SGLT-2 Inhibitors and Nephroprotection in Patients with Diabetic and Non-diabetic Chronic Kidney Disease

Curr Med Chem. 2023;30(18):2039-2060. doi: 10.2174/0929867329666220825121304.

Abstract

For several years, blood pressure control and blocking of the renin-angiotensin system (RAS) represented the cornerstones of chronic kidney disease (CKD) treatment. Cardiovascular outcome trials with sodium-glucose co-transporter-2 (SGLT-2) inhibitors in patients with type 2 diabetes mellitus (DM) suggested that these agents can effectively delay the progression of CKD in these individuals. A major nephroprotective effect of canagliflozin was also shown in a renal outcome trial in patients with proteinuric diabetic CKD. The Study-to- Evaluate-the-Effect- of-Dapagliflozin-on-Renal-Outcomes-and-Cardiovascular- Mortality-in-Patients-With-Chronic-Kidney-Disease (DAPA-CKD) is a recent milestone in the field, as it included patients with both diabetic and non-diabetic proteinuric CKD and showed impressive reduction in the primary renal outcome of CKD progression, as well as the risk of hospitalization for heart failure and all-cause mortality on top of standard- of-care treatment. These benefits were consistent for patients with diabetic and non-diabetic CKD, including patients with ischemic or hypertensive nephropathy and glomerulonephritides (IgA nephropathy, focal segmental glomerulosclerosis and membranous nephropathy). Based on the above, relevant guidelines should accommodate their recommendations to implement treatment with SGLT-2 inhibitors for CKD patients.

Keywords: Diabetic CKD; SGLT-2 inhibitors; canagliflozin; dapagliflozin; glomerulonephritis; non-diabetic CKD.

MeSH terms

  • Cardiovascular Diseases* / complications
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetic Nephropathies* / etiology
  • Humans
  • Hypoglycemic Agents
  • Renal Insufficiency, Chronic* / complications
  • Renal Insufficiency, Chronic* / drug therapy
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use

Substances

  • Sodium-Glucose Transporter 2 Inhibitors
  • Hypoglycemic Agents