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Cadaver Kidney Donation
485
Cadaver Kidney Donation SINCE 1956, when DEMPSTER and ROBperformed the first human renal allograft in Great Britain,
transplant surgeons have been involved in the problem of acquiring cadaver kidneys. As transplantation became more acceptable as a treatment for chronic renal failure, a cooperative scheme was established in March, 1969,2 so that more kidneys would become available. In February, 1972,3the Department of Health and Social Security took over this activity and set up the National Organ Matching Service
at
Bristol, which has done excellent work in
matching and transporting kidneys around the United Kingdom but has been able to do little to increase the supply of kidneys. Each year about 2000 people in the U.K. go into treatable end-stage renal failure. Hospital and home dialysis can cater for about 500 of them; thus, transplantation ought to be offered to the other 1500, of whom some will need a second and third transplant. If 3000 or so kidneys were available for transplantation, in conjunction with Eurotransplant and Scandatransplant, everybody needing a kidney could be offered a well-matched one. This is about the number of kidneys theoretically available in the United Kingdom; but nothing like this number is actually available because doctors hate asking permission of relatives at or near the time of death. There is an urgency about the actual removal of the kidneys. In the U.K. the Human Tissue Act 19614 makes no provision for the diagnosis of brain death, as the Law does in France and Scandinavia, and thus the surgeons have to wait for cardiac death. Inevitably the kidney is subjected to a period of poor blood-flow and hypoxia after the ventilator has been switched off. After cardiac arrest, the kidneys suffer further ischxmic damage (the warm ischemia time) whilst the surgeon removes them. In the U.K. most surgeons hesitate to remove kidneys for transplan1.
Joekes, A. M., Porter, 44, 607.
K. A.,
Dempster, W. J. Br. J. Surg. 1956-57,
Festenstein, H., Oliver, R. T. D., Sachs, J. A., Burke, J. M., Adams, E., Divver, W., Hyams, A., Pegrum, G. D., Balfour, I. C., Moorhead, J. F. Lancet, 1971, ii, 226. 3. Letter dated Dec. 22, 1971, from Chairman of the National Organ Matching Service to all directors of transplantation. 2.
4. Human Tissue Act 1961.
tation if the warm time is greater than 60 minutes.5,6s Once the kidneys have been removed and cooled, whether by simple surface cooling, flush cooling, or machine preservation, they can be stored for at least 12 hours and sometimes 24 or 36 hours.7-9 Thus the transplant surgeons have to be alerted before the death of potential donors, so that the kidneys can be taken out in less than 60 minutes. In many instances the surgeon has little time to get there and do the operation. But a more serious difficulty lies in contacting the relatives and interviewing them. The Department of Health says that the relatives must be asked in all cases for permission to remove the kidneys after death; but the Law is confused.10,11 The Act suggests that the potential donor, once dead, is the property of the hospital; and, if the hospital authorities agree, the transplant surgeon can go ahead without permission from the relatives, provided that the donor was carrying a donor card. Such a card seemingly would not have to bear the signature of a relative.
supply of donors be increased ? One attempt to meet the problem was the kidney-donor card issued by the Department. This was meant to be carried at all times (a tall order) and it did not require the next-of-kin’s signature. So far, this card has been found on two possible donors. Now a new How
can
the
version is to be issued which does have a space for the next-of-kin’s signature, but the Department continues to insist that a relative’s permission be obtained at or near the time of death. The whole concept of these cards seems to be wrong. 12 CALNE 13 has an scheme suggested opting-out whereby the kidneys from all suitable donors unless the could be removed donor of the relatives had specifically requested that this should not be done. The requests would be kept at the National Organ Matching Service at Bristol and, whenever a suitable donor became available, the doctors concerned would have only to ring Bristol to see if a refusal had been received. A disadvantage of this scheme is that it relies on the public to inform Bristol; even with good Press and advertising coverage some people not wishing their kidneys to be used would not notify Bristol. An alternative is the opting-in scheme 13 whereby wouldbe donors could complete a new form : this would give the potential donor’s name, signature, and address, perhaps a few physical characteristics, and the name and signature of the next-of-kin. Similar forms could be issued to parents who wished to 5. Williams, G. B., Gordon, E. M. Proc. R. Soc. Med. 1972, 65, 305. 6. Hulme, B., Snell, M. E., Kenyon, J. R., Owen, K., Peart, W. S. Br. med. J. 1972, iv, 139. 7. Collins, G. M., Hartley, L. C. J., Clunie, G. J. A. Br. J. Surg. 1972,
59, 187. 8. Belzer, F. O., Kauntz, S. L. Ann. Surg. 1970, 172, 394. 9. Claes, G., Blohme, I. Swedish National Medical November, 1970. 10. Br. med. J. 1973, iii, 189. 11. ibid. p. 360. 12. McKie, D. Lancet, Aug. 25, 1973, p. 436. 13. Wld Med. 1973, 8, 10.
Congress,
486
include their children within the scheme. The form would have a tear-off slip which the person would keep, and the more important part would be sent back to Bristol in a prepaid envelope for computer At regular intervals, perhaps annually, storage. everyone on the computer would receive from National Organ Matching Service another form which could be returned with any change of address or next-of-kin. It would also allow anyone who changes his mind to opt out. Such an opting-in scheme respects the rights of an individual, firstly, by catering for dissenters and, secondly, by ensuring that kidneys have a good chance of being used if that was the dead person’s wish-the term cadaver donor acquires a positive sense. For doctors, too, the scheme would be attractive. When a patient seemed a possible kidney donor, a call to Bristol would ascertain whether his name was on the computer. This being so, no interview with the relatives would be necessary; as soon as they had left the bedside, the kidneys could be taken out. The Department of Health should abandon its plans for a modified donor card and look seriously at a scheme such as this. It would not necessitate any change in the Law or any further interpretation of the Law as it stands.
Refractory Hypertension DEBATE about the management of high bloodpressure has largely centred on mild hypertension and the formidable economic and human problems associated with detecting and treating such a common condition.1 Very few competent physicians would ignore a diastolic blood-pressure of 130 or 140
Hg (although most could recollect one or two patients who have survived such pressures for many years). The outlook in severe hypertension has improved vastly with the progressively more powerful hypotensive drugs,2 but a minority of patientsexcluding those who do not take their tablets-do not respond well to conventional drugs. There is no ready definition of drug resistance here, since it is unlikely that every potent hypotensive agent would be successively administered to any one individual. Nevertheless, in practice, the patient who remains severely hypertensive despite maximal doses of methyldopa, guanethidine, bethanidine, or debrisoquine is familiar to most physicians. We have no estimate of the numbers of these patients, and the frequency in the population is likewise unknown. The attitude of the physician is all-important. Bloodpressures are not laboratory estimations which are carried out blind. When the therapeutic possibilities
mm.
1. 2.
Hypertension: A suitable case for treatment ? Office of Health Economics, London, 1971. Breckenridge, A., Dollery, C. T., Parry, E. H. O. Q. Jl Med. 1970, 39, 411.
almost exhausted a doctor is powerfully motivated to underestimate rather than overestimate the bloodpressure, or to overlook blood-pressures which exceed 110 or 120 mm. Hg in an otherwise apparently healthy individual. Yet there is no reason to believe that these patients do not share the poor prognosis of untreated patients with such blood-pressure levels. Refractory hypertension is usually associated with evidence of tissue damage in the form of retinal haemorrhages, exudates, and papilloedema, and/or renal impairment. The hypertension may be secondary to established renal disease or it may be primary. From the point of view of blood-pressure control the distinction is unimportant, since in either situation uncontrolled hypertension can cause a decline in renal function. Indeed, death from renal failure is a common outcome of refractory hyperWith the modern hypotensive drugs, tension.33 specialist hypertension clinics are seeing fewer patients who ultimately die of renal impairment 2; but it is possible that some of this decline may be due to the establishment of separate renal centres. Nephrologists often meet the problem when it has advanced to a point where it is life-threatening: primary hypertension is high on the list of causes of renal failure.4 Yet, where the blood-pressure can be controlled, renal function may improve.5,6 Where hypertension is refractory to medical treatment, the only feasible alternative is bilateral nephrectomy, followed by lifelong dialysis or renal transplantation.7 The economic and human cost of such an outcome is, of course, tremendous, and there is every incentive to find a satisfactory drug regimen. In the search for an effective agent, attention has lately been focused on vasodilators, which appear to have a unique therapeutic potency in this situation. The oldest of these compounds still in use, hydrallazine, fell into disrepute when it caused systemic lupus in some patients.8 But, in strictly limited dosage,9 it has now regained a major place in some treatment schedules, particularly in the U.S.A. Its combination with &bgr;-blocking drugs such as are
propranolol is, theoretically at least, an ingenious one, since, by preventing compensatory vasoconstriction, it supplements the fall in blood-pressure produced by the reduction of cardiac output. 10 However, this is probably an oversimplified view of a pharmacologically complex situation, and, because the dose of hydrallazine has to be kept low, it is too Kincaid-Smith, P., Fang, P., Laver, M. C. Clin. Sci. 1973, 45, suppl. 1, 75s. 4. Ross, E. J. in Renal Disease (edited by D. A. K. Black); p. 464. Oxford, 1973. 5. Woods, J. W., Blythe, W. B. New Engl. J. Med. 1967, 277, 57. 6. Sevitt, L. A., Evans, D. J., Wrong, O. M. Q. Jl Med. 1971, 40, 127. 7. Mahoney, J. F., Storey, B. G., Gibson, G. R., Stokes, G. S., Sheil, A. G. R., Stewart, J. H. Lancet, 1972, i, 1036. 8. Alarćon-Segovia, D., Wakim, K. G., Worthington, J. W., Ward, L. E. Medicine, Baltimore, 1967, 46, 1. 9. Frohlich, E. D. Ann. intern. Med. 1973, 78, 717. 10. Sannerstedt, R., Stenberg, J., Vedin, A., Wilhelmsson, C., Werko, L. Am. J. Cardiol. 1972, 29, 718. 3.
Cadaver Kidney Donation SINCE 1956, when DEMPSTER and ROBperformed the first human renal allograft in Great Britain,
transplant surgeons have been involved in the problem of acquiring cadaver kidneys. As transplantation became more acceptable as a treatment for chronic renal failure, a cooperative scheme was established in March, 1969,2 so that more kidneys would become available. In February, 1972,3the Department of Health and Social Security took over this activity and set up the National Organ Matching Service
at
Bristol, which has done excellent work in
matching and transporting kidneys around the United Kingdom but has been able to do little to increase the supply of kidneys. Each year about 2000 people in the U.K. go into treatable end-stage renal failure. Hospital and home dialysis can cater for about 500 of them; thus, transplantation ought to be offered to the other 1500, of whom some will need a second and third transplant. If 3000 or so kidneys were available for transplantation, in conjunction with Eurotransplant and Scandatransplant, everybody needing a kidney could be offered a well-matched one. This is about the number of kidneys theoretically available in the United Kingdom; but nothing like this number is actually available because doctors hate asking permission of relatives at or near the time of death. There is an urgency about the actual removal of the kidneys. In the U.K. the Human Tissue Act 19614 makes no provision for the diagnosis of brain death, as the Law does in France and Scandinavia, and thus the surgeons have to wait for cardiac death. Inevitably the kidney is subjected to a period of poor blood-flow and hypoxia after the ventilator has been switched off. After cardiac arrest, the kidneys suffer further ischxmic damage (the warm ischemia time) whilst the surgeon removes them. In the U.K. most surgeons hesitate to remove kidneys for transplan1.
Joekes, A. M., Porter, 44, 607.
K. A.,
Dempster, W. J. Br. J. Surg. 1956-57,
Festenstein, H., Oliver, R. T. D., Sachs, J. A., Burke, J. M., Adams, E., Divver, W., Hyams, A., Pegrum, G. D., Balfour, I. C., Moorhead, J. F. Lancet, 1971, ii, 226. 3. Letter dated Dec. 22, 1971, from Chairman of the National Organ Matching Service to all directors of transplantation. 2.
4. Human Tissue Act 1961.
tation if the warm time is greater than 60 minutes.5,6s Once the kidneys have been removed and cooled, whether by simple surface cooling, flush cooling, or machine preservation, they can be stored for at least 12 hours and sometimes 24 or 36 hours.7-9 Thus the transplant surgeons have to be alerted before the death of potential donors, so that the kidneys can be taken out in less than 60 minutes. In many instances the surgeon has little time to get there and do the operation. But a more serious difficulty lies in contacting the relatives and interviewing them. The Department of Health says that the relatives must be asked in all cases for permission to remove the kidneys after death; but the Law is confused.10,11 The Act suggests that the potential donor, once dead, is the property of the hospital; and, if the hospital authorities agree, the transplant surgeon can go ahead without permission from the relatives, provided that the donor was carrying a donor card. Such a card seemingly would not have to bear the signature of a relative.
supply of donors be increased ? One attempt to meet the problem was the kidney-donor card issued by the Department. This was meant to be carried at all times (a tall order) and it did not require the next-of-kin’s signature. So far, this card has been found on two possible donors. Now a new How
can
the
version is to be issued which does have a space for the next-of-kin’s signature, but the Department continues to insist that a relative’s permission be obtained at or near the time of death. The whole concept of these cards seems to be wrong. 12 CALNE 13 has an scheme suggested opting-out whereby the kidneys from all suitable donors unless the could be removed donor of the relatives had specifically requested that this should not be done. The requests would be kept at the National Organ Matching Service at Bristol and, whenever a suitable donor became available, the doctors concerned would have only to ring Bristol to see if a refusal had been received. A disadvantage of this scheme is that it relies on the public to inform Bristol; even with good Press and advertising coverage some people not wishing their kidneys to be used would not notify Bristol. An alternative is the opting-in scheme 13 whereby wouldbe donors could complete a new form : this would give the potential donor’s name, signature, and address, perhaps a few physical characteristics, and the name and signature of the next-of-kin. Similar forms could be issued to parents who wished to 5. Williams, G. B., Gordon, E. M. Proc. R. Soc. Med. 1972, 65, 305. 6. Hulme, B., Snell, M. E., Kenyon, J. R., Owen, K., Peart, W. S. Br. med. J. 1972, iv, 139. 7. Collins, G. M., Hartley, L. C. J., Clunie, G. J. A. Br. J. Surg. 1972,
59, 187. 8. Belzer, F. O., Kauntz, S. L. Ann. Surg. 1970, 172, 394. 9. Claes, G., Blohme, I. Swedish National Medical November, 1970. 10. Br. med. J. 1973, iii, 189. 11. ibid. p. 360. 12. McKie, D. Lancet, Aug. 25, 1973, p. 436. 13. Wld Med. 1973, 8, 10.
Congress,
486
include their children within the scheme. The form would have a tear-off slip which the person would keep, and the more important part would be sent back to Bristol in a prepaid envelope for computer At regular intervals, perhaps annually, storage. everyone on the computer would receive from National Organ Matching Service another form which could be returned with any change of address or next-of-kin. It would also allow anyone who changes his mind to opt out. Such an opting-in scheme respects the rights of an individual, firstly, by catering for dissenters and, secondly, by ensuring that kidneys have a good chance of being used if that was the dead person’s wish-the term cadaver donor acquires a positive sense. For doctors, too, the scheme would be attractive. When a patient seemed a possible kidney donor, a call to Bristol would ascertain whether his name was on the computer. This being so, no interview with the relatives would be necessary; as soon as they had left the bedside, the kidneys could be taken out. The Department of Health should abandon its plans for a modified donor card and look seriously at a scheme such as this. It would not necessitate any change in the Law or any further interpretation of the Law as it stands.
Refractory Hypertension DEBATE about the management of high bloodpressure has largely centred on mild hypertension and the formidable economic and human problems associated with detecting and treating such a common condition.1 Very few competent physicians would ignore a diastolic blood-pressure of 130 or 140
Hg (although most could recollect one or two patients who have survived such pressures for many years). The outlook in severe hypertension has improved vastly with the progressively more powerful hypotensive drugs,2 but a minority of patientsexcluding those who do not take their tablets-do not respond well to conventional drugs. There is no ready definition of drug resistance here, since it is unlikely that every potent hypotensive agent would be successively administered to any one individual. Nevertheless, in practice, the patient who remains severely hypertensive despite maximal doses of methyldopa, guanethidine, bethanidine, or debrisoquine is familiar to most physicians. We have no estimate of the numbers of these patients, and the frequency in the population is likewise unknown. The attitude of the physician is all-important. Bloodpressures are not laboratory estimations which are carried out blind. When the therapeutic possibilities
mm.
1. 2.
Hypertension: A suitable case for treatment ? Office of Health Economics, London, 1971. Breckenridge, A., Dollery, C. T., Parry, E. H. O. Q. Jl Med. 1970, 39, 411.
almost exhausted a doctor is powerfully motivated to underestimate rather than overestimate the bloodpressure, or to overlook blood-pressures which exceed 110 or 120 mm. Hg in an otherwise apparently healthy individual. Yet there is no reason to believe that these patients do not share the poor prognosis of untreated patients with such blood-pressure levels. Refractory hypertension is usually associated with evidence of tissue damage in the form of retinal haemorrhages, exudates, and papilloedema, and/or renal impairment. The hypertension may be secondary to established renal disease or it may be primary. From the point of view of blood-pressure control the distinction is unimportant, since in either situation uncontrolled hypertension can cause a decline in renal function. Indeed, death from renal failure is a common outcome of refractory hyperWith the modern hypotensive drugs, tension.33 specialist hypertension clinics are seeing fewer patients who ultimately die of renal impairment 2; but it is possible that some of this decline may be due to the establishment of separate renal centres. Nephrologists often meet the problem when it has advanced to a point where it is life-threatening: primary hypertension is high on the list of causes of renal failure.4 Yet, where the blood-pressure can be controlled, renal function may improve.5,6 Where hypertension is refractory to medical treatment, the only feasible alternative is bilateral nephrectomy, followed by lifelong dialysis or renal transplantation.7 The economic and human cost of such an outcome is, of course, tremendous, and there is every incentive to find a satisfactory drug regimen. In the search for an effective agent, attention has lately been focused on vasodilators, which appear to have a unique therapeutic potency in this situation. The oldest of these compounds still in use, hydrallazine, fell into disrepute when it caused systemic lupus in some patients.8 But, in strictly limited dosage,9 it has now regained a major place in some treatment schedules, particularly in the U.S.A. Its combination with &bgr;-blocking drugs such as are
propranolol is, theoretically at least, an ingenious one, since, by preventing compensatory vasoconstriction, it supplements the fall in blood-pressure produced by the reduction of cardiac output. 10 However, this is probably an oversimplified view of a pharmacologically complex situation, and, because the dose of hydrallazine has to be kept low, it is too Kincaid-Smith, P., Fang, P., Laver, M. C. Clin. Sci. 1973, 45, suppl. 1, 75s. 4. Ross, E. J. in Renal Disease (edited by D. A. K. Black); p. 464. Oxford, 1973. 5. Woods, J. W., Blythe, W. B. New Engl. J. Med. 1967, 277, 57. 6. Sevitt, L. A., Evans, D. J., Wrong, O. M. Q. Jl Med. 1971, 40, 127. 7. Mahoney, J. F., Storey, B. G., Gibson, G. R., Stokes, G. S., Sheil, A. G. R., Stewart, J. H. Lancet, 1972, i, 1036. 8. Alarćon-Segovia, D., Wakim, K. G., Worthington, J. W., Ward, L. E. Medicine, Baltimore, 1967, 46, 1. 9. Frohlich, E. D. Ann. intern. Med. 1973, 78, 717. 10. Sannerstedt, R., Stenberg, J., Vedin, A., Wilhelmsson, C., Werko, L. Am. J. Cardiol. 1972, 29, 718. 3.