Fluid homeostasis induced by sodium-glucose cotransporter 2 inhibitors: novel insight for better cardio-renal outcomes in chronic kidney disease.

Hypertension in chronic kidney disease (CKD) patients is a risk factor for end-stage renal disease, cardiovascular events, and mortality. Thus, the prevention and appropriate management of hypertension in these patients are essential strategies for better cardio-renal outcomes. In this review, we show novel risk factors for hypertension with CKD, several promising prognostic markers and treatment for cardio-renal outcomes. Of note, the clinical use of sodium-glucose cotransporter 2 (SGLT2) inhibitors has recently expanded to non-diabetic patients with CKD and heart failure as well as diabetic patients. SGLT2 inhibitors have an antihypertensive effect, but are also associated with a low risk of hypotension. This unique mechanism of blood pressure regulation by SGLT2 inhibitors may partially depend on body fluid homeostasis, which is mediated by the autoregulation property between "accelerator" (diuretic action) and "brake" (increase in anti-diuretic hormone vasopressin and fluid intake). Mineralocorticoid receptor (MR) blockers are used in the treatment of essential hypertension and hyperaldosteronism. Recently, a new MR blocker, finerenone, has been launched as a treatment for CKD with type 2 diabetes. These advances in relation to hypertension in CKD may contribute to the reduction of renal and cardiovascular events.