNS diagnosis and rituximab administration. The rates of CR were 90.3% and 21.4% in patients receiving rituximab within and after 6 months following SRNS diagnosis, respectively (p < 0.001). Five patients developed chronic kidney disease stage G5, including 2 of the 11 patients with PR and all 3 patients with NR, whereas none of the 31 patients with CR developed chronic kidney disease stage G5. CONCLUSION: Early administration of rituximab in combination with MPT and immunosuppressants might achieve favorable outcomes in patients with SRNS.

Changes in Patterns of Infection Associated with Pediatric Idiopathic Nephrotic Syndrome: A Single-Center Experience in Japan.

OBJECTIVE: We studied infection rates and risk factors for infection in current patients with idiopathic nephrotic syndrome (INS). STUDY DESIGN: This retrospective cohort study included the clinical data for children with diagnosed INS in our center between January 2010 and December 2020. The infection rates and risk factors were analyzed. RESULTS: We enrolled 187 patients, including 85 cases with steroid-dependent/frequently relapsing nephrotic syndrome and 45 with steroid-resistant nephrotic syndrome. Infection was observed a total of 84 times in 55 patients (95.5 per 1000 person-years). Pneumonia was the most common infection (21 cases, 23.9 per 1000 person-years), followed by febrile neutropenia (12 cases, 13.7 per 1000 person-years), whereas peritonitis and bacteremia were observed in only 3 and 2 cases, respectively. The multivariate analyses by logistic regression showed that rituximab treatment was significantly associated with infections in pediatric INS (P = .001). The infection rate during the B-cell-depleted state with immunosuppressants (318 per 1000 person-years) was greater than that with normal B-cell count with immunosuppressants (109 per 1000 person-years) or without immunosuppressants (76 per 1000 person-years). CONCLUSION: Common infections, such as peritonitis and bacteremia, decreased, whereas infections associated with medication (eg, rituximab) increased. The rate of infection increases during B-cell depletion after treatments with rituximab and other immunosuppressants.

Glucocorticoid discontinuation in pediatric-onset systemic lupus erythematosus: a single-center experience.

BACKGROUND: Glucocorticoid discontinuation, a challenge in systemic lupus erythematosus (SLE), might be achievable with the advent of new therapeutic options. METHODS: This single-center study included 31 children with newly diagnosed pediatric SLE between 2002 and 2021, after the exclusion of patients who were followed for less than 1 year after treatment initiation and those lost to follow-up. Patient characteristics, clinical course including flares, treatment, glucocorticoid discontinuation, and outcomes were retrospectively analyzed. RESULTS: Glucocorticoids could be discontinued in 19 (61%) patients during a median observation period of 105.5 (range, 17-221) months. Of these, 5 (26%), 12 (63%), and 18 (95%) patients could discontinue glucocorticoids in 3, 5, and 10 years from treatment initiation, respectively. Additionally, 18 of the 19 patients did not experience flares after glucocorticoid discontinuation during a median duration of 37.2 (7.2-106.8) months. Three of the nineteen patients achieved drug-free remission. At last follow-up, all patients achieved low disease activity with or without glucocorticoids and 19, 8, and 1 patient were receiving mycophenolate mofetil (MMF), MMF plus tacrolimus, and MMF plus ciclosporin A, respectively. Flares were observed in 15 patients during the observation period. MMF as initial immunosuppressant (P = 0.01) and shorter interval between therapy initiation and achieving maintenance prednisolone dose of 0.1-0.15 mg/kg/day (P = 0.001) were associated with significantly reduced flare risk. Femoral head necrosis was observed in two patients. CONCLUSION: Despite the small sample size, these results support glucocorticoid discontinuation as a therapeutic target in pediatric SLE.

Mycobacterium avium complex peritonitis in a pediatric patient on peritoneal dialysis: A case report.

INTRODUCTION: Peritonitis due to Mycobacterium avium complex (MAC) is a rare but life-threatening complication in patients on peritoneal dialysis (PD). However, optimal therapeutic regimen, treatment duration, and appropriate timing of kidney transplantation (KT) after treatment are unknown. SYMPTOMS: We herein report a 4-year-old boy on PD due to end-stage kidney disease resulting from bilateral hypoplastic kidneys. He was admitted for peritonitis complaining fever, abdominal pain, and cloudy peritoneal effluent on PD after accidentally biting and opening the PD catheter while in the bath. Initial treatment with vancomycin and ceftazidime for 2 weeks was successful, although peritonitis recurred 37 days after discharge. DIAGNOSIS: Mycobacterial culture was positive 9 days after readmission, and MAC was grown in the PD culture on day 30. We diagnosed him with MAC peritonitis that occurred on PD. INTERVENTIONS: Clarithromycin, ethambutol, and rifampicin were initiated. The PD catheter was removed, and hemodialysis was initiated with a cuffed catheter inserted in the internal jugular vein. Follow-up observation for 8 months after the cessation of 1-year anti-mycobacterial therapy confirmed no recurrence of MAC infection, and the patient received living-donor KT from his father. OUTCOMES: His renal function was stable, with no recurrence of MAC peritonitis at 2 years after the KT. CONCLUSION: To the best of our knowledge, this is the first report of a patient who successfully underwent KT after receiving treatment for MAC peritonitis. One-year anti-mycobacterial therapy, PD catheter removal, 8-month observation after the cessation of therapy led the successful KT, although further investigation is warranted to confirm the efficacy of this approach.

Impairment of Excitation-Contraction Coupling in Right Ventricular Hypertrophied Muscle with Fibrosis Induced by Pulmonary Artery Banding.

Interstitial myocardial fibrosis is one of the factors responsible for dysfunction of the heart. However, how interstitial fibrosis affects cardiac function and excitation-contraction coupling (E-C coupling) has not yet been clarified. We developed an animal model of right ventricular (RV) hypertrophy with fibrosis by pulmonary artery (PA) banding in rats. Two, four, and six weeks after the PA-banding operation, the tension and intracellular Ca2+ concentration of RV papillary muscles were simultaneously measured (n = 33). The PA-banding rats were clearly divided into two groups by the presence or absence of apparent interstitial fibrosis in the papillary muscles: F+ or F- group, respectively. The papillary muscle diameter and size of myocytes were almost identical between F+ and F-, although the RV free wall weight was heavier in F+ than in F-. F+ papillary muscles exhibited higher stiffness, lower active tension, and lower Ca2+ responsiveness compared with Sham and F- papillary muscles. In addition, we found that the time to peak Ca2+ had the highest correlation coefficient to percent of fibrosis among other parameters, such as RV weight and active tension of papillary muscles. The phosphorylation level of troponin I in F+ was significantly higher than that in Sham and F-, which supports the idea of lower Ca2+ responsiveness in F+. We also found that connexin 43 in F+ was sparse and disorganized in the intercalated disk area where interstitial fibrosis strongly developed. In the present study, the RV papillary muscles obtained from the PA-banding rats enabled us to directly investigate the relationship between fibrosis and cardiac dysfunction, the impairment of E-C coupling in particular. Our results suggest that interstitial fibrosis worsens cardiac function due to 1) the decrease in Ca2+ responsiveness and 2) the asynchronous activation of each cardiac myocyte in the fibrotic preparation due to sparse cell-to-cell communication.