Eculizumab Modifies Outcomes in Adults with Atypical Hemolytic Uremic Syndrome with Acute Kidney Injury

Abstract

Background: Atypical hemolytic uremic syndrome (aHUS) is a rare disease associated with congenital or acquired genetic abnormalities that result in uncontrolled complement activation, leading to thrombotic microangiopathy and kidney failure. Until recently, the only treatment was plasma exchange or plasma infusion (PE/PI), but 60% of patients died or had permanent kidney damage despite treatment. Eculizumab, a complement inhibitor, has shown promising results in aHUS. However, data are mainly extracted from case reports or studies of heterogeneous cohorts, and no direct comparison with PE/PI is available. Methods: An observational retrospective study of adult, dialysis-dependent aHUS patients with acute kidney injury (AKI) who were treated with either PE/PI alone or with second-line eculizumab in our center. We compared the effect of PE/PI and eculizumab on kidney function, hypertension, proteinuria, hematologic values, relapse, and death. Results: Thirty-one patients were included (females, 18; sporadic aHUS, 29; mean age, 46 ± 20 years). Twenty-six patients were treated with PE/PI alone, and 5 were deemed to be plasma-resistant and received eculizumab after stopping PE/PI. Among patients receiving eculizumab, 80% attained complete recovery of kidney function, 100% stopped dialysis, 20% had decreased proteinuria, and no patient relapsed (vs. 38.5, 50, 15.4, and 11.5%, respectively, of patients receiving only PE/PI). At 1-year of follow-up, no deaths had occurred in either group. Conclusion: Eculizumab shows greater efficacy than PE/PI alone for the treatment of adult aHUS patients with AKI. Prospective studies and meta-analyses are warranted to confirm our findings and set guidelines for treatment, monitoring, and maintenance.

Atypical Hemolytic Uremic Syndrome: New Challenges in the Complement Blockage Era

“…Quality of life improved in more than 70% of patients in both trials. Those results were confirmed in some studies performed in children and in adults [19, 64, 65], making nowadays eculizumab the first-line therapy in children with aHUS [24] and in adults after exclusion of other causes of TMA [6]. Eculizumab is more effective the earlier the onset of treatment after diagnosis [66].…”

Rapid Resolution of Atypical Hemolytic Uremic Syndrome by Eculizumab Treatment

“…But plasma therapy was not effective; historically, aHUS had a poor prognosis with significant morbidity and mortality, with up to 50% of pa www.chikd.org tients progressing to endstage renal disease (ESRD), and 10 to 15% mortality rate during the acute phase. Treatment with eculizumab was proven to be effective in aHUS, sub stantially improving patient survival and preventing prog ression to ESRD and disease recurrence 6,9,10) . Eculizumab in aHUS led to hematological normalization and reduced renal injury with significantly improved kidney function.…”

Familial Atypical Hemolytic Uremic Syndrome with Positive pS1191L (c.3572C> T) Mutation in CFH A Single-Center Experience

“…Eculizumab has been reported to be a fast, effective, and life-saving option in the treatment of aHUS [15,16,17,18]. Accordingly, we administered Eculizumab therapy to our index patient following plasmapheresis after the first admission.…”