7
Volume 69 July 1976
527
Section of Clinical Immunology & Allergy President J F Soothill FRCP
Meeting 10 November 1975
Assessment of Homograft Compatibility Mr John R Salaman (Renal Transplant Unit, Royal Infirmary, Cardiff, CF2 ISZ)
chances of survival and 80 % of such kidneys can be expected to be functioning a year after transplantation. However, in the United Kingdom live donor transplantation has never been popular and the majority of kidneys transplanted have come Current Status of Organ Transplantation from totally unrelated people who have died. Considerable effort has been expended in trying For ten years kidney transplantation has been to improve the quality of cadaver kidneys. When used as a method for treating patients with a person dies suddenly and unexpectedly there irreversible kidney failure. During this time the may be a delay of an hour or more while perprocedure has become safer for the patient but mission to remove kidneys is obtained from there has not been a corresponding improvement relatives and other arrangements have been put in the proportion of kidneys that survive. in hand for removal of the kidneys. During this Transplantation of organs other than kidney is period the kidneys can become severely damaged being attempted on a more limited scale. Liver and a proportion will never function again after transplantation is a formidable operation and transplantation. Nowadays kidneys are taken understandably its practice has become restricted mostly from patients who have suffered severe to a few centres (notably Denver and Cambridge) brain damage and who have been maintained on where skill and expertise can be properly con- ventilators. If the patient fails to recover, then centrated. Heart transplantation is technically ventilation is usually abandoned and the transeasier, and there seem to be fewer serious com- plant surgeons are duly notified so that they can plications afterwards. By far the best results have be on hand to remove the kidneys as soon as the emanated from Stanford where Shumway has heart has stopped. In many countries. when been performing heart transplants at the rate of kidneys are removed under these circumstances one a month. His results (50 % of patients surviv- the ventilator is switched off after the kidneys ing one year) can be compared favourably with have been removed rather than before. In this the survival of cadaver kidney transplants. way the kidneys suffer the least amount of ischmmic damage. This concept is gaining gradual About 40 persons per million of the population acceptance in the United Kingdom and as a develop kidney failure each year. Often these result the number of kidneys with 'primary nonpatients are young and a small proportion are function' should diminish considerably. children. Hemodialysis can keep these people Once the kidneys have been removed they will alive and 60 % of patients under treatment in this country are on home dialysis. None the less it is remain in good condition for 12-14 hours proan expensive undertaking and sooner or later vided they are kept cool. This is usually achieved these patients will require a kidney transplant, if by placing them in plastic bags and surrounding only to escape from the boredom of chronic them with ice. Preservation is improved if the himodialysis. Kidneys can be obtained from a blood is first washed out of the kidney by perwilling relative or from someone who has just fusing a solution through the renal artery. Various died. There is no doubt that a well-matched solutions have been advocated but the most kidney from a brother or sister offers the best commonly employed is Collins' C3 solution
528
Proc. roy. Soc. Med. Volume 69 July 1976
8
which resembles intracellular fluid in ionic com- Terasaki and his co-workers have shown that a position and strength. Twelve hours is usually proportion of patients will not develop antibodies quite sufficient time for transporting the kidney however many units of blood they receive (Opelz to the most suitable recipient and for making et al. 1972). These patients have been termed arrangements for the transplant operation. 'poor responders' and on receiving a kidney Occasionally longer periods of preservation are transplant appear to experience fewer rejection required and this can be achieved by perfusing problems. In these prople blood transfusions may the kidney on a special preservation machine. act in some beneficial way by generating enhancThe machine perfuses the kidneys with a cold ing antibodies. Certainly of the 'poor responder' plasma-based fluid which is kept oxygenated and patients those who have been deliberately at the correct pH. During perfusion the viability deprived of blood transfusions do much less well of the kidney can be assessed in some measure, after transplantation (Opelz & Terasaki 1974). allowing severely damaged ones to be identified Although serving a clinical need, kidney transand discarded. Whether perfused kidneys function longer is a matter for debate. In an Australian plantation is not as successful as desired. Just series of cadaver transplants a greater percentage under half the cadaver kidneys are lost, chiefly of perfused kidneys survived one year when com- from rejection, within the first year after transpared with those that had merely been cooled plantation. Close tissue matching between donor (Sheil et al. 1975). However, in a large series of and recipient has been the policy for a number of transplants carried out in California this was not years in most centres in the UK, but what inconfirmed; in fact, in this study the perfused fluence tissue matching has on kidney graft surkidneys functioned for a considerably shorter vival is still not clear. My personal belief is that the results of transplantation will improve only as time (Fine et al. 1975). a result of better immunosuppressive treatment. To prevent rejection of the kidney immunosuppressive drugs are given indefinitely. Initially REFERENCES A D, Coles G A & White H O prednisolone is administered in a high dose, but Barnes (1974) Transplantation 17, 491 over ensuing weeks this can usually be reduced. Clarke A G & Salaman J R Clinical Nephrology 2, 230 Antilymphocyte globulin (ALG) has been shown (1975) Fine S E, Clarke E A, Fine R N & Terasaki P I to have remarkable immunosuppressive pro- (1975) Transplantation Proceedings 7, No. 1, Suppl. 1, p 565 Opelz G, Mickey M R & Terasaki P I (1972) Lancet i, 868 perties in animals, and as a result it has been used Opelz G & Terasaki P I (1974) Lancet ii, 696 widely in man. However, there have been very Sheil A G R, Mears D, Kelly G E, Rogers J H, Storey B G, J R, May J, Charlesworth J, Kalowski S & Stewart J H few controlled clinical trials using this agent and JohnsonLancet i, 359 even now it is not clear whether it is effective. In (1971) Sheil A G R, Boulas J, Drummond J M, May J Rogers J H Australia a controlled trial demonstrated a & Storey B G (1975) Lancet ii, 287 beneficial effect of ALG (Sheil et al. 1971) but similar trials conducted in-the United States and elsewhere have failed to confirm this. A doubleblind controlled clinical trial is under way in the United Kingdom and its results are awaited with interest. Other drugs have been advocated as Dr John W Fabrel being helpful in preventing or delaying rejection. (Nuffield Department of Surgery, Anticoagulants came into vogue a few years ago The Radcliffe Infirmary, Oxford, OX2 6HE) but controlled studies reveal no benefit (Barnes et al. 1974). The management of rejection episodes Specific Suppression of Organ Graft Rejection has altered. High doses of orally administered steroids can produce severe complications and it The scope of transplantation as a therapeutic is now clear that rejection can be reversed as procedure and its utility even in well-established successfully by two or three intravenous 1 gram areas such as renal failure are limited by the doses of methylprednisolone. The mortality toxicity and inadequate potency of the immunoassociated with this treatment is much less than suppressive agents currently in use. These agents that which accompanies the use of high oral are largely nonspecific in their immunological doses of prednisolone (Clarke & Salaman 1975). effects and moreover they produce undesired The effect of previous blood transfusions on side-effects outside the immune system. Specific transplant survival has come under discussion. immunosuppression directs itself solely at the Previously it was thought that transfusing lymphocyte clones responsible for the rejection dialysis patients was unwise since a proportion of the particular graft the patient receives, and it would develop antibodies which could then react with a subsequent transplant. However, 'Wellcome Senior Research Fellow in Clinical Science
Volume 69 July 1976
527
Section of Clinical Immunology & Allergy President J F Soothill FRCP
Meeting 10 November 1975
Assessment of Homograft Compatibility Mr John R Salaman (Renal Transplant Unit, Royal Infirmary, Cardiff, CF2 ISZ)
chances of survival and 80 % of such kidneys can be expected to be functioning a year after transplantation. However, in the United Kingdom live donor transplantation has never been popular and the majority of kidneys transplanted have come Current Status of Organ Transplantation from totally unrelated people who have died. Considerable effort has been expended in trying For ten years kidney transplantation has been to improve the quality of cadaver kidneys. When used as a method for treating patients with a person dies suddenly and unexpectedly there irreversible kidney failure. During this time the may be a delay of an hour or more while perprocedure has become safer for the patient but mission to remove kidneys is obtained from there has not been a corresponding improvement relatives and other arrangements have been put in the proportion of kidneys that survive. in hand for removal of the kidneys. During this Transplantation of organs other than kidney is period the kidneys can become severely damaged being attempted on a more limited scale. Liver and a proportion will never function again after transplantation is a formidable operation and transplantation. Nowadays kidneys are taken understandably its practice has become restricted mostly from patients who have suffered severe to a few centres (notably Denver and Cambridge) brain damage and who have been maintained on where skill and expertise can be properly con- ventilators. If the patient fails to recover, then centrated. Heart transplantation is technically ventilation is usually abandoned and the transeasier, and there seem to be fewer serious com- plant surgeons are duly notified so that they can plications afterwards. By far the best results have be on hand to remove the kidneys as soon as the emanated from Stanford where Shumway has heart has stopped. In many countries. when been performing heart transplants at the rate of kidneys are removed under these circumstances one a month. His results (50 % of patients surviv- the ventilator is switched off after the kidneys ing one year) can be compared favourably with have been removed rather than before. In this the survival of cadaver kidney transplants. way the kidneys suffer the least amount of ischmmic damage. This concept is gaining gradual About 40 persons per million of the population acceptance in the United Kingdom and as a develop kidney failure each year. Often these result the number of kidneys with 'primary nonpatients are young and a small proportion are function' should diminish considerably. children. Hemodialysis can keep these people Once the kidneys have been removed they will alive and 60 % of patients under treatment in this country are on home dialysis. None the less it is remain in good condition for 12-14 hours proan expensive undertaking and sooner or later vided they are kept cool. This is usually achieved these patients will require a kidney transplant, if by placing them in plastic bags and surrounding only to escape from the boredom of chronic them with ice. Preservation is improved if the himodialysis. Kidneys can be obtained from a blood is first washed out of the kidney by perwilling relative or from someone who has just fusing a solution through the renal artery. Various died. There is no doubt that a well-matched solutions have been advocated but the most kidney from a brother or sister offers the best commonly employed is Collins' C3 solution
528
Proc. roy. Soc. Med. Volume 69 July 1976
8
which resembles intracellular fluid in ionic com- Terasaki and his co-workers have shown that a position and strength. Twelve hours is usually proportion of patients will not develop antibodies quite sufficient time for transporting the kidney however many units of blood they receive (Opelz to the most suitable recipient and for making et al. 1972). These patients have been termed arrangements for the transplant operation. 'poor responders' and on receiving a kidney Occasionally longer periods of preservation are transplant appear to experience fewer rejection required and this can be achieved by perfusing problems. In these prople blood transfusions may the kidney on a special preservation machine. act in some beneficial way by generating enhancThe machine perfuses the kidneys with a cold ing antibodies. Certainly of the 'poor responder' plasma-based fluid which is kept oxygenated and patients those who have been deliberately at the correct pH. During perfusion the viability deprived of blood transfusions do much less well of the kidney can be assessed in some measure, after transplantation (Opelz & Terasaki 1974). allowing severely damaged ones to be identified Although serving a clinical need, kidney transand discarded. Whether perfused kidneys function longer is a matter for debate. In an Australian plantation is not as successful as desired. Just series of cadaver transplants a greater percentage under half the cadaver kidneys are lost, chiefly of perfused kidneys survived one year when com- from rejection, within the first year after transpared with those that had merely been cooled plantation. Close tissue matching between donor (Sheil et al. 1975). However, in a large series of and recipient has been the policy for a number of transplants carried out in California this was not years in most centres in the UK, but what inconfirmed; in fact, in this study the perfused fluence tissue matching has on kidney graft surkidneys functioned for a considerably shorter vival is still not clear. My personal belief is that the results of transplantation will improve only as time (Fine et al. 1975). a result of better immunosuppressive treatment. To prevent rejection of the kidney immunosuppressive drugs are given indefinitely. Initially REFERENCES A D, Coles G A & White H O prednisolone is administered in a high dose, but Barnes (1974) Transplantation 17, 491 over ensuing weeks this can usually be reduced. Clarke A G & Salaman J R Clinical Nephrology 2, 230 Antilymphocyte globulin (ALG) has been shown (1975) Fine S E, Clarke E A, Fine R N & Terasaki P I to have remarkable immunosuppressive pro- (1975) Transplantation Proceedings 7, No. 1, Suppl. 1, p 565 Opelz G, Mickey M R & Terasaki P I (1972) Lancet i, 868 perties in animals, and as a result it has been used Opelz G & Terasaki P I (1974) Lancet ii, 696 widely in man. However, there have been very Sheil A G R, Mears D, Kelly G E, Rogers J H, Storey B G, J R, May J, Charlesworth J, Kalowski S & Stewart J H few controlled clinical trials using this agent and JohnsonLancet i, 359 even now it is not clear whether it is effective. In (1971) Sheil A G R, Boulas J, Drummond J M, May J Rogers J H Australia a controlled trial demonstrated a & Storey B G (1975) Lancet ii, 287 beneficial effect of ALG (Sheil et al. 1971) but similar trials conducted in-the United States and elsewhere have failed to confirm this. A doubleblind controlled clinical trial is under way in the United Kingdom and its results are awaited with interest. Other drugs have been advocated as Dr John W Fabrel being helpful in preventing or delaying rejection. (Nuffield Department of Surgery, Anticoagulants came into vogue a few years ago The Radcliffe Infirmary, Oxford, OX2 6HE) but controlled studies reveal no benefit (Barnes et al. 1974). The management of rejection episodes Specific Suppression of Organ Graft Rejection has altered. High doses of orally administered steroids can produce severe complications and it The scope of transplantation as a therapeutic is now clear that rejection can be reversed as procedure and its utility even in well-established successfully by two or three intravenous 1 gram areas such as renal failure are limited by the doses of methylprednisolone. The mortality toxicity and inadequate potency of the immunoassociated with this treatment is much less than suppressive agents currently in use. These agents that which accompanies the use of high oral are largely nonspecific in their immunological doses of prednisolone (Clarke & Salaman 1975). effects and moreover they produce undesired The effect of previous blood transfusions on side-effects outside the immune system. Specific transplant survival has come under discussion. immunosuppression directs itself solely at the Previously it was thought that transfusing lymphocyte clones responsible for the rejection dialysis patients was unwise since a proportion of the particular graft the patient receives, and it would develop antibodies which could then react with a subsequent transplant. However, 'Wellcome Senior Research Fellow in Clinical Science
