Sodium glucose co-transporter inhibitors put cardiovascular medicine at a crossroads – Cardiorenal interaction and clinical implications

Heart and kidney have essential homeostatic role in circulation balance to cope with variation of body biology needs, however the two organs physiology is designed to satisfy opposing demands. The heart has to provide with oxygen and nutrition of different organs and apparatus based on intercurrent demand without any predefined schedule. In contrast, the kidneys have to adapt the body’s fluid and electrolyte content to cope with changes in the internal and external environment. The heart and kidney function confront different physiological needs, namely the energy the body requires versus the body function equilibrium. In the specific the kidney has a role in maintaining renal glucose balance while it reabsorbs the 99% of filtrate sodium together with other filtered substances, including all glucose molecules. The kidneys reabsorb the filtered glucose prominently through the sodium-glucose cotransporters sodium-glucose cotransporter (SGLT)2, and only a limited percentage through the SGLT1. Both SGLTs are localized on the brush border membrane of the early proximal tubule working in tandem with the structurally interlinked Na+-H+ exchanger NHE3. The reabsorption of 50 to 60% of filtered sodium occurs in this section of the tubule by breaking down adenosine triphosphate to adenosine diphosphate to provide the energy affecting the renal oxygen demand. Any change in glomerular filtrate production directly affects the renal oxygen consumption that is the main drive of the renal sympathetic activity and regulates the SGLT2 expression. Present paper will focus on effects of SGLT2 inhibition over renal physiology and by consequence over heart failure outcome.