Protective Effect of Etanercept in Experimentally Generated Acute Kidney Failure Etanercept in Acute Kidney Failure

Main Article Content

Mehmet Kara
Mehmet Fatih Sönmez
Hasan Basri Ulusoy


Objective: Acute renal failure (ARF) is a clinical syndrome that causes a decrease in the glomerular filtration rate and leads to an accumulation of nitrogenous waste products and uremic toxins. This study investigated the protective effect of Etanercept on ARF.

Materials and Methods: Experiments were done on Balb-C female mice. Acute renal failure was created with an intraperitoneal folic acid injection. Etanercept was injected with folic acid in doses of 0.7 mg/kg, 3.5 mg/kg, and 7 mg/kg in treatment groups. Blood urea nitrogen levels, creatinine and cystatin-c were measured on the 7th day of the study. The kidneys were examined histologically with hematoxylin-eosin staining and Tunel assay.

Results: Etanercept improved kidney morphology damaged by folic acid. The apoptotic index was low, and there was less dilation in the renal tubules in the groups treated with Etanercept. Folic acid increased blood urea nitrogen levels. This increase was decreased gradually with increased doses of Etanercept. There were no differences in creatinine levels in all groups. 

Conclusion: This study investigated the protective effects of Etanercept in the context of Acute Renal Failure (ARF). The results demonstrated that Etanercept improved kidney morphology damaged by folic acid, reduced the apoptotic index, and gradually decreased elevated blood urea nitrogen levels. Although creatinine levels showed no significant differences among the treatment groups, the findings suggest that Etanercept may hold promise as a potential agent for the treatment of ARF. Further research and clinical studies are warranted to validate its effectiveness and safety in human subjects.


Download data is not yet available.

Article Details

How to Cite
Kara, M., Sönmez, M. F., & Ulusoy, H. B. (2023). Protective Effect of Etanercept in Experimentally Generated Acute Kidney Failure: Etanercept in Acute Kidney Failure. Medical Science and Discovery, 10(10), 825–830.
Research Article
Received 2023-10-10
Accepted 2023-10-15
Published 2023-10-16


Akcan-Arikan A, Zappitelli M, Loftis LL, et al. Modified RIFLE criteria in critically ill children with acute kidney injury. Kidney Int. 2007 May;71(10):1028-35. DOI:

Vogt BA, Avner ED. Renal Failure. In: Behrman RE, Kliegman RM, Jenson HB, editors. Nelson Textbook of Pediatrics 18 th edition. Philadelphia: WB Saunders, 2007; 2206-2209.

Fliser D, Laville M, Covic A, et al. A European Renal Best Practice (ERBP) position statement on the Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guidelines on acute kidney injury:, Global Outcomes (KDIGO) clinical practice guidelines on acute kidney injury: part 1: definitions, conservative management and contrast-induced nephropathy. Nephrol Dial Transplant 2012;27(12):4263–72. DOI:

Medve L, Antek C, Paloczi B, et al. Epidemiology of acute kidney injury in Hungarian intensive care units: a multicenter, prospective, observational study. BMC Nephrol. 2011;12:43–43. DOI:

Ettehadi P, Greaves MW, Wallach D, et al. Elevated tumour necrosis factor-alpha (TNF-alpha) biological activity in psoriatic skin lesions Clin Exp Immunol 1994;96:146-51. DOI:

Goffe B, Cather JC. Etanercept: An overview. J Am Acad Dermatol. 2003 Aug; 49(2Suppl):S105-11. DOI:

Wan B, Hao L, Qiu Y, et al. Blocking tumor necrosis factor-alpha inhibits folic acid-induced acute renal failure. Exp Mol Pathol. 2006 Dec;81(3):211-6. DOI:

Wen X, Peng Z, Li Y, et al. One dose of cyclosporine A is protective at initiation of folic acid-induced acute kidney injury in mice. Nephrol Dial Transplant. 2012 Aug;27(8):3100-9.. DOI:

Dai C, Yang J, Liu Y. Single injection of naked plasmid encoding hepatocyte growth factor prevents cell death and ameliorates acute renal failure in mice. J Am Soc Nephrol 2002;13:411–22. DOI:

Yuan HT, Li XZ, Pitera JE, et al. Peritubular capillary loss after mouse acute nephrotoxicity correlates with down-regulation of vascular endothelial growth factor-A and hypoxia-inducible factor-1 alpha. Am J Pathol. 2003; 163:2289–2301. DOI:

Wang HZ, Peng ZY, Wen XY, et al. N-acetylcysteine is effective for prevention but not for treatment of folic acid-induced acute kidney injury in mice. Crit Care Med. 2011 Nov;39(11):2487-94.. DOI:

Shimizu A., Yamanaka N. Apoptosis and cell desquamation in repair process of ischemic tubular necrosis. Virchows Arch B Cell Pathol Incl Mol Pathol 64:171, 1993. DOI:

Beutler B, Milsark IW, Cerami AC. "Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin". Science 1985 229 (4716): 869–71. DOI:

Black RA, Rauch CT, Kozlosky CJ, et al. A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cell. Nature 1997 385 (6618): 729–33. DOI:

Nedwin GE, Naylor SL, Sakaguchi AY, et al. Human lymphotoxin and tumor necrosis factor genes: structure, homology and chromosomal localization. Nucleic Acids Res. 1985 Sep 11;13(17):6361-73. DOI:

Hsu H, Xiong J, Goeddel DV. The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation. Cell 1995 81(4):495-504. DOI:

Feldman M, et al. Anti-TNF alpha Therapy is useful in Rheumatoid Arthritis and Crohn's disease: analysis of the mechanism of action predicts utility in other diseases. Transplant Proc. 1998. 30(8): p. 4126-7. DOI:

Feldmann M. Development of anti-TNF therapy for rheumatoid arthritis. Nat Rev Immunol. 2002 May;2(5):364-71.. DOI:

MacEwan DJ. TNF receptor subtype signalling: differences and cellular consequences. Cell Signal. 2002 Jun;14(6):477-92. DOI:

Harrington JF, Messier AA, Levine A, et al. Shedding of tumor necrosis factor type 1 receptor after experimental spinal cord injury. J Neurotrauma. 2005 Aug;22(8):919-28. DOI:

Choi DE, Jeong JY, Lim BJ, et al. Pretreatment with the tumor nerosis factor-alpha blocker etanercept attenuated ischemia-reperfusion renal injury.Transplant Proc. 2009 Nov;41(9):3590-6. DOI:

Lee YB, Yune TY, Baik SY, et al. Role of tumor mor necrosis factor–alpha in neuronal and glial apoptosis after spinal cord injury. Exp. Neurol. 2000 166, 190–195. DOI:

Hayashi M, Ueyama T, Nemoto K, et al. Sequential mRNA expression for immediate early genes, cytokines and neurotrophins in spinal cord injury. J Neurotrauma 2000;17:203–218. DOI:

Clausen BH, Degn M, Martin NA, et al. Systemically administered anti-TNF therapy ameliorates functional outcomes after focal cerebral ischemia. J Neuroinflammation. 2014 Dec 12;11:203. DOI: