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Improved renal recovery in patients with atypical hemolytic uremic syndrome following rapid initiation of eculizumab treatment.

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Published:25th Mar 2020
Author: Walle JV, Delmas Y, Ardissino G, Wang J, Kincaid JF, Haller H.
Ref.:J Nephrol. 2016 Mar 19. [Epub ahead of print]
DOI:10.1007/s40620-016-0288-3

Background: Eculizumab is approved for atypical hemolytic uremic syndrome (aHUS). Guidelines discuss the importance of prompt treatment. We report a post hoc analysis investigating the effect of baseline factors, including patient characteristics and time from the latest aHUS manifestation to eculizumab initiation, on change from baseline in estimated glomerular filtration rate (eGFR) and other outcomes.

Methods: Data were pooled from four phase 2, open-label, single-arm, prospective clinical studies of eculizumab for patients with aHUS. Multivariate regressions identified predictors of eGFR change from baseline. The proportion of patients achieving sustained eGFR increase (defined: ≥15 ml/min/1.73 m2 for ≥28 days) and platelet count normalization were evaluated 1 year post-treatment. Baseline characteristics and eGFR outcomes were summarized by time to treatment from last aHUS manifestation [≤7 days (n = 21) versus >7 days (n = 76)].

Results: Baseline eGFR were similar between groups. Multivariate regression analysis demonstrated time from aHUS manifestation to eculizumab treatment, age, baseline lactate dehydrogenase (LDH) and baseline hemoglobin were independently predictive of eGFR change from baseline. Mean eGFR change from baseline at 1 year was significantly higher in patients treated in ≤7 days than >7 days (57 vs. 23 ml/min/1.73 m2, p = 0.0098). After 1 year, 17/21 and 36/76 patients in the ≤7 and >7 day groups, respectively, achieved a sustained increase in eGFR. Mean time to platelet count normalization was similar between groups.

Conclusions: Younger age, higher baseline LDH and lower baseline hemoglobin were associated with greater eGFR improvements. Early eculizumab initiation led to improved renal recovery, demonstrating the importance of rapid diagnosis and treatment of patients with aHUS.

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