Continued Eculizumab Therapy for Persistent Atypical Hemolytic Uremic Syndrome

Abstract

Atypical hemolytic uremic syndrome (atypical HUS) is characterized by endothelial injury and microvascular thrombosis resulting in microangiopathic hemolytic anemia, thrombocytopenia, and ischemic injury to organs, especially the kidney. Activation of complements is involved in the pathogenesis of atypical HUS. Eculizumab, a neutralizing monoclonal antibody directed against complement C5, has shown salutary effects in patients with atypical HUS. In this report, we present a 23-year-old man with atypical HUSwho was treated with eculizumab. During the first four weeks of treatment, eculizumab failed to achieve a remission. Microangiopathic hemolytic anemia and thrombocytopenia persisted, while renal function deteriorated necessitating initiation of hemodialysis. Continuation of eculizumab therapy, however, led to marked improvement in hemolytic anemia, thrombocytopenia, and renal function. After 10 weeks of eculizumab therapy, hemodialysis was discontinued. At 5-month follow-up, serum creatinine was 1.1 mg/dL with continued eculizumab therapy every other week. In addition, platelet count was normal, while there was no evidence of hemolysis. We conclude that in patients with persistent atypical HUS continued treatment with eculizumab can be helpful in achieving remission.

The complement system and glomerular kidney diseases: Etiopathogenesis, diagnostics and treatment

“…aHuS is a disease with high morbidity and mortality rate, which usually occurs as the familial or sporadic atypical form. During the acute stage, the mortality rate is 25 %, while in 50% of the cases, the disease progresses to the end-stage (19,34). Genetic disorders associated with atypical hemolytic uremic syndrome (aHuS) are predisposing rather than directly causal (19).…”

“…Genetic disorders associated with atypical hemolytic uremic syndrome (aHuS) are predisposing rather than directly causal (19). Specific mutations have been found in 50% of patients with atypical hemolytic uremic syndrome (aHuS) (19,34). In over 60% of these patients, genetic studies have revealed the presence of mutations in genes encoding complement factors H, I, B (CFH, CFI, CFB) and the complement component C3 (19,34,35).…”

“…Specific mutations have been found in 50% of patients with atypical hemolytic uremic syndrome (aHuS) (19,34). In over 60% of these patients, genetic studies have revealed the presence of mutations in genes encoding complement factors H, I, B (CFH, CFI, CFB) and the complement component C3 (19,34,35). Genetic mutations for the complement factor H (CFH) are observed in 25-30% of patients, autoantibodies to the complement factor H are found in 6-10% of patients, while mutations in the gene for the complement factor I (CFI) are found in 5-10% of patients (19).…”

“…Genetic mutations for the complement factor H (CFH) are observed in 25-30% of patients, autoantibodies to the complement factor H are found in 6-10% of patients, while mutations in the gene for the complement factor I (CFI) are found in 5-10% of patients (19). Autoantibodies to complement regulatory proteins are also found (34).…”

“…Plasma infusion restores deficient proteins or improves impaired function of the existing ones, while plasmapheresis removes autoantibodies that inhibit complement regulatory proteins. However, long-term treatment with this form of therapy can be difficult, while in some patients there is no adequate therapeutic response to this treatment (34). Eculizumab has also been tested for treatment of patients with this disease (6,34).…”