Related Experiment Videos
Model development and analysis of tenidap-induced proteinuria in the rat
1Pfizer Incorporated, Central Research Division, Groton, Connecticut, USA.
The Journal of Pharmacology and Experimental Therapeutics
|December 1, 1996
Summary
Tenidap causes reversible proteinuria in rats by reducing albumin reabsorption in the proximal tubules. This effect is not linked to broader kidney damage or impaired overall renal function.
Area of Science:
- Nephrology
- Pharmacology
- Toxicology
Background:
- Tenidap, an antirheumatic agent, has shown mild, reversible proteinuria in human trials.
- Understanding the mechanism and safety of tenidap's proteinuric effects is crucial.
Purpose of the Study:
- To investigate the mechanistic basis and safety profile of tenidap-induced proteinuria in a rat model.
- To assess the reversibility of tenidap's renal effects and associated morphological changes.
Main Methods:
- Female Sprague-Dawley rats were administered tenidap orally for 4-6 weeks, followed by a reversal period.
- Pharmacokinetics, renal function, and histology were evaluated.
- In situ microperfusion of proximal tubules assessed albumin absorption rates.
Main Results:
- Tenidap increased urinary protein, albumin, and phosphate excretion (2-8 fold) in rats.
- These effects were reversible within 9 days and preceded papillary degeneration.
- Proximal tubule albumin reabsorption decreased by 68% without affecting other renal functions or causing significant histological damage.
Conclusions:
- Tenidap induces rapid, stable, and reversible phosphaturia, microalbuminuria, and proteinuria in rats.
- The proteinuric effect stems from impaired proximal tubule albumin reabsorption.
- These renal changes were not associated with systemic renal dysfunction or tubulointerstitial nephritis.