Effect of mineralocorticoids on acid-base balance

Abstract

Aldosterone is classically associated with the regulation of salt and potassium homeostasis but has also profound effects on acid-base balance. During acidosis, circulating aldosterone levels are increased and the hormone acts in concert with angiotensin II and other factors to stimulate renal acid excretion. Pharmacological blockade of aldosterone action as well as inherited or acquired syndromes of impaired aldosterone release or action impair the renal response to acid loading and cause hyperkalemic renal tubular acidosis. The mineralocorticoid receptor (MR) mediating the genomic effects of aldosterone is expressed in all cells of the distal nephron including all subtypes of intercalated cells. In acid-secretory type A intercalated cells, aldosterone stimulates proton secretion into urine, whereas in non-type A intercalated cells, aldosterone increases the activity of the luminal anion exchanger pendrin stimulating bicarbonate secretion and chloride reabsorption. Aldosterone has also stimulatory effects on proton secretion that may be mediated by a non-genomic pathway. In addition, aldosterone indirectly stimulates renal acid excretion by enhancing sodium reabsorption through the epithelial sodium channel ENaC. Increased sodium reabsorption enhances the lumen-negative transepithelial voltage that facilitates proton secretion by neighboring intercalated cells. This indirect coupling of sodium reabsorption and proton secretion is thought to underlie the fludrocortisone-furosemide test for maximal urinary acidification in patients with suspected distal renal tubular acidosis. In patients with CKD, acidosis-induced aldosterone may contribute to progression of kidney disease. In summary, aldosterone is a powerful regulator of renal acid excretion required for normal acid-base balance.