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Eculizumab use for kidney transplantation in patients with a diagnosis of atypical hemolytic uremic syndrome

(2019) KIDNEY INTERNATIONAL REPORTS. 4(3). p.434-446
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IWT SBO 130033: SAFE-PEDRUG: Integrating multidisciplinary translational bottom-up approaches towards a new paradigm for paedriatic investigations: the next step in ethical paediatric drug research
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.
Keywords
HUS, atypical hemolytic uremic syndrome, dialysis, eculizumab, kidney observational study, transplantation, COMPLEMENT INHIBITOR ECULIZUMAB, EFFICACY, OUTCOMES, SAFETY, AHUS, RECURRENCE, RECIPIENTS, GENES

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MLA
Siedlecki, Andrew M et al. “Eculizumab Use for Kidney Transplantation in Patients with a Diagnosis of Atypical Hemolytic Uremic Syndrome.” KIDNEY INTERNATIONAL REPORTS 4.3 (2019): 434–446. Print.
APA
Siedlecki, A. M., Isbel, N., Vande Walle, J., Eggleston, J. J., Cohen, D. J., Licht, C., Frémeaux-Bacchi, V., et al. (2019). Eculizumab use for kidney transplantation in patients with a diagnosis of atypical hemolytic uremic syndrome. KIDNEY INTERNATIONAL REPORTS, 4(3), 434–446.
Chicago author-date
Siedlecki, Andrew M, Nicole Isbel, Johan Vande Walle, Jennifer James Eggleston, David J Cohen, Christoph Licht, Véronique Frémeaux-Bacchi, et al. 2019. “Eculizumab Use for Kidney Transplantation in Patients with a Diagnosis of Atypical Hemolytic Uremic Syndrome.” Kidney International Reports 4 (3): 434–446.
Chicago author-date (all authors)
Siedlecki, Andrew M, Nicole Isbel, Johan Vande Walle, Jennifer James Eggleston, David J Cohen, Christoph Licht, Véronique Frémeaux-Bacchi, Gema Ariceta, Gianluigi Ardissino, Fadi Fakhouri, Larry Greenbaum, Sally Johnson, Franz Schaefer, Marie Ann Scully, Leonard Woodward, Masayo Ogawa, Christoph Gasteyger, Miquel Blasco, Donata Cresseri, Galina Generolova, Nicholas Webb, Patricia Hirt-Minkowski, Natalya Lvovna Kozlovskaya, Danny Landau, Anne-Laure Lapeyraque, Chantal Loirat, Christoph Mache, Michal Malina, Leena Martola, Annick Massart, Eric Rondeau, and Lisa Sartz. 2019. “Eculizumab Use for Kidney Transplantation in Patients with a Diagnosis of Atypical Hemolytic Uremic Syndrome.” Kidney International Reports 4 (3): 434–446.
Vancouver
1.
Siedlecki AM, Isbel N, Vande Walle J, Eggleston JJ, Cohen DJ, Licht C, et al. Eculizumab use for kidney transplantation in patients with a diagnosis of atypical hemolytic uremic syndrome. KIDNEY INTERNATIONAL REPORTS. 2019;4(3):434–46.
IEEE
[1]
A. M. Siedlecki et al., “Eculizumab use for kidney transplantation in patients with a diagnosis of atypical hemolytic uremic syndrome,” KIDNEY INTERNATIONAL REPORTS, vol. 4, no. 3, pp. 434–446, 2019.
@article{8605450,
  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.},
  author       = {Siedlecki, Andrew M and Isbel, Nicole and Vande Walle, Johan and Eggleston, Jennifer James and Cohen, David J and Licht, Christoph and Frémeaux-Bacchi, Véronique and Ariceta, Gema and Ardissino, Gianluigi and Fakhouri, Fadi and Greenbaum, Larry and Johnson, Sally and Schaefer, Franz and Scully, Marie Ann and Woodward, Leonard and Ogawa, Masayo and Gasteyger, Christoph and Blasco, Miquel and Cresseri, Donata and Generolova, Galina and Webb, Nicholas and Hirt-Minkowski, Patricia and Kozlovskaya, Natalya Lvovna and Landau, Danny and Lapeyraque, Anne-Laure and Loirat, Chantal and Mache, Christoph and Malina, Michal and Martola, Leena and Massart, Annick and Rondeau, Eric and Sartz, Lisa},
  issn         = {2468-0249},
  journal      = {KIDNEY INTERNATIONAL REPORTS},
  keywords     = {HUS,atypical hemolytic uremic syndrome,dialysis,eculizumab,kidney observational study,transplantation,COMPLEMENT INHIBITOR ECULIZUMAB,EFFICACY,OUTCOMES,SAFETY,AHUS,RECURRENCE,RECIPIENTS,GENES},
  language     = {eng},
  number       = {3},
  pages        = {434--446},
  title        = {Eculizumab use for kidney transplantation in patients with a diagnosis of atypical hemolytic uremic syndrome},
  url          = {http://dx.doi.org/10.1016/j.ekir.2018.11.010},
  volume       = {4},
  year         = {2019},
}

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