TY - JOUR
T1 - Eculizumab Use for Kidney Transplantation in Patients With a Diagnosis of Atypical Hemolytic Uremic Syndrome
AU - Global aHUS Registry
AU - Siedlecki, Andrew M.
AU - Isbel, Nicole
AU - Vande Walle, Johan
AU - James Eggleston, Jennifer
AU - Cohen, David J.
AU - Licht, Christoph
AU - Frémeaux-Bacchi, Véronique
AU - Ariceta, Gema
AU - Ardissino, Gianluigi
AU - Fakhouri, Fadi
AU - Greenbaum, Larry
AU - Johnson, Sally
AU - Schaefer, Franz
AU - Scully, Marie Ann
AU - Woodward, Leonard
AU - Ogawa, Masayo
AU - Gasteyger, Christoph
AU - Blasco, Miquel
AU - Cresseri, Donata
AU - Generolova, Galina
AU - Webb, Nicholas
AU - Hirt-Minkowski, Patricia
AU - Kozlovskaya, Natalya Lvovna
AU - Landau, Danny
AU - Lapeyraque, Anne Laure
AU - Loirat, Chantal
AU - Mache, Christoph
AU - Malina, Michal
AU - Martola, Leena
AU - Massart, Annick
AU - Rondeau, Eric
AU - Sartz, Lisa
N1 - Publisher Copyright:
© 2018 International Society of Nephrology
PY - 2019/3
Y1 - 2019/3
N2 - 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.
AB - 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.
KW - atypical hemolytic uremic syndrome
KW - dialysis
KW - eculizumab
KW - kidney observational study
KW - transplantation
UR - http://www.scopus.com/inward/record.url?scp=85061946530&partnerID=8YFLogxK
U2 - 10.1016/j.ekir.2018.11.010
DO - 10.1016/j.ekir.2018.11.010
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AN - SCOPUS:85061946530
SN - 2468-0249
VL - 4
SP - 434
EP - 446
JO - Kidney International Reports
JF - Kidney International Reports
IS - 3
ER -