Changes in glutathione levels in the renal cortex of dogs during preservation by continuous hypothermic pulsatile perfusion

: A loss of glutathione (GT) from the kidney can cause increased sensitivity to oxygen free radical-induced injury. In this study we investigated the effects of kidney preservation on GT concentration in the cortex tissue, and how various GT precursors affect GT concentration in the dog kidney. During five day continuous machine perfusion of the kidney at 5 degrees C, there was a loss of GT from the cortex tissue (524 +/- 1% GT remained after 5 days). Perfusion with reduced glutathione (GSH, 3 mM) suppressed this loss (77 +/- 11% of GT remained after 5 days). Oxidized glutathione (GSSG) did not prevent the loss of GT. The addition of the three amino acids that make up GT (glycine, glutamic acid, and cysteine, 3 mM each) stimulated the synthesis of GT in the kidney during hypothermic perfusion (137 +/- 23% of control values at 5 days). The increase in tissue GT stimulated by GSH or other precursors was sensitive to the GT synthetase inhibitor, buthionine sulfoximine. This indicated active GT metabolism even at 5 degrees C in perfused kidneys. This study showed that in kidney preservation there was a loss of GT that could be suppressed by the addition of various precursors for GT synthesis. The loss of GT from preserved kidneys may be one cause of post-transplant renal injury which could be prevented by utilization of the appropriate GT precursors.