Related Experiment Video

Updated: Jan 10, 2026

A Mouse Model to Evaluate the Long-Term Structural and Functional Outcomes after the Reversal of Prolonged Unilateral Ureteric Obstruction
05:34

A Mouse Model to Evaluate the Long-Term Structural and Functional Outcomes after the Reversal of Prolonged Unilateral Ureteric Obstruction

Published on: July 18, 2025

461

Biphasic actions of the adenosine A2a receptor antagonist istradefylline in mice with obstructive uropathy

Emily S H Yeung1,2, Duc Tin Tran1, Sri Nagarjun Batchu1

  • 1Keenan Research Centre for Biomedical Science, St. Michael's Hospital, 6-151 61 Queen Street East, Toronto, ON, M5C 2T2, Canada.

Scientific Reports
|November 20, 2025
PubMed

Insights

Repurposing the Parkinson's drug istradefylline for kidney disease showed promise. Late intervention with istradefylline attenuated kidney fibrosis, but early intervention increased mortality in mice.

Area of Science:

  • Nephrology
  • Pharmacology
  • Fibrosis Research

Background:

  • Progressive kidney fibrosis characterizes chronic kidney disease (CKD) regardless of cause.
  • The adenosine A2a receptor is present on activated kidney fibroblasts.
  • Istradefylline, an adenosine A2a receptor antagonist, is approved for Parkinson's disease.

Purpose of the Study:

  • To investigate the potential of repurposing istradefylline for treating kidney fibrosis.
  • To evaluate the efficacy and safety of istradefylline in a mouse model of kidney fibrosis.

Main Methods:

  • Mice with kidney fibrosis induced by unilateral ureteral obstruction (UUO) were treated with vehicle or istradefylline.
  • Intervention timing was varied: early (post-surgery day 1) or late (post-surgery day 7).
  • Gene expression and extracellular matrix protein levels were analyzed in kidney tissue and fibroblasts.

Main Results:

  • Early istradefylline intervention increased mortality and inflammatory gene expression in UUO mice.
  • Late istradefylline intervention attenuated profibrotic markers, including Il11 and extracellular matrix proteins.
  • Istradefylline reduced Il11, Col1a1, and Fn1 expression in fibroblasts stimulated with transforming growth factor-β1.

Conclusions:

  • Adenosine A2a receptor antagonism has a narrow therapeutic window for slowing CKD progression due to dual anti-inflammatory and profibrotic roles.
  • Late-stage intervention with istradefylline shows potential for mitigating kidney fibrosis.
  • Further research is needed to optimize istradefylline's use in kidney disease treatment.

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