In extreme cases, adult patients with pseudohypoaldosteronism type 1 carrying heterozygous loss-of-function mutations in the MR, who are able to maintain normal sodium and potassium balance and blood pressure through increase of renin and aldosterone levels, with time develop partially autonomous aldosterone production with increased aldosterone to renin ratio compared to a control population63. Here, REN is linked to pseudohypoaldosteronism type 1.