Calculation of glomerular filtration rate in conscious rats by the use of a bolus injection of iodixanol and a single blood sample

Abstract

Introduction: To establish a simple and convenient procedure for the determination of glomerular filtration rate (GFR) in conscious rats, we developed a single-blood-sample method, in contrast to the conventional three-sample method, using a bolus injection of the nonionic contrast medium iodixanol.

Methods: Iodixanol was intravenously administered at 1500 mg I/kg to healthy or renal-impaired rats, and blood was collected 60, 120, and 180 min later. Serum iodixanol concentrations were measured by HPLC, and serum urea nitrogen (UN) and creatinine concentrations were determined as renal function tests.

Results: In rats subjected to 1/2 and 3/4 nephrectomies, GFR values decreased significantly without and with increases in serum UN and creatinine concentrations, respectively. In rats treated subcutaneously with gentamicin sulfate (GM) at 80 mg/kg/day or puromycin aminonucleoside (PAN) at 15 mg/kg/day for 10 consecutive days, the GFR values decreased or showed a tendency to decrease before increases in serum UN and creatinine concentrations. Accordingly, when the GFR decreased to more than 60% of the basal value, serum UN or creatinine concentrations became elevated. The GFR values obtained from the three-sample method were closely correlated (r=0.83) with those calculated from the estimated distribution volume (V) and serum iodixanol concentration 120 min after iodixanol injection in the single-blood-sample method in which serum iodixanol concentrations ranged between 20 and 250 microg I/mL.

Discussion: These results suggest that the single-blood-sample method with a bolus injection of iodixanol, allowing for the repeated use of the same animals, is an expedient procedure without ensuring accurate urine collection.