MP175ATYPICAL HEMOLYTIC UREMIC SYNDROME - VERY EARLY TREATMENT IS A WAY TO SUCCESS?

Abstract

INTRODUCTION AND AIMS: Atypical hemolytic uremic syndrome (aHUS) is a life-threatening thrombotic microangiopathy (TMA) with predominant kidney involvement. It is caused by complement dysregulation. Specific treatment with eculizumab is currently available and it should be initiated as soon as possible. We describe a case of 21-year-old woman treated early with excellent outcomes. METHODS: RESULTS: 21-year-old woman was admitted to intensive care unit with signs of acute kidney injury with oligoanuria, moderate thrombocytopenia and microangiopathic hemolytic anemia. Slight diarrhea with subfebrility lasting previous 3 days were noted in her medical history, and further, start of oral contraception a month ago, too. Initial immunology tests were unremarkable, anti-FH and anti-C1q autoantibodies were negative, apart from slightly decreased C3. Serum creatinine was 1040μmol/l, proteinuria 5,72g/l, hemoglobin 67g/l, schistocytes were present and haptoglobin was immeasurably low, platelets (PLT) 107 000/ml, normal were fibrinogen, dimer D, antithrombin, and coagulation times. Thus renal biopsy was performed showing severe TMA. Normal activity of ADAMTS13, negative STEC O157:H7, were found. These findings together lead to diagnosis of aHUS. Initially, pulses of corticosteroids (3x500mg iv) and plasmapheresis commenced, without any appreciable effect. Hemodialysis was necessary for first 7 days. Fourth day after admission eculizumab was administered (900mg iv weekly). Then, during 2 weeks, diuresis was restored fully, proteinuria decreased to mild range, creatinine started to fall reaching 130 μmol/l in four weeks time , at that time PLT were 206 000/ml and hemoglobin 95g/l. Of note, hematologic parameters started to normalize only after second dose of eculizumab, which is quite untypical. Patient was discharged after 3 weeks and now is treated as an outpatient, with nearly normal GFR (1,23 ml/s), residual proteinuria (0,7g/24hrs) and otherwise normal hematological and biochemical lab findings. Later-on, genetic analysis confirmed patient to be: (1) heterozygous for the mutation in C3 protein (p.L189F), not yet reported, with not known pathogenicity but probably risky (categorized as “M3”) for developing aHUS; (2) heterozygous for CFH c.-331C>T polymorphism, and (3) homozygous for the MCPggaac haplotype of CD46 gene, both reported as a risk factor of developing aHUS. CONCLUSIONS: Despite excellent clinical-laboratory outcome after 5 months of disease onset, several questions remain unanswered: (1) Why was this strong genetic background silent for 21 years? Was the onset of contraception the disease trigger? (2) For how long will be eculizumab treatment necessary? Is there a room for dose lowering? How should be accuracy of dosing assessed.?