立枩 良崇

Atypical hemolytic uremic syndrome (aHUS) is a rare and life-threatening disease often complicated by end-stage renal disease. Anti-C5 antibody agents have been developed for the treatment of aHUS: these are highly effective but limited in use owing to the difficulty of diagnosing aHUS in the acute clinical phase. The pathophysiology of aHUS is a thrombotic microangiopathy (TMA) caused by complement dysregulation triggered by environmental factors in susceptible individuals with genetic factors. Although several germline variants associated with aHUS have been identified, approximately half of patients with aHUS lack known pathogenic variants. It is essential to recognize the characteristic clinical features of aHUS. These include the triad of hemolytic anemia, thrombocytopenia, and renal impairment, without the presence of Shiga toxin-producing Escherichia coli infection, thrombotic thrombocytopenic purpura associated with ADAMTS13 deficiency, or TMA from secondary cause. In this case, plasma exchange could not be continued owing to allergy. Early diagnosis allowed for prompt administration of eculizumab at the time of relapse, with favorable outcomes. Based on the finding of no genetic abnormalities, eculizumab was discontinued after 12 months, with no recurrence for 3 years. On day 27 of hospitalization, renal biopsy revealed endothelial damage. Since a definitive diagnosis cannot be made with genetic testing in the acute stage and approximately half of patients have no genetic abnormalities, it is suggested to diagnose the condition as per the clinical definition and commence treatment with plasma exchange. If thrombotic thrombocytopenic purpura is excluded, switching to eculizumab is another treatment option according to clinical conditions.

Introduction Coronary artery and heart valve calcification is a risk factor for cardiovascular death in haemodialysis patients, so calcification prevention should be started as early as possible. Treatment with concomitant calcimimetics and low-dose vitamin D receptor activators (VDRAs) is available, but not enough evidence has been obtained on the efficacy of this regimen, particularly in patients with short dialysis duration. Therefore, this study will evaluate the efficacy and safety of early intervention with upacicalcet, a calcimimetic used to prevent coronary artery calcification in this patient population. Methods and analysis This multicentre, open-label, randomised, parallel-group controlled study will compare an early intervention group, which received upacicalcet and a low-dose VDRA, with a conventional therapy group, which received a VDRA. The primary endpoint is a change in log coronary artery calcium volume score from baseline to 52 weeks. The main inclusion criteria are as follows: (1) age 18 years or older; (2) dialysis is planned or dialysis duration is less than 60 months; (3) intact parathyroid hormone (PTH) >240 pg/mL or whole PTH level>140 pg/mL; (4) serum-corrected calcium≥8.4 mg/dL and (5) Agatston score >30. The main exclusion criteria are as follows: (1) history of parathyroid intervention or fracture in the past 12 weeks; (2) history of myocardial infarction, stroke or leg amputation in the past 12 weeks; (3) history of coronary angioplasty and (4) heart failure of New York Heart Association class III or worse. Ethics and dissemination The study will comply with the Declaration of Helsinki and the Japanese Clinical Trials Act. The study protocol has been approved by the Fujita Health University Certified Review Board (file no. CR22-052). Written informed consent will be obtained from all participants. Study results will be presented in academic meetings and peer-reviewed academic journals. Trial registration number jRCTs041220126.