Development of a test to evaluate the transtubular potassium concentration gradient in the cortical collecting duct in vivo.

The purpose of these investigations was to develop a noninvasive test to estimate the transtubular potassium concentration gradient (TTKG) and thereby aldosterone action in the late distal convoluted tubule and the cortical collecting duct in patients with disorders of potassium excretion. Experiments were performed in rats under conditions where the ratio of urine to renal venous potassium concentration could reflect this TTKG. A large furosemide-induced diuresis ensured that sodium delivery was adequate and minimized the change in water content during transit through the medullary collecting duct (equal osmolality and TF/P inulin at the base and the tip of the medullary collecting duct). There was no significant potassium reabsorption nor secretion during transit through the medulla as shown by micropuncture and microcatheterization. Thus the potassium concentration in the urine should mirror that in the lumen at the major nephron sites of potassium secretion. The potassium concentration in the renal vein provides the simplest estimate of the cortical peritubular potassium concentration (the mean renal A-V difference for potassium was 1.2 mM); with a very high fractional excretion of potassium, an adjustment can be made to the arterial potassium concentration to correct for the potassium extracted. If the urine/plasma potassium concentration ratio were a quantitative reflection, then the transepithelial potential difference (TEPD) would be close to -40 mV in normal rats. The TTKG fell to unity when amiloride was given, consistent with an abolition of the apparent TEPD in vivo by this drug. Similar results were obtained in non-diuretic rats. The clinical implications of these findings are discussed.