Potassium Excretion During Antinatriuresis: Perspective from a Mathematical Model of Distal Nephron (DN)

Abstract

Renal excretion of Na+ and K+ is complicated by the fact that changing excretion of one solute requires adjusting the transport of both, “aldosterone (Aldo) paradox”. In this work, a DN model (Am. J. Physiol. 295:F1353, 2008), including distal convoluted tubule (DCT), connecting segment (CNT), and collecting duct (CD), is used to examine renal K+ excretion during antinatriuresis, with emphasis on hypovolemia and familial hyperkalemic hypertension (FHH). Na+ avidity is represented by modulation of DCT NaCl reabsorption, and the K+ secretion signal is an Aldo‐like effect on principal cells of CNT and CD. The first model prediction is that changes in DCT NaCl reabsorption are mediated by NaCl cotransporter density in conjunction with both peritubular Na,K‐ATPase and KCl cotransport. A second observation is that the CNT response to increased DCT NaCl reabsorption, should not only stabilize CD K+ delivery, but also compensate for increased CD K+ reabsorption, due to low CD Na+ delivery. Aldo provides this response in hypovolemia, while in FHH there is enhanced DCT NaCl transport but blunted Aldo effect. Conversely, when a K+ load increases Aldo, the model requires a concomitant decrease in DCT NaCl transport to stabilize Na+ excretion. The model emphasizes the need for two distinct DN signals, regulating Na+ excretion and K+ excretion, in contrast to a single switch apportioning NaCl reabsorption and Na+‐for‐K+ exchange.