Eculizumab Use for Kidney Transplantation in Patients With a Diagnosis of Atypical Hemolytic Uremic Syndrome

Abstract

Introduction Recurrence of atypical hemolytic uremic syndrome (aHUS) in renal allografts is common, leading to dialysis and graft failure. Pretransplant versus posttransplant initiation of eculizumab treatment in patients with aHUS has not been rigorously investigated. We hypothesized eculizumab pretransplant would reduce dialysis incidence posttransplant. Methods Of patients enrolled in the Global aHUS Registry ( n = 1549), 344 had ≥1 kidney transplant. Of these, 188 had received eculizumab. Eighty-eight patients (47%) were diagnosed with aHUS and received eculizumab before, and during, their most recent transplant (group 1). A total of 100 patients (53%; group 2) initiated eculizumab posttransplantation. This second group was subdivided into those diagnosed with aHUS before ( n = 52; group 2a) or after ( n = 48; group 2b) their most recent transplant. Results Within 5 years of transplantation, 47 patients required dialysis; the risk of dialysis after transplantation was significantly increased in group 2b (hazard ratio [HR] 4.6; confidence interval [CI] 1.7–12.4) but not 2a (HR 2.3; CI 0.9–6.2). Graft function within 6 months of transplantation was significantly better in group 1 (median estimated glomerular filtration rate of 60.6 ml/min per 1.73 m 2 ) compared with 31.5 and 9.6 ml/min per 1.73 m 2 in groups 2a ( P = 0.004) and 2b ( P = 0.0001), respectively. One meningococcal infection (resolved with treatment) and 3 deaths (deemed unrelated to eculizumab) were reported. Conclusions Outcomes for transplant patients with aHUS treated with eculizumab were improved compared with previous reports of patients with aHUS not treated with eculizumab. Our findings suggest delayed aHUS diagnosis and therefore treatment is associated with an increased risk of dialysis posttransplantation and reduced allograft function.

Kidney transplantation in children with CAKUT and non‐CAKUT causes of chronic kidney disease: Do they have the same outcomes?

“…29 Treatment with eculizumab before KTx may avoid this complication. 30 In our cohort, only three out of 11 recipients with aHUS received eculizumab, two of whom are currently disease free with a functioning…”

“…21 Currently, its use in pediatric transplantation has been increasing regardless of the type of donor. [26][27][28][29][30][31][32][33] In univariate analysis, both in CAKUT and non-CAKUT glomerular patients, early and late AR were predictors of graft loss (Tables 6 and 7). However, in multivariate analysis, early AR in non-CAKUT glomerular and late AR in CAKUT patients were independently related to graft failure (Tables 6 and 7).…”

Optimal duration of treatment with eculizumab in atypical hemolytic uremic syndrome (aHUS)—a question to be addressed in a scientific way

“…Finally, the proposed restrictive approach in aHUS in adult transplant patients or in adult candidates for KTx [57] is highly questionable due to controversial results, limited recovery after eculizumab resumption, and lack of alignment with expert recommendations [22][23][24]33]. New information from the Global aHUS Registry analyzing the outcome of 188 KTx patients with at least 1 year of followup after their most recent transplant demonstrated significantly better 2-year eGFR (70.2 ml/min/1.73m 2 ) in the subgroup of patients receiving eculizumab beginning at the time of transplantation in comparison with the subgroup receiving eculizumab after KTx with a previous diagnosis of aHUS (44.8 ml/min/1.73m 2 ) or the subgroup diagnosed with aHUS and treated after KTx (24.2 ml/ min/1.73m 2 ) [58].…”

Consensus regarding diagnosis and management of atypical hemolytic uremic syndrome

“…The use of eculizumab as a preemptive strategy in KT candidates with known aHUS is ongoing. Several studies have reported the clinical outcomes of KT recipients with ec-ulizumab prophylaxis [89][90][91]. The results showed that eculizumab prophylaxis at the time of KT markedly reduced the incidence of recurrent TMA events, compared to data from the era before eculizumab [28,86].…”