Pathogenic Variants in Complement Genes and Risk of Atypical Hemolytic Uremic Syndrome Relapse after Eculizumab Discontinuation
Open Access
- 31 October 2016
- journal article
- Published by Wolters Kluwer Health in Clinical Journal of the American Society of Nephrology
- Vol. 12 (1), 50-59
- https://doi.org/10.2215/cjn.06440616
Abstract
Background and objectives The complement inhibitor eculizumab has dramatically improved the outcome of atypical hemolytic uremic syndrome. However, the optimal duration of eculizumab treatment in atypical hemolytic uremic syndrome remains debated. We report on the French atypical hemolytic uremic syndrome working group’s first 2-year experience with eculizumab discontinuation in patients with atypical hemolytic uremic syndrome. Design, setting, participants & measurements Using the French atypical hemolytic uremic syndrome registry database, we retrospectively identified all dialysis–free patients with atypical hemolytic uremic syndrome who discontinued eculizumab between 2010 and 2014 and reviewed their relevant clinical and biologic data. The decision to discontinue eculizumab was made by the clinician in charge of the patient. All patients were closely monitored by regular urine dipsticks and blood tests. Eculizumab was rapidly (24–48 hours) restarted in case of relapse. Results Among 108 patients treated with eculizumab, 38 patients (nine children and 29 adults) discontinued eculizumab (median treatment duration of 17.5 months). Twenty-one patients (55%) carried novel or rare complement genes variants. Renal recovery under eculizumab was equally good in patients with and those without complement gene variants detected. After a median follow-up of 22 months, 12 patients (31%) experienced atypical hemolytic uremic syndrome relapse. Eight of 11 patients (72%) with complement factor H variants, four of eight patients (50%) with membrane cofactor protein variants, and zero of 16 patients with no rare variant detected relapsed. In relapsing patients, early reintroduction (≤48 hours) of eculizumab led to rapid (Conclusions Pathogenic variants in complement genes were associated with higher risk of atypical hemolytic uremic syndrome relapse after eculizumab discontinuation. Prospective studies are needed to identify biomarkers predictive of relapse and determine the best strategy of retreatment in relapsing patients.Keywords
This publication has 24 references indexed in Scilit:
- Discontinuation of Eculizumab Maintenance Treatment for Atypical Hemolytic Uremic Syndrome: A Report of 10 CasesAmerican Journal of Kidney Diseases, 2014
- Dynamics of complement activation in aHUS and how to monitor eculizumab therapyBlood, 2014
- Insights From the Use in Clinical Practice of Eculizumab in Adult Patients With Atypical Hemolytic Uremic Syndrome Affecting the Native Kidneys: An Analysis of 19 CasesAmerican Journal of Kidney Diseases, 2014
- Genetics and Outcome of Atypical Hemolytic Uremic SyndromeClinical Journal of the American Society of Nephrology, 2013
- Use of eculizumab for atypical haemolytic uraemic syndrome and C3 glomerulopathiesNature Reviews Nephrology, 2012
- Relative Role of Genetic Complement Abnormalities in Sporadic and Familial aHUS and Their Impact on Clinical PhenotypeClinical Journal of the American Society of Nephrology, 2010
- Mutations in components of complement influence the outcome of Factor I-associated atypical hemolytic uremic syndromeKidney International, 2010
- New Equations to Estimate GFR in Children with CKDJournal of the American Society of Nephrology, 2009
- Atypical Haemolytic Uraemic Syndrome Associated with a Hybrid Complement GenePLoS Medicine, 2006
- A More Accurate Method To Estimate Glomerular Filtration Rate from Serum Creatinine: A New Prediction EquationAnnals of Internal Medicine, 1999