A Role for SGLT-2 Inhibitors in Treating Non-diabetic Chronic Kidney Disease

In recent years, inhibitors of the sodium-glucose co-transporter 2 (SGLT2 inhibitors) have been shown to have significant protective effects on the kidney and the cardiovascular system in patients with diabetes. This effect is also manifested in chronic kidney disease (CKD) patients and is minimally due to improved glycaemic control. Starting from these positive findings, SGLT2 inhibitors have also been tested in patients with non-diabetic CKD or heart failure with reduced ejection fraction. Recently, the DAPA-CKD trial showed a significantly lower risk of CKD progression or death from renal or cardiovascular causes in a mixed population of patients with diabetic and non-diabetic CKD receiving dapagliflozin in comparison with placebo. In patients with heart failure and reduced ejection fraction, two trials (EMPEROR-Reduced and DAPA-HF) also found a significantly lower risk of reaching the secondary renal endpoint in those treated with an SGLT2 inhibitor in comparison with placebo. This also applied to patients with CKD. Apart from their direct mechanism of action, SGLT2 inhibitors have additional effects that could be of particular interest for patients with non-diabetic CKD. Among these, SGLT2 inhibitors reduce blood pressure and serum acid uric levels and can increase hemoglobin levels. Some safety issues should be further explored in the CKD population. SGLT2 inhibitors can minimally increase potassium levels, but this has not been shown by the CREDENCE trial. They also increase magnesium and phosphate reabsorption. These effects could become more significant in patients with advanced CKD and will need monitoring when these agents are used more extensively in the CKD population. Conversely, they do not seem to increase the risk of acute kidney injury.