Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Apr 1;107(4):994-1003.
doi: 10.1097/TP.0000000000004355. Epub 2023 Mar 31.

Assessing the Impact of Prophylactic Eculizumab on Renal Graft Survival in Atypical Hemolytic Uremic Syndrome

Emily K Glover  1   2 , Kate Smith-Jackson  1   2   3 , Vicky Brocklebank  1   2   3 , Valerie Wilson  1 , Patrick R Walsh  1   2 , Emma K Montgomery  1 , Edwin K S Wong  1   2 , Sally Johnson  1   2   3   4 , Michal Malina  1   2   4 , David Kavanagh  1   2   3 , Neil S Sheerin  1   2   3 ; UK aHUS Transplant Consortium
Collaborators, Affiliations

Assessing the Impact of Prophylactic Eculizumab on Renal Graft Survival in Atypical Hemolytic Uremic Syndrome

Emily K Glover et al. Transplantation. .

Abstract

Background: Atypical hemolytic uremic syndrome (aHUS) is a rare cause of end-stage kidney disease and associated with poor outcomes after kidney transplantation from early disease recurrence. Prophylactic eculizumab treatment at the time of transplantation is used in selected patients with aHUS. We report a retrospective case note review describing transplant outcomes in patients with aHUS transplanted between 1978 and 2017, including those patients treated with eculizumab.

Methods: The National Renal Complement Therapeutics Centre database identified 118 kidney transplants in 86 recipients who had a confirmed diagnosis of aHUS. Thirty-eight kidney transplants were performed in 38 recipients who received prophylactic eculizumab. The cohort not treated with eculizumab comprised 80 transplants in 60 recipients and was refined to produce a comparable cohort of 33 transplants in 32 medium and high-risk recipients implanted since 2002. Complement pathway genetic screening was performed. Graft survival was censored for graft function at last follow-up or patient death. Graft survival without eculizumab treatment is described by complement defect status and by Kidney Disease: Improving Global Outcomes risk stratification.

Results: Prophylactic eculizumab treatment improved renal allograft survival ( P = 0.006) in medium and high-risk recipients with 1-y survival of 97% versus 64% in untreated patients. Our data supports the risk stratification advised by Kidney Disease: Improving Global Outcomes.

Conclusions: Prophylactic eculizumab treatment dramatically improves graft survival making transplantation a viable therapeutic option in aHUS.

PubMed Disclaimer

Figures

None
Graphical abstract
FIGURE 1.
FIGURE 1.
Consort diagram. Identification of control and prophylactic treatment cohorts and historic cohort not treated with eculizumab, from the National Renal Complement Therapeutics Centre database.
FIGURE 2.
FIGURE 2.
Death-censored renal graft survival with and without prophylactic eculizumab treatment. Kaplan-Meier analysis of renal graft survival for grafts received after 2002 in recipients at medium or high risk of recurrence of atypical hemolytic uremic syndrome. Those who received prophylactic eculizumab treatment from the time of transplantation compared with those who did not receive eculizumab treatment for the duration of the transplant (control). Numbers at risk in each group at 6 monthly time points are detailed below the graph. Log-rank P = 0.006.
FIGURE 3.
FIGURE 3.
Death-censored renal graft survival without eculizumab treatment. Kaplan-Meier analysis of overall renal graft survival in recipients transplanted between 1978 and 2016 for atypical hemolytic uremic syndrome who did not receive eculizumab treatment with the transplant. Survival is censored for patient death with a functioning graft and for functioning graft at last follow-up. Numbers at risk in each group at 12 monthly time points are detailed below the graph. A. Graft survival by complement defect. Grafts grouped by presence of autoantibodies against Factor H (anti-FH), variant of uncertain significance (VUS) or pathogenic variant in complement factor I (CFI), complement factor H (CFH), membrane cofactor protein (CD46), or C3 in recipient. B. Graft survival by risk of relapse. Grafts grouped by low, medium, or high risk of atypical hemolytic syndrome recurrence (as stratified by KDIGO) in the recipient.
See this image and copyright information in PMC

References

    1. Kavanagh D, Goodship TH, Richards A. Atypical hemolytic uremic syndrome. Semin Nephrol. 2013;33:508–530. - PMC - PubMed
    1. Brocklebank V, Wood KM, Kavanagh D. Thrombotic microangiopathy and the kidney. Clin J Am Soc Nephrol. 2018;13:300–317. - PMC - PubMed
    1. Goodship TH, Cook HT, Fakhouri F, et al. ; Conference Participants. Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a “Kidney Disease: Improving Global Outcomes” (KDIGO) Controversies Conference. Kidney Int. 2017;91:539–551. - PubMed
    1. Warwicker P, Goodship TH, Donne RL, et al. . Genetic studies into inherited and sporadic hemolytic uremic syndrome. Kidney Int. 1998;53:836–844. - PubMed
    1. Legendre CM, Licht C, Muus P, et al. . Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med. 2013;368:2169–2181. - PubMed

Publication types