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

Loay Salman1, Laisel Martinez2, Geovani Faddoul1

  • 1Division of Nephrology and Hypertension, Department of Medicine, Albany Med Health System, Albany, New York.

Kidney360
|April 14, 2023
PubMed

Insights

Diabetic kidney disease (DKD) remains a major health issue. Targeting hyaluronan (HA) synthesis may offer a new treatment approach for DKD by addressing arteriolar hyalinosis (AH).

Area of Science:

  • Nephrology
  • Endocrinology
  • Pharmacology

Background:

  • Diabetic kidney disease (DKD) is the primary cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) globally.
  • Current treatments, including ACE inhibitors, ARBs, SGLT2 inhibitors, finerenone, and GLP-1 RAs, slow DKD progression but leave significant residual risk.
  • Arteriolar hyalinosis (AH), characterized by excessive hyaluronan (HA) accumulation in kidney arterioles, is a key pathological finding in DKD.

Purpose of the Study:

  • To explore the potential of targeting arteriolar hyalinosis (AH) as a therapeutic strategy for diabetic kidney disease (DKD).
  • To investigate the role of hyaluronan (HA) synthesis inhibition in managing DKD-associated renal pathology.

Main Methods:

  • Review of existing literature on diabetic kidney disease (DKD) pathophysiology and current treatment modalities.
  • Analysis of the role of arteriolar hyalinosis (AH) and hyaluronan (HA) accumulation in DKD progression.
  • Discussion of the potential therapeutic application of hyaluronan (HA) synthesis inhibitors for DKD.

Main Results:

  • Arteriolar hyalinosis (AH) is a significant pathological feature in DKD resulting from excessive hyaluronan (HA) deposition.
  • Current pharmacotherapies for DKD do not specifically target AH or excessive renal HA accumulation.
  • Hyaluronan (HA) synthesis inhibition presents a novel, targeted approach to address AH in DKD.

Conclusions:

  • Targeting hyaluronan (HA) synthesis offers a promising new therapeutic avenue for diabetic kidney disease (DKD).
  • A selective therapy aimed at reducing HA deposits and mitigating arteriolar hyalinosis (AH) could address the unmet needs in DKD management.
  • Further research into HA synthesis inhibitors is warranted to evaluate their efficacy and safety in treating DKD.

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