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 m²) compared with 31.5 and 9.6 ml/min per 1.73 m² 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.

Keywords: atypical hemolytic uremic syndrome; dialysis; eculizumab; kidney observational study; transplantation.

Graphical abstract

Figure 1

Patient disposition by timing of eculizumab initiation and diagnosis. *Includes patients who discontinued eculizumab before KTx and never restarted and patients without valid dates for their eculizumab treatment. aHUS, atypical hemolytic uremic syndrome; KTx, kidney transplant.

Figure 2

Geographical distribution of patients analyzed in the study. The analysis population comprised patients from 17 countries, with most enrolled in Europe or North America. Shading indicates relative proportion of patients in groups 1, 2a, and 2b for each country.

Figure 3

Cumulative proportion of patients receiving any dialysis posttransplantation. (a) Time from most recent transplant to any dialysis (cumulative proportion) for patients in group 1 and group 2. (b) Time from most recent transplant to any dialysis (cumulative proportion) for patients in group 1 and group 2 subdivided by atypical hemolytic uremic syndrome (aHUS) diagnosis date before transplantation (group 2a) and after transplantation (group 2b).

Figure 4

Forest plot depicting hazard ratios (HRs) for time to any dialysis posttransplant. (a) Unadjusted HR (± 95% confidence interval [CI]) based on univariate analysis of each variable. (b) Adjusted HR (± 95% CI) based on multivariate analysis of all variables with P < 0.1 (eculizumab treatment status, gender, age at transplantation, prior chronic dialysis [within 12 months]). *Age was a continuous variable. KTx, kidney transplant.

Figure 5

Median estimated glomerular filtration rate (eGFR) for patients in group 1, 2a, and 2b over time. Baseline is the first value recorded posttransplant (but within 6 months of transplantation). Values for each group are staggered at each timepoint to allow error bars to be clearly discerned and do not indicate differences in the time of measurement. Patients on dialysis had an imputed eGFR of 5 ml/min per 1.73 m². Data are median (interquartile range [IQR]). *P < 0.01 versus group 1; ^†P < 0.01 versus group 2a. aHUS, atypical hemolytic uremic syndrome.

Figure 6

Plasma exchange posttransplant. Time from most recent kidney transplant to requirement for plasma exchange. (a) Cumulative proportion of patients receiving plasma exchange. Data shown up to 5 years of follow-up; 2 events occurred in group 2a and 10 events in group 2b at more than 5 years posttransplant. (b) Time to plasma exchange for patients receiving plasma exchange in the first month following transplantation. aHUS, atypical hemolytic uremic syndrome.