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Progression to end-stage renal disease is reduced with eculizumab in patients with atypical haemolytic uraemic syndrome

Introduction

Atypical haemolytic uraemic syndrome (aHUS) is associated with severe kidney damage; almost one-half of adults with aHUS progress to end-stage renal disease (ESRD) after the first episode [1]. Two prospective clinical trials have assessed the efficacy of eculizumab (Ecu) in patients with aHUS [2]. We now evaluate data on progression to ESRD before and during Ecu treatment.

Methods

Patients with chronic kidney disease (CKD) stage 1 to 4 were analysed for progression to an ESRD event (two consecutive glomerular filtration rate measurements <15 ml/minute/1.73m2 (CKD stage 5)). ESRD incidence rate ratios during supportive care (SC) and Ecu treatment phases were calculated using a negative binomial regression analysis. Kaplan-Meier analyses were calculated for all patients and stratified by CKD stages 2 to 4 at baseline. Hazard ratios (HR) were calculated from Cox proportional hazard models.

Results

The SC and Ecu treatment phases included 32 and 33 patients, respectively. With SC, during a median (range) of 211 (7 to 745) days, 13 (41%) patients had a total of 16 ESRD events. On Ecu treatment, during a median (range) of 924 (73 to 1,254) days, three (9%) patients had a total of five ESRD events. The ESRD event rate was 92% lower during Ecu treatment versus the SC phase (0.36 vs. 0.07; P = 0.001); the incidence rate ratio was 0.08 (95% CI = 0.02 to 0.37; P = 0.001). HR for progression to ESRD for patients on Ecu versus SC was 0.03 (95% CI <0.01 to 0.34), a 97% reduction (Figure 1). Stratification by baseline CKD stage showed no patients with CKD stage 2 or 3 at baseline progressed to ESRD over 3 years of Ecu treatment.

Figure 1
figure1

Kaplan-Meier analysis of ESRD progression for SC and Ecu treatment for all patients.

Conclusion

Ecu treatment reduces the number of ESRD events and the rate of progression to ESRD; thus initiation of Ecu early after aHUS diagnosis may prevent cumulative kidney damage and progression to ESRD.

References

  1. 1.

    Fremeaux-Bacchi V, et al: CJASN. 2013, 8: 554-62.

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  2. 2.

    Legendre C, et al: N Engl J Med. 2013, 368: 2169-81. 10.1056/NEJMoa1208981.

    CAS  Article  PubMed  Google Scholar 

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Walle, J.V., Johnson, S., Harvey, E. et al. Progression to end-stage renal disease is reduced with eculizumab in patients with atypical haemolytic uraemic syndrome. Crit Care 19, P329 (2015). https://doi.org/10.1186/cc14409

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Keywords

  • Chronic Kidney Disease
  • Supportive Care
  • Chronic Kidney Disease Stage
  • Prospective Clinical Trial
  • Kidney Damage
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