Unilateral Ureteral Obstruction (UUO) induces a progressive renal fibrosis, similar to that seen in most human progressive renal diseases. Surgical UUO in murines is a good model for screening the efficacy of compounds used to treat progressive renal diseases.
Preclinical Drug Efficacy Studies
Mice (C57BL/6, Female)
Mice are anesthetized by i.p. injection, and then shaved on the left side of the abdomen. A vertical incision is made through the skin with a scalpel and the skin is retracted. A second incision is made through the peritoneum and that skin is also retracted to reveal the kidney. Using forceps the kidney is brought to the surface and the ureter is tied with surgical silk, twice, below the kidney. The ligated kidney is placed gently back into its correct anatomical position and sterile saline is added to replenish loss of fluid. The incisions are sutured and mice are caged individually. 6-days post ligation, mice are placed in metabolic cages for the collection of urine. Animals are sacrificed 12-hours later and blood and tissues are collected. Dose administration will follow the experimental protocol.
Clinical observations, body weight, blood plasma for albumin and creatinine, histological examination (H&E) and immunohistochemical staining for identification of accumulated macrophages in kidney sections.
Chevalier RL, Forbes MS, Nornhill BA. (2009) Ureteral obstruction as a model of renal interstitial fibrosis and obstructive nephropathy. Kidney Int.; 75(11): 1145-52.