* Corresponding Author
The effects of furosemide on kidney damage in acute kidney injury rat models
https://doi.org/10.19106/JMedScie/005003201801 Afifah Afifah(1*), . Ngatidjan(2), Nur Arfian(3)
(1) Departement of Pharmacology and Therapy, Faculty of Medicine, Universitas Jenderal Soedirman, Purwokerto, Indonesia
(2) Departement of Pharmacology and Therapy, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
(3) Departement of Anatomy, Embryology, and Anthropology, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
(*) Corresponding Author
Abstract
that causes inflammation. Furosemide is still used in AKI’s therapy. The advantages and
disadvantages of furosemide in AKI remain controversial. The aim of the study was to
investigate the effect of furosemide on kidney damage in AKI rat models. Twenty-five
male (2-3 months old) Sprague-Dawley rats were divided into 5 groups; sham operation
(SO, n=5), ischemic-reperfusion (IR, n=5), IR+furosemide 3.6 mg/kgBW (IR+F1,
n=5), IR+furosemide 7.2 mg/kgBW (IR+F2, n=5), and IR+furosemide 14.4 mg/kgBW
(IR+F3, n=5). Abdominal surgery was performed under ketamine anesthesia to produce
ischemic reperfusion (IR) by mean of renal artery clamping for 45 min. Urine output,
serum creatinine level, tubular injury score, and TLR4 gene expression were examined
to investigate kidney damage. Periodic acid-schiff (PAS) staining was measured to
examine kidney tubular injury. Data were analyzed using One-Way ANOVA and Kruskal-
Wallis test with significance level of p<0.05. AKI rat models which were given 3.6 and
7.2 mg/kgBW of furosemide (0.014±0.001 mL/min; and 0.012±0.007) showed higher
(p>0.05) creatinine clearance compared to IR (0.009±0.003) while administration of 14.4
mg/kgBW furosemide (0.009±0.004) denoted equal creatinine clearance to IR (p>0,05).
Kidney tubular injury score of 3.6 mg/kgBW furosemide (2.89±0.13) was lower (p>0.05)
than IR (3.26±0.19) whereas 7.2 mg/kgBW and 14.4 mg/kgBW furosemide (3.55±0.26;
3.83±0.19) were higher (p<0.05) than IR. Administration of 3.6 mg/kgBW furosemide
(0.99±0.08) indicated lower (p<0.05) TLR4 gene expression than IR (1.20±0.08) whilst
7.2 mg/kgBW furosemide (1.23±0.13) was not-significantly higher (p>0.05) and 14.4 mg/
kgBW furosemide (1.63±0.12) was significantly higher (p<0.05) than IR. In conclusion,
administration of 3.6 mg/kgBW furosemide reduces kidney damage in AKI rat models
while higher dosages (7.2 mg/kgBW and 14.4 mg/kgBW) increase kidney damage.
Keywords
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REFERENCES 1. Chertow GM, Burdick E, Honour M, Bonventre J V, Bates DW. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol. 2005;16(11):3365–70. 2. Ali T, Khan I, Simpson W, Prescott G, Townend J, Smith W, et al. Incidence and outcomes in acute kidney injury: a comprehensive population-based study. J Am Soc Nephrol. 2007;18(4):1292–8. 3. Lafrance J-P, Miller DR. Acute kidney injury associates with increased long-term mortality. J Am Soc Nephrol. 2010;21(2):345–52. 4. Kam Tao Li P, Burdmann E a, Mehta RL. Acute kidney injury: Global health alert. J Nephropathol. 2013;2(2):90–7. 5. Sawhney S, Mitchell M, Marks A, Fluck N, Black C. Long-term prognosis after acute kidney injury (AKI): what is the role of baseline kidney function and recovery? A systematic review. Basic Med J. 2015;5(1):e006497–e006497. 6. Coca SG, S. Si, Parikh CR. Chronic Kidney Disease after Acute Kidney Injury: A Systematic Review and Meta-analysis. Kidney Int. 2012;29(6):997–1003. 7. Kerr M, Bedford M, Matthews B, O’donoghue D. The economic impact of acute kidney injury in England. Nephrol Dial Transplant. 2014;29(7):1362–8. 8. Kalambokis G, Economou M, Fotopoulos A, Al Bokharhii J, Katsaraki A, Tsianos E V. Renal effects of treatment with diuretics, octreotide or both, in non-azotemic cirrhotic patients with ascites. Nephrol Dial Transplant. 2005;20(8):1623–9. 9. Lassnigg a, Donner E, Grubhofer G, Presterl E, Druml W, Hiesmayr M. Lack of renoprotective effects of dopamine and furosemide during cardiac surgery. J Am Soc Nephrol. 2000;11(1):97–104. 10. Santoso JT, Lucci J a., Coleman RL, Schafer I, Hannigan E V. Saline, mannitol, and furosemide hydration in acute cisplatin nephrotoxicity: A randomized trial. Cancer Chemother Pharmacol. 2003;52(1):13–8. 11. Solomon, R., Werner, C., Mann, Denise., D’Elia, J, Silva P. Effect of Saline, Mannitol, and Furosemide on Acute Decreases in Renal Function Induced by Radiocontrast Agents. 1994; 12. Mehta RL, Mehta RL, Pascual MT, Pascual MT, Soroko S, Soroko S, et al. Diuretics, mortality, and nonrecovery of renal function in acute renal failure. JAMA. 2002;288(20):2547–53. 13. Aravindan N, Aravindan S, Riedel BJ, Weng H-R, Shaw AD. Furosemide prevents apoptosis and associated gene expression in a rat model of surgical ischemic acute renal failure. Ren Fail. 2007;29(4):399–407. 14. Leif Oxburgh and Mark P. de Caestecker. Kidney Development Methods and Protocols. Michos O, editor. Humana Press; 2012. 363-379 p. 15. Younan SM, Shawky HM, Rashed LA. Effect of Ischemic Postconditioning on Renal Ischemia-Reperfusion Injury in Male Rats. 2012;18(2):23–38. 16. Cantarovich F, Rangoonwala B, Lorenz H, Verho M, Esnault VLM. High-dose furosemide for established ARF: A prospective, randomized, double-blind, placebo-controlled, multicenter trial. Am J Kidney Dis. 2004;44(3):402–9. 17. Wu H, Chen G, Wyburn KR, Yin J, Bertolino P, Eris JM, et al. TLR4 activation mediates kidney ischemia/reperfusion injury. J Clin Invest. 2007;117(10):2847–59. 18. Perrone RD, Madias NE, Levey a S. Serum creatinine as an index of renal function: new insights into old concepts. ClinChem. 1992;38(0009-9147):1933–53. 19. Tortora, G.J., Derrickson B. Principles of Anatomy and Physiology. 13th ed. USA; 2012. 1065-1109 p. 20. Urakami Y, Kimura N, Okuda M, Inui KI. Creatinine transport by basolateral organic cation transporter hOCT2 in the human kidney. Pharm Res. 2004;21(6):976–81. 21. Arya V, Yang X, Balimane P, Chinn L, Hinderling P, Vaidyanathan J, et al. Creatinine As an Endogenous Marker for Renal Function — Emerging Role of Transporters in the Overall Assessment of Renal Toxicity. ASCPT Annu Meet. 2014;67637. 22. Lepist EI, Zhang X, Hao J, Huang J, Kosaka a, Birkus G, et al. Contribution of the organic anion transporter OAT2 to the renal active tubular secretion of creatinine and mechanism for serum creatinine elevations caused by cobicistat. Kidney Int. 2014;86(2):350–7. 23. Hasannejad H, Takeda M, Taki K. Interactions of human organic anion transporters with diuretics. Pharmacol. 2004;308(3):1021–9. 24. Kim G, Na KY, Kim S, Joo KW, Oh YK, Chae S, et al. Up-regulation of organic anion transporter 1 protein is induced by chronic furosemide or hydrochlorothiazide infusion in rat kidney. 2003;1505–11. 25. Uwai Y, Saito H, Hashimoto Y, Inui KI. Interaction and transport of thiazide diuretics, loop diuretics, and acetazolamide via rat renal organic anion transporter rOAT1. J Pharmacol Exp Ther. 2000;295(1):261–5. 26. Kim G-H, Na KY, Kim S-Y, Joo KW, Oh YK, Chae S-W, et al. Up-regulation of organic anion transporter 1 protein is induced by chronic furosemide or hydrochlorothiazide infusion in rat kidney. Nephrol Dial Transplant. 2003;18(8):1505–11. 27. Zhang R, Yang X, Li J, Wu J, Peng WX, Dong XQ, et al. Upregulation of rat renal cortical organic anion transporter (OAT1 and OAT3) expression in response to ischemia/reperfusion injury. Am J Nephrol. 2008;28(5):772–83. 28. Heyman SN, Brezis M, Greenfeld Z, Rosen S. Protective role of furosemide and saline in radiocontrast-induced acute renal failure in the rat. Am J Kidney Dis. 1989;14(5):377–85. 29. Wei Q, Dong Z. Mouse model of ischemic acute kidney injury: Technical notes and tricks. AJP Ren Physiol. 2012;30912(1). 30. Zhang B, Ramesh G, Uematsu S, Akira S, Reeves WB. TLR4 signaling mediates inflammation and tissue injury in nephrotoxicity. J Am Soc Nephrol. 2008;19(5):923–32. 31. Wu K, Lei W, Tian J, Li H. Atorvastatin treatment attenuates renal injury in an experimental model of ischemia-reperfusion in rats. BMC Nephrol. 2014;15(1):14. 32. Heyman SN, Rosen S, Epstein FH, Spokes K, Brezis ML. Loop diuretics reduce hypoxic damage to proximal tubules of the isolated perfused rat kidney. Kidney Int. 1994;45(4):981–5. 33. Brunton, L., Parker, K., Blumental, D., Buxton I. Goodman and Gilman’s Manual of Pharmacology and Therapeutics. USA: Mc Graw hill Companies; 2008. 475-497 p. 34. Ives HE. Basic and Clinical Pharmacology. 12th ed. Katzung, BG., Masters, SB., Trevor A, editor. USA: Mc Graw hill Companies; 2012. 251-255 p. 35. Zuk A, Bonventre J V, Brown D, Matlin KS. Polarity, integrin, and extracellular matrix dynamics in the postischemic rat kidney. Am J Physiol. 1998;275(3 Pt 1):C711–31. 36. Basile D, Anderson M, Sutton T. Pathophysiology of Acute Kidney Injury. Compr Physiol. 2012;2(2):1303–53. 37. Bonventre J V., Zuk A. Ischemic acute renal failure: An inflammatory disease? Kidney International. 2004. p. 480–5.
DOI: https://doi.org/10.19106/JMedScie/005003201801
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