Present and future directions in diabetic kidney disease

Abstract

Diabetic kidney disease (DKD) is the leading cause of kidney failure and is associated with substantial risk of cardiovascular disease, morbidity, and mortality. Traditionally, DKD prevention and management have focused on addressing hyperglycemia, hypertension, obesity, and renin-angiotensin system activation as important risk factors for disease. Over the last decade, sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists have been shown to meaningfully reduce risk of diabetes-related kidney and cardiovascular complications. Additional agents demonstrating benefit in DKD such as non-steroidal mineralocorticoid receptor antagonists and endothelin A receptor antagonists are further contributing to the growing arsenal of DKD therapies. With the availability of greater therapeutic options comes the opportunity to individually optimize DKD prevention and management. Novel applications of transcriptomic, proteomic, and metabolomic/lipidomic technologies, as well as use of artificial intelligence and reinforced learning methods through consortia such as the Kidney Precision Medicine Project and focused studies in established cohorts hold tremendous promise for advancing our understanding and treatment of DKD. Specifically, enhanced understanding of the molecular mechanisms underlying DKD pathophysiology may allow for the identification of new mechanism-based DKD subtypes and the development and implementation of targeted therapies. Implementation of personalized care approaches has the potential to revolutionize DKD care.

Keywords: Chronic kidney disease; Diabetic kidney disease; Omics; Precision medicine.