Mineralocorticoid Resistance

David S. Geller


Clin Endocrinol. 2005;62(5):513-520. 

In This Article

Clinical Mineralocorticoid Resistance

Although the genetic examples of mineralocorticoid resistance cited above shed light on the mechanisms by which aldosterone regulates extracellular volume in the kidney, these are indications rarely encountered in clinical practice. There are some clinical situations in which mineralocorticoid resistance is encountered in the absence of an underlying genetic defect. Transient pseudohypoaldosteronism has been described in infants with urinary tract obstruction[52] or urinary tract infection,[53] and is reversible with treatment of the primary problem. A PHA1-like picture, with hypovolaemia, hyperkalaemia and elevated aldosterone levels, has been reported in patients following small bowel resection, but these patients probably have intestinal salt wasting and an appropriate renal response to the actions of aldosterone. The most common clinical scenario of aldosterone resistance occurs in patients receiving a calcineurin inhibitor, such as cyclosporin or tacrolimus, for immunosuppression. Hyperkalaemia is a common side-effect of these medications, but the mechanism(s) underlying resistance to aldosterone-induced kaliuresis remain poorly understood. These medications inhibit renin (and presumably aldosterone) secretion but also result in tubular insensitivity to aldosterone effect.[54,55] Recent studies suggest that aldosterone resistance may be mediated by a reduction in mineralocorticoid receptor expression, perhaps mediated through transcriptional mechanisms.[56—58] Further understanding of the mechanisms of aldosterone resistance induced by these agents may help us to prevent this common and dose-limiting side-effect.