Background Atypical hemolytic uremic syndrome (aHUS) is a rare, complement-mediated disease associated with poor outcomes if untreated. Ravulizumab, a long-acting C5 inhibitor developed through minimal, targeted modifications to eculizumab was recently approved for the treatment of aHUS. Here, we report outcomes from a pediatric patient cohort from the ravulizumab clinical trial (NCT03131219) who were switched from chronic eculizumab to ravulizumab treatment. Methods Ten patients received a loading dose of ravulizumab on Day 1, followed by maintenance doses administered initially on Day 15, and then, every 4–8 weeks thereafter, depending on body weight. All patients completed the initial evaluation period of 26 weeks and entered the extension period. Results No patients required dialysis at any point throughout the study. The median estimated glomerular filtration rate values remained stable during the trial: 99.8 mL/min/1.73m2 at baseline, 93.5 mL/min/1.73m2 at 26 weeks, and 104 mL/min/1.73m2 at 52 weeks. At last available follow-up, all patients were in the same chronic kidney disease stage as recorded at baseline. Hematologic variables (platelets, lactate dehydrogenase, and hemoglobin) also remained stable throughout the initial evaluation period and up to the last available follow-up. All patients experienced adverse events; the most common were upper respiratory tract infection (40%) and oropharyngeal pain (30%). There were no meningococcal infections reported, no deaths occurred, and no patients discontinued during the study. Conclusions Overall, treatment with ravulizumab in pediatric patients with aHUS who were previously treated with eculizumab resulted in stable kidney and hematologic parameters, with no unexpected safety concerns when administered every 4–8 weeks. Trial registration Trial identifiers: Trial ID: ALXN1210-aHUS-312 Clinical trials.gov: NCT03131219 EudraCT number: 2016-002499-29

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Background and Aims Ravulizumab is a long-acting C5 inhibitor that has recently demonstrated its effectiveness in adult and pediatric patients for the control of hemolytic uremic syndrome compared to eculizumab, allowing average annual infusion times of up to 70% less. There is still little evidence in the literature of naïve treatment with this drug in pediatrics. Method We present the first two pediatric cases worldwide with the use of de novo Ravulizumab: the first one in the onset of the disease and the second one, post-kidney transplant Results 13-year-old girl referred from another country with 1 week history of acute gastroenteritis with bloody stools, vomiting and compromise of consciousness. Deterioration of general condition, with laboratory tests compatible with thrombotic microangiopathy (TMA), evolves to anuria and convulsive episode requiring invasive mechanical ventilation, corticosteroid boluses, 6 plasmapheresis sessions and 4 intermittent hemodialysis. One Eculizumab dose (600 mg) was administered in the center of origin and STEC was isolated. At admission presented compromised renal function (AKI III), hemolytic anemia, thrombocytopenia, normal ADAMTS-13, negative direct Coombs and decreased complement. Brain MRI study shows images compatible with multiple foci of necrosis. Due to the persistent requirement of renal replacement therapy and persistent TMA, Ravulizumab was started with a loading dose (2400 mg) and a second dose after 2 weeks. The need for renal replacement therapy ceased with improvement of hemolysis and renal function. Genetic study showed mutation of uncertain significance in heterozygosis in exon 6 (c.881_883, p.Ala292del) with risk polymorphism for HUSa (deletion CFHR3-CFHR1)  Case 2: 7-year-old girl (stage 5 CKD) in chronic hemodialysis 3 times/week secondary to aHUS (CD46 mutation) was admitted for kidney transplant from a living donor (father), performing hemodialysis session before surgical intervention. Low-intermediate immunological risk (PRA 0%, 9 HLA matches) and high CMV infectious risk (valganciclovir prophylaxis). Induction treatment: Basiliximab, tacrolimus, mycophenolate and steroids. First dose of Ravulizumab was infused the day before transplantation (900mg), well tolerated. 36 hours after presented acute pulmonary edema as well as a drop in hemoglobin (4g/dL). With normal laboratory hemolysis parameters, urgent abdominal-pelvic CT was performed due to suspicion of bleeding, confirming an active bleeding. Surgical reintervention was decided due to ureteral bleeding and the tunnel was redone with good results. The patient has had a favorable evolution of renal function, with a normal value of creatinine at discharge (0.43 mg/dl). Protein/Creatinine urine ratio (iPr/Cr) increases to a maximum of 8 mg/mg. Negative DSA levels but the option of renal biopsy was assessed and ruled out due to a decrease in proteinuria (iPr/Cr 0.51 mg/mg). She received second dose of ravulizumab after 2 weeks, remain stable with no data on recurrence of her underlying disease today. Conclusión: In the two patients, the initial treatment with Ravulizumab was satisfactory, both in the acute phase of the disease and in the immediate post-transplantation. In the first case we observed a functional recovery from the first dose with no notable adverse effects up today, as in the post-transplant patient, maintaining a good control of TMA despite more spaced dosing (8 weeks). The inclusion of this drug in the therapeutic arsenal opens a new safe treatment route in pediatric patients with HUSa