1. ¹Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Hospital Mannheim, University of Heidelberg, Mannheim, Germany
2. ²Hôpital Kirchberg, Service de Médecine Interne et Néphrologie, Luxembourg, Brussels

Correspondence: U Gottmann, Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Hospital Mannheim, University of Heidelberg, Mannheim D-68135, Germany. E-mail: uwe.goettmann@med5.ma.uni-heidelberg.de

Received 23 June 2005; Revised 4 January 2006; Accepted 7 February 2006; Published online 7 June 2006.

Abstract

Treatment of organ donors with catecholamines reduces acute rejection episodes and improves long-term graft survival after renal transplantation. The aim of this study was to investigate the effect of catecholamine pre-treatment on ischemia/reperfusion (I/R)- and cold preservation injury in rat kidneys. I/R-injury was induced by clamping the left kidney vessels for 60 min along with a contralateral nephrectomy. Cold preservation injury was induced by storage of the kidneys for 24 h at +4°C in University of Wisconsin solution, followed by syngeneic transplantation. Rats were pre-treated with either dopamine (DA), dobutamine (DB), or norepinephrine (2, 5, and 10 g/kg/min, each group) intravenously via an osmotic minipump for 24 h before I/R- and cold preservation injury. Pre-treatment with DA (2 or 5 g/kg/min) and DB (5 g/kg/min) improved recovery of renal function after I/R-injury and dose dependently reduced mononuclear and major histocompatibility complex class II-positive cells infiltrating the kidney after I/R-injury. One day after I/R-injury, upregulation of transforming growth factor (TGF)- 1 and 2 and phosphorylation of p42/p44 mitogen-activated protein kinases was observed in kidneys of animals treated with DA or DB. DA (5 g/kg/min) and DB (5 g/kg/min) pre-treatment reduced endothelial cell damage after 24 h of cold preservation. Only DA pre-treatment improved renal function and reduced renal inflammation after 24 h of cold preservation and syngeneic transplantation. Our results demonstrate a protective effect of pre-treatment with catecholamines on renal inflammation and function after I/R- or cold preservation injury. This could help to explain the potent organoprotective effects of catecholamine pre-treatment observed in human kidney transplantation.