Renal Effects of SGLT2 Inhibitors: An Update

Josselin Nespoux; Volker Vallon


Curr Opin Nephrol Hypertens. 2020;29(2):190-198. 

In This Article

SGLT2 Inhibition may Mimic Systemic Hypoxia to the Oxygen Sensor in the Kidney Thereby Stimulating Erythropoiesis and Improving Oxygen Delivery to Kidney and Heart

SGLT2 blockade shifts Na and glucose reabsorption to downstream tubular segments in the outer medulla, a kidney region with physiologically low PO2 (Figure 3). The resulting increase in oxygen consumption may further reduce medullary PO2. This can trigger hypoxia-inducible factor (HIF)-1 and HIF-2 dependent pathways, upregulate downstream effectors, such as erythropoietin (EPO), and be protective in the long-term by improving cortical and medullary oxygen delivery[5,13] (Figure 3). Mathematical modeling studies proposed that these effects of SGLT2 inhibition are preserved in CKD.[13]