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.
Subject(s)
Acute Kidney Injury/therapy , Antibodies, Monoclonal, Humanized/administration & dosage , Atypical Hemolytic Uremic Syndrome/complications , Complement Inactivating Agents/administration & dosage , Plasma Exchange , Acute Kidney Injury/etiology , Acute Kidney Injury/physiopathology , Adult , Aged , Atypical Hemolytic Uremic Syndrome/therapy , Female , Follow-Up Studies , Humans , Kidney/drug effects , Kidney/physiology , Male , Middle Aged , Renal Dialysis , Retrospective Studies , Secondary Prevention/methods , Treatment OutcomeABSTRACT
Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by hemolysis, thrombocytopenia, and renal failure. It is related to genetic mutations of the alternative complement pathway and is difficult to differentiate from other prothrombotic microangiopathies. Eosinophilic granulomatosis with polyangiitis (EGPA) (Churg-Strauss syndrome, CSS) is a systemic ANCA-associated vasculitis and a hypereosinophilic disorder where eosinophils seem to induce cell apoptosis and necrosis and therefore, vasculitis. Here, we report the case of two CSS patients with a genetic complement disorder consistent with aHUS diagnosis. Both patients showed histologic features that supported the diagnosis of CSS, and a genetic complement study confirmed the suspected aHUS diagnosis. In the case where eculizumab was administered, the global response was excellent. There is very limited understanding of the genetics and epidemiology of both, atypical HUS and EGPA, but considering our two patients we suggest that an etiopathogenic link exists among patients diagnosed with both entities.