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

Abstract

Background 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. Methods 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). Results 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. Conclusion 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.

New findings in preventing recurrence and improving renal function in AHUS patients after renal transplantation treated with eculizumab: a systemic review and meta-analyses

“…However, some studies showed that early use of eculizumab did not help the kidneys of patients with AHUS [ 33 ], and their studies have certain limitations. When to discontinue the drug after use is also important in the eculizumab approach to evaluate AHUS recurrence [ 16 , 34 ]. Two studies mentioned that eculizumab was once recommended for lifelong treatment, but a prospective phase 4, multicenter, uncontrolled study provided evidence that once complete remission is achieved, most patients with AHUS are safe to discontinue eculizumab [ 17 ].…”

Complement‐driven hemolytic uremic syndrome

“…renal function improvement upon treatment critically depends on the time interval between aHUS onset and eculizumab start: the shorter, the better. 86,90 Similarly, the use of eculizumab in kidney transplant recipients with aHUS resulted in a highly significant decrease in TMArelated graft loss rates, as evidenced by nationwide studies carried out in Brazil, 91 France, 33 and USA. 92 As a striking consequence, the proportion of aHUS under chronic dialysis was halved over 5 years in France, following eculizumab approval.…”

Baseline characteristics and evolution of Brazilian patients with atypical hemolytic uremic syndrome: first report of the Brazilian aHUS Registry

“…aHUS is a rare genetic disease and the knowledge of its epidemiological data, natural history, genetic profile and pathophysiology have been increasing over recent years [ 5 ]. However, reports from low-middle income countries' populations of aHUS are restricted to a few cohort series [ 6–12 ]. The availability of data from these countries can broaden the spectrum of genotype according to the region.…”