Renal potassium physiology: integration of the renal response to dietary potassium depletion
Authors: Kamel S. Kamel, Martin Schreiber, Mitchell L. Halperin
Journal: Kidney International (2017)

The physiology of the renal regulation of K+ excretion was summarized, emphasizing recent advances. An integrative view of the renal response to K+ depletion induced by dietary K+ restriction involves multiple nephron segments and is summarized in Table 1. The implications of this physiology for the link between K+ depletion and hypertension and between K+ depletion and the formation of calcium oxalate kidney stones were discussed.Table 1Integration of the renal response to dietary K+ depletionNephron segmentMechanismEffectPCTActivation of NHE3 by Ang II and intracellular acidosis in PCT cells increases the reabsorption of NaHCO3 and NaCl.Decreased Na+ delivery to ASDN leading to decreased rate of electrogenic Na+ reabsorption and decreased flow rate in ASDN.PCTStimulation of ammonium production by intracellular acidosis.Ammonium inhibits ENaC and K+ secretion in ASDN.PCTStimulation of ammoniagenesis by intracellular acidosis leads to an increase in the delivery of the organic anion α-ketoglutarate to the CCD.Binding of α-ketoglutarate to its receptor Oxgrl activates pendrin and may result in an increase in the electroneutral reabsorption of NaCl in the ASDN.PCTStimulation of ammoniagenesis by intracellular acidosis leads to increased availability of NH3, the H+ acceptor for the electroneutral HKA2 in the CCD and MCD.Increased K+ reabsorption in CCD and MCD.DCT1Increased activity of the NCC due to activation of the WNK-SPAK/OSR1-NCC pathway by K+ depletion, Ang II, and decrease in intracellular concentration. of Cl− in DCT1 cells.Decreased Na+ delivery to the ASDN leading to a decreased rate of electrogenic Na+ reabsorption and decreased flow rate in the ASDN.ASDNDecreased SGK1 level as a result of diminished release of aldosterone.Decreased rate of electrogenic reabsorption of Na+ in the ASDN.ASDNDecreased abundance of ROMK in the luminal membrane of principal cells as a result of decreased trafficking of ROMK due to a low level of SGK1 and increased endocytosis of ROMK mediated by Ang II, WNK4, and L-WNK1.Decreased rate of K+ secretion by ROMK.MCDK+ depletion enhances the expression of HKA2 in the luminal membrane of α-intercalated cells.Increased rate of K+ reabsorption.MCDHypokalemia increases the expression of Rhcg and hence the transport of NH3 from the medullary interstitial compartment into the lumen of the MCD.Increased rate of K+ reabsorption.Inner MCDK+ depletion leads to decreased abundance of urea transporters and therefore may decrease the amount of urea that recycles.Decreased flow rate in the ASDN.Ang II, angiotensin II; ASDN, aldosterone-sensitive distal nephron; CCD, cortical collecting duct; DCT1, first portion of the distal convoluted tubule; ENaC, epithelial sodium channel; HKA2, hydrogen-potassium ATPase type 2; L-WNK1, long WNK1 isoform; MCD, medullary collecting duct; NCC, sodium chloride cotransporter; NHE3, sodium hydrogen exchanger 3; OSR1, oxidative stress response kinase type 1; PCT, proximal convoluted tubule; Rhcg, Rh C glycoprotein; ROMK, renal outer medullary potassium channel; SGK1, serum and glucocorticoid regulated kinase 1; SPAK, STE20-related proline-alanine–rich kinase. Open table in a new tab