Multigene kinase network, kidney transport, and salt in essential hypertension

Kidney Int. 2010 Jun;77(12):1063-9. doi: 10.1038/ki.2010.103. Epub 2010 Apr 14.

Abstract

Evidence is mounting that a multi-gene kinase network is central to the regulation of renal Na(+) and K(+) excretion and that aberrant signaling through the pathway can result in renal sodium retention and hypertension (HTN). The kinase network minimally includes the Ste20-related proline-alanine-rich kinase (SPAK), the with-no-lysine kinases (WNKs), WNK4 and WNK1, and their effectors, the thiazide-sensitive NaCl cotransporter and the potassium secretory channel, ROMK. Available evidence indicates that the kinase network normally functions as a switch to change the mineralocorticoid hormone response of the kidney to either conserve sodium or excrete potassium, depending on whether aldosterone is induced by a change in dietary sodium or potassium. Recently, common genetic variants in the SPAK gene have been identified as HTN susceptibility factors in the general population, suggesting that altered WNK-SPAK signaling plays an important role in essential HTN. Here, we highlight recent breakthroughs in this emerging field and discuss areas of consensus and uncertainty.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Biological Transport
  • Humans
  • Hypertension / etiology*
  • Kidney / metabolism*
  • Phosphotransferases / genetics*
  • Protein-Serine-Threonine Kinases / genetics
  • Sodium Chloride, Dietary / metabolism

Substances

  • Sodium Chloride, Dietary
  • Phosphotransferases
  • Protein-Serine-Threonine Kinases
  • STK39 protein, human