Eculizumab for Atypical Hemolytic Uremic Syndrome Recurrence in Renal Transplantation

Abstract

Eculizumab (anti-C5) has been sporadically reported as an efficient therapy for atypical hemolytic uremic syndrome (aHUS). However, the lack of series precludes any firm conclusion about the optimal use of anti-C5 for preventing or treating aHUS posttransplant aHUS recurrence. We thoroughly studied 22 renal transplant recipients with aHUS who received offlabel therapy with anti-C5, including 12 cases, which have not been reported yet. Nine patients, all carrying a complement genetic abnormality associated with a high risk of aHUS recurrence, received prophylactic anti-C5 therapy to prevent posttransplant recurrence. Eight of them had a successful recurrencefree posttransplant course and achieved a satisfactory graft function, while the remaining patient experienced early arterial thrombosis of the graft. Thirteen renal transplant recipients were given anti-C5 for posttransplant aHUS recurrence. A complete reversal of aHUS activity was obtained in all of them. Importantly, the delay of anti-C5 initiation after the onset of the aHUS episode inversely correlated with the degree of renal function improvement. Three patients in whom anti-C5 was subsequently stopped experienced a relapse. Altogether these data suggest that long-term eculizumab is highly effective for preventing and treating posttransplant aHUS recurrence. Our study also indicates that anti-C5 should be promptly started if a recurrence occurs.

Genetics and Outcome of Atypical Hemolytic Uremic Syndrome

“…Between 2000 and 2008, the mean number of patients referred each year at the time of the first episode of aHUS was 15 (range, [8][9][10][11][12][13][14][15][16][17][18][19][20][21], suggesting that the annual incidence of aHUS is at least 0.23/year per 10 6 people in the French population.…”

Update on hemolytic uremic syndrome: Diagnostic and therapeutic recommendations

“…More recently, eculizumab efficacy was also documented in aHUS recurrence after renal transplantation [134] . Overall, these data suggest that long-term eculizumab treatment is highly effective for the prevention and treatment of post-transplant aHUS recurrence and indicate that anti-C5 therapy should be started promptly after a recurrence.…”

Combined liver and kidney transplantation in children

“…This antibody prevents the formation of C5b and the C5b-C9 complex (membrane attack complex), and the recent findings indicate that anti-C5 is effective in treating aHUS patients. Moreover, recent data suggest that eculizumab is effective in preventing and treating post-transplant recurrences of aHUS after isolated KT [36]. The first two doses can be given just before and after KT followed by maintenance infusions at 2-week intervals.…”