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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) CLl f : 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 CL1 f 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.

A Simplified Iohexol-Based Method to Measure Renal Function in Sheep Models of Renal Disease