Clinical evidence and outcomes of atypical hemolytic uremic syndrome in terms of genetic complement abnormalities

The aim of this retrospective study was to comparatively analyze the clinical course and outcomes of aHUS with genetic complement abnormalities using both our own data and published literature.

Materials and methods. This retrospective study included 55 patients with aHUS (mean age 36.4±8.9 years, 56% male, 44% female) treated between January 2014 and August 2024 at the Moscow Scientific and Practical Center of Nephrology and Pathology of Transplanted Kidney of Moscow City Hospital No 52.

Results. Genetic abnormalities were identified in 61% of patients with aHUS. The most frequently detected variants were CFHR3/CFHR1 (29%), C3 (20%) and CFH (15%). Patients with and without genetic mutations did not differ significantly in sex, age, presence of the full TMA triad, malignant arterial hypertension (MAH), or extrarenal manifestations (р>0.05). Cardiac involvement was more common in patients with CFH variants (24%), and intestinal involvement was more frequent in patients with CFHR3/CFHR1 (56%); however these differences did not reach statistical significance (р>0.05). Five-year renal survival did not differ significantly between patients with or without genetic mutations (50% vs. 65%, respectively, р=0.413), or depending on the presence of MAH (38% vs. 64%, р=0.08) or extrarenal manifestations (43% vs. 64%, р=0.17). All patients with CFH mutation experienced loss of renal function within 5 years despite treatment with eculizumab. A significant improvement in renal survival was observed only in patients who initiated eculizumab therapy within first month of disease onset, compared with those who started treatment after a month or later (89% vs. 11%, respectively, р=0.0001). The five-year mortality rate among patients with aHUS was 7%. Mortality did not differ significantly based on the presence of genetic abnormalities (0% vs. 16%, р=0.295), MAH (33% and 6%, р>0.5) or extrarenal manifestations (14% vs. 0%, р=0.451).

Conclusions. Demographic and clinical characteristics did not differ significantly between patients with or without complement-related genetic abnormalities. A pronounced decrease in renal survival was observed found in patients with CFH mutations compared with whose carrying CFHR1/CFHR3 or without genetic mutations. Five-year renal survival and mortality rate were not significantly associated with other genetic variants, MAH, or extrarenal involvement. Early initiation of eculizumab therapy – within the first month after disease onset – markedly improved renal outcomes and reduces mortality.

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