Eculizumab exposure in children and young adults: indications, practice patterns, and outcomes-a Pediatric Nephrology Research Consortium study.

BACKGROUND: Eculizumab is approved for the treatment of atypical hemolytic uremic syndrome (aHUS). Its use off-label is frequently reported. The aim of this study was to describe the broader use and outcomes of a cohort of pediatric patients exposed to eculizumab. METHODS: A retrospective, cohort analysis was performed on the clinical and biomarker characteristics of eculizumab-exposed patients < 25 years of age seen across 21 centers of the Pediatric Nephrology Research Consortium. Patients were included if they received at least one dose of eculizumab between 2008 and 2015. Traditional summary statistics were applied to demographic and clinical data. RESULTS: A total of 152 patients were identified, mean age 9.1 (+/-6.8) years. Eculizumab was used "off-label" in 44% of cases. The most common diagnoses were aHUS (47.4%), Shiga toxin-producing Escherichia coli HUS (12%), unspecified thrombotic microangiopathies (9%), and glomerulonephritis (9%). Genetic testing was available for 60% of patients; 20% had gene variants. Dosing regimens were variable. Kidney outcomes tended to vary according to diagnosis. Infectious adverse events were the most common adverse event (33.5%). No cases of meningitis were reported. Nine patients died of noninfectious causes while on therapy. CONCLUSIONS: This multi-center retrospective cohort analysis indicates that a significant number of children and young adults are being exposed to C5 blockade for off-label indications. Dosing schedules were highly variable, limiting outcome conclusions. Attributable adverse events appeared to be low. Cohort mortality (6.6%) was not insignificant. Prospective studies in homogenous disease cohorts are needed to support the role of C5 blockade in kidney outcomes.

Epiphyseal stapling and recombinant human growth hormone for correction of genu valgum in children with chronic renal insufficiency.

Genu valgum (GV) and growth retardation are known complications of chronic renal insufficiency (CRI) in children. Physeal stapling is the preferred method for GV correction, provided epiphyseal growth continues after stapling. Growth retardation in these children thus renders this mode of therapy unreliable. The only alternative is corrective osteotomy with the associated risks, such as non-union of bone and recurrence. The authors sought to determine if recombinant human growth hormone (rhGH) administered after stapling can bring about continued physeal growth needed for correction. The medical records of five patients with CRI, GV, and growth retardation who had physeal stapling performed and received rhGH were reviewed. Resolution of GV and improvement in linear height was achieved in four patients within 2 years. The authors conclude that children with CRI, growth retardation, and moderate GV benefit from the simultaneous use of rhGH and knee stapling for correction of GV, thus avoiding osteotomies.

Post-biopsy renal arteriovenous fistula.

A 6-yr-old boy developed progressively severe hypertension, which was unresponsive to medications, 1 week after percutaneous biopsy of his renal transplant. Renal angiogram revealed an arteriovenous fistula (AVF) in the lower pole at the site of the biopsy. Case findings and resolution after embolization are described, and the current literature is briefly reviewed.