Evaluation of methods for producing renal dysfunction in rats

The following methods for producing renal dysfunction in rats were compared: single-step 5/6th nephrectomy, two-step 5/6th nephrectomy, bilateral ureteral ligation, and uranyl nitrate injection. Control groups consisted of single- and two-step sham-operated animals and animals that received an injection of normal saline solution. The methods were evaluated on the basis of the following criteria, which were assessed daily for 6 days: survival, body weight, hematocrit, serum creatinine concentration, serum urea nitrogen concentration, serum glutamic pyruvic transaminase activity, serum albumin concentration, and serum protein binding of salicylate (determined every other day). Animals with bilateral ureteral ligation survived only 2 days, single-step 5/6th nephrectomy caused a high incidence of fatalities. Some of the methods were associated with the development of hypoalbuminemia, but no significant elevation of transaminase activity occurred. Serum protein binding of salicylate was reduced in rats with renal dysfunction. A strong positive correlation between the creatinine and urea nitrogen concentrations in the serum of animals with renal dysfunction (r = 0.91, p less than 0.001) and a negative correlation between the serum albumin concentration and salicylate free fraction (r = -0.71, p less than 0.001) were found. Uranyl nitrate injection has the advantages of technical simplicity, a high survival rate (no deaths in this study), and relatively consistent and sustained diminution of renal function (as reflected by serum creatinine and urea nitrogen concentrations).