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

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 pr...

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Autores principales: Siedlecki, Andrew M., Isbel, Nicole, Vande Walle, Johan, James Eggleston, Jennifer, Cohen, David J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409407/
https://www.ncbi.nlm.nih.gov/pubmed/30899871
http://dx.doi.org/10.1016/j.ekir.2018.11.010
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author Siedlecki, Andrew M.
Isbel, Nicole
Vande Walle, Johan
James Eggleston, Jennifer
Cohen, David J.
author_facet Siedlecki, Andrew M.
Isbel, Nicole
Vande Walle, Johan
James Eggleston, Jennifer
Cohen, David J.
author_sort Siedlecki, Andrew M.
collection PubMed
description 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.
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spelling pubmed-64094072019-03-21 Eculizumab Use for Kidney Transplantation in Patients With a Diagnosis of Atypical Hemolytic Uremic Syndrome Siedlecki, Andrew M. Isbel, Nicole Vande Walle, Johan James Eggleston, Jennifer Cohen, David J. Kidney Int Rep Clinical Research 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. Elsevier 2018-12-03 /pmc/articles/PMC6409407/ /pubmed/30899871 http://dx.doi.org/10.1016/j.ekir.2018.11.010 Text en © 2018 International Society of Nephrology. Published by Elsevier Inc. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Clinical Research
Siedlecki, Andrew M.
Isbel, Nicole
Vande Walle, Johan
James Eggleston, Jennifer
Cohen, David J.
Eculizumab Use for Kidney Transplantation in Patients With a Diagnosis of Atypical Hemolytic Uremic Syndrome
title Eculizumab Use for Kidney Transplantation in Patients With a Diagnosis of Atypical Hemolytic Uremic Syndrome
title_full Eculizumab Use for Kidney Transplantation in Patients With a Diagnosis of Atypical Hemolytic Uremic Syndrome
title_fullStr Eculizumab Use for Kidney Transplantation in Patients With a Diagnosis of Atypical Hemolytic Uremic Syndrome
title_full_unstemmed Eculizumab Use for Kidney Transplantation in Patients With a Diagnosis of Atypical Hemolytic Uremic Syndrome
title_short Eculizumab Use for Kidney Transplantation in Patients With a Diagnosis of Atypical Hemolytic Uremic Syndrome
title_sort eculizumab use for kidney transplantation in patients with a diagnosis of atypical hemolytic uremic syndrome
topic Clinical Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409407/
https://www.ncbi.nlm.nih.gov/pubmed/30899871
http://dx.doi.org/10.1016/j.ekir.2018.11.010
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