Renal function in the noninsulin-dependent diabetic rat: effects of unilateral nephrectomy

A new model of noninsulin-dependent diabetic (NIDD) is described which exhibits more prominent defects in renal function than does the standard neonatal NIDD model. To produce this model, 2-day-old neonatal male Wistar Kyoto (WKY) rats were injected intraperitoneally with streptozotocin (90 mg/kg; NIDD), while their corresponding nondiabetic controls were administered vehicle (citrate buffer, pH: 4.5; control). At 3 weeks of age, the animals were weaned, and 1 week later, under ether anesthesia, the animals underwent a right nephrectomy or a sham operation. Diabetes was confirmed by intraperitoneal administration of a glucose load (2g/kg), which resulted in significantly higher blood glucose concentration in the NIDD, compared to the nondiabetic rats. Surgical reduction of renal mass had no effect on the glycemic response to a glucose tolerance test in either group. Intravenous administration of an isotonic saline load resulted in a similar pattern of enhanced sodium and fluid excretion in the two-kidney sham-operated nondiabetic and NIDD rats. These responses were significantly higher than those observed in their counterparts with one remaining kidney. Yet, the natriuretic and diuretic responses to the saline load were significantly lower in the nephrectomized NIDD, compared to the nephrectomized nondiabetic rats. The glomerular filtration rate was similar in the sham-operated (two kidneys) NIDD and nondiabetic rats. In contrast, both the basal and saline-stimulated glomerular filtration rate were lower in the nephrectomized NIDD rats compared to the nephrectomized nondiabetic group. Mean arterial pressure was similar between the two nephrectomized groups, thereby ruling out a significant contribution from the pressure-diuresis-natriuresis mechanism to the reduction in sodium and fluid excretion in the nephrectomized NIDD rats. Thus, unilateral nephrectomy is an effective method of accelerating the manifestation of NIDD-related renal alterations. The mild, but progressive, nature of diabetes in this model should facilitate the investigation of temporal changes in renal function in NIDDM.