Hyaluronan Inhibition as a Therapeutic Target for Diabetic Kidney Disease: What Is Next?

Abstract

Diabetic kidney disease (DKD) is the leading cause of CKD and ESKD in the United States and worldwide. Pharmacotherapy and lifestyle modifications for glycemia, dyslipidemia, and BP control have shown success in slowing the progression of DKD. Traditional treatments, such as angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and more recently the use of sodium-glucose cotransporter 2 inhibitors, nonsteroidal selective mineralocorticoid receptor antagonists, such as finerenone, and glucagon-like peptide 1 receptor agonists, have led to added benefits on various outcomes. However, significant residual risk for DKD progression remains despite the current standard-of-care approaches. Arteriolar hyalinosis (AH) is among the key findings seen on kidney biopsies of patients with DKD. It results from the excessive accumulation of hyaluronan (HA) in the arterioles. AH has not been targeted specifically by any of the therapeutic methods currently being used. We discuss in this manuscript the potential use of a selective therapy targeting AH and the increased total renal HA deposits using a HA synthesis inhibitor in DKD.