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K. El Karoui et al.
eculizumab had a major beneficial effect in noHE-aHUS patients, since their 5-year renal survival was 100% vs. 40% in those treated or not with eculizumab, respective- ly (P<0.001) (Figure 4B). Conversely, in HE-aHUS patients, we did not observe a significant improvement in prognosis with eculizumab (5-year renal survival 46% vs. 23% in HE-aHUS patients treated or not with eculizum- ab, respectively; P=0.18) (Figure 4C, Online Supplementary Table S6). The presence of rare complement variants was associated with a trend to improved prognosis after eculizumab treatment, since the 1-year renal survival was 85% vs. 50% in HE-aHUS patients with or without rare complement variants, respectively (P=0.06) (Online Supplementary Figure S4).
Multivariate analysis demonstrated that eculizumab treatment and dialysis at onset were independently asso-
ciated with renal prognosis in the whole cohort, but not in HE-aHUS patients (Online Supplementary Tables S5 and S6).
Characteristics and outcome according to clinical factors and rare complement variants
The patients’ characteristics were studied according to the presence or absence of HE and rare complement vari- ants (Table 3A, B). Among HE-aHUS patients, only slight differences in age and platelet count were observed between patients with or without rare complement vari- ants. However, low C3 was significantly more frequent in cases with rare complement variants (11/41 vs. 1/35; P=0.004).
After exclusion of patients treated with eculizumab, a comparison of outcome according to the presence of HE
Figure 3. Distribution of rare complement variants observed in the whole cohort. Rare complement genetic variants found in patients with atypical hemolytic uremic syndrome are presented above and below the schematic gene representation for those with or without hypertensive emergency, respectively. The nucleotide and amino acid numbering refer to the translation start site (A in ATG is +1), as recommended by the Human Genome Variation Society. Bold characters indicate muta- tions identified in two or more unrelated patients, suggesting that they may represent mutational hot spots. CFH: complement factor H; MCP: membrane cofactor protein; CFI: complement factor I; CFB: complement factor B; C3: complement component 3: THBD: thrombomodulin.
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