Extending the use of SGLT2 inhibitors from diabetic to non-diabetic kidney disease

During the last years a new group of medicines, named sodium-glucose co-transporter 2 (SGLT2) inhibitors, came on the market for patients with diabetes mellitus. Sodium-glucose co-transporters reabsorb glucose (and sodium) that is filtered by the kidneys. By inhibiting SGLT2 less glucose (and sodium) are reabsorbed and more glucose (and sodium) are excreted by the urine, which results in reduced blood glucose levels. Large clinical outcome trials showed that SGLT2 inhibitors reduce the risk for cardiovascular death and kidney failure. The exact mechanisms by which SGLT2 inhibitors exert their salutary effects are incompletely understood. In this thesis we examined the effects of SGLT2 inhibitors on the kidney and the cardiovascular system. We showed that SGLT2 inhibition decreases plasma volume and reduces kidney injury- and inflammation markers. Whether the beneficial effects of SGLT2 inhibitors are also present in patients with diabetes and chronic kidney disease (CKD) was unclear. We showed that SGLT2 inhibitor therapy reduces blood pressure, body weight, and proteinuria in this patient population. Finally, we performed an international, multicenter study to examine the effects of SGLT2 inhibitors in patients with CKD without diabetes mellitus, and found beneficial effects on kidney function, body weight, and on volume-markers. This suggests beneficial effects in this patient population on the long term.