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This study was designed to investigate if the dopamine derivate N-octanoyl-dopamine (NOD) has a benefit on acute ischemic kidney injury and on the outcome of renal transplantation after cold ischemia. For that reason the effect on renal function, renal inflammation, the incurrence of rejection and on graft survival has been evaluated.
After all, renal perfusion has been determined in the MRI to examine the hypothesis if NOD, known as a TRPV1-agonist, has the capacity to improve renal perfusion. The beneficial effect of donor dopamine treatment in a setting of acute kidney injury could already be demonstrated. We have also demonstrated that NOD has nephro-protective properties in vitro and after bolus pre-treatment application in vivo.
In this study NOD treatment is exerted in three experimental settings – warm ischemia model, acute and chronic renal transplantation setting. For renal function, creatinine and urea were analyzed in the blood plasma. In addition creatinine clearance was determined in a chronic transplantation setting. Renal inflammation was constituted using immunohistochemical methods like ED1 staining for activated macrophages and MHC II staining in general for antigen presenting cells. Evaluation of acute and chronic rejection was performed using Banff criteria. The data of this study revealed that NOD treatment over 5 days after acute kidney injury improves renal function and reduces renal inflammation which occurs after warm ischemiareperfusion injury.
The application of NOD as a therapeutic agent after renal transplantation, either in an acute or in a chronic setting, offers in contrast to the findings after acute kidney injury no beneficial effect on renal function, renal inflammation, on rejection or longtime survival. Presumptive, the non-beneficial properties of NOD on renal transplantation could be substantially caused by kidney injuries after prolonged cold preservation which cannot attenuate by NOD application afterwards. Donor dopamine treatment before transplantation would reduce the kidney injury after cold ischemia and would probably enhance NOD’s protective abilities.
Whereas NOD was identified as a TRPV1-agonist before, it has been investigated if NOD treatment ameliorates renal perfusion. Stimulation of TRPV1 is followed by the release of CGRP and substance P which are two potent vasodilators. Renal perfusion was measured in the MRI using ASL as a completely non-invasive measurement.
We have shown a possible connection between perfusion and renal function as well as between the severity of vascular alterations in the graft but in general NOD treatment has no beneficial effect on renal perfusion in this study design.