Chronic Hematuria Increases Chronic Kidney Injury and Epithelial-Mesenchymal Transition in 5/6 Nephrectomy Rats

Min Xiao1, Ajay K Medipally1, Laura Biederman1,2

  • 1Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, United States.

Frontiers in Medicine
|December 13, 2021
PubMed

Insights

Chronic hematuria worsens chronic kidney disease (CKD) progression. This study found that hematuria increases kidney damage, oxidative stress, and cell changes linked to fibrosis in a rat model.

Area of Science:

  • Nephrology
  • Pathology
  • Biochemistry

Background:

  • Chronic kidney disease (CKD) is characterized by interstitial fibrosis and tubular atrophy (IFTA).
  • Hematuria, common in kidney diseases, involves free hemoglobin which can generate reactive oxygen species (ROS).
  • Epithelial-mesenchymal transition (EMT) is implicated in IFTA development.

Purpose of the Study:

  • To investigate the impact of chronic hematuria on CKD progression.
  • To assess the effects of induced hematuria on kidney histology and cellular markers in a 5/6 nephrectomy (5/6NE) rat model.

Main Methods:

  • Rats underwent 5/6 nephrectomy (5/6NE) and were treated with warfarin (to induce hematuria) or vehicle.
  • Prothrombin time, serum creatinine, and hematuria were monitored weekly for 26 weeks.
  • Kidney tissues were analyzed for iron deposition, IFTA, ROS markers (HMOX1, protein carbonyls), EMT markers, and apoptosis (TUNEL assay).

Main Results:

  • Warfarin treatment increased hematuria, serum creatinine, and prothrombin time.
  • Increased iron-positive tubular cells, prominent IFTA, elevated ROS, and enhanced EMT markers were observed in warfarin-treated rats.
  • Apoptosis of tubular epithelial cells was significantly higher in the warfarin group.

Conclusions:

  • Chronic hematuria exacerbates CKD progression in rats.
  • Hematuria contributes to kidney damage through increased iron deposition, ROS generation, EMT, and apoptosis.
  • These findings highlight a significant role for chronic hematuria in driving CKD advancement.

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