New approach for chronic renal failure model by direct kidney injection of doxorubicin in rats.

Abstract

Several experimental chronic renal failure (CRF) models are available for testing new drugs. A CRF model induced by the intravenous injection of 2 mg/kg of doxorubicin (DXR) twice during a 20-day interval reportedly results in pathological characteristics similar to glomerular sclerosis seen clinically. However, it normally takes more than 16 weeks to create this CRF model. We used three methods of direct drug injection into the kidney of rats to determine the method that would induce CRF within 4 weeks; Method A: DXR was injected directly into both kidneys; Method B: DXR was injected directly into the left kidney immediately after right nephrectomy; Method C: DXR was injected directly into the left kidney 1 week before right nephrectomy, and DXR was injected again directly into the left kidney. As a result, urinary protein, blood urea nitrogen (BUN), creatinine and creatinine clearance were significantly changed >1 week after the injection of DXR by Method C. Quantification of tissue transforming growth factor-beta1 (TGF-beta1), which is a prime fibrogenic cytokine in renal fibrosis, significantly increased in the kidney. A light microscopic image showed glomerular decrement, tubular dilation and atrophy and vacuolation of parenchyma. In conclusion, the results of this study demonstrate that the DXR model using Method C develops CRF within 4 weeks.