Hyperkalemia: An adaptive response in chronic renal insufficiency

Kidney Int. 2002 Jul;62(1):1-9. doi: 10.1046/j.1523-1755.2002.00350.x.


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.

Publication types

  • Review

MeSH terms

  • Adaptation, Physiological
  • Aldosterone / pharmacology
  • Animals
  • Homeostasis
  • Humans
  • Hyperkalemia / metabolism*
  • Kidney / metabolism
  • Kidney Failure, Chronic / metabolism*
  • Potassium / metabolism
  • Sodium-Potassium-Exchanging ATPase / metabolism


  • Aldosterone
  • Sodium-Potassium-Exchanging ATPase
  • Potassium