Outcomes of Kidney Transplant Patients with Atypical Hemolytic Uremic Syndrome Treated with Eculizumab: A Systematic Review and Meta-Analysis

Maria L Gonzalez Suarez; Charat Thongprayoon; Michael A Mao; Napat Leeaphorn; Tarun Bathini; Wisit Cheungpasitporn

doi:10.3390/jcm8070919

Outcomes of Kidney Transplant Patients with Atypical Hemolytic Uremic Syndrome Treated with Eculizumab: A Systematic Review and Meta-Analysis

J Clin Med. 2019 Jun 27;8(7):919. doi: 10.3390/jcm8070919.

Authors

Maria L Gonzalez Suarez¹, Charat Thongprayoon², Michael A Mao³, Napat Leeaphorn⁴, Tarun Bathini⁵, Wisit Cheungpasitporn⁶

Affiliations

¹ Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, MS 39216, USA. malourdes.gonzalez@gmail.com.
² Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, USA.
³ Division of Nephrology and Hypertension, Mayo Clinic, Jacksonville, FL 32224, USA.
⁴ Department of Nephrology, Department of Medicine, Saint Luke's Health System, Kansas City, MO 64111, USA.
⁵ Department of Internal Medicine, University of Arizona, Tucson, AZ 85721, USA.
⁶ Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, MS 39216, USA.

Abstract

Background: Kidney transplantation in patients with atypical hemolytic uremic syndrome (aHUS) is frequently complicated by recurrence, resulting in thrombotic microangiopathy in the renal allograft and graft loss. We aimed to assess the use of eculizumab in the prevention and treatment of aHUS recurrence after kidney transplantation.

Methods: Databases (MEDLINE, EMBASE and Cochrane Database) were searched through February 2019. Studies that reported outcomes of adult kidney transplant recipients with aHUS treated with eculizumab were included. Estimated incidence rates from the individual studies were extracted and combined using random-effects, generic inverse variance method of DerSimonian and Laird. Protocol for this systematic review has been registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42018089438).

Results: Eighteen studies (13 cohort studies and five case series) consisting of 380 adult kidney transplant patients with aHUS who received eculizumab for prevention and treatment of post-transplant aHUS recurrence were included in the analysis. Among patients who received prophylactic eculizumab, the pooled estimated incidence rates of recurrent thrombotic microangiopathy (TMA) after transplantation and allograft loss due to TMA were 6.3% (95%CI: 2.8-13.4%, I² = 0%) and 5.5% (95%CI: 2.9-10.0%, I² = 0%), respectively. Among those who received eculizumab for treatment of post-transplant aHUS recurrence, the pooled estimated rates of allograft loss due to TMA was 22.5% (95%CI: 13.6-34.8%, I² = 6%). When the meta-analysis was restricted to only cohort studies with data on genetic mutations associated with aHUS, the pooled estimated incidence of allograft loss due to TMA was 22.6% (95%CI: 13.2-36.0%, I² = 10%). We found no significant publication bias assessed by the funnel plots and Egger's regression asymmetry test (p > 0.05 for all analyses).

Conclusions: This study summarizes the outcomes observed with use of eculizumab for prevention and treatment of aHUS recurrence in kidney transplantation. Our results suggest a possible role for anti-C5 antibody therapy in the prevention and management of recurrent aHUS.

Keywords: atypical hemolytic uremic syndrome; eculizumab; kidney transplantation; meta-analysis; renal transplantation.

Grants and funding

U54 GM115428/GM/NIGMS NIH HHS/United States