Iohexol plasma clearance, a simple and reliable method to measure renal function in conscious mice.
In mice, renal function evaluated by serum creatinine has limitations. Gold standard methods using radioactive markers are cumbersome. We aimed to develop the iohexol plasma clearance as a simple assessment of renal function in conscious mice. We used two groups of mice: testing and validation, formed by 16 animals (8 male and 8 female) each. Iohexol was injected intravenously into the tail vein (6.47 mg), and tail tip blood samples were collected at 1, 3, 7, 10, 15, 35, 55, and 75 min. Iohexol plasma clearances were calculated in two ways: (1) two-compartment model (CL2) using all time points and (2) one-compartment model (CL1) using only the last four points. In the testing group, CL1 overestimated the true clearance (CL2). Therefore, CL1 was recalculated applying a correction factor calculated as the ratio between CL2/CL1. The latter was considered as the simplified method. CL2 averaged 223.3 ± 64.3 μl/min and CL1 252.4 ± 76.4 μl/min, which lead to a CF of 0.89. Comparable results for CL2, CL1, and simplified method were observed in the validation group. Additionally, we demonstrated the capacity of the simplified method to quantitatively assess different degrees of renal function in three mouse models: hyperoxaluric-CKD (87.4 ± 28.3 μl/min), heminephrectomized (135-0 ± 50.5 μl/min), and obese (399.6 ± 112.1 μl/min) mice. We have developed a simple and reliable method to evaluate renal function in conscious mice under diverse clinical conditions. Moreover, the test can be repeated in the same animal, which makes the method useful to examine renal function changes over time.
Nephrology Department, University Hospital of the Canary Islands, La Laguna, Tenerife, Spain.|University of La Laguna, Instituto Tecnologías Biomédicas (ITB), Tenerife, Spain.
Sergio
S
Luis-Lima
Research Unit, University Hospital of the Canary Islands, La Laguna, S/C Tenerife, Spain.
Ana Elena
AE
Rodríguez-Rodríguez
Department of Pathology, Centre for Biomedical Research on Rare Diseases (CIBERER), La Laguna, S/C Tenerife, Spain.
Cristina
C
Martín-Higueras
Department of Physiology and Institute of Biomedical Technologies, University of La Laguna, Tenerife, Spain (D.A.d.l.R.), La Laguna, S/C Tenerife, Spain.
Catalina
C
Sierra-Ramos
IRCCS- Istituto di Ricerche Farmacologiche Mario Negri, Clinical Research Center for Rare Diseases 'Aldo & Cele Daccò', Ranica, BG, Italy.
Fabiola
F
Carrara
Pharmacology Unit, Medical School, University of La Laguna, La Laguna, S/C Tenerife, Spain.
María Rosa
MR
Arnau
Department of Physiology and Institute of Biomedical Technologies, University of La Laguna, Tenerife, Spain (D.A.d.l.R.), La Laguna, S/C Tenerife, Spain.
Diego
D
Alvarez de la Rosa
Department of Pathology, Centre for Biomedical Research on Rare Diseases (CIBERER), La Laguna, S/C Tenerife, Spain.
Eduardo
E
Salido
IRCCS- Istituto di Ricerche Farmacologiche Mario Negri, Clinical Research Center for Rare Diseases 'Aldo & Cele Daccò', Ranica, BG, Italy.
Flavio
F
Gaspari
University of La Laguna, Instituto Tecnologías Biomédicas (ITB), Tenerife, Spain. esteban.l.porrini@gmail.com.
Esteban
E
Porrini
D000818:Animals; D003243:Consciousness; D003287:Contrast Media / Q000493:pharmacokinetics*; D005260:Female; D007472:Iohexol / Q000493:pharmacokinetics*; D007668:Kidney / Q000502:physiology*; D007677:Kidney Function Tests / Q000379:methods*; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D065667:Renal Elimination
D003287:Contrast Media; D007472:Iohexol
Conscious mice; Glomerular filtration rate; Gold standard technique; Iohexol plasma clearance; One-compartment model