Although it is too early to draw any definite conclusions from these results, as a period of two years is probably necessary to evaluate cadaver kidney transplantation in humans, it appears that our well-matched patients have much fewer problems than our poorly matched patients. It is hoped that by preservation methods such as those discussed, improved methods of tissue typing, and better immunosuppressive therapy, we will be able to raise the survival level of cadaver kidney transplantations to the level between 80 and 85% presently being obtained in transplantations using living, related donors

Belzer, Folkert O.

VCU Scholars Compass

The Role of Preservation m Transplantation* FOLKERT 0. BELZER Department of Surgery, University of California, San Francisco Medical Center, San Francisco 94122 Introduction Let us look first into the advan-tages and disadvantages of preser-vation in clinical transplantation. I should mention that we are talk-ing of short-term preservation up to 72 hours, rather than preserva-tion for indefinite periods of time. The latter will have to wait until problems of freezing and thawing have been solved, but this still ap-pears to be something for the dis-tant future. What, then, are the ad-vantages? First, it minimizes the total anoxia time. Although it is well known that human cadaver kidneys can maintain viability up to ten hours by simple hypothermia, it is our feeling that this is not good enough. In cadaver kidneys, the organ is already damaged during the agonal period of the donor, and the additional cold storage time undoubtedly further damages the organ, perhaps permanently. Fur-thermore, if preservation for more than ten hours is necessary, some method of perfusion is needed. Second, it allows potential recip-ients to stay at home either on central dialysis or chronic dialysis until a properly matched kidney becomes available. The patients ac-tually do not have to be called until a matched kidney is known to be present, thus eliminating unneces-sary admissions and great disap-pointments. Furthermore, if the po-tential recipient cannot be reached * Presented at the Fortieth Annual McGuire Lecture Series, October 31-November 1, 1968, Medical College of Virginia, Richmond. MCV QUARTERLY 5(4): 171-172, 1969 immediately, he is still not excluded from receiving that particular kid-ney. It, of course, allows the total recipient pool to be tremendously increased, because patients who are dialyzed in different centers or in different cities can be selected by computer and can be considered for a transplantation. Third, adequate preservation al-lows for histocompatibility testing between the donor and a pool of recipients and the direct cross match between the donor white cells and the best matched recipients. Fourth, function and damage can be evaluated before the actual trans-plant, thus eliminating those organs which have been irreversibly dam-aged during the agonal period of the donor. This aspect is still in the investigational stage, but it ap-pears that the perfusion characteris-tics are of the greatest importance. Fifth, adequate preservation is essential for organs such as the liver and heart, because preparation of the recipient is more time-consum-ing. This problem at the present time is usually eliminated by pres-ervation in the donor, the so-called heart-beating cadaver. Sixth, it makes the transplant an elective instead of an emergency operation, which can be of the greatest importance if the kidney becomes available during a period of time when all operating rooms are filled. Seventh, if preservation and se-lection of organs could be per-fected, a much larger source of donor organs would become avail-able. If we are going to be using the so-called neurological deaths only, not enough kidneys will be-come available to treat all patients in chronic renal failure. However, if we could use kidneys from other patients, such as automobile acci-dent victims or other trauma cases who either enter the emergency room dead on arrival or die within the first 20 minutes, the number of available organs would be tremen-dously increased. Finally, it does allow a smaller staff on the transplant team, since the donor nephrectomies, as well as the transplantations, can be done by one team. Methods Perhaps at this point we should briefly mention the different meth-ods that have been used for preser-vation of whole organs. They are hypothermia, hyperbaric oxygen, isolated perfusion, metabolic inhib-itors, and, finally, a combination of the above methods. When our studies were initiated, we felt that perfusion would theoretically be the best method, as pxygen could be supplied, and C02 and metabolic waste products could be removed. To eliminate the problems of micro-emboli, we started with an acellular perfusate such as serum or plasma. However, we were plagued initially by the same problems that all other investigators have had with isolated perfusion-increasing perfusion pressure, decreased flow, and tissue edema. On implantation, even after short periods of preservation, the organs did not function ; or, if they did function, they showed evidence of some permanent damage. We then noticed that, if the plasma were frozen and quickly 171 thawed, a precipitate developed in the plasma, producing a completely opalescent solution. We found that the most efficient way of removing this precipitate was by serial filtra-tion through Millipore filters, and that, by so doing, a clear solution was obtained. Perfusion with this cryoprecipitated plasma eliminated the problems of rising perfusion pressure and tissue edema. When fat stains were used on the kidneys perfused with normal plasma, mul-tiple fat droplets were seen in the capillaries, the glomeruli and the tubules. Fat stains of kidneys per-fused with cryoprecipitated and fil-tered plasma did not show these fat emboli; thus, it became obvious that the etiology of the rising perfusion pressure was due to fat emboli ob-structing the capillary system. When blood is used, these emboli can come from blood cell aggre-gates; but even if the cellular com-ponents are removed, the end stable lipoproteins denature, and their ag-gregates are just as destructive. Furthermore, this process is self-perpetuating. Once decreased capil-lary flow is produced, it results in tissue hypoxia, which is shown to produce cellular swelling, especially when combined with hypothermia. The cellular swelling by itself pro-duces increased capillary resistance and further decreased capillary flow, and the cycle continues until death of the cells and the organ results. Results We next performed 24-hour and 72-hour preservation studies in dogs, and autotransplantation was combined with immediate contra-lateral nephrectomy. All animals in both groups survived. The average BUN rise in the 24-hour group was 80 mg%, occurring usually on the third or fourth day, while in the 72-hour group the BUN rose to an av-erage of 140, again on the third or fourth day. However, there was a subsequent rapid decline in the BUN, so that the 24-hour groups 172 F. 0. BELZER had normal BUNs by the seventh or tenth day, while in the 72-hour group the BUN returned to normal by the third week. The animals were then retested after six months, and conventional as well as electronmicroscopy studies re-vealed normal architecture. Para-aminohippuric acid and inulin clearance studies were within nor-mal limits, and none of the animals developed hypertension. In order to be sure that there was no ac-celeration in the rejection process, we did several homotransplants using 24-hour perfused kidneys, and the animals rejected their kid-neys in the normal period of time ranging from 7 to 21 days. In August, 1967,. we did our first human preservation study; in this, the kidney was preserved for 17 hours. The patient subse-quently developed tubular necrosis lasting two weeks, after which the kidney started to open up. His creatinine clearance went as high as 40, at which time he had his first rejection episode. This was par-tially reversed, but he subsequently had two more rejection episodes requiring maintenance on fairly high doses of steroids. Six months after transplantation he entered the hospital with a ruptured gallbladder secondary to amyloidosis, from which he later succumbed. Of par-ticular interest is the fact that no amyloid was found in the trans-planted kidney six months after transplantation. At that time, our equipment was not transportable, and we found that if the kidney was obtained in one hospital and had to be trans-ferred to the Medical Center be-fore preservation could be started, the anoxia time was still con-siderable. The preservation unit was thus made transportable, so that it could be moved to the op-erating room where the donor kid-neys were obtained. The perfusion. circuit, details of which have been published in several other articles, basically consists of a pulsatile pump, a heat exchanger, an organ chamber, a membrane oxygen.ator, a cooling system, a pressure re-corder and a battery system. For perfusing human kidneys, we use fresh frozen AB+ plasma which is cryoprecipitated immediately be-fore use. The final filter in the Mil-lipore filter system is 0.22µ. and acts also as a bacterial filter. Imme-diately before use, several addi-tives, such as phen.olsulfthalein, magnesium, steroids and antibiotics, are added to the perfusate. We have used this method in 42 patients, and the longest period of preserva-tion has been 36 hours. The kidney functioned immediately. Summary Although it is too early to draw any definite conclusions from these results, as a period of two years is probably necessary to evaluate cadaver kidney transplantation in humans, it appears that our well-matched patients have much fewer problems than our poorly matched patients. It is hoped that by pres-ervation methods such as those dis-cussed, improved methods of tis-sue typing, and better immunosup-pressive therapy, we will be able to raise the survival level of cadaver kidney transplantations to the level between 80 and 85% presently be-ing obtained in transplantations us-ing living, related donors. 

The Role of Preservation in Transplantation

http://scholarscompass.vcu.edu/cgi/viewcontent.cgi?article=1243&context=mcvq

The Role of Preservation in Transplantation

Abstract

Similar works

Full text

Available Versions

VCU Scholars Compass