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

Kidney360. 2023 Jun 1;4(6):e851-e860. doi: 10.34067/KID.0000000000000126. Epub 2023 Apr 14.

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.

Trial registration: ClinicalTrials.gov NCT00225537 NCT05386420 NCT05295680 NCT05128929 NCT02780752.

Publication types

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

MeSH terms

  • Angiotensin Receptor Antagonists / pharmacology
  • Angiotensin Receptor Antagonists / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Diabetes Mellitus* / drug therapy
  • Diabetic Nephropathies* / drug therapy
  • Humans
  • Hyaluronic Acid / pharmacology
  • Hyaluronic Acid / therapeutic use
  • Renin-Angiotensin System

Substances

  • Hyaluronic Acid
  • Angiotensin-Converting Enzyme Inhibitors
  • Angiotensin Receptor Antagonists

Associated data

  • ClinicalTrials.gov/NCT00225537
  • ClinicalTrials.gov/NCT05386420
  • ClinicalTrials.gov/NCT05295680
  • ClinicalTrials.gov/NCT05128929
  • ClinicalTrials.gov/NCT02780752