Mutations in factor H (CFH), factor I (IF), and membrane cofactor protein (MCP) genes have been described as risk factors for atypical hemolytic uremic syndrome (aHUS). This study analyzed the impact of complement mutations on the outcome of 46 children with aHUS. A total of 52% of patients had mutations in one or two of known susceptibility factors (22, 13, and 15% of patients with CFH, IF, or MCP mutations, respectively; 2% with CFHϩIF mutations). Age Ͻ3 mo at onset seems to be characteristic of CFH and IF mutation-associated aHUS. The most severe prognosis was in the CFH mutation group, 60% of whom reached ESRD or died within Ͻ1 yr. Only 30% of CFH mutations were localized in SCR20. MCP mutation-associated HUS has a relapsing course, but none of the children reached ESRD at 1 yr. Half of patients with IF mutation had a rapid evolution to ESRD, and half recovered. Plasmatherapy seemed to have a beneficial effect in one third of patients from all groups except for the MCP mutation group. Only eight (33%) of 24 kidney transplantations that were performed in 15 patients were successful. Graft failures were due to early graft thrombosis (50%) or HUS recurrence. In conclusion, outcome of HUS in patients with CFH mutation is catastrophic, and posttransplantation outcome is poor in all groups except for the MCP mutation group. New therapies are urgently needed, and further research should elucidate the unexplained HUS group.

The hepatocyte nuclear factor-1␤ encoded by the TCF2 gene plays a role for the specific regulation of gene expression in various tissues such as liver, kidney, intestine, and pancreatic islets and is involved in the embryonic development of these organs. TCF2 mutations are known to be responsible for the maturity-onset diabetes of the young type 5 associated with renal manifestations. Several observations have suggested that TCF2 mutations may be involved in restricted renal phenotypes. Eighty children (median age at diagnosis 0.2 yr) with renal cysts, hyperechogenicity, hypoplasia, or single kidneys were studied. Quantitative multiplex PCR amplification of short fluorescence fragments for the search of large genomic rearrangements and sequencing for the detection of point mutations were performed. TCF2 anomalies were detected in one third of patients (25 of 80). The main alteration was the complete deletion of the TCF2 gene detected in 16 patients. Family screening revealed de novo TCF2 anomalies in nine of 17 probands with a high prevalence of deletions (seven of nine). TCF2 anomalies were associated with bilateral renal anomalies (P < 0.001) and bilateral cortical cysts (P < 0.001). However, abnormal renal function, detected in 40% of patients, was independent of the TCF2 genotype. No difference in renal function or severity of renal morphologic lesions was observed between patients with a TCF2 deletion and those with point mutations. In conclusion, TCF2 molecular anomalies are involved in restricted renal phenotype in childhood without alteration of glucose metabolism. These findings have important implications in the diagnosis of patients with renal dysplasia with cysts and their follow-up.

Several case reports suggest that rituximab (RTX) could be effective in steroid-dependent nephrotic syndrome, but RTX efficacy has not yet been studied in a series of patients. Safety and efficacy of RTX were assessed in a multicenter series of 22 patients aged 6.3-22 years with severe steroid-dependent nephrotic syndrome or steroid-resistant but cyclosporin-sensitive idiopathic nephrotic syndrome. Patients were treated with two to four infusions of RTX. Seven patients were nephrotic at the time of RTX treatment. Peripheral B cells were depleted in all subjects. Remission was induced in three of the seven proteinuric patients. One or more immunosuppressive (IS) treatments could be withdrawn in 19 patients (85%), with no relapse of proteinuria and without increasing other IS drugs. RTX was effective in all patients when administered during a proteinuria-free period in association with other IS agents. When relapses occurred, they were always associated with an increase in CD19 cell count. Adverse effects were observed in 45% of cases, but most of them were mild and transient. This study suggests that RTX could be an effective treatment for severe steroid-dependent nephrotic syndrome.

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We analyzed urinary polypeptides from individuals with neonatal ureteropelvic junction (UPJ) obstruction to predict which individuals with this condition will evolve toward obstruction that needs surgical correction. We identified polypeptides that enabled diagnosis of the severity of obstruction and validated these biomarkers in urine collected in a prospective blinded study. Using these noninvasive biomarkers, we were able to predict, several months in advance and with 94% precision, the clinical evolution of neonates with UPJ obstruction.