Next-generation therapeutics for diabetic kidney disease.

Diabetes mellitus is the leading cause of chronic kidney disease and kidney failure worldwide, and diabetic kidney disease (DKD) is associated with excess cardiovascular and all-cause mortality. The pathophysiology of DKD is complex and multifactorial, characterized by physiologically redundant haemodynamic, metabolic and inflammatory pathways that promote maladaptive renal remodelling and accelerate disease progression. Current management of DKD centres around four key pillars of guideline-directed medical therapy (GDMT): renin-angiotensin-aldosterone system inhibitors, sodium-glucose cotransporter-2 inhibitors, non-steroidal mineralocorticoid receptor antagonists and glucagon-like peptide-1 receptor agonists. These therapies are increasingly used in combination for cardiorenal protection in DKD. However, substantial residual cardiorenal risk persists even among patients receiving optimal GDMT. Next-generation therapies for DKD that are currently in development include various incretin-based therapies, endothelin receptor antagonists, aldosterone synthase inhibitors, soluble guanylate cyclase agonists and anti-inflammatory agents. These therapies are expected to complement current GDMT and further improve kidney and cardiovascular outcomes in patients with DKD.