biology Article Simplified Iohexol-Based Method for Measurement of Glomerular Filtration Rate in Goats and Pigs Maaike K. van Gelder 1,† , Jasper Stevens 2,† , Tobias T. Pieters 1 , Koen R. D. Vaessen 3 , Jaap A. Joles 1 , Marianne C. Verhaar 1 and Karin G. F. Gerritsen 1, *   Citation: van Gelder, M.K.; Stevens, J.; Pieters, T.T.; Vaessen, K.R.D.;Joles, J.A.; Verhaar, M.C.; Gerritsen, K.G.F. Simplified Iohexol-Based Method for Measurement of Glomerular Filtration Rate in Goats and Pigs. Biology 2021, 10, 461. https:// doi.org/10.3390/biology10060461 Academic Editor: Isabel R. Dias Received: 6 May 2021 Accepted: 15 May 2021 Published: 23 May 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Department of Nephrology and Hypertension, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands; m.k.vangelder-7@umcutrecht.nl (M.K.v.G.); T.T.Pieters-4@umcutrecht.nl (T.T.P.); J.A.Joles@umcutrecht.nl (J.A.J.); M.C.Verhaar@umcutrecht.nl (M.C.V.) 2 Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; j.stevens@umcg.nl 3 Central Laboratory Animal Research Facility, Utrecht University, Heidelberglaan 8, 3584 CS Utrecht, The Netherlands; K.R.D.Vaessen@uu.nl * Correspondence: K.G.F.Gerritsen@umcutrecht.nl † Both authors contributed equally. Simple Summary: To improve the treatment of patients with kidney disease, new therapies are being developed. Before being used on humans, such therapies need to be tested on animals with kidney disease because reduced kidney function may influence the safety and efficacy of the treatment. Using large animals for this purpose is important because they tolerate frequent blood sampling, which allows for repeated monitoring. Goats seem particularly suitable for the evaluation of novel hemodialysis therapies since they are docile, have easily accessible neck veins to obtain blood access and body weights comparable with humans. Currently, no simple method is available to measure kidney function in goats (with or without impaired kidney function). Therefore, we developed a simple method to measure the kidney function in goats and pigs, which is based on a single injection of iohexol and requires three blood samples. Subsequently, kidney function can be calculated using a formula derived from pharmacokinetic modelling. The measurement of kidney function using our simplified method is relatively easy to perform, reduces total blood sampling and eliminates the need for an indwelling bladder catheter as compared to existing methods that require continuous infusion of a substance and timed urine collection. Abstract: The preclinical evaluation of novel therapies for chronic kidney disease requires a simple method for the assessment of kidney function in a uremic large animal model. An intravenous bolus of iohexol was administered to goats (13 measurements in n = 3 goats) and pigs (23 measurements in n = 5 pigs) before and after induction of kidney failure, followed by frequent blood sampling up to 1440 min. Plasma clearance (CL) was estimated by a nonlinear mixed-effects model (CL NLME ) and by a one-compartmental pharmacokinetic disposition model using iohexol plasma concentrations during the terminal elimination phase (CL 1CMT ). A simple method (CL SM ) for the calculation of plasma clearance was developed based on the most appropriate relationship between CL NLME and CL 1CMT . CL SM and CL NLME showed good agreement (CL NLME /CL SM ratio: 1.00 ± 0.07; bias: 0.03 ± 1.64 mL/min; precision CL SM and CL NLME : 80.9% and 80.7%, respectively; the percentage of CL SM estimates falling within ±30% (P30) or ±10% (P10) of CL NLME : 53% and 12%, respectively). For mGFR NLME vs. mGFR SM , bias was −0.25 ± 2.24 and precision was 49.2% and 53.6%, respectively, P30 and P10 for mGFR based on CL SM were 71% and 24%, respectively. A simple method for measurement of GFR in healthy and uremic goats and pigs was successfully developed, which eliminates the need for continuous infusion of an exogenous marker, urine collection and frequent blood sampling. Keywords: glomerular filtration rate; iohexol; plasma clearance; uremic animal model; goat; chronic kidney disease Biology 2021, 10, 461. https://doi.org/10.3390/biology10060461 https://www.mdpi.com/journal/biology