Long-term outcomes of the Atypical Hemolytic Uremic Syndrome after kidney transplantation treated with eculizumab as first choice

Abstract

IntroductionThe treatment of choice for Atypical Hemolytic Uremic Syndrome (aHUS) is the monoclonal antibody eculizumab. The objective of this study was to assess the efficacy and safety of eculizumab in a cohort of kidney transplant patients suffering from aHUS.MethodsDescription of the prospective cohort of all the patients primarily treated with eculizumab after transplantation and divided into the therapeutic (onset of aHUS after transplantation) and prophylactic use (patients with previous diagnosis of aHUS undergoing kidney transplantation).ResultsSeven cases were outlined: five of therapeutic use and two, prophylactic. From the five cases of therapeutic use, there was improvement of the thrombotic microangiopathy in the 48 hours following the start of the drug and no patient experienced relapse during an average follow-up of 21 months in the continuous use of eculizumab (minimum of 6 and maximum of 42 months). One patient died at 6 months, due to Aspergillus infection. From the two cases of prophylactic use, one patient experienced relapsed thrombotic microangiopathy after 4 months and another patient remained asymptomatic after 16 months of follow-up, both on chronic treatment.DiscussionThe therapeutic use of eculizumab showed to be effective, with improvement of the microangiopathy parameters and persisting up to the end of the follow-up, without relapses. The additional risk of immunosuppression, leading to opportunistic infections, was well tolerated. The prophylactic use showed to be effective and safe; however, the doses and intervals should be individualized in order to avoid relapsed microangiopathy, especially in patients with factor H mutation.

Histopathological features of thrombotic microangiopathies in renal biopsies

“…Graft survival after de novo TMA was 43% in 4 years, significantly less than those who did not have TMA after kidney transplant (85.6%) (18). The early CNI withdrawal in de novo TMA patients probably decreased biopsies indications after kidney transplant in our hospital, which performs on average 120 kidney transplants a year (19).…”

The Inhibition of Complement System in Formal and Emerging Indications: Results from Parallel One-Stage Pairwise and Network Meta-Analyses of Clinical Trials and Real-Life Data Studies

“…Fifteen real-life NRSI including individuals with PNH ( n = 4189) and aHUS ( n = 1090) were assessed mathematically into pairwise level. As observed in Figure 4 , a protective effect from eculizumab was evident in hemolysis in PNH [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ], TMA in aHUS [ 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 ], and AKI in aHUS [ 53 , 54 , 55 , 56 , 57 , 58 , …”

“…Furthermore, clinical trials and real-life NRSI did not assess adult and pediatric populations separately [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , ...…”

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

“…An additional three articles were excluded because they were case reports or single cases treated with eculizumab [8,38,39]. Ultimately 18 studies (13 cohort studies and five case series) [5,9,15,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54] consisting of 380 patients with a history of aHUS who received eculizumab for prevention and treatment of post-transplant recurrent aHUS were included into the final analysis. The literature review and selection process are shown in Figure 1.…”