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 language | English (US) |
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Pages (from-to) | 1063-1069 |
Number of pages | 7 |
Journal | Kidney international |
Volume | 77 |
Issue number | 12 |
DOIs | |
State | Published - Jun 2 2012 |
Externally published | Yes |
Keywords
- NaCl cotransporter
- aldosterone
- angiotensin
- hypertension
- potassium channels
ASJC Scopus subject areas
- Nephrology