Abstract-Unilateral primary aldosteronism is the most common surgically correctable form of endocrine hypertension and is usually differentiated from bilateral forms by adrenal venous sampling (AVS) or computed tomography (CT

Abstract-Urinary exosomes are vesicles derived from renal tubular epithelial cells. Exosomes often contain several disease-associated proteins and are thus useful targets for identifying biomarkers of disease. Here, we hypothesized that the phosphorylated (active) form of the sodium chloride cotransporter (pNCC) or prostasin could serve as biomarkers for aldosteronism. We tested this in 2 animal models of aldosteronism (aldosterone infusion or low-sodium diet) and in patients with primary aldosteronism. Urinary exosomes were isolated from 24-hour urine or spot urine using ultracentrifugation. In rats, a normal or a high dose of aldosterone for 2, 3, or 8 days increased pNCC 3-fold in urinary exosomes (PϽ0.05 for all). A low-sodium diet also increased pNCC in urinary exosomes approximately 1.5-fold after 4 and after 8 days of treatment. The effects of these maneuvers on prostasin in urinary exosomes were less clear, showing a significant 1.5-fold increase only after 2 and 3 days of high-aldosterone infusion. In urinary exosomes of patients with primary aldosteronism, pNCC was 2.6-fold higher (PϽ0.05) while prostasin was 1.5-fold higher (Pϭ0.07) than in patients with essential hypertension. Urinary exosomal pNCC and, to a lesser extent, prostasin are promising markers for aldosteronism in experimental animals and patients. These markers may be used to assess the biological activity of aldosterone and, potentially, as clinical biomarkers for primary aldosteronism. 1 Exosomes are low-density membrane vesicles that originate from multivesicular bodies. Urinary exosomes have sparked interest as potential biomarkers for human disease. 1-3The presence of urinary exosomes and a reproducible method for their isolation were reported in 2004 by Pisitkun and colleagues. 4 Proteomic analysis of these exosomes showed that they contain many disease-related proteins 4,5 ; however, the question remained whether the presence of a given protein in urinary exosomes could provide information on physiological or disease processes in the kidney. Studies addressing this question analyzed urinary exosomes in patients with monogenetic diseases, resulting in inactivity or overactivity of renal sodium transport proteins. For example, in Bartter and Gitelman syndrome, in which the sodium potassium chloride cotransporter and the sodium chloride cotransporter (NCC) are genetically inactivated, these proteins were also found to be absent or reduced in urinary exosomes. 5,6 Conversely, Mayan et al found the abundance of NCC to be increased in patients with familial hyperkalemic hypertension, in which mutations in NCC-regulating kinases cause overactivity of this cotransporter.7 Thus, in these homogeneous groups, the expression of sodium-transport proteins in urinary exosomes correlated with what one would expect from their renal expression. The next step in assessing the potential of exosomes as urinary biomarkers is to analyze their performance in acquired disease. Therefore, in this study, we asked whether various forms of aldosteronism result...

ARR sensitivity for primary aldosteronism is low when the recommended cut-off is used. Reproducibility is also poor, stressing the need for alternative screening tests.

The role of the renin-angiotensin-aldosterone system (RAAS) in hypertension has since long been recognized and aldosterone has been acknowledged as one of the key hormones in the pathophysiology, not only in primary aldosteronism but also in essential hypertension and drug-resistant hypertension. Aldosterone-receptor antagonists (ARAs) are increasingly used in patients with resistant hypertension, often with impressive results. However, definitive evidence for the benefit of ARAs in these patients from randomized, controlled trials is lacking. This review gives an overview of the current data on this topic. Future studies should focus on the identification of factors that are able to predict the response to treatment, as to select patients who will benefit most from treatment with ARAs. On the basis of the current knowledge, we recommend prescription of ARAs to patients with primary aldosteronism, resistant hypertension and patients with hypertension and hypokalemia.