Combination therapy for kidney disease in people with diabetes mellitus

Nat Rev Nephrol. 2024 Jul;20(7):433-446. doi: 10.1038/s41581-024-00827-z. Epub 2024 Apr 3.

Abstract

Diabetic kidney disease (DKD), defined as co-existing diabetes and chronic kidney disease in the absence of other clear causes of kidney injury, occurs in approximately 20-40% of patients with diabetes mellitus. As the global prevalence of diabetes has increased, DKD has become highly prevalent and a leading cause of kidney failure, accelerated cardiovascular disease, premature mortality and global health care expenditure. Multiple pathophysiological mechanisms contribute to DKD, and single lifestyle or pharmacological interventions have shown limited efficacy at preserving kidney function. For nearly two decades, renin-angiotensin system inhibitors were the only available kidney-protective drugs. However, several new drug classes, including sodium glucose cotransporter-2 inhibitors, a non-steroidal mineralocorticoid antagonist and a selective endothelin receptor antagonist, have now been demonstrated to improve kidney outcomes in people with type 2 diabetes mellitus. In addition, emerging preclinical and clinical evidence of the kidney-protective effects of glucagon-like-peptide-1 receptor agonists has led to the prospective testing of these agents for DKD. Research and clinical efforts are geared towards using therapies with potentially complementary efficacy in combination to safely halt kidney disease progression. As more kidney-protective drugs become available, the outlook for people living with DKD should improve in the next few decades.

Publication types

  • Review
  • Research Support, U.S. Gov't, P.H.S.
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetic Nephropathies* / drug therapy
  • Diabetic Nephropathies* / etiology
  • Drug Therapy, Combination*
  • Endothelin Receptor Antagonists / therapeutic use
  • Glucagon-Like Peptide-1 Receptor / agonists
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Mineralocorticoid Receptor Antagonists / therapeutic use
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use

Substances

  • Sodium-Glucose Transporter 2 Inhibitors
  • Hypoglycemic Agents
  • Mineralocorticoid Receptor Antagonists
  • Endothelin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Glucagon-Like Peptide-1 Receptor