Thrombotic microangiopathy after kidney transplantation: Analysis of the Brazilian Atypical Hemolytic Uremic Syndrome cohort.

Silvana Maria Carvalho Miranda,Valter Duro Garcia,Gerson Marques Pereira,Lilian Monteiro Pereira Palma,Roger Kist,Luis Gustavo Modelli de Andrade,Ida Maria Maximina Fernandes-Charpiot,Pedro Augusto Macedo de Souza,Hong Si Nga,Miguel Ernandes Neto

doi:10.1371/journal.pone.0258319

Abstract

Atypical Hemolytic Uremic Syndrome (aHUS) is an ultra-rare disease that potentially leads to kidney graft failure due to ongoing Thrombotic Microangiopathy (TMA). The aim was evaluating the frequency of TMA after kidney transplantation in patients with aHUS in a Brazilian cohort stratified by the use of the specific complement-inhibitor eculizumab. This was a multicenter retrospective cohort study including kidney transplant patients diagnosed with aHUS. We collected data from 118 transplant centers in Brazil concerning aHUS transplanted patients between 01/01/2007 and 12/31/2019. Patients were stratified into three groups: no use of eculizumab (No Eculizumab Group), use of eculizumab for treatment of after transplantation TMA (Therapeutic Group), and use of eculizumab for prophylaxis of aHUS recurrence (Prophylactic Group). Thirty-eight patients with aHUS who received kidney transplantation were enrolled in the study. Patients' mean age was 30 years (24-40), and the majority of participants was women (63% of cases). In the No Eculizumab Group (n = 11), there was a 91% graft loss due to the TMA. The hazard ratio of TMA graft loss was 0.07 [0.01-0.55], p = 0.012 in the eculizumab Prophylactic Group and 0.04 [0.00-0.28], p = 0.002 in the eculizumab Therapeutic Group. The TMA graft loss in the absence of a specific complement-inhibitor was higher among the Brazilian cohort of kidney transplant patients. This finding reinforces the need of eculizumab use for treatment of aHUS kidney transplant patients. Cost optimization analysis and the early access to C5 inhibitors are suggested, especially in low-medium income countries.

Highlights

Thirty-eight patients with Atypical Hemolytic Uremic Syndrome (aHUS) who received kidney transplantation were enrolled in the study
The Thrombotic Microangiopathy (TMA) graft loss in the absence of a specific complement-inhibitor was higher among the Brazilian cohort of kidney transplant patients
This finding reinforces the need of eculizumab use for treatment of aHUS kidney transplant patients

Summary

Introduction

The atypical Hemolytic Uremic Syndrome (aHUS) is an ultra-rare disease with an incidence of approximately 0.5 cases per million inhabitants per year, and more than half of patients affected by this disease have an intrinsic or acquired abnormality related to the complement system [1]. The use of plasmapheresis is the primary supportive treatment in suspected aHUS, almost 70% of cases progress to renal replacement therapy and death within 3 years after diagnosis [3]. Atypical Hemolytic Uremic Syndrome (aHUS) is an ultra-rare disease that potentially leads to kidney graft failure due to ongoing Thrombotic Microangiopathy (TMA). The aim was evaluating the frequency of TMA after kidney transplantation in patients with aHUS in a Brazilian cohort stratified by the use of the specific complement-inhibitor eculizumab

Objectives

Results

Conclusion