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Background: Complement 3 glomerulopathy (C3G) and immune complex membranoproliferative glomerulonephritis (IC-MPGN) are ultra-rare chronic kidney diseases with an overall poor prognosis, with approximately 40–50% of patients progressing to kidney failure within 10 years of diagnosis. C3G is characterized by a high rate of disease recurrence in the transplanted kidney. However, there is a lack of published data on clinical outcomes in the pediatric population following transplantation. Methods: In this multicenter longitudinal cohort study of the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry, we compared the post-transplant outcomes of pediatric patients with C3G (n = 17) or IC-MPGN (n = 3) with a matched case–control group (n = 20). Results: Eleven of 20 children (55%) with C3G or IC-MPGN experienced a recurrence within 5 years post-transplant. Patients with C3G or IC-MPGN had a 5-year graft survival of 61.4%, which was significantly (P = 0.029) lower than the 5-year graft survival of 90% in controls; five patients with C3G or IC-MPGN lost their graft due to recurrence during this observation period. Both the 1-year (20%) and the 5-year (42%) rates of biopsy-proven acute rejection episodes were comparable between patients and controls. Complement-targeted therapy with eculizumab, either as prophylaxis or treatment, did not appear to be effective. Conclusions: These data in pediatric patients with C3G or IC-MPGN show a high risk of post-transplant disease recurrence (55%) and a significantly lower 5-year graft survival compared to matched controls with other primary kidney diseases. These data underscore the need for post-transplant patients for effective and specific therapies that target the underlying disease mechanism. [ABSTRACT FROM AUTHOR]

Background/Objectives: Eculizumab is a first-line treatment for atypical hemolytic uremic syndrome (aHUS), and patients undergoing eculizumab therapy may become more susceptible to infection caused by Neisseria meningitidis (Nm). While meningococcal vaccination is required for patients undergoing eculizumab therapy, there is limited knowledge about meningococcal carriage in children with aHUS. We aimed to evaluate (1) the prevalence of Nm carriage, (2) serogroup distribution, and (3) the immunization status of children undergoing eculizumab treatment for aHUS. Methods: The Meningo-aHUS study is a prospective, multi-center study evaluating meningococcal carriage in children and adolescents in Türkiye receiving eculizumab for aHUS. We noted the age, gender, daycare, school, or university attendance, passive smoking status, previous infection and antibiotic use, and previous immunization history, including meningococcal vaccines, from the medical records of those children with aHUS. We collected nasopharyngeal samples, tested them for Nm using real-time polymerase chain reaction, and performed a serogroup analysis on the positive samples. Results: We collected nasopharyngeal samples from 62 children with aHUS. Out of 62 children, 61 (98.4%) had received at least one dose of the meningococcal vaccine. The median time since the last meningococcal vaccine dose was 15 months (1–59 months). We detected meningococcal carriage in three (4.8%, 95% CI 1.0–13.5) children, and all three strains were non-groupable (NG). No other serogroups were detected. Conclusions: Almost all the children received their risk-group meningococcal immunization, including booster doses. A 4.8% of children with aHUS carried NG meningococci and, no vaccine serogroups were detected. Patients treated with eculizumab remain profoundly susceptible to IMD due to these NG meningococcal strains. The occurrence of breakthrough cases and carriage of Nm, especially NG strains, highlights the significance of maintaining a state of constant alertness, promptly seeking medical attention, and swiftly treating any symptoms that align with IMD, regardless of their vaccination status or antibiotic prophylaxis. [ABSTRACT FROM AUTHOR]

Background: Alport syndrome (AS) is an inherited glomerular disease caused by mutations in COL4A3, COL4A4, or COL4A5. Associations between clinical manifestations and genotype are not yet well defined. Our study aimed to define clinical and genetic characteristics, establish genotype–phenotype correlations, and determine prognosis of AS in children. Methods: A total of 87 children with AS from 10 pediatric nephrology centers, whom had genetic analyses performed at the Hacettepe University Nephrogenetics Laboratory between February 2017 and February 2019, were included. Data regarding demographics, family history, clinical and laboratory characteristics, histopathological and genetic test results, treatments, and yearly follow-up results were retrospectively analyzed. Results: Of 87 patients, 16% presented with nephrotic syndrome. In patients with nephrotic syndrome, kidney biopsy findings showed focal segmental glomerulosclerosis (FSGS) in 79%, and COL4A3 mutations were the leading genetic abnormality (50%). Twenty-four percent of all patients progressed to chronic kidney disease (CKD). The rate of progression to CKD and the decline in the glomerular filtration rate of the patients with COL4A3 mutation were higher than other mutation groups (p < 0.001 and p = 0.04, respectively). In kidney survival analysis, nephrotic syndrome presentation, histopathology of FSGS, COL4A3 mutations, and autosomal recessive inheritance were found as independent risk factors for earlier progression to CKD. Cyclosporin A treatment did not improve kidney survival. Conclusions: We emphasize that genetic testing is important for patients suspected as having AS. Furthermore, COL4A mutations should be considered in patients with FSGS and steroid-resistant nephrotic syndrome. This approach will shed light on the prognosis of patients and help with definitive diagnosis, preventing unnecessary and potentially harmful medications. [ABSTRACT FROM AUTHOR]

Background: CD80 (also known as B7‐1) is a co‐stimulatory molecule that is expressed in biopsies and also excreted in urine in patients with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). CD80 is inhibited by the cytotoxic T‐lymphocyte‐associated‐antigen 4 (CTLA4), which is mainly expressed on regulatory T cells (Tregs). Ineffective circulating Treg response is involved in the pathogenesis of nephrotic syndrome. In this study, we evaluated CD80 expression and infiltrating Tregs in children with MCD and FSGS. Methods: Evaluation of CD80 expression and semi‐quantitative evaluation of Tregs (FOXP3‐positive CD4 T cells) were carried out in 31 kidney biopsies (12 MCD, 19 FSGS) with immunofluorescence and immunohistochemistry staining. Results: All MCD sections were stained negative; whereas six out of 19 FSGS sections (all from steroid‐resistant (SR) patients), including one from a Wilms' tumor 1 (WT1) mutation‐positive FSGS patient, stained positive for anti‐CD80 goat antibody, and negative for anti‐CD80 rabbit antibody. FSGS biopsy specimens had significantly higher FOXP3‐positive cells/mm2 compared with MCD and control samples (P < 0.001). Biopsy samples from SR‐FSGS patients (n = 12) with positive CD80 staining (n = 6) had significantly less Tregs (FOXP3‐positive CD4 T cells) compared with CD80 (−) biopsies (n = 6; P = 0.004). Conclusion: CD80 expression was not detected in the majority of the archival biopsy sections and the results were not consistent across the different antibodies. In the SR‐FSGS sections, however, CD80‐positive biopsies had decreased FOXP3‐positive CD4 T cells, suggesting that a decreased anti‐inflammatory milieu may be the cause of increased CD80 expression. [ABSTRACT FROM AUTHOR]

The preliminary study was performed to determine the frequency of tuberculin skin test (TST) positivity among 26 patients and their donors screened by TST to investigate whether tuberculin positivity of a recipient or donor influenced the rate of tuberculosis disease, transplant-related events, and to evaluate the effectiveness of isoniazide (INAH) prophylaxis administered to those with positive TST. The frequency of TST positivity was 23% (n = 6) among recipients and also 23% (n = 6) among donors. Two recipients and five donors with positive TST received INAH prophylaxis for six months. Our use of INAH prophylaxis in transplant patients was very conservative because of the risk of drug interaction. The transplantation procedure was not postponed for either recipient or donor TST positivity. Despite the high frequency of tuberculosis in our country, we have not detected any case of tuberculosis in our center, either among the purified protein derivative-screened (n = 26) or non-screened (n = 128) patients except for disseminated tuberculosis infection because of BCG vaccination in two patients with severe combined immunodeficiency. In conclusion, TST positivity in either recipient or donor may not be a contraindication for bone marrow transplantation and the procedure may not be postponed. Pretransplantation TST screening may be needed in countries where tuberculosis is common in the general population. [ABSTRACT FROM AUTHOR]