The Low-Renin Hypertension Phenotype: Genetics and the Role of the Mineralocorticoid Receptor

Abstract

A substantial proportion of patients with hypertension have a low or suppressed renin. This phenotype of low-renin hypertension (LRH) may be the manifestation of inherited genetic syndromes, acquired somatic mutations, or environmental exposures. Activation of the mineralocorticoid receptor is a common final mechanism for the development of LRH. Classically, the individual causes of LRH have been considered to be rare diseases; however, recent advances suggest that there are milder and "non-classical" variants of many LRH-inducing conditions. In this regard, our understanding of the underlying genetics and mechanisms accounting for LRH, and therefore, potentially the pathogenesis of a large subset of essential hypertension, is evolving. This review will discuss the potential causes of LRH, with a focus on implicated genetic mechanisms, the expanding recognition of non-classical variants of conditions that induce LRH, and the role of the mineralocorticoid receptor in determining this phenotype.

Keywords: aldosterone; genetics; hypertension; low-renin; mineralocorticoid receptor; renin.

Figure 1

A proposed approach to the patient with low-renin hypertension. ENaC = epithelial sodium channel; 11-βHSD2 = 11-β hydroxysteroid dehydrogenase type 2; 11β-OH = 11-β hydroxylase; 17α-OH = 17-α hydroxylase.