Potassium excretion during antinatriuresis: perspective from a distal nephron model.

Renal excretion of Na(+) and K(+) must be regulated independently within the distal nephron, but is complicated by the fact that changing excretion of one solute requires adjustments in the transport of both. It is long known that hypovolemia increases Na(+) reabsorption while impairing K(+) excretion, even when distal Na(+) delivery is little changed. Renewed interest in this micropuncture observation came with identification of the molecular defects underlying familial hyperkalemic hypertension (FHH), which also increases distal Na(+) reabsorption and impairs K(+) excretion. In this work, a mathematical model of the distal nephron (Weinstein AM. Am J Physiol Renal Physiol 295: F1353-F1364, 2008), including the distal convoluted tubule (DCT), connecting segment (CNT), and collecting duct (CD), is used to examine renal K(+) excretion during antinatriuresis. Within the model, Na(+) avidity is represented as the modulation of DCT NaCl reabsorption, and the K(+) secretion signal is an aldosterone-like effect on principal cells of the CNT and CD. The first model prediction is that changes in DCT NaCl reabsorption are not mediated by NaCl cotransporter density alone, but require additional adjustments of both peritubular Na-K-ATPase and KCl cotransport. A second observation is that the CNT response to increased DCT Na(+) reabsorption should not only stabilize CD K(+) delivery but also compensate for the compromise of K(+) excretion downstream, as low Na(+) delivery increases CD K(+) reabsorption. Such anticipatory regulation is seen with the aldosterone response of hypovolemia, while the FHH phenotype manifests enhanced DCT NaCl transport but a blunted aldosterone effect. The model emphasizes the need for two distinct signals to the distal nephron, regulating Na(+) excretion and K(+) excretion, in contrast to a single switch apportioning NaCl reabsorption and Na(+)-for-K(+) exchange.