Prophylactic eculizumab after renal transplantation in atypical hemolytic-uremic syndrome.

To the Editor: Atypical hemolytic–uremic syndrome is a rare microangiopathic hemolytic condition characterized by thrombocytopenia and acute renal failure.1 The prognosis for patients with atypical hemolytic–uremic syndrome with a factor H mutation is poor; 60% have end-stage renal disease or die within a year.2 The expected rate of graft failure due to recurrent atypical hemolytic–uremic syndrome among patients with a factor H or factor I mutation is 80% within 1 to 2 years.3 Here, we describe a child with atypical hemolytic–uremic syndrome and a known factor H mutation who had normal renal function 1 year after high-risk kidney transplantation with prophylactic dosing of the terminal complement inhibitor eculizumab. Our patient received a diagnosis of atypical hemolytic–uremic syndrome and a factor H mutation at 4 years of age. During the following 6 years, his renal function remained abnormal, necessitating intermittent peritoneal dialysis and later, continuous cycling peritoneal dialysis. At 9 years of age, severe septicemia developed in association with catheter use, rapid deterioration of renal function ensued, and additional hemodialysis was needed, ultimately resulting in transplantation of a kidney from a deceased donor. Within 48 hours after transplantation, urine output was high, and the creatinine level decreased to within the normal range. Plasma exchange was performed on a daily basis until 9 days after transplantation. On day 10, the patient received the first dose (600 mg) of eculizumab. No plasma exchange was performed thereafter. Subsequent doses of 600 mg were given every 2 weeks. Peak and trough levels of the drug were measured after each of the first four doses were given, to ensure sufficient drug levels. With ongoing treatment with 600 mg of eculizumab every 2 weeks, there was no evidence of active disease for over 1 year after transplantation. During this period, the patient’s complement component 3 values, platelet counts, and haptoglobin levels all stabilized in the middle of the normal range (Fig. 1). Terminal complement is necessary to prevent and limit the severity of infection with Neisseria meningitidis. Owing to the mechanism of action of eculizumab, our patient was vaccinated against meningococcal infection before the initiation of eculizumab treatment.5 Unabated complement activation due to the production of mutant factor H may explain the high rate of recurrence of atypical hemolytic– uremic syndrome, and overall lack of success of renal transplantation, in patients with factor H mutation. Recent reports have shown that treatment with eculizumab during recurrence can improve renal function.5,6 However, we began prophylactic treatment before there was any evidence of recurrence, to maintain chronic suppression of complement activity in an attempt to reduce the risk of progression to graft failure in our high-risk patient with factor H mutation. To date, the patient shows no signs of graft rejection or recurrence of atypical hemolytic–uremic