Schematic illustrating TNFα-induced WNK pathway activation and salt-sensitive hypertension in chronic kidney disease (CKD) (IMAGE)

Tokyo Medical and Dental University

Schematic illustrating TNFα-induced WNK pathway activation and salt-sensitive hypertension in chronic kidney disease (CKD)

Caption

WNK phosphorylation cascade plays an important role in sodium handling in the distal nephron of the kidney. Over-activation of this pathway increases sodium reabsorption through NaCl cotransporter (NCC) and causes salt-sensitive hypertension. This study demonstrated that TNFα activates WNK1-SPAK-NCC phosphorylation cascade by suppressing NEDD4-2 which degrades WNK1, contributing to salt-sensitive hypertension in CKD with increased renal TNFα. Therefore, WNK phosphorylation cascade may be a link between immune systems and hypertension. In addition, TNFα-WNK1-SPAK-NCC axis may be activated in patients with CKD for whom thiazide diuretics, NCC inhibitors, are effective.

Credit

Department of Nephrology,TMDU

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