Ravulizumab in Renal Transplantation: Results of a Spanish Multicenter Study

Background Atypical hemolytic uremic syndrome (aHUS), a rare form of thrombotic microangiopathy, is caused by complement pathway dysregulation. Ravulizumab, a complement C5 inhibitor, approved for aHUS treatment, has limited data in kidney transplant recipients. This multicenter study evaluated efficacy and safety of ravulizumab in patients with aHUS undergoing kidney transplantation. Methods This retrospective observational study, conducted across 14 Spanish hospitals, included adult patients diagnosed with aHUS before or after undergoing kidney transplantation who received ravulizumab for three different clinical indications: as a switch from eculizumab, as prophylaxis at the time of transplantation, or as post–transplant de-novo/recurrent aHUS episode treatment. Patients were also classified into high, moderate, or low recurrence–risk groups based on complement variants. Demographic characteristics, hematologic parameters (hemoglobin, platelet count), and renal function (serum creatinine, estimated glomerular filtration rate eGFR), were evaluated at baseline, 3 months, and 6 months after first ravulizumab administration. Safety was also evaluated. Results Data from 68 patients were analyzed (mean ± SD age: 46.84 ± 13.44 years). Most frequent reason for ravulizumab administration was switch (n = 51; 75.0%), followed by prophylaxis (n = 14; 20.6%) and treatment (n = 3; 4.4%). Most frequent complement genetic variant was factor H (35.3%); 43 (63.2%) patients were classified as high risk, 23 (33.8%) as moderate risk, and 2 (2.9%) as low risk for recurrence. At 6 months, significant improvements were observed in hemoglobin (p = 0.03), platelet count (p = 0.03), and eGFR (p = 0.016), and decrease in serum creatinine (p = 0.001) in overall cohort; similar results were observed in prophylaxis group (p< 0.05 for all). No recurrences or graft losses occurred; one patient died due to malignancy after follow-up. Urinary tract infections occurred in 24.6% of patients. Conclusions Ravulizumab use across different indications in transplant recipients with aHUS was effective and well-tolerated, maintaining disease control with extended dosing intervals. These findings support its use as a valid option for first–line treatment of aHUS in kidney transplantation.