Ofatumumab treatment for nephrotic syndrome recurrence after pediatric renal transplantation.

BACKGROUND: Relapsing nephrotic syndrome (NS) after transplantation can be a challenge to treat. The result of the consequent long-lasting proteinuria is the loss of the graft. Disease recurrence after renal transplantation occurs in around half of cases, and the efficacy of therapeutic strategies is often limited. Recently, ofatumumab, a second-generation and fully human anti-CD20 monoclonal antibody, has been shown to be effective in severe situations. METHODS: We retrospectively collected data from the medical records of children with recurrence of NS after renal transplantation treated with ofatumumab in France, after failure of previous treatments. RESULTS: Six patients were included in this study in five centers with a median duration of follow-up of 10.5 months. Two different ofatumumab regimens were administered. The primary outcome was proteinuria at 6 months after the last dose of ofatumumab. No patient achieved a complete remission, 3/6 had a partial remission, and 3/6 had no response to ofatumumab. Four patients exhibited a minor allergic reaction with the first infusion. One patient died of infection, as a consequence of multiple factors. No malignancies were observed; however, the time of follow-up was not sufficient to see such disease. CONCLUSIONS: Altogether, these results suggest ofatumumab has a poor efficacy in treating recurrence of NS after renal transplantation. However, it could be discussed in multidrug-resistant refractory NS, but infectious complications and overimmunosuppression have to be balanced. There is a need for further studies to confirm these findings and safety and to determine a standardized protocol in this indication.

School level of children carrying a HNF1B variant or a deletion.

The prevalence of neurological involvement in patients with a deletion of or a variant in the HNF1B gene remains discussed. The aim of this study was to investigate the neuropsychological outcomes in a large cohort of children carrying either a HNF1B whole-gene deletion or a disease-associated variant, revealed by the presence of kidney anomalies. The neuropsychological development-based on school level-of 223 children included in this prospective cohort was studied. Data from 180 children were available for analysis. Patients mean age was 9.6 years, with 39.9% of girls. Among these patients, 119 carried a HNF1B deletion and 61 a disease-associated variant. In the school-aged population, 12.7 and 3.6% of patients carrying a HNF1B deletion and a disease-associated variant had special educational needs, respectively. Therefore, the presence of a HNF1B deletion increases the risk to present with a neuropsychiatric involvement when compared with the general population. On the other hand, almost 90% of patients carrying a HNF1B disease-associated variant or deletion have a normal schooling in a general educational environment. Even if these findings do not predict the risk of neuropsychiatric disease at adulthood, most patients diagnosed secondary to kidney anomalies do not show a neurological outcome severe enough to impede standard schooling at elementary school. These results should be taken into account in prenatal counseling.