Background: Animal models are important tools needed to understand the mechanisms underlying the progression of renal disease and to implement new therapeutic approaches. A non-surgical model of chronic kidney disease (CKD) developed by chemical nephrectomy using an adenine-enriched diet has been shown to be a robust model to induce kidney failure in mice and rats. The purpose of this study was to implement an adenine diet to induce CKD in rabbits. Methods: Male New Zealand rabbits were fed for 4 weeks with a diet containing 0.75% (w/w) adenine, and renal function was assessed by measuring plasma urea and creatinine concentrations. The glomerular filtration rate (GFR) was measured using the plasmatic clearance of Iohexol. Kidney histology was performed with haematoxylin erythrosine saffron and Sirius red staining. Results: In contrast to what was observed in rodents, adenine diet failed to induce kidney failure in rabbits as is evident in the plasma concentrations of creatinine and urea and the direct measurement of GFR or histopathological studies. Conclusion: Adenine diet is not a surrogate of subtotal nephrectomy to induce kidney failure in rabbits. Several interspecies differences in metabolism and renal physiology could account for this observation.

Keywords:
Rabbit, Chronic kidney disease, Adenine, Chemical nephrectomy, Animal model
1.
Becker GJ, Hewitson TD: Animal models of chronic kidney disease: useful but not perfect. Nephrol Dial Transplant 2013;28:2432-2438.
2.
Hewitson TD, Ono T, Becker GJ: Small animal models of kidney disease: a review. Methods Mol Biol 2009;466:41-57.
3.
Rabe M, Schaefer F: Non-transgenic mouse models of kidney disease. Nephron 2016;133:53-61.
4.
Yang HC, Zuo Y, Fogo AB: Models of chronic kidney disease. Drug Discov Today Dis Models 2010;7:13-19.
5.
Dai C, Kiss LP, Liu Y: Animal models of kidney diseases; in Conn PM (ed): Sourcebook of Models for Biomedical Research. Humana Press, 2008, pp 657-664.
6.
Kujal P, Vernerová Z: [5/6 nephrectomy as an experimental model of chronic renal failure and adaptation to reduced nephron number]. Cesk Fysiol 2008;57:104-109.
7.
Yokozawa T, Oura H, Okada T: Metabolic effects of dietary purine in rats. J Nutr Sci Vitaminol (Tokyo) 1982;28:519-526.
8.
Yokozawa T, Zheng PD, Oura H, Koizumi F: Animal model of adenine-induced chronic renal failure in rats. Nephron 1986;44:230-234.
9.
Okada H, Kaneko Y, Yawata T, Uyama H, Ozono S, Motomiya Y, et al: Reversibility of adenine-induced renal failure in rats. Clin Exp Nephrol 1999;3:82-88.
10.
Ienaga K, Mikami H, Yokozawa T: First indications demonstrating the preventive effects of NZ-419, a novel intrinsic antioxidant, on the initiation and/or progression of chronic renal failure in rats. Biol Pharm Bull 2009;32:1204-1208.
11.
Shuvy M, Nyska A, Beeri R, Abedat S, Gal-Moscovici A, Rajamannan NM, et al: Histopathology and apoptosis in an animal model of reversible renal injury. Exp Toxicol Pathol 2011;63:303-306.
12.
Vitić J, Stevanović J: Comparative studies of the serum lipoproteins and lipids in some domestic, laboratory and wild animals. Comp Biochem Physiol B 1993;106:223-229.
13.
Bergen WG, Mersmann HJ: Comparative aspects of lipid metabolism: impact on contemporary research and use of animal models. J Nutr 2005;135:2499-2502.
14.
Yin W, Carballo-Jane E, McLaren DG, Mendoza VH, Gagen K, Geoghagen NS, et al: Plasma lipid profiling across species for the identification of optimal animal models of human dyslipidemia. J Lipid Res 2012;53:51-65.
15.
Diehl KH, Hull R, Morton D, Pfister R, Rabemampianina Y, Smith D, et al: A good practice guide to the administration of substances and removal of blood, including routes and volumes. J Appl Toxicol 2001;21:15-23.
16.
Van Teijlingen ME, Borgdorff P, Van Wijhe MH, Van Lambalgen TA, Wee PM, Tangelder GJ: In vivo visualization of hemodialysis-induced alterations in leukocyte-endothelial interactions. Kidney Int 2000;57:2608-2617.
17.
Gotloib L, Crassweller P, Rodella H, Oreopoulos DG, Zellerman G, Ogilvie R, et al: Experimental model for studies of continuous peritoneal' dialysis in uremic rabbits. Nephron 1982;31:254-259.
18.
Bas S, Bas A, Estepa JC, Mayer-Valor R, Rodriguez M, Aguilera-Tejero E: Parathyroid gland function in the uremic rabbit. Domest Anim Endocrinol 2004;26:99-110.
19.
Bonilla-Felix M, Hamm LL, Herndon J, Vehaskari VM: Response of cortical collecting ducts from remnant kidneys to arginine vasopressin. Kidney Int 1992;41:1150-1154.
20.
Fiehn W, Seiler D, Heimberg KW: Transport ATPases of cardiac sarcolemma in experimental uremia. Clin Chim Acta 1976;73:93-96.
21.
Fisher JW, Foley JE, Moriyama Y, Ohno Y, Modder B, Lertora JJ: Studies on the mechanism of the anemia of renal insufficiency. Proc Clin Dial Transplant Forum 1976;6:42-49.
22.
Kamstrup O, Tvedegaard E: Increased uptake of cholesterol and increased mineral content in the aorta of long-term uremic rabbits. Nephron 1983;33:267-270.
23.
Kilicarslan H, Yildirim S, Bagcivan I, Gokce G, Sarac B, Sarioglu Y: The effect of chronic renal failure on phosphodiesterase inhibitor-induced relaxation responses in rabbit cavernosal strips. Eur J Pharmacol 2003;462:155-160.
24.
Kirschenbaum MA, Serros ER: Effect of prostaglandin inhibition on glomerular filtration rate in normal and uremic rabbits. Prostaglandins 1981;22:245-254.
25.
Oreopoulos AK, Balaskas EV, Rodela H, Anderson GH, Oreopoulos DG: An animal model for the study of amino acid metabolism in uremia and during peritoneal dialysis. Perit Dial Int 1993;13(suppl 2):S499-S507.
26.
Tvedegaard E: Arterial disease in chronic renal failure - an experimental study in the rabbit. Acta Pathol Microbiol Immunol Scand A 1987;290:1-28.
27.
Kumano K, Kogure K, Tanaka T, Sakai T: A new method of inducing experimental chronic renal failure by cryosurgery. Kidney Int 1986;30:433-436.
28.
Hughes M, Health JBS of P: The Principles of Humane Experimental Technique. Johns Hopkins Bloom School of Public Health. http://altweb.jhsph.edu/pubs/books/humane_exp/het-toc.
29.
Buchanan-Smith H, Rennie A, Vitale A, Pollo S, Prescott M, Morton D: Harmonising the definition of refinement. Anim Welf 2005;14:379-384.
31.
Wang L, Wang J, Wang Y, Fu Q, Lei YH, Nie ZY, et al: Protective effect of exogenous matrix metalloproteinase-9 on chronic renal failure. Exp Ther Med 2014;7:329-334.
32.
Soman RS, Zahir H, Akhlaghi F: Development and validation of an HPLC-UV method for determination of iohexol in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci 2005;816:339-343.
33.
Michigoshi Y, Yamagishi N, Satoh H, Kato M, Furuhama K: Using a single blood sample and inulin to estimate glomerular filtration rate in rabbits. J Am Assoc Lab Anim Sci 2011;50:702-707.
34.
Michigoshi Y, Katayama R, Yamagishi N, Kato M, Saito J, Satoh H, et al: Estimation of glomerular filtration rate in rabbits by a single-sample method using iodixanol. Lab Anim 2012;46:341-344.
35.
Peck CC, Bailey FJ, Moore GL: Enhanced solubility of 2,8 dihydroxyadenine (DOA) in human urine. Transfusion 1977;17:383-390.
36.
Seegmiller JE: Xanthine stone formation. Am J Med 1968;45:780-783.
37.
Coe FL: Uric acid and calcium oxalate nephrolithiasis. Kidney Int 1983;24:392-403.
38.
Donoso VS, Grantham JJ: Characteristics of renal p-aminohippurate and urate excretion in rabbits. J Lab Clin Med 1986;107:315-321.
39.
Pascual E, Perdiguero M: Gout, diuretics and the kidney. Ann Rheum Dis 2006;65:981-982.
40.
Sasaki Y, Iwama R, Sato T, Heishima K, Shimamura S, Ichijo T, et al: Estimation of glomerular filtration rate in conscious mice using a simplified equation. Physiol Rep 2014;2:e12135.
41.
Fleck C: Determination of the glomerular filtration rate (GFR): methodological problems, age-dependence, consequences of various surgical interventions, and the influence of different drugs and toxic substances. Physiol Res 1999;48:267-279.
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