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

Paul A. Welling, Yen Pei C. Chang, Eric Delpire, James B. Wade

Research output: Contribution to journalShort survey

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.

Original languageEnglish (US)
Pages (from-to)1063-1069
Number of pages7
JournalKidney international
Volume77
Issue number12
DOIs
StatePublished - Jun 2 2012
Externally publishedYes

Keywords

  • NaCl cotransporter
  • aldosterone
  • angiotensin
  • hypertension
  • potassium channels

ASJC Scopus subject areas

  • Nephrology

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