1. Infusion experiments were performed on chronically catheterized conscious rats to assess kidney function before and after the induction of diabetes mellitus with streptozotocin. 2. Two infusion regimens were used, a conventional constant-infusion protocol and a novel computer-driven, servo-controlled fluid replacement technique. The latter enables body fluid status to be maintained throughout a study occasion by servo-controlled replacement of spontaneous urinary fluid losses. 3. The chronically catheterized conscious rat infused using a servo-controlled system appears to be the optimum model for a study of diabetic renal function. The conscious preparation circumvents problems associated with anaesthesia and acute surgery. The servo-controlled infusion protocol maintains the altered fluid status of the diabetic condition. Both hyperfiltration and polyuria, characteristics of human diabetes often absent in anaesthetized and/or constantly infused diabetic rats, were seen in all conscious servo-controlled diabetic animals. 4. The new regimen enables a more accurate assessment of renal function in experimental diabetes than with previous protocols. It should prove useful in future studies, particularly those assessing the role of anti-diabetic drugs on the kidney.

SUMMARYStandard renal clearance techniques were used to compare the effects of D-glucose, L-glucose and D-mannitol on renal calcium handling and general renal function in the anaesthetized rat. A significant (P < 0 01) calciuresis was seen in animals infused with D-glucose. This resulted from a decreased tubular reabsorption of calcium. A similar response was not seen with Lglucose or D-mannitol. The contrasting actions of the three sugars on tubular calcium transport may relate to their different transport characteristics, since only D-glucose is actively reabsorbed. Responses of the three sugars also differed with respect to fractional fluid and sodium reabsorption which were significantly (P < 0-001) lower in animals infused with Lglucose and D-mannitol, and plasma insulin concentrations which were significantly (P < 0.01) elevated only in the D-glucose group. An unexpected finding was a highly significant (P < 0 001) and progressive fall in glomerular filtration rate (GFR) in animals infused with Lglucose. The reasons for this are not known.

1. Rats with streptozotocin (STZ) diabetes are protected from gentamicin (GEN) nephrotoxicity. Because the chronic renal damage from GEN is preceded by acute renal functional changes (notably hypercalciuria), the present study aims to determine whether diabetes may also protect against the acute effects of the drug. If there is a link between the rapid physiological actions of GEN and its subsequent nephrotoxicity, the former may also be affected by the diabetic condition. 2. Standard renal clearance techniques were performed on anaesthetized rats that had been injected with STZ or vehicle 2 weeks previously. All animals were infused with 0.9% NaCl for 5 h and then either GEN (0.28 mg/kg per min) or 0.9% NaCl alone for 2 h. 3. Baseline fractional calcium excretion (FE(Ca)) of diabetic rats was three-fold that of control animals (6.6+/-0.2 vs 2.2+/-0.2%, respectively; P<0.01, MANOVA). Following GEN infusion, a comparable increase in FE(Ca) occurred in control and diabetic rats (5.3+/-0.6 vs 5.3+/-0.8%, respectively; NS). 4. Streptozotocin diabetes, therefore, does not alter the acute hypercalciuric response to GEN. This may suggest that the acute effects of GEN on renal calcium handling do not contribute to the subsequent nephrotoxicity. However, the higher baseline FE(Ca) seen in diabetic rats may afford protection against the renal injury caused by gentamicin.