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Updated: Jun 17, 2026
Ischemia-reperfusion Model of Acute Kidney Injury and Post Injury Fibrosis in Mice
Published on: August 9, 2013
Mycophenolic acid predose concentrations and renal function in a mouse model for progressive renal fibrosis
Gunnar Brandhorst1, Franziska Brehmer, Darinka T Petrova
1Department of Clinical Chemistry, University Hospital Goettingen, Goettingen, Germany. gunnar.brandhorst@med.uni-goettingen.de
Abstract:
Within the scope of this study, the potential antifibrotic effect of mycophenolate mofetil (MMF) on COL4A3-deficient mice as an animal model for progressive renal fibrosis was investigated regarding kidney function and survival. Thirty-five animals were randomly assigned to one of five groups and treated with doses of 0, 10, 50, 100, or 150 mg/kg MMF per day, respectively. When increasing somnolence was observed, indicating end-stage renal disease, the mice were euthanized and blood was obtained. Serum concentrations of creatinine, urea nitrogen, total protein, mycophenolic acid (MPA), and mycophenolic acid glucuronide (MPAG) were quantified. The kidney histology was examined using hematoxylin and eosin as well as trichrome staining. The mean overall survival was 65.9 (+/-6.1) days with no significant difference between the treatment groups (P > 0.05, Mantel-Cox test). Serum predose concentrations of MPA and MPAG showed considerable interindividual variability. There was no correlation between survival time and MPA or MPAG concentrations (P > 0.05, Spearman rank correlation). However, an apparent decrease in serum creatinine and urea nitrogen concentrations was observed at higher doses of MMF, eg, -54% for creatinine in the 150-mg/kg/day group compared with placebo. A highly significant reciprocal correlation between MPA concentrations and serum creatinine was demonstrated (P < 0.01, r = -0.655, Spearman rank correlation). In conclusion, MMF may be a candidate drug for preserving kidney function in progressive renal fibrosis.
Insights
Mycophenolate mofetil (MMF) showed potential in preserving kidney function in a progressive renal fibrosis mouse model. Higher MMF doses correlated with reduced creatinine and urea nitrogen levels, suggesting therapeutic promise.
Area of Science:
- Nephrology
- Pharmacology
- Immunology
Background:
- Progressive renal fibrosis is a significant cause of kidney disease.
- COL4A3 deficiency serves as a relevant animal model for studying renal fibrosis.
- Mycophenolate mofetil (MMF) is an immunosuppressant with potential antifibrotic properties.
Purpose of the Study:
- To investigate the antifibrotic effects of MMF in a COL4A3-deficient mouse model.
- To assess the impact of MMF on kidney function and survival rates.
- To explore the correlation between MMF dosage, drug concentrations, and renal biomarkers.
Main Methods:
- Thirty-five COL4A3-deficient mice were randomized into five groups receiving varying MMF doses (0-150 mg/kg/day).
- Kidney function was evaluated by measuring serum creatinine, urea nitrogen, and total protein.
- Pharmacokinetic analysis of mycophenolic acid (MPA) and its glucuronide (MPAG) was performed, alongside histological examination of kidney tissue.
Main Results:
- No significant difference in overall survival was observed across MMF treatment groups.
- Higher MMF doses demonstrated a notable decrease in serum creatinine and urea nitrogen levels.
- A significant inverse correlation was found between MPA concentrations and serum creatinine levels.
Conclusions:
- MMF may be a potential therapeutic agent for preserving kidney function in progressive renal fibrosis.
- The observed reduction in key renal biomarkers suggests a renoprotective effect of MMF.
- Further research is warranted to elucidate the precise mechanisms and clinical efficacy of MMF in renal fibrosis.
