Adriamycin-induced Nephropathy

RenaSci offers the adriamycin-induced nephropathy mouse model of chronic kidney disease (CKD). Adriamycin is a drug used in cancer chemotherapy. When given to animals it produces glomerulosclerosis and changes in tubulo-interstitial pathology that mirror the pathological changes seen in human chronic kidney disease. Another key feature of this model is kidney fibrosis.

These changes are robust and reproducible and occur within days following intravenous administration of adriamycin. They are accompanied by impaired kidney function as shown by marked increases in urine albumin excretion, uACR and uPCR. Mice treated with adriamycin also develop interstitial and glomerular kidney fibrosis.

We have validated the adriamycin-induced nephropathy mouse model using enalapril, an angiotensin-converting enzyme (ACE) inhibitor approved for the treatment of chronic kidney disease and diabetic nephropathy.

Enalapril improved the plasma, urinary and histological end-points of renal disease and also the kidney fibrosis which develops in the adriamycin-induced nephropathy model. These results demonstrate the usefulness of the adriamycin-induced nephropathy model to assess the efficacy of new drugs to treat chronic kidney disease.

 

 

Enalapril decreased the increase in urinary albumin/creatine ratio and urinary protein/creatine ratio induced by Adriamycin

adriamycin-induced nephropathy
Mice were given adriamycin on Day 0. Elanapril was given from Day 1 to 14. Urine samples were collected overnight
(16 h, ending on Day 15). Results are means and SEM (n=5-9). ***p<0.001 vs vehicle. ††p<0.01, †††p<0.001 vs adriamycin.

 

 

Enalapril reduced the histological end-points of renal disease induced by adriamycin

adriamycin-induced nephropathy

Mice were given adriamycin on Day 0. Elanapril was given from Day 1 to 14.
Results are individual scores and means and SEM (n=8-9). **p<0.01, ***p<0.001 vs vehicle. †p<0.05, ††p<0.01 vs Adriamycin.

 

Enalapril also reduces the increase in uACR and uPCR when administration begins over a week after adriamycin ie after the kidney damage had developed.

 

 

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