Pilot Application of Isolated Perfused Chronic Kidney Transgenic Rat Kidney Model for Discovery and Evaluation of Chronic Kidney Disease Drug

doi:10.3969/j.issn.1674-5817.2017.05.004

Abstract

Abstract: Objective To establish isolated perfused kidney (IPK) model in chronic kidney disease (CKD) transgenic rat, as a screening tool for CKD drug. Method Seven CKD transgenic rats were perfused with 1 μmol/L CysA for 60 minutes, the content of albumin in urine were detected before and after treatment to evaluate the effect of CysA. Five CKD transgenic rats were treated with 20 mg/kg CysA/day for 15 days, the content of albumin in urine were compared to 5 control CKD transgenic rats to evaluate in vivo effect of CysA. Results After perfusing 1 μmol/L CysA for 60 minutes, the content of albumin in urine were decrease signicantly. In in vivo efficacy study,after dosing CysA 15days, the content of albumin in urine were also decrease signicantly. Conclusion The consistency of CysA efficacy of decreasing the content of albumin in urine bewteen IPK model and in vivo animal model in CKD transgenic rat is good. The IPK model on CKD transgenic rat have potential to be a further screening tool for CKD drug.

Key words: Isolated perfused kidney(IPK), Cyclosporin A (CysA), Chronic kidney disease (CKD)

CLC Number:

Q95-33

FU Ting-ting,LIU Yan. Pilot Application of Isolated Perfused Chronic Kidney Transgenic Rat Kidney Model for Discovery and Evaluation of Chronic Kidney Disease Drug[J]. Laboratory Animal and Comparative Medicine, 2017, 37(5): 357-362. DOI: 10.3969/j.issn.1674-5817.2017.05.004.

References

[1] Black D, Rose G, Brewer D.Controlled trail of prednisone in adult patient with the nephrotic sydrome[J]. Br Med J, 1970,3(5720):421-426.
[2] Nair RB, Date A, Kirubakaran MG, et al.Minimal change nephrotic syndrome in adults treated with alternate-day steroid[J]. Nephro, 1987, 47(3):209-210.
[3] Nakayama M, Katafuchi R, Yanase T, et al.Steroid responsiveness and frequency of relapse in adult-on-set minimal change nephrotic sydrome[J]. Am J Kideny Dis, 2002, 39(3):503-512.
[4] Waldman MCR, Valeri A, Brusch J, et al.Adult minimal-change-disesae: Clinical characteristics, treatment, and outcomes[J]. Clin J Am Soc Nephrol, 2007, 2(3):445-453.
[5] Taft D R.The isolated perfused rat kidneymodel: a useful tool for drug discovery and development[J]. Curr Drug Discov Technol, 2004, 1(1):97-111.
[6] Wang J, Nation R L, EvansA M, et al. Isolated rat kidney perfused with dextran and bovine serum albumin: a stable model forinvestigating renal drug handling[J]. J Pharmacol Toxicol Methods, 2004, 49(2):105-113.
[7] Lep sy CS, Guttendorf RJ, Kugler AR, et al. Effects of organic anion, organic cation, and dipep tide transport inhibitors on cefdinir in the isolated perfused rat kidney[J]. AAC, 2003, 47(2):689-696.
[8] 朱深银, 周远大, 刘庆山, 等. 离体大鼠肾脏灌流技术在发现和评价促尿酸排泄药物中的初步应用[J]. 中国药理学通报, 2006, 22(12):1452-1456.
[9] Little JR, Cohen JJ.Effect of albumin concentration on function of isolated perfused rat kidney[J]. Am J Physiol, 1974, 226(3):512-517.
[10] Alphonse Nize.The isolated perfused kidney: Possibilities, limitations and results[J]. Kidney Int, 1975, 7(1):1-11.
[11] Chang HH, Choong B, Phillips A, et al.The isolated perfused rat kidney: a technical update[J]. Exp Anim, 2013, 62(1):19-23.
[12] Georgiev T, Iliev R, Mihailova S, et al.The isolated perfused kidney model-certain aspects[J]. Trakia Journal of Sciences,2011, 9(3):82-87.
[13] Taft DR, Dontabhaktuni A, Babayeva M, et al.Application of the isolated perfused rat kidney model to assess gender effects on drug excretion[J]. Drug Dev Ind Pharm, 2006, 32(8):919-928.
[14] Zhou C, Yool AJ, Byard RW, et al.An isolated perfused rat kidney model for the evaluation of the effect og glucose on renal tubular epithelial morphology[J]. J Forensic Sci, 2016, 62(1):126-130.
[15] Tamhane M, Chakilam AR, Jayaraj A, et al.Comparative renal excretion of VX-702, a novel p38 MAPK inhibitor, and methotrexate in the perfused rat kidney model[J]. Drug Dev Ind Pharm, 2010, 36(3):315-322.
[16] Kahan BD.Cyclosporine. Medical intelligence[J]. N Engl J Med,1989, 321(25):1725-1738.
[17] Meyrier A, Noel LH, Auriche P, et al.Long-term renal tolerance of cyclosporin A treatment in adult idiopathic nephrotic syndrome[J]. Kidney Int, 1994, 45(5):1446-1456.
[18] Troyanov S, Wall CA, Miller JA, et al.Focal and segmental glomerulosclerosis: definition and relevance of a partial remission[J]. J Am Soc Nephrol, 2005, 16(4):1061-1068.
[19] Roby KA, Shaw LM.Effects of cyclosporine and its metabolites in the isolated perfused rat kidney[J]. J Am Soc Nephrol, 1993, 4(2):168-177.
[20] Cattran DC, Alexopoulos E, Heering P, et al.Cyclosporin in idiopathic glomerular disease associated with the nephrotic syndrome : Workshop recommendations[J]. Kidney Int,2007, 72(12):1429-1447.
[21] Eknoyan G, Hostetter T, Bakris GL, et al.Proteinuria and other markers of chronic kidney disease: A position statement of the national kidney foundation(NKF) and the national institute of diabetes and digestive and kidney diseases(NIDDK)[J]. Am J Kidney Dis, 2003, 42(4):617-622.
[22] Christians U, McCreey S, Klawitter J, et al. The role of proteomics in the study of kidney diseases and in the development of diagnostic tools[A]. In: Harlesl, Edelstein (ed). Biomarkers of Kidney Disease [M]. London:An imprint of Elsevier, 2011:101-176.
[23] Turner JM, Bauer C, Abramowitz MK, et al.Treatment of chronic kidney disease[J]. Kidney Int, 2012, 81(4):351-362.
[24] Vassalotti JA, Centor R, Turner BJ, et al.Practical approach to detection and management of chronic kidney disease for the primary dare clinican[J]. Am J Med, 2016, 129(2):153-162.
[25] Klaassen I, Özgören B, Sadowski CE, et al.Response to cyclosporine in steroid-resistant nephrotic syndrome: discontinuation is possible[J]. Pediatr Nephrol, 2015, 30(9):1477-1483.
[26] Pollard S, Nashan B, Johnston A, et al.A pharmacokinetic and clinical review of the potential clinical impact of using different formulations of Cyclosporin A[J].Clin Ther, 2003, 25(6):1654-1669.