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In the present study functional values for isolated kidneys with different perfusion …

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- Reference values and physiological characterization of a specific isolated pig kidney perfusion model

A variety of isolated and perfused kidney models has been used for the study of renal functional parameters [1-6]. If the kidneys are perfused normothermically with autologous blood, they exhibit unique possibilities for pharmacology and toxicology studies and for the improvement of the graft function after transplantation. As the donor kidneys are subject to warm and cold ischemia due to the explantation process and the preservation [7-10], the investigation of ischemia- and reperfusion-related injuries [11-15] which cause a great number of organ failures, is still very important.

While easy in use, the perfusion of small laboratory animal kidneys has often been unsatisfactory since the renal function of these animals largely differ in comparison to the human organ [16-18]. In contrast to the situation in rodent organisms, the functional morphology of porcine kidneys is closer to the situation in humans. Therefore porcine kidney perfusion systems are often used in experimental nephrology [1,19-21].

Next to the renal anatomy and function, a further advantage of porcine organs is based on the availability of organs from commercially slaughtered animals. The use of these slaughterhouse kidneys can lead to the reduction in the number of experimental animals. Legally, slaughterhouse kidney perfusion studies are not defined as animal experiments and therefore fulfill international standards in terms of establishing alternatives to animal experimentations [22].

Many perfusion settings exist for porcine kidney perfusion models but reference values for different perfusion conditions have not been defined so far. Physiological reference values out of in vivo animal studies are of limited meaning for the validation of the isolated kidney function due to the organ's separation from extra-organic nervous and humoral control mechanisms. For example strong poliuric states with urine flow rates of 10 ml/min and more may occur, caused partly by the absence of ADH control in this kidney model.

Therefore the present study was performed, to define comparative values of renal functional parameters in both, laboratory and slaughterhouse harvested isolated porcine kidneys. The organs were studied under different preservation and perfusion conditions and were compared to the in vivo renal function of pigs. Physiologically the focus was set 1.) on the glomerular filtration, determined by the exogenous creatinine clearance [23-25] and 2.) on postglomerular mechanisms, controlling renal sodium handling. Sodium reabsorption is an active, oxygen-consuming process dependent upon sodium potassium pumps [26-28]. This had been studied already for the isolated kidney of the rat [29] and also for the state of postischemic acute renal failure [30]. The metabolic coupling between the sodium reabsorption and the oxygen consumption [31-34] therefore is used here as a further indicator for the performance of the isolated pig kidney.

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