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Thoughts about kidney homotransplantation in children
EDITOR'S COLUMN
Thoughts about kidney homotransplantation in children tion or generalized systemic disease), and make the further assumption that this technique is going to receive general acceptance, it seems appropriate to consider the special case of children in relation to renal transplantation. The aphorism that "a child is not just a miniature adult" is the justification for the existence of pediatrics as a special branch of medical care and study. The pediatrician prides himself not only on his knowledge of the differences and similarities of the physiology operating in varying age groups; he also likes to think he has a special awareness of the child's emotional processes. The young child is acutely aware of his state of bodily and emotional comfort of the moment, with little conscious memory of the past and little concern for anything but the immediate future. The preadolescent and adolescent child begins to develop concerns for the future but not always in a realistic or reasoned fashion. He has not achieved a philosophy of "quid pro quo" which encourages him to accept immediate and foreseeable discomfort for future well-being. Witness the adolescent's refusal to avoid acquiring the cigarette habit despite his acceptance of its dangers for his longevity. Therefore in considering what to do for a child it is necessary to give serious thought to the "discomfort factors" as well as to the
T ~ E ethics, morals and philosophy of transplanting whole organs from one living human to another have been questioned searchingly and eloquently both in public and private. T M Some of the questioners are without personal experience in the field, and others speak from their acquaintance both with patients and donors and with the professional teams involved. The major question raised is that of the "rightness," from a human point of view, of risking both the organic and psychologic well-being of one individual by asking him to sacrifice a major organ, potentially vital to his body economy, for the possible, but by no means proved, benefit of another. Criticism of the misleading headlines and reports in the lay press has also been voiced. I think we all deplore this, but many of us have come to accept it as a fact of twentieth century life. It may be that better cooperation by physicians with enlightened reporters will improve the kind of information and implications reaching the lay public. One can hope that the present physician's paranoia about publicity can be superseded by an acceptance of the need for intelligent dissemination of important information. Editorial comment so far has concerned itself with the over-all propriety of the procedure. If we assume that the prospective recipient has been carefully selected from the medical point of view (he is free from infec797
798
Editor's column
physiologic factors. If the discomfort involved is not more than balanced by the length of life achieved, the trauma may well exceed any benefit gained. This is a matter for judgment. It is not an easy decision even for the physician who presumably can be objective about it. It is an impossible one for the emotionally involved and often guiltridden parents. In the literal sense, the final choice is the parents'. They should, however, be firmly guided in the decision by the doctor who has weighed the odds carefully and in detached fashion. It is not always possible to break down strong determination on the part of the parents despite all unfavorable odds--and this may be a factor to be weighed in guiding a decision. But the doctor can be helpful in letting parents with doubts live with themselves if they decide against the procedure. The factors to be considered when chiIdren are concerned, are the same for the most part as those to be thought of with adults. The weight attached to the individual factors may be quite different. On the positive side, we know it is technically possible to transplant a kidney from one human to another, child or adult, and expect immediate good function. We further know that we usualIy can suppress earIy physiologic rejection of the implanted organ. We know that many recipients have returned to increasingly active life out of the hospital within 2 or 3 months after operation, and the number surviving for over a year is steadily increasing as our experience grows and as our approach to management improves. The number and proportion of patients so treated having survived over 2 years is still small. But as management techniques change, survival times shouId increase. On the negative side there are many known problems which must be given great weight when viewed through the eyes of a child. The preoperative period, with its preparatory dialyses, is associated with pain, fright, and separation from parents. The immediate postoperative period extends this ordeal. Recovery from the operation and the pre-existing chronic uremia is slow, and full
November 1964
strength may not be regained for many months. During this period the patient is taking multiple medications--corticosteroids, antimetabolites, antihypertensive agents, and often antipeptic ulcer agents. Once discharged from the hospital he must return for frequent "needle work" (at least weekly in the early days) : blood counts, blood urea nitrogen determinations, creatinine clearance. He will have an excretory urogram at some point. If he does not live in the city where the operations are being done, the entire family may have to move to aliow for this kind of surveillance, or else accept prolonged separation. In addition to the predictable discomforts are the complications which have occurred in a high proportion of cases. These have included unexplained pulmonary disease, late signs of rejection, intercurrent infection, obstructive uropathy, steroid induced diabetes, and cryptogenic central nervous system disease, to name a few. Thus the chance of recurring hospitalization is a fairly real threat. In some of the identical twins who have survived a transplant for a relatively long time, there has been recurrence of the original kidney disease. A special problem in children is the growth-suppressing effect of the corticosteroids. Perhaps this part of the immunosuppressive program can eventually be eliminated, but present experience does not suggest so. It is possible, therefore, that if aI1 goes well in the long run, the implanted kidney may be housed in a healthy dwarf. In addition to these factors which may afflict the child himself are the possible effects on the siblings and the family as a whole. An event of such major proportions is bound to be reflected in parental attitudes toward other offspring. They may be sent to live with relatives, they may be kept at home but excluded from the close-knit family circle while the adults understandably pour out all their emotional energy on the mortally sick one. Such a breach in normal family life could be something never to be healed. All of the "discomfort factors" noted make the picture sound very bleak indeed, but in
Volume 65 Number 5
the eyes of a mature adult who is potentially productive the total discomfort might well seem a small price to pay for a year or two of extra life. Seen from the point of view of a child or even of an adolescent these negative factors could well outweigh a small extension of life. At the present time when the potential extension of life expectancy is unknown a physician must proceed with what knowledge and empathy he possesses. In our Colorado experience we have had 5 pre-teen-age children as well as several adolescents. Of the five youngest 3 are alive 8 to 18 months after transplant in generally good condition but with some persistent proteinuria or hypertension. Since the discomfort factors have to be balanced against the length of normal life achieved, a dimension still unknown, no final evaluation as to the value of the procedure can currently be made. It may be of interest to recount one case in which, even allowing for the possibility that life will not be very much prolonged, we still feel that the operation has been "right" in all senses of the word. The patient was a 10-year-old girl who had had progressive uremia for over a year. She herself was an amazingly mature child whose relations with her parents had been surprisingly adult. Her father's occupation was such that he could be transferred to another city with no economic hardship, and the family had been sufficiently nomadic so that no deep-rooted social ties were broken. Accordingly, the whole family moved to Denver with the express purpose of having a transplant done. T h e little girl was well aware that her kidneys were very bad off and knew that she would receive a new one, presumably from her mother. She was bubbly and excited that she was to be one of the early patients so treated. She complained only at the delay of 2 or 3 months while the professional team decided when the best time to do it would be. Fortunately, her mother when genotyped had remarkably high blood compatibility with the patient. Furthermore, the mother's
Editor's column
7 99
attitude toward being a prospective donor could be likened to that of a woman with a normal pregnancy. She knew there could be some risk involved but seemed to feel that nothing could be more natural than to offer a part of herself for the welfare of her child. The father gave the impression of having the same reaction and the other two children appeared not to have been excluded from the warm family life by the chronic illness of their sister. The operation went well and neither mother nor daughter gave evidence that her attitudes were significantly changed by the ensuing physical discomfort. Physical complications did occur but were surmounted without apparent serious psychologic damage to either the patient or the family. At present, 8 months later, the patient is leading what appears to be a happy and normal life. The one major abnormality is her small size. Needless to say, her eventual prognosis is highly uncertain. I t must be emphasized, as anyone familiar with children will recognize, that the total situation here described is unique or at least very rare, but it does show that even with our present knowledge a decision for positive action can sometimes be made. In the other children at the present date it is possible to raise serious questions as to the propriety of having intervened in this way. Finally the question of whom to select as the donor deserves passing consideration. This has been extensively discussed by Woodruff 4 so we shall not dwell on it at length. From an immunologic point of view, our preliminary impression is that a mother-child combination offers the best hope of success if there are no major blood incompatibilities. From the donor's psychologic viewpoint this combination would seem to be an almost natural extension of the child-bearing process. These conditions do not always obtain. If one has to seek an alternate donor, then the total situation must be very carefully evaluated before making the decision to proceed. A donor should not be coerced either by outside pressure or by his own guilty conscience. It is at this point when knowledge of all the
800
Editor's column
discomfort factors may allow the potential donor to voice any ambivalence and to withdraw without any feeling of having "betrayed" the patient. In fact the knowledge of all the negative factors may prove an effective test of the potential donor's basic desire to give. Although presently unexplored, the reaction of the recipient to the fact of the donor's giving is another area for concern. One can wonder what feelings of guilt might accrue to the patient if anything untoward happened to the donor either immediately or at a later date. As a speculation, I would suggest that the mother-child relationship might be the combination most easily accepted by the recipient. In this essay I have not attempted to expIore the "rightness" or "wrongness" of organ transplantation between living humans. I have tried to examine the special considerations to be taken into account relative to children. Two major judgments must be made and balanced against each other: the first, the length of prolongation of life at present can only be a guess; the second, the expected totality of "discomfort factors" as
November 1964
seen through the eyes of the child is better estimated. As life extension increases with increasing knowledge, discomfort will lose its relative importance. In any event, the thoughtful physician must try to judge these imponderables objectively and conscientiously so that he can hopefully guide parents to a decision which will be best for the child and the family as a whole. The doctor's authoritative position makes this responsibility one not to be undertaken lightly. CONRAD M. RILE"~ ~ . D . PROFESSOR AND CI-IAIRIVfAN D E P A R T M E N T OF PREVENTIVE MEDICINE AND PROFESSOR OF PEDIATRICS U N I V E R S I T Y OF COLORADO, DENVER~ COLO.
REFERENCES
1. Elkinton, J. R.: Moral problems in the use of borrowed organs, artificial and transplanted, Ann. Int. Med. 60: 309, 1964. 2. Page, I.: Unwise publicity, Modern Medicine, January 20, t964, p. 81. 3. News item: Organ transplants pose moral issues, Medical Tribune, April 25-26, 1964, p. 9. 4. Woodruff, M. E. A.: Ethical problems in organ transplantation, Brit. M. J. h 1457, 1964.
Thoughts about kidney homotransplantation in children tion or generalized systemic disease), and make the further assumption that this technique is going to receive general acceptance, it seems appropriate to consider the special case of children in relation to renal transplantation. The aphorism that "a child is not just a miniature adult" is the justification for the existence of pediatrics as a special branch of medical care and study. The pediatrician prides himself not only on his knowledge of the differences and similarities of the physiology operating in varying age groups; he also likes to think he has a special awareness of the child's emotional processes. The young child is acutely aware of his state of bodily and emotional comfort of the moment, with little conscious memory of the past and little concern for anything but the immediate future. The preadolescent and adolescent child begins to develop concerns for the future but not always in a realistic or reasoned fashion. He has not achieved a philosophy of "quid pro quo" which encourages him to accept immediate and foreseeable discomfort for future well-being. Witness the adolescent's refusal to avoid acquiring the cigarette habit despite his acceptance of its dangers for his longevity. Therefore in considering what to do for a child it is necessary to give serious thought to the "discomfort factors" as well as to the
T ~ E ethics, morals and philosophy of transplanting whole organs from one living human to another have been questioned searchingly and eloquently both in public and private. T M Some of the questioners are without personal experience in the field, and others speak from their acquaintance both with patients and donors and with the professional teams involved. The major question raised is that of the "rightness," from a human point of view, of risking both the organic and psychologic well-being of one individual by asking him to sacrifice a major organ, potentially vital to his body economy, for the possible, but by no means proved, benefit of another. Criticism of the misleading headlines and reports in the lay press has also been voiced. I think we all deplore this, but many of us have come to accept it as a fact of twentieth century life. It may be that better cooperation by physicians with enlightened reporters will improve the kind of information and implications reaching the lay public. One can hope that the present physician's paranoia about publicity can be superseded by an acceptance of the need for intelligent dissemination of important information. Editorial comment so far has concerned itself with the over-all propriety of the procedure. If we assume that the prospective recipient has been carefully selected from the medical point of view (he is free from infec797
798
Editor's column
physiologic factors. If the discomfort involved is not more than balanced by the length of life achieved, the trauma may well exceed any benefit gained. This is a matter for judgment. It is not an easy decision even for the physician who presumably can be objective about it. It is an impossible one for the emotionally involved and often guiltridden parents. In the literal sense, the final choice is the parents'. They should, however, be firmly guided in the decision by the doctor who has weighed the odds carefully and in detached fashion. It is not always possible to break down strong determination on the part of the parents despite all unfavorable odds--and this may be a factor to be weighed in guiding a decision. But the doctor can be helpful in letting parents with doubts live with themselves if they decide against the procedure. The factors to be considered when chiIdren are concerned, are the same for the most part as those to be thought of with adults. The weight attached to the individual factors may be quite different. On the positive side, we know it is technically possible to transplant a kidney from one human to another, child or adult, and expect immediate good function. We further know that we usualIy can suppress earIy physiologic rejection of the implanted organ. We know that many recipients have returned to increasingly active life out of the hospital within 2 or 3 months after operation, and the number surviving for over a year is steadily increasing as our experience grows and as our approach to management improves. The number and proportion of patients so treated having survived over 2 years is still small. But as management techniques change, survival times shouId increase. On the negative side there are many known problems which must be given great weight when viewed through the eyes of a child. The preoperative period, with its preparatory dialyses, is associated with pain, fright, and separation from parents. The immediate postoperative period extends this ordeal. Recovery from the operation and the pre-existing chronic uremia is slow, and full
November 1964
strength may not be regained for many months. During this period the patient is taking multiple medications--corticosteroids, antimetabolites, antihypertensive agents, and often antipeptic ulcer agents. Once discharged from the hospital he must return for frequent "needle work" (at least weekly in the early days) : blood counts, blood urea nitrogen determinations, creatinine clearance. He will have an excretory urogram at some point. If he does not live in the city where the operations are being done, the entire family may have to move to aliow for this kind of surveillance, or else accept prolonged separation. In addition to the predictable discomforts are the complications which have occurred in a high proportion of cases. These have included unexplained pulmonary disease, late signs of rejection, intercurrent infection, obstructive uropathy, steroid induced diabetes, and cryptogenic central nervous system disease, to name a few. Thus the chance of recurring hospitalization is a fairly real threat. In some of the identical twins who have survived a transplant for a relatively long time, there has been recurrence of the original kidney disease. A special problem in children is the growth-suppressing effect of the corticosteroids. Perhaps this part of the immunosuppressive program can eventually be eliminated, but present experience does not suggest so. It is possible, therefore, that if aI1 goes well in the long run, the implanted kidney may be housed in a healthy dwarf. In addition to these factors which may afflict the child himself are the possible effects on the siblings and the family as a whole. An event of such major proportions is bound to be reflected in parental attitudes toward other offspring. They may be sent to live with relatives, they may be kept at home but excluded from the close-knit family circle while the adults understandably pour out all their emotional energy on the mortally sick one. Such a breach in normal family life could be something never to be healed. All of the "discomfort factors" noted make the picture sound very bleak indeed, but in
Volume 65 Number 5
the eyes of a mature adult who is potentially productive the total discomfort might well seem a small price to pay for a year or two of extra life. Seen from the point of view of a child or even of an adolescent these negative factors could well outweigh a small extension of life. At the present time when the potential extension of life expectancy is unknown a physician must proceed with what knowledge and empathy he possesses. In our Colorado experience we have had 5 pre-teen-age children as well as several adolescents. Of the five youngest 3 are alive 8 to 18 months after transplant in generally good condition but with some persistent proteinuria or hypertension. Since the discomfort factors have to be balanced against the length of normal life achieved, a dimension still unknown, no final evaluation as to the value of the procedure can currently be made. It may be of interest to recount one case in which, even allowing for the possibility that life will not be very much prolonged, we still feel that the operation has been "right" in all senses of the word. The patient was a 10-year-old girl who had had progressive uremia for over a year. She herself was an amazingly mature child whose relations with her parents had been surprisingly adult. Her father's occupation was such that he could be transferred to another city with no economic hardship, and the family had been sufficiently nomadic so that no deep-rooted social ties were broken. Accordingly, the whole family moved to Denver with the express purpose of having a transplant done. T h e little girl was well aware that her kidneys were very bad off and knew that she would receive a new one, presumably from her mother. She was bubbly and excited that she was to be one of the early patients so treated. She complained only at the delay of 2 or 3 months while the professional team decided when the best time to do it would be. Fortunately, her mother when genotyped had remarkably high blood compatibility with the patient. Furthermore, the mother's
Editor's column
7 99
attitude toward being a prospective donor could be likened to that of a woman with a normal pregnancy. She knew there could be some risk involved but seemed to feel that nothing could be more natural than to offer a part of herself for the welfare of her child. The father gave the impression of having the same reaction and the other two children appeared not to have been excluded from the warm family life by the chronic illness of their sister. The operation went well and neither mother nor daughter gave evidence that her attitudes were significantly changed by the ensuing physical discomfort. Physical complications did occur but were surmounted without apparent serious psychologic damage to either the patient or the family. At present, 8 months later, the patient is leading what appears to be a happy and normal life. The one major abnormality is her small size. Needless to say, her eventual prognosis is highly uncertain. I t must be emphasized, as anyone familiar with children will recognize, that the total situation here described is unique or at least very rare, but it does show that even with our present knowledge a decision for positive action can sometimes be made. In the other children at the present date it is possible to raise serious questions as to the propriety of having intervened in this way. Finally the question of whom to select as the donor deserves passing consideration. This has been extensively discussed by Woodruff 4 so we shall not dwell on it at length. From an immunologic point of view, our preliminary impression is that a mother-child combination offers the best hope of success if there are no major blood incompatibilities. From the donor's psychologic viewpoint this combination would seem to be an almost natural extension of the child-bearing process. These conditions do not always obtain. If one has to seek an alternate donor, then the total situation must be very carefully evaluated before making the decision to proceed. A donor should not be coerced either by outside pressure or by his own guilty conscience. It is at this point when knowledge of all the
800
Editor's column
discomfort factors may allow the potential donor to voice any ambivalence and to withdraw without any feeling of having "betrayed" the patient. In fact the knowledge of all the negative factors may prove an effective test of the potential donor's basic desire to give. Although presently unexplored, the reaction of the recipient to the fact of the donor's giving is another area for concern. One can wonder what feelings of guilt might accrue to the patient if anything untoward happened to the donor either immediately or at a later date. As a speculation, I would suggest that the mother-child relationship might be the combination most easily accepted by the recipient. In this essay I have not attempted to expIore the "rightness" or "wrongness" of organ transplantation between living humans. I have tried to examine the special considerations to be taken into account relative to children. Two major judgments must be made and balanced against each other: the first, the length of prolongation of life at present can only be a guess; the second, the expected totality of "discomfort factors" as
November 1964
seen through the eyes of the child is better estimated. As life extension increases with increasing knowledge, discomfort will lose its relative importance. In any event, the thoughtful physician must try to judge these imponderables objectively and conscientiously so that he can hopefully guide parents to a decision which will be best for the child and the family as a whole. The doctor's authoritative position makes this responsibility one not to be undertaken lightly. CONRAD M. RILE"~ ~ . D . PROFESSOR AND CI-IAIRIVfAN D E P A R T M E N T OF PREVENTIVE MEDICINE AND PROFESSOR OF PEDIATRICS U N I V E R S I T Y OF COLORADO, DENVER~ COLO.
REFERENCES
1. Elkinton, J. R.: Moral problems in the use of borrowed organs, artificial and transplanted, Ann. Int. Med. 60: 309, 1964. 2. Page, I.: Unwise publicity, Modern Medicine, January 20, t964, p. 81. 3. News item: Organ transplants pose moral issues, Medical Tribune, April 25-26, 1964, p. 9. 4. Woodruff, M. E. A.: Ethical problems in organ transplantation, Brit. M. J. h 1457, 1964.