Purpose of review: The purpose of this review is to describe the renin-angiotensin-aldosterone system and its regulatory control of sodium, potassium, chloride, hydrogen ion, and water homeostasis through its effects on the expression and activity of distal renal tubular cotransporter proteins and to discuss the gene mutations encoding these structures that disturb the function of this system.
Recent findings: Primary hypoaldosteronism may be the result of acquired or congenital errors in renal juxtaglomerular function (the source of renin), angiotensin generation or activity, or aldosterone synthesis. Secondary hypoaldosteronism (pseudohypoaldosteronism) occurs as a consequence of mutations in genes encoding the mineralocorticoid receptor (MR), the three subunits of the aldosterone-responsive, amiloride-sensitive nonvoltage-gated sodium channel encoded by SCNN1A, SCNN1B, and SCNN1G, the gene that regulates posttranslational phosphorylation (encoded by WNK4) of the thiazide-sensitive sodium chloride cotransporter encoded by SLC12A3, and those that regulate phosphorylation and ubiquitination of cofactors encoded by WNK1, KLH3, and CUL3 that affect WNK4 function.
Summary: Acquired disorders of renal function as well as mutations in many genes may adversely affect aldosterone-mediated mineral homeostasis.