PS-BPR03-8: MALIGNANT HYPERTENSION WITH ACUTE KIDNEY INJURY AND THROMBOTIC MICROANGIOPATHY SUCCESSFULLY TREATED WITH ANGIOTENSIN RECEPTOR NEPRILYSIN INHIBITOR

Abstract

Background: Malignant hypertension is a disease characterized by severe hypertension and multi-organ damage. Sacubitril/valsartan, a first-in-class angiotensin receptor neprilysin inhibitor (ARNi), has already demonstrated the superiority of reducing blood pressure versus olmesartan in patients with hypertension. ARNi has also been shown to improve cardiac biomarkers, cardiac remodeling, and prognosis in patients with heart failure, and a new AHA/ACC/HFSA guideline (2022) redefined to recommend ARNi as first-line renin-angiotensin-system inhibitors (class 1a) in patients with HFrEF (heart failure with reduced ejection fraction). However, the evidence about the efficacy and safety of ARNi in end-stage renal disease (ESRD) patients undergoing hemodialysis has been limited. Presentation: A 23-year-old man with no prior medical history was admitted to the previous hospital with severe hypertension (blood pressure 224/159 mmHg) associated with acute kidney injury (BUN 228.5 mg/dl, serum creatinine 25.50 mg/dl) and was referred to our hospital with the initiation of hemodialysis. He was also complicated with hypertensive heart failure with a preserved ejection fraction (NT-proBNP 172113 pg/ml). Blood test results also revealed thrombocytopenia (platelet 11.9 x 103/μL), hemolytic anemia (hemoglobin 7.4 g/dl, LDH 1076 U/L, haptoglobin < 10 mg/dl), and schistocyte on the blood smear, which was suggestive of thrombotic microangiopathy. His blood cell counts and serum LDH levels improved after antihypertensive treatment. Secondary hypertension, such as primary aldosteronism, Cushing's syndrome, pheochromocytoma, and renal artery stenosis, was deniable by further examination. The elevated levels of renin (65.5 ng/ml/hr) and aldosterone (685 pg/ml) were consistent with malignant hypertension. Serum antibody tests for screening of autoimmune disease were all negative. Renal biopsy revealed findings of malignant nephrosclerosis: glomerular collapse, glomerulosclerosis, endothelial swelling, and media thickening of the arteries. Oliguria recovered during the clinical course; however, his renal function did not fully recover. An arterio-venous fistula was created, and maintenance hemodialysis two times per week was continued during hospitalization. Even though his dry weight was adjusted to normal by repeated dialysis, his blood pressure was poorly controlled to systolic blood pressure of 160–170 mmHg by calcium channel blockers, angiotensin II receptor blocker (ARB), and alpha/beta-blockers. After switching from ARB to ARNi by increasing the dose to a maximum of 400 mg, his systolic blood pressure improved to 130–140 mmHg and was stable throughout the day, assessed by ambulatory blood pressure monitoring. Conclusion: Through our experience, it is conceivable that ARNi may be helpful in the settings of resistant hypertension in ESRD patients undergoing hemodialysis.