Vol. 280, Issue 2, 786-794, 1997

Neutrophils Accentuate Renal Cold Ischemia-Reperfusion Injury. Dose-Dependent Protective Effect of a Platelet-Activating Factor Receptor Antagonist¹

M. Riera² , J. Torras, I. Herrero³ , J. Valles, M. Paubert-Braquet, J. M. Cruzado, J. Alsina and J. M. Grinyo

Nephrology Service, Hospital of Bellvitge (J.T., J.M.C., J.A., J.M.G.), Fundació August Pi i Sunyer (M.R., I.H.), Department of Medicine, University of Barcelona (J.M.G.), Ciutat Sanitària i Universitària de Bellvitge and LASA Laboratories (J.V.), Barcelona, Spain, and Bio-Inova, Plaisir, France (M.P.B)

This study was undertaken to evaluate whether the renal damage induced by cold ischemia-reperfusion was worsened by neutrophils (PMN), and if blockade of platelet-activating factor (PAF) could effectively decrease this injury. After flushing with EuroCollins, 85 kidneys from Sprague-Dawley rats underwent either no cold ischemia or a 4-h cold ischemia, and then were reperfused for 75 min at 37°C and 100 mm Hg in an isolated perfusion circuit. Reperfusion was performed with a Krebs-Henseleit solution containing 4.5% albumin, with and without human PMN (7.5 × 10⁵ cells/ml) and with and without addition of a PAF receptor antagonist (BN 52021). Hemodynamic and functional parameters were continuously assessed during reperfusion. At end of the study, PAF production was evaluated. Presence of PMN during reperfusion of nonischemic kidneys produced no alteration of functional parameters or PAF production. After 4-h cold ischemia, the presence of PMN during reperfusion produced a significant worsening of plasma flow rate, glomerular filtration rate and sodium reabsorption in comparison with kidneys reperfused without PMN. Also, higher production of PAF was observed in the kidneys reperfused with PMN than in the kidneys reperfused without PMN. After 4-h cold ischemia, addition of BN 52021 during reperfusion in the presence of PMN significantly increased the plasma flow rate, glomerular filtration rate and sodium reabsorption in comparison with kidneys reperfused without this PAF antagonist. This effect was dose dependent. After 4-h cold ischemia, addition of BN 52021 during reperfusion in the absence of PMN produced no significant effect on functional parameters in comparison with kidneys reperfused without this PAF antagonist. These results indicate that PMN contribute to renal cold ischemia-reperfusion injury evaluated in the isolated perfused kidney. Treatment with a PAF receptor antagonist attenuated this injury in a dose-dependent manner, which suggests that it is mediated by PAF.