Survival Rate for aHUS with Prompt Eculizumab Treatment
When atypical hemolytic uremic syndrome (aHUS) is diagnosed and treated promptly with eculizumab, the survival rate is excellent, with mortality being rare and 5-year kidney survival (freedom from end-stage kidney disease) reaching approximately 85.5%. 1
Mortality Outcomes
- Death is uncommon with prompt eculizumab treatment, as demonstrated in observational studies where no deaths occurred during follow-up periods in eculizumab-treated cohorts. 2
- The most critical survival concern is meningococcal infection, which occurs at a rate 550 times greater than the general population, making vaccination and antibiotic prophylaxis mandatory. 1
- Delays in initiating treatment are associated with increased morbidity and mortality, emphasizing the need for treatment within hours of diagnosis. 3
Kidney Survival and Function Recovery
The 5-year cumulative estimate of end-stage kidney disease (ESKD)-free survival improved dramatically from 39.5% in untreated historical controls to 85.5% in eculizumab-treated patients (hazard ratio 4.95; number needed to treat 2.17). 1
Recovery Rates by Treatment Timing
- Complete kidney function recovery occurs in approximately 80% of patients who receive eculizumab after plasma exchange failure, compared to only 38.5% with plasma exchange alone. 2
- At 3-month follow-up in eculizumab-treated patients: approximately 37% achieve normal kidney function, 42% have non-dialysis-dependent chronic kidney disease, and 21% remain dialysis-dependent. 4
- By final follow-up (4-22 months): approximately 47% achieve normal kidney function, 37% have non-dialysis-dependent chronic kidney disease, and only 16% remain dialysis-dependent. 4
Factors Predicting Better Outcomes
Shorter time between presentation and first eculizumab dose is the most critical modifiable factor for achieving estimated glomerular filtration rate >60 mL/min at 6 months. 1
Additional favorable prognostic factors include:
- Lower serum creatinine at presentation 1
- Lower platelet count at presentation 1
- Younger age at presentation 1
- Lower blood pressure at presentation 1
Hematologic Recovery
- Platelet count normalization occurs rapidly, with a median time of 6 days (range 2-42 days) after eculizumab initiation. 4
- Hemolysis resolves in 100% of patients receiving eculizumab. 2
- No relapses occur during maintenance therapy when complement activity is adequately suppressed. 5
Genotype-Specific Considerations
Treatment outcomes vary by underlying genetic mutation, with some biallelic pathogenic mutations in RNA-processing genes (such as EXOSC3) causing eculizumab-nonresponsive aHUS. 1
- Patients with pathogenic complement gene mutations have excellent responses when treated promptly. 1
- Recessive HSD11B2 mutations causing apparent mineralocorticoid excess may present with thrombotic microangiopathy and require alternative management. 1
Critical Treatment Caveats
Initiating treatment within 4-8 hours from diagnosis is essential, as delays are directly associated with increased morbidity and mortality. 3
Mandatory infection prevention measures include:
- Quadrivalent meningococcal conjugate vaccine (serogroups A, C, W, Y) 3, 6
- Meningococcal B vaccine 3, 6
- Long-term antimicrobial prophylaxis with penicillin (or macrolides for penicillin-allergic patients) for the duration of treatment 3, 6
Discontinuation of eculizumab carries significant risk, with relapse rates of approximately 1 per 9.5 person-years for patients with pathogenic mutations, though no individual who restarted eculizumab after relapse progressed to ESKD. 1