To study the effects of chronic osmotic diuresis which were not associated with hyperglycaemia on the rat kidney, osmotic diuresis was induced byi. v. infusion of urea. A 5 mol/1 urea solution was continuously infused at a rate of 100 ml. kg-1. day-t on the basis of body weight on day 0. Duration of infusion was 2, 6,10 or 14 days. Control rats received continuously infused Ringer's solution. Urea-treated groups developed osmotic diuresis (urine flow = about 0.04 ml-min-1.100 g body weight -1) comparable to that in rats with experimental diabetes mellitus induced by i.v. streptozotocin (55 mg/kg), however urea-induced osmotic diuresis was not associated with blood glucose level increases. Compared with their controls, rats receiving urea for 2-14 days had markedly increased kidney weight. Rats receiving urea for 10 days showed greatest kidney weight increase, 0.565 + 0.044 g/100 g body weight (mean + SD), representing a 53 % increase compared with the control (0.369 + 0.034 g/100 g body weight). Kidney weight was associated with increases in kidney protein content. In contrast, none of control kidney weight values differed significantly from day 0 values ( = normal rats; 0.387 + 0.028 g/100 g body weight). Creatinine clearance values in urea-treated groups were also higher than those in controls. The maximum value, 0.65+0.17.ml.min -1.100 g body weight-1, was recorded in the 14-day group and was significantly higher than the corresponding control value (0.34 + 0.07 ml. min-1.100 g body weight-1) (p < 0.001). Urea clearance values were also significantly higher in urea-treated groups than in respective controls. This study suggests that osmotic diuresis may induce renal hypertrophy/hyperplasia and glomerular hyperfiltration immediately after development of diabetes. [Diabetologia (1994) 37: 225-231] Key words Osmotic diuresis, urea, renal hypertrophy, glomerular hyperfiltration, diabetes, rat.
Renal hypertrophy and glomerular hyperfiltration develop early in the course of diabetic nephropathy [1-3]. Mogensen et al. [4] delineated five stages of diabetic nephropathy in insulin-dependent diabetes mellitus and defined the first phase as the appearance of renal hypertrophy and glomerular hyperfiltration. Studies