A 47-year-old Japanese man presented to the emergency department with dyspnea. He had a markedly elevated blood pressure (205/129 mmHg) and severe renal failure (serum creatinine (sCr): 11.6 mg/dL), and was referred to our department for further management. The patient had a history of hematuria and acute renal failure at 8 years of age, and was diagnosed with TMA of unknown origin. He recovered without specific treatment and his renal function had not been followed up. The patient started having annual medical check-ups several years ago, and hypertension (blood pressure of ~ 180/100 mmHg) and mild renal insufficiency (sCr 1.07 mg/dL 1 year before admission) were detected; however, he did not visit a doctor. The patient had a history of drinking 1,500 mL of beer and smoking 20 cigarettes per day for 27 years. There was a family history of atypical hemolytic uremic syndrome (aHUS) with a C3 gene mutation (p.I1157T) in his niece, who had several episodes of aHUS in her childhood. Although aHUS recurred when she was 28 years old, she promptly recovered after eculizumab treatment The patient was awake and alert on admission. His height was 177 cm, and body weight was 84.7 kg. Blood pressure was 205/129 mmHg, pulse rate 92 beats/min, and body temperature 36.8 °C. He had oliguria, and a physical examination revealed coarse crackles in both lung fields and mild leg edema. Chest X-ray showed decreased permeability in both lower lung fields, and diffuse myocardial hypertrophy was noted on cardiac echocardiography. The plasma level of brain natriuretic peptide increased to 1,282.7 pg/mL (normal range 0 – 18.4 U/L); however, the left ventricular ejection fraction was preserved (65%). These findings indicated acute hypertensive decompensated heart failure. A neurological examination revealed no focal signs, and there were no findings of cerebral infarction or microhemorrhage on head magnetic resonance imaging. Fundoscopy demonstrated stage III on the Keith-Wagener classification in both eyes, including findings of retinal hemorrhage and soft exudates, which were compatible with mHTN. A laboratory examination revealed the following (): sCr, 11.57 mg/dL (normal range 0.65 – 1.07 mg/dL); blood urea nitrogen, 106 mg/dL (normal range 8 – 20 mg/dL); serum uric acid, 9.8 mg/dL (normal range 3.7 – 7.8 mg/dL); lactate dehydrogenase, 816 U/L (normal range 124 – 222 U/L); hemoglobin, 10.3 g/dL (normal range 13.7 – 16.8 g/dL); platelet count, 52,000/μL (normal range 158,000 – 348,000/μL). The minimum levels of hemoglobin and the platelet count during the clinical course were 9.0 g/dL and 51,000/μL, respectively. Blood transfusion was not performed before or after admission. A peripheral blood smear revealed 1% schistocytes (normal range < 1%). Urinalysis showed proteinuria (6.23 g/gCr), 3+ hematuria (10 – 19 erythrocytes/high-power field), and various sediments. C3 and C4 levels were 82 mg/dL (normal range 73 – 138 mg/dL) and 31 mg/dL (normal range 11 – 31 mg/dL), respectively. The level of haptoglobin was below detectable ranges. A disintegrin-like and metalloprotease with thrombospondin type 1 motifs 13 (ADAMTS-13) activity was 52% (normal range > 78%), and an ADAMTS-13 inhibitor was not detected. Plasma renin activity and the plasma concentration of aldosterone were 13 ng/mL/h (normal range 0.3 – 2.9 ng/mL/h) and 285 pg/mL (normal range 29.9 – 159 pg/mL), respectively. Based on these findings, the patient was diagnosed with secondary TMA with mHTN. The continuous intravenous infusion of nicardipine was started as initial therapy for severe hypertension (). His previous medical history of TMA and family history of aHUS suggested that mHTN developed as a part of aHUS. Plasma exchange was performed for 3 days until improvements were detected in hematological abnormalities. However, eculizumab was not administered because the patient expressed concerns about adverse effects. Hemodialysis was required for oliguria and uremia, but was withdrawn within 2 weeks. Severe hypertension was treated with multiple antihypertensive drugs, including a Ca blocker (CCB) and angiotensin receptor blocker (ARB). Renal biopsy was performed on the 10th day after onset. Among the 17 glomeruli examined, 3 were globally sclerosed. Although there were no apparent thrombi in glomeruli, ischemic changes were observed (A – D), which were presumably associated with arteriolar narrowing due to intimal thickening (E, F). Tubular atrophy and interstitial fibrosis were observed in 30% of the area (A). Direct immunofluorescence microscopy showed no deposits of immunoglobulins or complements (C3 and C4) (G, H). Slight subendothelial edema was detected on electron microscopy (I). These pathological findings were consistent with acute hypertensive nephrosclerosis and also aHUS. After the withdrawal of dialysis, the level of sCr slowly decreased (7.5 mg/dL), and the patient was discharged on the 29th day. A genetic analysis was subsequently conducted at the aHUS office of Tokyo University, and the same pathogenic mutation in C3 (c.3470T>C, p.I1157T) as that of his niece was identified. No other pathogenic mutations in complement-related genes or the anti-CFH antibody were detected. Renal function gradually improved to a sCr level of 2.7 mg/dL under anti-hypertensive therapy for 2 years after the event. There was no recurrence and renal function was preserved throughout the 3-year follow-up.