A Simplified Iohexol-Based Method to Measure Renal Function in Sheep Models of Renal Disease
Abstract
:1. Introduction
2. Material and Methods
2.1. Ethics Statement
2.2. Animals and Experimental Design
2.3. Iohexol Measurements
2.4. Calibration and Quality Control Standards
2.5. Pharmacokinetic Analyses: One- and Two-compartment Models
2.6. Sensitivity Analysis
2.7. Statistical Analysis: Tests of Agreement
3. Results
3.1. Iohexol Plasma Analysis
3.2. Pharmacokinetic Clearance Profiles
3.3. Two-Compartment: CL2
3.4. One-Compartment Model: CL1
3.5. One-Compartment Model Adjusted by a Formula: CL1f
3.6. Simplified Two-Compartment Model (SM)
3.7. Analysis of Agreement
3.8. Sensitivity Analysis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Houdebine, L.M. The mouse as an animal model for human diseases. In The Laboratory Mouse; Hedrich, H., Ed.; Academic Press: Cambridge, MA, USA, 2004; pp. 99–110. [Google Scholar]
- Muhammad, S. Nephrotoxic nephritis and glomerulonephritis: Animal model versus human disease. Br. J. Biomed. Sci. 2014, 71, 168–171. [Google Scholar] [CrossRef]
- Betz, B.; Conway, B.R. Recent advances in animal models of diabetic nephropathy. Nephron Exp. Nephrol. 2014, 126, 191–195. [Google Scholar] [CrossRef] [PubMed]
- Herrmann, S.M.; Sethi, S.; Fervenza, F.C. Membranous nephropathy: The start of a paradigm shift. Curr. Opin. Nephrol. Hypertens. 2012, 21, 203–210. [Google Scholar] [CrossRef] [PubMed]
- Taylor, C.M.; Williams, J.M.; Lote, C.J.; Howie, A.J.; Thewles, A.; Wood, J.A.; Milford, D.V.; Raafat, F.; Chant, I.; Rose, P.E. A laboratory model of toxin-induced hemolytic uremic syndrome. Kidney Int. 1999, 55, 1367–1374. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yokota, S.D.; Benyajati, S.; Dantzler, W.H. Comparative aspects of glomerular filtration in vertebrates. Ren. Physiol. 1985, 8, 193–221. [Google Scholar] [CrossRef] [PubMed]
- Hamernik, D.L. Farm animals are important biomedical models. Anim. Front. 2019, 9, 3–5. [Google Scholar] [CrossRef] [Green Version]
- Buys-Gonçalves, G.F.; De Souza, D.B.; Sampaio, F.J.; Pereira-Sampaio, M.A. Anatomical relationship between the kidney collecting system and the intrarenal arteries in the sheep: Contribution for a new urological model. Anat. Rec. 2016, 299, 405–411. [Google Scholar] [CrossRef] [PubMed]
- Becker, G.J.; Hewitson, T.D. Animal models of chronic kidney disease: Useful but not perfect. Nephrol. Dial. Transplant. 2013, 28, 2432–2438. [Google Scholar] [CrossRef] [Green Version]
- Bujok, J.; Walski, T.; Czerski, A.; Gałecka, K.; Grzeszczuk-Kuć, K.; Zawadzki, W.; Witkiewicz, W.; Komorowska, M. Sheep model of haemodialysis treatment. Lab. Anim. 2018, 52, 176–185. [Google Scholar] [CrossRef]
- Lankadeva, Y.R.; Kosaka, J.; Iguchi, N.; Evans, R.G.; Booth, L.C.; Bellomo, R.; May, C.N. Effects of Fluid Bolus Therapy on Renal Perfusion, Oxygenation, and Function in Early Experimental Septic Kidney Injury. Crit. Care Med. 2019, 47, e36–e43. [Google Scholar] [CrossRef]
- Alexander Springer, A.; Kratochwill, K.; Bergmeister, H.; Csaicsich, D.; Huber, J.; Bilban, M.; Mayer, B.; Mühlberger, I.; Amann, G.; Horcher, E.; et al. A Combined Transcriptome and Bioinformatics Approach to Unilateral Ureteral Obstructive Uropathy in the Fetal Sheep Model. J. Urol. 2012, 187, 751–756. [Google Scholar] [CrossRef] [PubMed]
- Lankadeva, Y.R.; Singh, R.R.; Tare, M.; Moritz, K.M.; Denton, K.M. Loss of a Kidney During Fetal Life: Long-Term Consequences and Lessons Learned. Am. J. Physiol. Renal. Physiol. 2014, 306, F791–F800. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Peters, C.A. Animal Models of Fetal Renal Disease. Prenat. Diagn. 2001, 21, 917–923. [Google Scholar] [CrossRef] [PubMed]
- Singh, R.R.; McArdle, Z.M.; Iudica, M.; Easton, L.K.; Booth, L.C.; May, C.N.; Parkington, H.C.; Lombardo, P.; Head, G.A.; Lambert, G.; et al. Sustained Decrease in Blood Pressure and Reduced Anatomical and Functional Reinnervation of Renal Nerves in Hypertensive Sheep 30 Months After Catheter-Based Renal. Denervation. Hypertension 2019, 73, 718–727. [Google Scholar] [CrossRef]
- Bloor, I.D.; Sebert, S.P.; Mahajan, R.P.; Symonds, M.E. The Influence of Sex on Early Stage Markers of Kidney Dysfunction in Response to Juvenile Obesity. Hypertension 2012, 60, 991–997. [Google Scholar] [CrossRef] [Green Version]
- Vernon, K.A.; Pickering, M.C.; Cook, T. Experimental Models of Membranoproliferative Glomerulonephritis, Including Dense Deposit Disease. Contrib. Nephrology 2011, 169, 198–210. [Google Scholar]
- Connolly, F.; Rae, M.T.; Späth, K.; Boswell, L.; McNeilly, A.S.; Duncan, W.C. In an Ovine Model of Polycystic Ovary Syndrome (PCOS) Prenatal Androgens Suppress Female Fetal Renal Gluconeogenesis. PLoS ONE 2015, 10, e0132113. [Google Scholar] [CrossRef]
- Delanaye, P.; Ebert, N.; Melsom, T.; Gaspari, F.; Mariat, C.; Cavalier, E.; Björk, J.; Christensson, A.; Nyman, U.; Porrini, E.; et al. Iohexol plasma clearance for measuring glomerular filtration rate in clinical practice and research: A review. Part 1: How to measure glomerular filtration rate with iohexol? Clin. Kidney J. 2016, 9, 682–699. [Google Scholar] [CrossRef]
- Delanaye, P.; Melsom, T.; Ebert, N.; Bäck, S.E.; Mariat, C.; Cavalier, E.; Björk, J.; Christensson, A.; Nyman, U.; Porrini, E.; et al. Iohexol plasma clearance for measuring glomerular filtration rate in clinical practice and research: A review. Part 2: Why to measure glomerular filtration rate with iohexol? Clin. Kidney J. 2016, 9, 700–704. [Google Scholar] [CrossRef]
- Donadio, C.; Tramonti, G.; Giordani, R.; Lucchetti, A.; Calderazzi, A.; Bassani, L.; Bianchi, C. Effects on renal hemodynamics and tubular function of the contrast medium iohexol in renal patients. Ren. Fail. 1990, 12, 141–146. [Google Scholar] [CrossRef]
- Sterner, G.; Frennby, B.; Mansson, S.; Nyman, U.; Van Westen, D.; Almén, T. Determining ’True’ Glomerular Filtration Rate in Healthy Adults Using Infusion of Inulin and Comparing It With Values Obtained Using Other Clearance Techniques or Prediction Equations. Scand. J. Urol. Nephrol. 2008, 42, 278–285. [Google Scholar] [CrossRef] [PubMed]
- Nesje, M.; Flåøyen, A.; Moe, L. Estimation of Glomerular Filtration Rate in Normal Sheep by the Disappearance of Iohexol From Serum. Vet. Res. Commun. 1997, 21, 29–35. [Google Scholar] [CrossRef] [PubMed]
- Russell, W.M. The development of the Animal Care. Lab. Anim. Care 1969, 19, 403–405. [Google Scholar]
- Luis-Lima, S.; García-Contreras, C.; Vázquez-Gómez, M.; Astiz, S.; Carrara, F.; Gaspari, F.; Negrín-Mena, N.; Jiménez-Sosa, A.; Jiménez-Hernández, H.; González-Bulnes, A.; et al. A Simple Method to Measure Renal Function in Swine by the Plasma Clearance of Iohexol. Int. J. Mol. Sci. 2018, 19, 232. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schwartz, G.J.; Furth, S.; Cole, S.R.; Warady, B.; Muñoz, A. Glomerular filtration rate via plasma iohexol disappearance: Pilot study for chronic kidney disease in children. Kidney Int. 2006, 69, 2070–2077. [Google Scholar] [CrossRef] [Green Version]
- Krutzén, E.; Bäck, S.E.; Nilsson-Ehle, I.; Nilsson-Ehle, P. Plasma Clearance of a New Contrast Agent, Iohexol: A Method for the Assessment of Glomerular Filtration Rate. J. Lab. Clin. Med. 1984, 104, 955–961. [Google Scholar]
- Luis-Lima, S.; Gaspari, F.; Porrini, E.; García-González, M.; Batista, N.; Bosa-Ojeda, F.; Oramas, J.; Carrara, F.; González-Posada, J.M.; Marrero, D.; et al. Measurement of glomerular filtration rate: Internal and external validations of the iohexol plasma clearance technique by HPLC. Clin. Chim. Acta 2014, 430, 84–85. [Google Scholar] [CrossRef]
- Schwartz, G.J.; Abraham, A.G.; Furth, S.L.; Warady, B.A.; Muñoz, A. Optimizing Iohexol Plasma Disappearance Curves to Measure the Glomerular Filtration Rate in Children with Chronic Kidney Disease. Kidney Int. 2010, 77, 65–71. [Google Scholar] [CrossRef] [Green Version]
- Åsberg, A.; Bjerre, A.; Almaas, R.; Luis-Lima, S.; Robertsen, I.; Salvador, C.L.; Porrini, E.; Schwartz, G.J.; Hartmann, A.; Bergan, S. Measured GFR by Utilizing Population Pharmacokinetic Methods to Determine Iohexol Clearance. Kidney Int. Rep. 2019, 5, 189–198. [Google Scholar] [CrossRef] [Green Version]
- Bland, J.M.; Altman, D.G. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986, 1, 307–310. [Google Scholar] [CrossRef]
- Lin, L.; Hedayat, A.; Wu, W. Statistical Tools for Measuring Agreement; Springer: New York, NY, USA, 2012. [Google Scholar]
- Lin, L.; Hedayat, A.; Sinha, B.; Yang, M. Statistical methods in assessing agreement: Models, issues, and tools. J. Am. Stat. Assoc. 2002, 97, 257–270. [Google Scholar] [CrossRef]
Sheep | Gender | Weight (kg) | CL2 | CL1 | CL1f | CL SM | MAPE CL2 vs. CL1f | MAPE SM vs. CL2 |
---|---|---|---|---|---|---|---|---|
1 | F | 56 | 125 | 135 | 121 | 130 | 3.1 | 3.3 |
2 | F | 49 | 111 | 128 | 116 | 116 | 4.2 | 5.1 |
3 | F | 52 | 171 | 208 | 174 | 170 | 1.5 | 0.5 |
4 | F | 48 | 79 | 89 | 84 | 75 | 5.7 | 5.0 |
5 | F | 40 | 92 | 101 | 94 | 90 | 1.8 | 2.3 |
6 | F | 51 | 99 | 112 | 103 | 96 | 3.8 | 3.6 |
7 | F | 45 | 106 | 120 | 109 | 102 | 3.0 | 3.7 |
8 | M | 45 | 98 | 110 | 101 | 97 | 3.2 | 0.9 |
9 | M | 49 | 101 | 111 | 102 | 97 | 0.9 | 4.6 |
10 | M | 67 | 171 | 194 | 164 | 174 | 4 | 1.5 |
11 | M | 54 | 117 | 121 | 110 | 115 | 6 | 2.2 |
12 | M | 65 | 119 | 132 | 119 | 120 | 0.2 | 1.0 |
13 | M | 49 | 100 | 106 | 98 | 99 | 2.2 | 1.9 |
14 | M | 51 | 116 | 130 | 117 | 114 | 1.0 | 1.6 |
15 | M | 104 | 167 | 189 | 161 | 165 | 3.7 | 1.1 |
Model | Total Deviation Index (%) | Concordance Correlation Coefficient (%) | Coverage Probability (%) | Limits of Agreement (mL/min) |
---|---|---|---|---|
CL1 vs. CL2 | 21.7 (26.3) | 0.887 (0.795) | 36.1 (20.3) | −1.7 to 30.2 |
CL1f vs. CL2 | 6.12 (8.54) | 0.987 (0.971) | 98.6 (87.1) | −8.3 to 8.4 |
SM vs. CL2 | 4.95 (6.88) | 0.992 (0.983) | 99.8 (93.6) | −6.7 to 5.1 |
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Luis-Lima, S.; Mas-Sanmartin, C.; Rodríguez-Rodríguez, A.E.; Porrini, E.; Ortiz, A.; Gaspari, F.; Diaz-Martin, L.; Åsberg, A.; Jenssen, T.; Jiménez-Sosa, A.; et al. A Simplified Iohexol-Based Method to Measure Renal Function in Sheep Models of Renal Disease. Biology 2020, 9, 259. https://doi.org/10.3390/biology9090259
Luis-Lima S, Mas-Sanmartin C, Rodríguez-Rodríguez AE, Porrini E, Ortiz A, Gaspari F, Diaz-Martin L, Åsberg A, Jenssen T, Jiménez-Sosa A, et al. A Simplified Iohexol-Based Method to Measure Renal Function in Sheep Models of Renal Disease. Biology. 2020; 9(9):259. https://doi.org/10.3390/biology9090259
Chicago/Turabian StyleLuis-Lima, Sergio, Carolina Mas-Sanmartin, Ana Elena Rodríguez-Rodríguez, Esteban Porrini, Alberto Ortiz, Flavio Gaspari, Laura Diaz-Martin, Anders Åsberg, Trond Jenssen, Alejandro Jiménez-Sosa, and et al. 2020. "A Simplified Iohexol-Based Method to Measure Renal Function in Sheep Models of Renal Disease" Biology 9, no. 9: 259. https://doi.org/10.3390/biology9090259