Does the kidney 'escape' from the kaliuretic action of mineralocorticoids?

The purpose of this study was to determine if there are renal mechanisms which limit the magnitude of potassium loss during mineralocorticoid-induced hypokalemia. To study the renal effects of mineralocorticoids in vivo, the 'cortical distal nephron' transtubular [K] gradient (TTKG) was calculated by dividing the urine [K] by the urine to plasma osmolality ratio; this in turn was divided by the arterial plasma [K]. Hypokalemia (2.6 +/- 0.1 mM) was induced in rabbits by the daily administration of 5 mg deoxycorticosterone acetate (DOCA) for 9-13 days. Infusion of a K-free isotonic solution into these rabbits resulted in more severe hypokalemia (1.6 +/- 0.1 mM) and a TTKG of 4.3 +/- 0.3. The subsequent infusion of a 60-mM K-containing solution elevated the plasma [K] to 5.1 +/- 0.1 mM and was associated with a significant rise in the TTKG to 5.9 +/- 0.4 (p less than 0.05). A K-free solution was then infused to lower the plasma [K]; when the plasma [K] fell below 4 mM, the TTKG decreased to 4.4 +/- 0.3 (p less than 0.05), and was equal to the preinfusion value. Thus, DOCA-induced hypokalemia diminishes renal K excretion by two mechanisms: first, the lower value for the denominator of the TTKG (the plasma [K]) results in a lower luminal [K] at a given TTKG. Second, the TTKG fell during hypokalemia and thereby decreased the luminal [K] in the cortical distal nephron. Hence the urinary K excretion rate was diminished to a greater extent than that predicted from the fall in the plasma [K] despite continuing mineralocorticoid action.

Renal potassium handling during states of low aldosterone bio-activity: a method to differentiate renal and non-renal causes.

The purpose of this study was to examine renal potassium handling in patients with low aldosterone bio-activity. The patients with a normal renal response to aldosterone were identified by finding both a low plasma aldosterone concentration during hyperkalaemia and a transtubular potassium concentration gradient (TTKG) in the cortical distal nephron of 6 or greater within 4 h after the administration of a physiologic dose of mineralocorticoid hormone. In contrast, patients with a primary renal potassium excretion defect represent a heterogeneous population. In some, the TTKG rose when a pharmacologic but not a physiologic dose of mineralocorticoid was given; others had little renal response to the administration of this hormone. Furthermore, this renal response may be delayed and require more than 24 h to become manifest.

New clinical approach to evaluate disorders of potassium excretion.

A new clinical approach to patients with disorders of potassium excretion is reported. This approach uses a urinary index, the ratio of potassium concentrations in the urine to vein after adjusting the urine potassium concentration for medullary water abstraction. This index provides a semiquantitative assessment of the apparent transtubular potassium concentration gradient (TTKG) in the major distal nephron segment where potassium is secreted. Three clinical situations are presented where the use of this index provided a better indication of the renal action of mineralocorticoids than did the traditional approach; in each case, the presence of mineralocorticoids was known as drugs with this action were administered. We emphasize that use of this index is restricted to situations where the urine is not hypotonic and distal nephron sodium delivery is not limiting for potassium secretion (greater than 25 mM, twice the sodium concentration required for maximum potassium transport at this nephron site).