A Limited Sampling, Simple, and Useful Method for Determination of Glomerular Filtration Rate in Cats by Using a New Accurate HPLC Method to Measure Iohexol Plasmatic Concentrations
Glomerular filtration rate (GFR) is still a highly underutilized tool in cats because available methods are not easy to be performed in clinical practice. Iohexol (IOX) has been shown to be a useful and reliable marker of GFR both in animals and in humans. The aim of the present study was to develop a rapid and reliable method for measuring IOX in feline plasma and to evaluate the accuracy of limited sampling models to establish a low-cost and clinically suitable GFR test. IOX concentrations were determined by using a new HPLC-UV method. GFR was assessed as plasma clearance of IOX, which was calculated by dividing dose administered by area under the curve of plasmatic concentration versus time (AUC), and indexed to body weight (BW). Correlation and agreement analysis between the GFR values obtained by a seven-point clearance method and the GFR values determined by the application of simplified sample combinations indicated that the 3-blood sample clearance model (5, 30, and 60？min) was the best simplified method because it provided an accurate GFR value in only one hour. The reported method is a simple and accurate way of GFR determination, which may be easily used in a clinical setting. 1. Introduction Chronic kidney disease (CKD) is one of the most common disorders in cats, especially in older ones for which it represents a major cause of illness and death [1, 2]. Plasma creatinine (PCr) and urea (PU), the most used parameters for assessing renal function in veterinary practice, cannot be used in the early diagnosis of renal failure because they start to rise too late, when the 75% of functioning nephrons are lost [3, 4], and are also affected by several extra renal factors [5]. Glomerular filtration rate (GFR), directly related to the functional renal mass, is considered the most sensitive and early marker of kidney failure [6]. At present, in veterinary medicine, GFR can be assessed by using different methods, which have both advantages and disadvantages. Many methods have several disadvantages including the labour intense nature, risks caused by anaesthesia, cost of the test substance, assay of the substance used, or need for specialized licensing and equipment. The traditional gold standard for measurement of GFR (urinary clearance of inulin) is not suitable in a clinical setting [7, 8]. These methods are labor intensive and require the placement of an indwelling urinary catheter with associated risk of sedation and of causing lower urinary tract infection. Over the past two decades, many alternative methods for determining GFR have been shown to
References
[1]
E. M. Lund, P. J. Armstrong, C. A. Kirk, L. M. Kolar, and J. S. Klausner, “Health status and population characteristics of dogs and cats examined at private veterinary practices in the United States,” Journal of the American Veterinary Medical Association, vol. 214, no. 9, pp. 1336–1341, 1999.
[2]
A. D. J. Watson, “Indicators of renal insufficiency in dogs and cats presented at a veterinary teaching hospital,” Australian Veterinary Practitioner, vol. 31, no. 2, pp. 54–59, 2001.
[3]
D. R. Finco, S. A. Brown, S. L. Vaden, et al., “Relationship between plasma creatinine concentration and glomerular filtration rate in dogs,” American Journal of Veterinary Research, vol. 33, pp. 2447–2450, 1995.
[4]
A. Gleadhill, “Evaluation of screening tests for renal insufficiency in the dog,” Journal of Small Animal Practice, vol. 35, pp. 391–396, 1994.
[5]
Y. Miyagawa, N. Takemura, and H. Hirose, “Assessments of factors that affect glomerular filtration rate and indirect markers of renal function in dogs and cats,” Journal of Veterinary Medical Science, vol. 72, no. 9, pp. 1129–1136, 2010.
[6]
D. Polzin, C. Osborne, and S. Ross, “Chronic kidney disease,” in Textbook of Veterinary Internal Medicine, S. J. Ettinger and E. Feldman, Eds., pp. 1698–1703, Elsevier Saunders, Philadelphia, Pa, USA, 6th edition, 2004.
[7]
K. S. Rogers, A. Komkov, S. A. Brown, G. E. Lees, D. Hightower, and E. A. Russo, “Comparison of four methods of estimating glomerular filtration rate in cats,” American Journal of Veterinary Research, vol. 52, no. 6, pp. 961–964, 1991.
[8]
L. A. Ross and D. R. Finco, “Relationship of selected clinical renal function tests to glomerular filtration rate and renal blood flow in cats,” American Journal of Veterinary Research, vol. 42, no. 10, pp. 1704–1710, 1981.
[9]
S. A. Brown, C. Haberman, and D. R. Finco, “Use of plasma clearance of inulin for estimating glomerular filtration rate in cats,” American Journal of Veterinary Research, vol. 57, no. 12, pp. 1702–1705, 1996.
[10]
M. J. Fettman, T. A. Allen, W. L. Wilke, M. J. Radin, and M. C. Eubank, “Single-injection method for evaluation of renal function with 14C-inulin and 3H-tetraethylammonium bromide in dogs and cats,” American Journal of Veterinary Research, vol. 46, no. 2, pp. 482–485, 1985.
[11]
M. Haller, K. Rohner, W. Müller et al., “Single-injection inulin clearance for routine measurement of glomerular filtration rate in cats,” Journal of Feline Medicine and Surgery, vol. 5, no. 3, pp. 175–181, 2003.
[12]
M. E. Kerl and C. R. Cook, “Glomerular filtration rate and renal scintigraphy,” Clinical Techniques in Small Animal Practice, vol. 20, no. 1, pp. 31–38, 2005.
[13]
K. Miyamoto, “Evaluation of plasma clearance of inulin in clinically normal and partially nephrectomized cats,” American Journal of Veterinary Research, vol. 62, no. 8, pp. 1332–1335, 2001.
[14]
K. Miyamoto, “Use of plasma clearance of iohexol for estimating glomerular filtration rate in cats,” American Journal of Veterinary Research, vol. 62, no. 4, pp. 572–575, 2001.
[15]
D. Uribe, D. R. Krawiec, A. R. Twardock, and H. B. Gelberg, “Quantitative renal scintigraphic determination of the glomerular filtration rate in cats with normal and abnormal kidney function, using 99mTc-diethylenetriaminepentaacetic acid,” American Journal of Veterinary Research, vol. 53, no. 7, pp. 1101–1107, 1992.
[16]
R. Heiene, B. S. Reynolds, N. H. Bexfield, S. Larsen, and R. J. Gerritsen, “Estimation of glomerular filtration rate via 2- and 4-sample plasma clearance of iohexol and creatinine in clinically normal cats,” American Journal of Veterinary Research, vol. 70, no. 2, pp. 176–185, 2009.
[17]
N. C. Finch, H. M. Syme, J. Elliott et al., “Glomerular filtration rate estimation by use of a correction formula for slope-intercept plasma iohexol clearance in cats,” American Journal of Veterinary Research, vol. 72, no. 12, pp. 1652–1659, 2011.
[18]
N. C. Finch, R. Heiene, J. Elliott, et al., “A single method for estimating glomerular filtration rate in cats,” Journal of Veterinary Internal Medicine, vol. 27, pp. 782–790, 2013.
[19]
Y. Miyagawa, N. Takemura, and H. Hirose, “Evaluation of a single sampling method for estimation of plasma iohexol clearance in dogs and cats with various kidney functions,” Journal of Veterinary Medical Science, vol. 72, no. 3, pp. 271–278, 2010.
[20]
R. Katayama, J. Saito, M. Katayama, et al., “Simplified procedure for estimation of glomerular filtration rate following intravenous administration of iodixanol in cats,” American Journal of Veterinary Research, vol. 73, pp. 1344–1349, 2012.
[21]
I. Goy-Thollot, S. Besse, F. Garnier, M. Marignan, and P. Y. Barthez, “Simplified methods for estimation of plasma clearance of iohexol in dogs and cats,” Journal of Veterinary Internal Medicine, vol. 20, no. 1, pp. 52–56, 2006.
[22]
F. Gaspari, N. Perico, M. Matalone et al., “Precision of plasma clearance of iohexol for estimation of GFR in patients with renal disease,” Journal of the American Society of Nephrology, vol. 9, no. 2, pp. 310–313, 1998.
[23]
I. Goy-Thollot, C. Chafotte, S. Besse, F. Garnier, and P. Y. Barthez, “Iohexol plasma clearance in healthy dogs and cats,” Veterinary Radiology and Ultrasound, vol. 47, no. 2, pp. 168–173, 2006.
[24]
W. E. Braselton, K. J. Stuart, and J. M. Kruger, “Measurement of serum iohexol by determination of iodine with inductively coupled plasma-atomic emission spectroscopy,” Clinical Chemistry, vol. 43, no. 8, pp. 1429–1435, 1997.
[25]
V. Meucci, A. Gasperini, G. Soldani, G. Guidi, and M. Giorgi, “A New HPLC method to determine glomerular filtration rate and effective renal plasma flow in conscious dogs by single intravenous administration of iohexol and p-aminohippuric acid,” Journal of Chromatographic Science, vol. 42, no. 2, pp. 107–111, 2004.
[26]
I. van Hoek, H. P. Lefebvre, H. S. Kooistra et al., “Plasma clearance of exogenous creatinine, exo-iohexol, and endo-iohexol in hyperthyroid cats before and after treatment with radioiodine,” Journal of Veterinary Internal Medicine, vol. 22, no. 4, pp. 879–885, 2008.
[27]
I. van Hoek, E. Vandermeulen, L. Duchateau et al., “Comparison and reproducibility of plasma clearance of exogenous creatinine, exo-iohexol, endo-iohexol, and 51Cr-EDTA in young adult and aged healthy cats,” Journal of Veterinary Internal Medicine, vol. 21, no. 5, pp. 950–958, 2007.
[28]
S.-E. B？ck, P. Masson, and P. Nilsson-Ehle, “A simple chemical method for the quantification of the contrast agent iohexol, applicable to glomerular filtration rate measurements,” Scandinavian Journal of Clinical and Laboratory Investigation, vol. 48, no. 8, pp. 825–829, 1988.
[29]
Z. K. Shihabi and M. S. Constantinescu, “Iohexol in serum determined by capillary electrophoresis,” Clinical Chemistry, vol. 38, no. 10, pp. 2117–2120, 1992.
[30]
B. Frennby and G. Sterner, “Contrast media as markers of GFR,” European Radiology, vol. 12, no. 2, pp. 475–484, 2002.
[31]
P. Nilsson-Ehle, “Iohexol clearance for the determination of glomerular filtration rate: 15 years experience in clinical practice,” Electronic Journal Journal of the International Federation of Clinical Chemistry, vol. 13, no. 2, 2001, http://www.ifcc.org/ifcc-communications-publications-division-(cpd)/ifcc-publications/ejifcc-(journal)/e-journal-volumes/ejifcc-2002-vol-13/vol-13-no-2/iohexol-clearance-for-the-determination-of-glomerular-filtration-rate-15-years-experience-in-cl/.
[32]
“ICH harmonised tripartite guideline, validation of analytical procedures: text and methodology Q2(R1), current step 4 version,” in Proceedings of the International Conference on Harmanisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, November 2005, http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q2_R1/Step4/Q2_R1__Guideline.pdf.
[33]
R. Heiene and H. P. Lefebvre, “Assessment of renal function,” in Manual of Canine and Feline Nephrology and Urology, J. Elliott and G. F. Grauer, Eds., pp. 117–125, BSAVA, Gloucester, UK, 2nd edition, 2007.
[34]
J. Coresh, E. Selvin, L. A. Stevens et al., “Prevalence of chronic kidney disease in the United States,” Journal of the American Medical Association, vol. 298, no. 17, pp. 2038–2047, 2007.
[35]
Q.-L. Zhang and D. Rothenbacher, “Prevalence of chronic kidney disease in population-based studies: systematic review,” BMC Public Health, vol. 8, article 117, 2008.
[36]
L. A. Stevens and A. S. Levey, “Measured GFR as a confirmatory test for estimated GFR,” Journal of the American Society of Nephrology, vol. 20, no. 11, pp. 2305–2313, 2009.
[37]
B. Frennby, G. Sterner, T. Almén, C. M. Chai, B. A. J？nsson, and S. M？nsson, “Clearance of iohexol, chromium-51-ethylenediaminetetraacetic acid, and creatinine for determining the glomerular filtration rate in pigs with normal renal function: comparison of different clearance techniques,” Academic Radiology, vol. 3, no. 8, pp. 651–659, 1996.
[38]
B. Frennby, G. Sterner, T. Almén, C.-M. Chai, B. A. J？nsson, and S. M？nsson, “Clearance of iohexol, 51Cr-EDTA and endogenous creatinine for determination of glomerular filtration rate in pigs with reduced renal function: a comparison between different clearance techniques,” Scandinavian Journal of Clinical and Laboratory Investigation, vol. 57, no. 3, pp. 241–252, 1997.
[39]
K. E. Wilson, J. R. Wilcke, M. V. Crisman, D. L. Ward, H. C. McKenzie, and W. K. Scarratt, “Comparison of serum iohexol clearance and plasma creatinine clearance in clinically normal horses,” American Journal of Veterinary Research, vol. 70, no. 12, pp. 1545–1550, 2009.
[40]
I. Lippi, V. Meucci, M. Sgorbini, C. Michele, and G. Guidi, “Valutazione della velocità di filtrazione glomerulare nellasino sorcino crociato dellAmiata mediante clearance plasmatica dello ioexolo con metodica HPLC,” in Proceed of the Società Italiana Veterinari per Equini (SIVE '10), pp. 1–2, Montesilvano, Italy, 2010.
[41]
N. H. Bexfield, R. Heiene, R. J. Gerritsen et al., “Glomerular filtration rate estimated by 3-sample plasma clearance of iohexol in 118 healthy dogs,” Journal of Veterinary Internal Medicine, vol. 22, no. 1, pp. 66–73, 2008.
[42]
G. J. Schwartz and S. L. Furth, “Glomerular filtration rate measurement and estimation in chronic kidney disease,” Pediatric Nephrology, vol. 22, no. 11, pp. 1839–1848, 2007.
[43]
A. D. J. Watson, H. P. Lefebvre, D. Concordet et al., “Plasma exogenous creatinine clearance test in dogs: comparison with other methods and proposed limited sampling strategy,” Journal of Veterinary Internal Medicine, vol. 16, no. 1, pp. 22–33, 2002.
[44]
I. Lippi, V. Meucci, G. Guidi, et al., “Velocita di filtrazione glomerulare mediante clearance plasmatica dello ioexolo nel cane: confronto tra metodi semplificati,” Veterinaria, vol. 22, pp. 53–60, 2008.
[45]
T. Buclin, A. Pechère-Bertschi, R. Séchaud et al., “Sinistrin clearance for determination of glomerular filtration rate: a reappraisal of various approaches using a new analytical method,” Journal of Clinical Pharmacology, vol. 37, no. 8, pp. 679–692, 1997.
