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A SORAFENIB INDUCED MODEL OF GLOMERULAR KIDNEY DISEASE

A Stavniichuk1, O Savchuk1, Abdul Hye Khan2

  • 1Taras Shevchenko National University, Kyiv, Ukraine.

Visnyk Kyivs'Koho Natsional'Noho Universytetu Imeni Tarasa Shevchenka. Biolohiia
|November 30, 2020
PubMed

Insights

Researchers developed a rat model for chronic kidney disease using sorafenib, a cancer drug. This model shows key features of kidney disease, including glomerular injury and protein loss, aiding future research.

Area of Science:

  • Nephrology
  • Pharmacology
  • Oncology

Background:

  • Glomerular injury and proteinuria are hallmarks of chronic kidney disease (CKD).
  • Sorafenib, a tyrosine kinase inhibitor targeting VEGF signaling, is used in cancer therapy but causes renal side effects.
  • Developing reliable preclinical models for CKD is crucial for understanding disease mechanisms and testing interventions.

Purpose of the Study:

  • To establish a novel rat model of chronic kidney disease (CKD) utilizing the nephrotoxic effects of sorafenib.
  • To characterize the pathological and molecular changes in the kidney following sorafenib administration.

Main Methods:

  • Rats were administered sorafenib and a high-salt diet (8% NaCl) for 8 weeks.
  • Physiological parameters (blood pressure, proteinuria) and glomerular injury were assessed.
  • Renal mRNA expression of structural proteins (nephrin, podocin, etc.) and markers of endothelial-to-mesenchymal transition (EndoMT) were quantified.

Main Results:

  • Sorafenib-treated rats developed significant hypertension, proteinuria, and glomerular injury compared to controls.
  • A marked decrease in mRNA expression of key glomerular structural proteins was observed.
  • Evidence of activated renal cortical endothelial-to-mesenchymal transition (EndoMT) was detected, indicated by altered expression of endothelial and mesenchymal markers.

Conclusions:

  • A reproducible rat model of sorafenib-induced chronic kidney disease (CKD) characterized by glomerular injury has been successfully developed.
  • The model demonstrates molecular alterations including reduced expression of essential glomerular proteins and activation of kidney EndoMT.
  • This preclinical model offers a valuable tool for investigating CKD pathogenesis and evaluating potential therapeutic strategies.
Keywords:
glomerular injurysorafenibvascular endothelial growth factor

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