Hematological and renal responses to eculizumab. (A) Renal function 6 months after eculizumab commenced in the treated CaHUS cohort compared with that at presentation. Not available for 6 individuals; 4 individuals died. (B) Hematological response to eculizumab, defined by the number of days from the first dose of eculizumab to platelet normalization (>150 × 109/L). Median, interquartile range, 1.5× interquartile range, and outliers are shown. There were no statistically significant differences between the mutation types. Three extreme outliers are not shown in the chart: 70 and 90 days (CFH) and 96 days (CD46). Twenty-nine percent already had normal platelets at the time of the first eculizumab dose. In 11 individuals, the platelet count did not normalize; 8 out of 11 had no mutation detected, 2 had VUS (1 had hypersplenism), and 1 had FHAA (and von Willebrand Disease). Of the 17 individuals with a response time of >2 weeks (range, 15-96 days), 3 had a CFH mutation, 1 had a CFI mutation, 2 had a CD46 mutation, 3 had a C3 mutation, 1 had FHAA, 4 had a VUS, and 3 had no mutation detected; 4 out of 17 developed ESKD, 2 of whom died. Fifty-eight percent received plasma exchange before the first dose of eculizumab (supplemental Figure 8B). The subgroup analysis of hematological response in those who received eculizumab but not plasma exchange is shown in supplemental Figure 8C, the median time to platelet normalization in individuals with CaHUS was 5 days. (C) Renal response to eculizumab in the treated CaHUS cohort. Changes in creatinine as a percentage of creatinine in patients with CaHUS (this includes only those who recovered renal function and not those who remained dialysis-dependent) at 1 week, 2 weeks, 1 month, 3 months, 6 months, and 12 months after commencing eculizumab treatment. The complete data set is available for n = 101. Solid circles with a connecting line, mean; bars, 95% CI; x, median. A Wilcoxon Signed Ranks Test demonstrated that there was a statistically significant difference in the mean change in creatinine between all the time points recorded (P value shown). (D) Renal response to eculizumab in the CaHUS cohort. The mean change in creatinine as a percentage of creatinine in patients with CaHUS by mutation type (this includes only those who recovered renal function, not those who remained dialysis-dependent) at 1 week, 2 weeks, 1 month, 3 months, 6 months, and 12 months after commencing eculizumab treatment. (E) Recovery from dialysis dependency in the CaHUS cohort. The proportion of patients with CaHUS on dialysis in the first year after commencing eculizumab. At presentation, 66.7% received dialysis, and at 6 months, 65.7% became dialysis-independent, with 22.9% remaining on dialysis. (F) Recovery from dialysis dependency in the CaHUS cohort. The proportion of patients with CaHUS on dialysis for the first year after commencing eculizumab according to mutation type.
