Beneficial effect of sodium-glucose cotransporter 2 inhibitors on kidney function can be just a mirage

Figure 1 The increase in the glomerular filtration rate induced by sodium-glucose cotransporter-2 inhibitors does not correspond to an improvement in kidney function. Sodium-glucose cotransporter-2 (SGLT2) inhibitors induce: (1) Adaptive glomerular hyperfiltration in response to glucosuria and subsequent osmotic diuresis; and (2) Loss of skeletal muscle mass that reduces serum creatinine concentration. Lower serum creatinine level leads to an overestimation of kidney function when estimated glomerular filtration rate (GFR) is calculated with serum creatinine-based equations. The increase in serum creatinine-based estimated GFR associated with SGLT2 inhibitors may be attributable to either one or both of these confounding processes and may not reflect a beneficial effect on kidney function. SGLT2: Sodium-glucose cotransporter-2; GFR: Glomerular filtration rate.

Figure 2 The sodium glucose cotransporter-2 protein conveys glucose and sodium from the lumen of the kidney proximal tubule to the blood. SGLT2: Sodium-glucose cotransporter-2.

Figure 3 Sodium glucose cotransporter-2 inhibitors induce glucosuria and subsequent osmotic diuresis. SGLT2: Sodium-glucose cotransporter-2.

Figure 4 Glucosuria induces osmotic diuresis and subsequent glomerular hyperfiltration. A: In healthy humans with blood glucose concentration below the kidney threshold for glucose reabsorption (approximately 180-200 mg/dL or 10-11 mmol/L), glucose is reabsorbed in the proximal tubule and no glucose is detectable in urine; B: Glucosuria occurs when glucose reabsorption in the proximal tubule is inhibited or when the plasma glucose concentration exceeds the kidney threshold for glucose reabsorption. The presence of glucose in urine requires concomitant elimination of water (osmotic diuresis). Glomerular hyperfiltration may be an adaptive response that arises in order to supply the obligatory loss of water in urine in the setting of glucosuria and osmotic diuresis.