Atypical hemolytic uremic syndrome (aHUS) is a life-threatening thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. Abnormalities involving complement regulatory proteins and complement components have been recognized in most cases.Cardiovascular involvement is described up to 43% (Neuhaus TJ et al. Arch Dis Child. 1997;76:518-521). Hemodialysis discontinuation is described to occur in 80% of cases after therapy with eculizumab (Legendre et al. NEJM) 2013; 368: 2169-81), but few data on long term discontinuation are available.
We describe a case of a 53 year old caucasian man with aHUS (end of march 2013), and oliguric renal failure who needed renal replacement therapy. Due to an unsuccessful plasma exchange cycle, 2 weeks later he started eculizumab. He had developed hypertension which was controlled with betablockers, diuretics, and calcium channel blockers. At admission the echocardiogram EC was normal with fractional ejection FE of 65%. The renal biopsy disclosed typical severe thrombotic microangiopathy.The activity of ADAMTS 13 was normal. Molecular analyses of genes of the complement cascade was carried out, identifying mutations in the CHF gene (N516K) and the MCP gene (c.286+2T>G) (Mario Negri Institute,Bergamo). The average serum creatinine in the interdialytic period was 7.0 mg/dl, with a daily urine output of approx. 500 ml. By mid May, he gradually developed cardiac failure up to class NYHA III. (EC showed significant dilation and dysfunction of the left ventricle with FE 25%). A cardiac CT showed no coronary stenosis with an Agatston calcium score of 15 unit.Treatment was eculizumab 900 mg every two weeks, dialysis three times per week. After two months, urine volumes gradually increased and on August, the frequency of HD was reduced to twice per week. He was still in NYHA III, with slight overhydration. The average serum creatinine was 3.9 mg/dl.On December, the average serum creatinine was 3.2 mg/dl, diuresis had recovered and HD was discontinued. NYHA class was II. Repeated ECs disclosed a gradual improvement of FE. On March 2014 the average serum creatinine was 2.7 mg/dl, and FE 45%. Actually NYHA class is I.
This case is unusual because of the severe heart failure the patient developed. Based on these results, we suggest that in our case, prolonged treatment with eculizumab allowed discontinuation of dialysis and improvement of heart failure.