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Kidney International (1993) 43, 1397–1401; doi:10.1038/ki.1993.196

Glycerol induced ARF in rats is mediated by tumor necrosis factor-alpha

Lester M Shulman1, Yael Yuhas1, Ina Frolkis1, Slava Gavendo1, Aaron Knecht1 and Haskel E Eliahou1

1Nephrology Department, Chaim Sheba Medical Center, Tel Hashomer, Israel

Correspondence: Dr Lester M Shulman, Head, Nephrology Laboratory, Chaim Sheba Medical Center, Tel Hashomer, Israel, 52621.

Received 11 January 1993; Revised 15 March 1993; Accepted 15 March 1993.

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Abstract

Glycerol induced ARF in rats is mediated by tumor necrosis factor-alpha. Glycerol-induced acute renal failure (ARF) in rats is a model of acute trauma in which intra-muscular injection of 50% glycerol causes rapid myoglobinuria, oliguria, and a rapid reduction in glomerular filtration rate. We found that plasma tumor necrosis factor-alpha (TNF-alpha) is rapidly induced in glycerol injected rats. It can be detected in some animals as early as 30 minutes post-injection, peaks at one hour (range: 4 to 32 U/ml) with no significant difference between blood from renal vein and vena cava, and decreases by three hours. None was detected in control saline injected rats (P < 0.001). Four out of five rats infused with neutralizing anti-TNF-alpha antiserum (200 microl/300 g body wt) immediately prior to glycerol injection had significantly protected kidney function (P = 0.001). In these rats, plasma urea (104.8 plusminus 58.9 mg%) and creatinine (1.16 plusminus 0.38 mg%) were lower and creatinine clearance higher (0.34 plusminus 011 ml/min) than in glycerol injected animals pretreated with normal serum (291.8 plusminus 41.8 mg%, 3.15 plusminus 0.74 mg%, and 0.03 plusminus 0.03 ml/min, respectively) or animals injected with glycerol alone (302.6 plusminus 76.8 mg%, 3.45 plusminus 0.97 mg%, and 0.03 plusminus 0.03 ml/min, respectively). These results imply a direct role for TNF-alpha in pathogenesis of glycerol induced ARF in rats.

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