This concept was suggested many years ago24 and previous studies have suggested that physiological phenotyping of sodium/volume status (for which plasma renin is a surrogate) have suggested that this can predict the most effective treatment.25 In this regard, our primary hypothesis states that we expect the most common underlying pathophysiology for resistant hypertension will be sodium/volume overload, resulting in a low plasma renin at baseline, and consequently the best response will be obtained with further diuretic therapy, that is, spironolactone, in most patients. This evidence concerns the gene REN and Hypertension resistant to conventional therapy.