Kidney preservation in the next millenium

Abstract

For the past decades, severe hypothermia has represented the foundation of organ preservation in clinical transplantation. Beneficial as hypothermia has proven to be in preserving grafts from heartbeating donors, hypothermia does not seem to provide the window necessary for the prospective evaluation of organ function. With the increasing use of non-heart-beating donors, it is logical to propose that if organs are to be evaluated prospectively, it will be necessary to preserve them at warmer temperatures. Since both glomerular and tubular functions are inhibited at temperatures below 18 "C, such a goal will necessitate organ preservation at a temperature above 20 "C. The principle of preservation at warmer temperatures is not new, but with future developments and approaches, successful realization appears within reach. In this overview, a brief history of previous attempts at warm preservation, in the context of the current status of kidney preservation, is presented. Future developments and approaches, with the potential for prospective testing of the function and enhanced resistance to ischemic damage, will be discussed.Key words Kidney preservation . Viability testing . Ischemia . Non-heartbeating donor . Heart-beating donor Organ preservation and the organ shortageThe evolution of transplantation has made kidney allografting the preferred treatment for patients with endstage renal failure. Transplantation provides improved quality of life and is more cost-effective than dialysis [33]. Currently, l-year graft survival rates for cadaveric donor transplants are above 80% and l-year patient survival rates 95 % [loo].Offsetting this success is the increasing discrepancy between the availability of, and demand for, transplantable kidneys. Within the Eurotransplant region, procurement rates remained stable during 1996 and 1997, whereas the number of potential recipients on the waiting list increased by 4 % [2S], resulting in approximately 3,000 procedures compared to 11,000 patients awaiting transplantation [70].A major factor contributing to the organ shortage is the detrimental effect of ischemia. Upon harvesting, the loss of the vascular circulation causes ischemia, with the concomitant depletion of oxygen and nutrients to the kidney. The ischemia, with the resulting loss of metabolic activity, initiates a cascade of cellular damage. This injury cascade leads to the breakdown of high-energy compounds necessary for cellular metabolism, a generalized loss of cellular integrity, and activation of degenerative enzymes. The result is the loss of all structural and functional components of the cell. While it has been proposed that the kidney can tolerate as much as 2 h of warm ischemia before the damage becomes so severe that it is irreversible and reperfusion with blood will not restore a life-sustaining function, transplanting an allograft with warm ischemic exposure of this magnitude is never considered clinically. Once a 84 kidney is removed, preservation techniques must preserve the organ sufficiently to...

The clinical and cost-effectiveness of pulsatile machine perfusion versus cold storage of kidneys for transplantation retrieved from heart-beating and non-heart-beating donors

“…One reason for this is hypothermia, which, while greatly reducing the amount of renal damage, also makes evaluation of renal function impossible. As a result there is now also renewed interest in normothermic machine preservation, 8 although this remains, as yet, completely experimental.…”

Caracterización histológica y hemodinámica del injerto con isquemia caliente según el método de preservación

“…Mediante la biopsia, un procedimiento dañino para el injerto o a través de test diseñados para evaluar la resistencia vascular 27 , la producción o fluctuación de determinadas enzimas 20,28 , se ha intentado responder a esta pregunta, aunque desafortunadamente todos estos métodos están entorpecidos por la preservación en hipotermia o por su viabilidad clínica 29 . El daño asociado a la isquemia/reperfusión durante el trasplante es una variable muy importante a tener en cuenta, con consecuencias en la clínica, como el rechazo y la disfunción tardía del injerto.…”

Kidney warming during transplantation

“…Kidney temperature in the recipient was different from animal kidney temperature, which is less than 4 "C [2, 221. In such studies, kidney temperature often corresponds to the kidney temperature at removal from the container [2] because it is an auto-transplantation or a kidney placed in an incubator [22,231 without previous ex vivo preparation and washing. These situations do not exactly reproduce the specific physiological conditions in human renal transplantation.…”