To estimate the glomerular filtration rate (GFR) in conscious rabbits, a single-sample method using the non-ionic contrast medium iodixanol was compared with a three-sample method using the standard agent inulin. Iodixanol and inulin were co-administered intravenously to male New Zealand White rabbits at 60 mg I/kg and 40 mg/kg, respectively, and blood was collected 30, 60, 90 and 120 min later. Serum iodixanol and inulin concentrations were separately determined by high performance liquid chromatography and colorimetry, respectively. Serum urea nitrogen (UN) and creatinine concentrations were also determined. Based on the data from healthy and cisplatin-treated rabbits, the GFR estimated by iodixanol was well consistent with that by inulin. Further, when the GFR decreased to more than 60% of the reference value, serum creatinine concentrations became elevated. However, serum UN concentrations exhibited wide fluctuations, presumably due to a difference in renal handlings. The single-sample method using iodixanol was considered to be an expedient tool in both clinical and research settings, because the stress due to a multi-sample method was reduced.
Keywords: Glomerular filtration rate (GFR), inulin, iodixanol, rabbits, serum clearanceLaboratory Animals 2012; 46: 341-344. DOI: 10.1258/la.2012.011065In humans, glomerular filtration rate (GFR) is the best overall index of renal function in diseases and their treatment and management. Inulin 1 and the non-ionic monomeric X-ray contrast medium iohexol 2 are considered the gold standard tracers for estimating the GFR. For experimental animals, however, inulin requires specialized technical procedures and has low solubility that needs a relatively large volume of injectable solution and blood collection. Meanwhile, iohexol was reported to possess a deteriorating potential in patients with impaired renal function.3 Here, we focused on the isotonic non-ionic dimeric X-ray contrast medium iodixanol as a novel tracer, because little information is available on the measurement of rabbit GFR under conscious conditions without undergoing surgical manipulations. Iodixanol is rapidly excreted into urine without metabolic degradation and no or very little protein binding 4,5 as was the case in iohexol. Interestingly, iodixanol has been reported to be less nephrotoxic than the low-osmolar contrast media including iohexol in randomized double-blind, prospective multicenter studies using high-risk patients with chronic renal diseases. 3,6 Moreover, iodixanol has twice the amount of iodine in one molecule with low osmolarity compared with iohexol, presumably showing the same pharmacodynamic action as half the exposure dose of the whole body to iohexol.In humans, the concentration of a tracer in a single plasma sample taken a few hours after injection was previously reported to correlate with renal clearance.7 Based on this information, Jacobsson 8 devised a formula derived from a simple one-compartment model combined with the distribution volume and optimum time for taking ...