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

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. He...

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Published inBiology (Basel, Switzerland) Vol. 9; no. 9; p. 259
Main Authors Luis-Lima, Sergio, Mas-Sanmartin, Carolina, Rodríguez-Rodríguez, Ana Elena, Porrini, Esteban, Ortiz, Alberto, Gaspari, Flavio, Diaz-Martin, Laura, Åsberg, Anders, Jenssen, Trond, Jiménez-Sosa, Alejandro, Martinez-Ros, Paula, Gonzalez-Bulnes, Antonio
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 01.09.2020
MDPI
Subjects
Agreements
Calibration
Contrast media
Glomerular filtration rate
Hogs
Housing
iohexol plasma clearance
Kidney diseases
Laboratory animals
Measurement
Methods
Pathogenesis
Pharmacokinetics
Physiology
Plasma
Quality control
Quality standards
Renal function
Sheep
sheep model
Statistical analysis
Spain
sheep model
renal function
iohexol plasma clearance
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Summary: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 : 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 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.
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ISSN:2079-7737
2079-7737
DOI:10.3390/biology9090259