Decaying kidney function during cirrhosis correlates with remodeling of distal colon aldosterone target gene expression.

Liver cirrhosis is associated to circulatory abnormalities leading to hypovolemia and stimulation of the renin-angiotensin-aldosterone system (RAAS). Advanced stages of the disease cause renal failure, impairing K and Na homeostasis. It has been proposed that the distal colon undergoes functional remodeling during renal failure, in particular by aldosterone-driven increased K excretion.

Increased SGK1 activity potentiates mineralocorticoid/NaCl-induced kidney injury.

Serum and glucocorticoid-regulated kinase 1 (SGK1) stimulates aldosterone-dependent renal Na reabsorption and modulates blood pressure. In addition, genetic ablation or pharmacological inhibition of SGK1 limits the development of kidney inflammation and fibrosis in response to excess mineralocorticoid signaling. In this work, we tested the hypothesis that a systemic increase in SGK1 activity would potentiate mineralocorticoid/salt-induced hypertension and kidney injury.

SGK1 activation exacerbates diet-induced obesity, metabolic syndrome and hypertension.

The serum- and glucocorticoid-induced kinase 1 (SGK1) is a transcriptional target of steroid hormones including glucocorticoids or aldosterone in addition to other stimuli such as glucose. SGK1 is activated via phosphoinositide 3-kinase, placing it downstream of insulin signaling. SGK1 participates in the upregulation of kidney Na+ reabsorption by aldosterone and has been linked to obesity-related hypertension in humans.