Abstract
There is no simple method to measure glomerular filtration rate (GFR) in swine, an established model for studying renal disease. We developed a protocol to measure GFR in conscious swine by using the plasma clearance of iohexol. We used two groups, test and validation, with eight animals each. Ten milliliters of iohexol (6.47 g) was injected into the marginal auricular vein and blood samples (3 mL) were collected from the orbital sinus at different points after injection. GFR was determined using two models: two-compartment (CL2: all samples) and one-compartment (CL1: the last six samples). In the test group, CL1 overestimated CL2 by ~30%: CL2 = 245 ± 93 and CL1 = 308 ± 123 mL/min. This error was corrected by a first-order polynomial quadratic equation to CL1, which was considered the simplified method: SM = −47.909 + (1.176xCL1) − (0.00063968xCL12). The SM showed narrow limits of agreement with CL2, a concordance correlation of 0.97, and a total deviation index of 14.73%. Similar results were obtained for the validation group. This protocol is reliable, reproducible, can be performed in conscious animals, uses a single dose of the marker, and requires a reduced number of samples, and avoids urine collection. Finally, it presents a significant improvement in animal welfare conditions and handling necessities in experimental trials.
Highlights
Translational studies in animal models are necessary to evaluate the pathogenesis of renal disease
Iohexol eluted from the chromatographic column as two peaks at 4.03 and 4.47 min, reflecting the isomers present in the pharmacologic preparation
No interfering peaks were observed in the iohexol-free samples
Summary
Translational studies in animal models are necessary to evaluate the pathogenesis of renal disease. During the last decades, rodents have been extensively used as models for human renal disease [2]. Rodents do not completely recapitulate human renal disease. Kidney structure and function in animal models should be similar to that in humans. Humans and swine share similar features of kidney structure, function, and physiology [6,7,8,9]. Swine kidneys are multipyramidal with a cortex and several different medullary structures; each medullary pyramid forms a separate papilla and their fusion results in the formation of some compound papillae. Swine is currently recognized as an amenable model for renal pathology [10,11]
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