Editorial Comment The renal WNK kinase pathway: a new link to hypertension

The renal WNK kinase pathway: a new link to hypertension The discovery of the renal WNK kinase pathway is offer-ing new insights into sodium, potassium and blood pressure regulation in the distal nephron. It has also largely explained the pathogenesis of a genetic form of hypertension called familial hyperkalaemic hypertension (FHHt, also known as pseudohypoaldosteronism type II or Gordon’s syndrome), because it is caused by mutations in WNK kinases. How-ever, the question is: do the renalWNKkinases have clinical significance beyond this rare syndrome? Here, we review the most recent data on renal WNK kinase physiology and discuss their potentially broader roles in electrolyte trans-port and hypertension. The renal WNK kinase pathway: current status As so often in science, the identification of the WNK kinases was a serendipitous finding. In 2000, Xu et al. pursued a nested polymerase chain reaction cloning strat-egy to identify novel members of the mitogen-activated protein/extracellular signal-regulated protein kinase fam-ily [1]. Instead, they found a new member of the serine/ threonine kinase family. They named the new kinaseWNK, which stands forWith NoK, with ‘K ’ referring to the amino acid lysine. The name highlights their unique characteris-tic: the location of the catalytic lysine crucial for binding to ATP in subdomain I instead of II, as is the case in all other protein kinases. To date, fiveWNK kinases have been iden-tified, namely WNK1 through WNK4 and kidney-specific WNK1 (KS-WNK1, a second transcript from the WNK1 gene). The physiological functions of the WNK kinases ar