Development of canine chronic kidney disease model: A pilot study

Abstract

Chronic kidney disease (CKD) is a worldwide health problem with a poor prognosis. The exploration of possible medical intervention requires the presence of a suitable animal model. This work aims to induce a model of canine CKD with persistent uremia. Three dogs were used to develop canine CKD models with different techniques based on the remnant kidney model. Model (1) was subjected to excision of one renal pole of the right kidney. Model (2) was subjected to the excision of two renal poles of the right kidney. Model (3) underwent ligation of two renal arterial branches of the right kidney. A contralateral nephrectomy was performed in the three models after two weeks from the first operation. Blood and 24-hour urine samples were collected weekly to determine renal function parameters. Histopathology, Immunohistochemistry of α-SMA expression, and quantitative real-time PCR for Kim-1 & NGAL gene expression were performed on kidney tissues. According to the IRIS staging system in dogs, model (1) represented stage one of CKD with less expression of genes and α-SMA in the interstitial tissue. Model (2) represented stage three of CKD with moderate expression of genes and α-SMA and moderate glomerulointerstitial nephritis. Model (3) suffered from severe uremia. It showed the highest expression of genes and α-SMA with severe glomerulointerstitial nephritis and infarction. Therefore, model (2) was considered the best technique for developing a model of canine CKD with persistent uremia. The dog in this model became uremic and remained stable for a long time which would allow experimental manipulation.