title: Hyperkalemia: An adaptive response in chronic renal insufficiency.
abstract: BACKGROUND
  Hyperkalemia is a common feature of chronic renal insufficiency, usually ascribed to impaired K+ homeostasis. However, various experimental observations suggest that the increase in extracellular [K+] actually functions in a homeostatic fashion, directly stimulating renal K+ excretion through an effect that is independent of, and additive to, aldosterone.
  
  
  METHODS
  We have reviewed relevant studies in experimental animals and in human subjects that have examined the regulation of K+ excretion and its relation to plasma [K+].
  
  
  RESULTS
  Studies indicate that (1) extracellular [K+] in patients with renal insufficiency correlates directly with intracellular K+ content, and (2) hyperkalemia directly promotes K+ secretion in the principal cells of the collecting duct by increasing apical and basolateral membrane conductances. The effect of hyperkalemia differs from that of aldosterone in that K+ conductances are increased as the primary event. The changes in principal cell function and structure induced by hyperkalemia are indistinguishable from the effects seen in adaptation to a high K+ diet.
  
  
  CONCLUSIONS
  We propose that hyperkalemia plays a pivotal role in K+ homeostasis in renal insufficiency by stimulating K+ excretion. In patients with chronic renal insufficiency, a new steady state develops in which extracellular [K+] rises to the level needed to stimulate K+ excretion so that it again matches intake. When this new steady state is achieved, plasma [K+] remains stable unless dietary intake increases, glomerular filtration rate falls, or drugs are given that disrupt the new balance.
authors.affiliation: Fletcher Allen Health Care, University of Vermont College of Medicine, Burlington, VT 05401, USA. fgennari@zoo.uvm.edu
authors.forename: F John
authors.initials: FJ
authors.lastname: Gennari
authors.forename: Alan S
authors.initials: AS
authors.lastname: Segal
mesh_terms: D000222:Adaptation, Physiological; D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D006706:Homeostasis; D006801:Humans; D006947:Hyperkalemia / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D000450:Aldosterone; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium