Monogenic forms of low-renin hypertension: clinical and molecular insights

• Published in: Pediatric nephrology (Berlin, West) Vol. 37; no. 7; pp. 1495 - 1509
• Main Authors: Khandelwal, Priyanka, Deinum, Jaap
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-07-2022; Springer; Springer Nature B.V
• Subjects: Age; Aldosterone; Angiotensin; Blood levels; Catecholamines; Complications; Diagnosis; DNA sequencing; Educational Review; Endocrine disorders; Genetic aspects; Glucocorticoids; Health aspects; Hyperactivity; Hyperplasia; Hypertension; Hypokalemia; Medicine; Medicine & Public Health; Methods; Nephrology; Nucleotide sequencing; Pediatrics; Potassium; Prognosis; Pseudohypoaldosteronism; Renin; Urology; What’s new in Hypertension; India; Hypokalemia; Hyperkalemia; Next-generation sequencing; Phenotypic variability; Metabolic alkalosis
• ISSN: 0931-041X; 1432-198X
• DOI: 10.1007/s00467-021-05246-x

Monogenic disorders of hypertension are a distinct group of diseases causing dysregulation of the renin–angiotensin–aldosterone system and are characterized by low plasma renin activity. These can chiefly be classified as causing (i) excessive aldosterone synthesis (familial hyperaldosteronism), (ii) dysregulated adrenal steroid metabolism and action (apparent mineralocorticoid excess, congenital adrenal hyperplasia, activating mineralocorticoid receptor mutation, primary glucocorticoid resistance), and (iii) hyperactivity of sodium and chloride transporters in the distal tubule (Liddle syndrome and pseudohypoaldosteronism type 2). The final common pathway is plasma volume expansion and catecholamine/sympathetic excess that causes urinary potassium wasting; hypokalemia and early-onset refractory hypertension are characteristic. However, several single gene defects may show phenotypic heterogeneity, presenting with mild hypertension with normal electrolytes. Evaluation is based on careful attention to family history, physical examination, and measurement of blood levels of potassium, renin, and aldosterone. Genetic sequencing is essential for precise diagnosis and individualized therapy. Early recognition and specific management improves prognosis and prevents long-term sequelae of severe hypertension.