Abstract
Sheep are highly adequate models for human renal diseases because of their many similarities in the histology and physiology of kidney and pathogenesis of kidney diseases. However, the lack of a simple method to measure glomerular filtration rate (GFR) limits its use as a model of renal diseases. Hence, we aimed to develop a simple method to measure GFR based on the plasma clearance of iohexol by assessing different pharmacokinetic models: (a) CL2: two-compartment (samples from 15 to 420 min; reference method); (b) CL1: one-compartment (samples from 60 to 420 min); (c) CLlf: CL1 adjusted by a correction formula and (d) SM: simplified CL2 (15 to 300 min). Specific statistics of agreement were used to test the models against CL2. The agreement between CL1 and CL2 was low, but both CL1f and SM showed excellent agreement with CL2, as indicated by a total deviation index of ~5–6%, a concordance correlation of 0.98–0.99% and a coverage probability of 99–100%, respectively. Hence, the SM approach is preferable due to a reduced number of samples and shorter duration of the procedure; two points that improve animal management and welfare.
Highlights
Preclinical research on the pathogenesis and treatment of renal disease is largely sustained on translational studies in animal models
We aimed to develop a simple and reliable method to measure glomerular filtration rate (GFR) using the plasma clearance of iohexol, with a reduced number of blood samples and/or a shorter time for the procedure in conscious and unrestrained sheep
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Summary
Preclinical research on the pathogenesis and treatment of renal disease is largely sustained on translational studies in animal models. Mainly mice and rats, are the species generally preferred in preclinical studies, because of the benefits related to cost, short lifecycle and the availability of genetically modified strains [1,2]. These models are useful for analyzing molecular aspects of Biology 2020, 9, 259; doi:10.3390/biology9090259 www.mdpi.com/journal/biology. There is a profuse use of large animal models (i.e., sheep and pig [7]) for the study of renal diseases. The advantages of these models are multiple. The only difference among human, swine and sheep kidneys is that the collecting ducts of sheep consist only of a renal pelvis with several recesses [8]
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