648
Hospital Practice ONE HUNDRED KIDNEY TRANSPLANTS IN THE BELFAST CITY HOSPITAL MARY G. MCGEOWN W. G. G. LOUGHRIDGE J. A. ALEXANDER
J. A. KENNEDY J. DOUGLAS S. D. CLARKE* J. C. HEWITT‡
J. McEVOY† Belfast City Hospital, Belfast BT9 7AB S. D. NELSON
Craigavon Hospital, Belfast 100 kidney transplants have been carried out on 91 patients (7 had 2 transplants and 2 had 3 transplants). 4 transplants were from living related donors and 96 from cadavers. 76 patients survive, all but one with functioning kidneys. The cumulative survival of patients was 82% at 2 years and 80·7% at 5 years. 8 patients died with functioning grafts, and 2 of the other deaths took place more than 3 months after removal of a rejected kidney and resumption of hæmodialysis. There were no deaths from sepsis in the first 60 days after transplantation. The cumulative survival of all grafts was 82·1% at 2 and 5 years. The cumulative survival of first grafts was 82·5% at 2 and 5 years.
Summary
INTRODUCTION
91 patients received 100 kidney transplants in the Belfast City Hospital between November, 1968, and November, 1976. There were 7 second transplants and 2 third transplants. PATIENTS AND METHODS
the commonest primary diseases treated were glomerulonephritis (48%), chronic pyelonephritis (18%), polycystic disease (16%), and hypoplastic kidneys (16%). The age range of patients was 13 to 53 years; 34 were between 15 and 34 at the time of the first graft, 25 between 41 and 49 and 7 were aged 50 or over. 79 patients were transplanted after hospital haemodialysis, 10 from hospital peritoneal dialysis, and 1 from home haemodialysis. The median time on dialysis was 9 months; 44 patients received a kidney in less than 9 months, 47 after 9 or more months, and 9 patients waited longer than 2 years. All the patients had a micturating cystogram to determine the adequacy of bladder capacity and bladder emptying and the presence or absence of reflux. All had a barium meal. Recently more detailed tests of gastric function have been carried out because it is known that bleeding can take place during dialysis from duodenal ulcers not shown on the barium meal.’ 1 patient had recurrence of bleeding after vagotomy and had a subtotal gastrectomy. 72 patients underwent bilateral nephrectomy before the transplant and 1 patient after the transplant. 1 patient had unilateral nephrectomy before the transplant. The spleen was *Present address: Kuwait Oil Company, Kuwait. †Present address: Department of Internal Medicine, The Christ Hospi tal, Cincinatti, Ohio. ‡Royal Infirmary, Hull.
removed from 1 patient. Only 6 patients did not receive any blood transfusion. Tissue typing was carried out with a standard microlymphocyte toxicity method. 7 transplants were carried out before the tissue typing service was established and these grafts were based on an ABO match only. The donor tissue type was known and was used to select the best matched recipient for the other 93 transplants. The direct cross-match was negative in all except 1 patient where the cross-match was not carried out because the kidney was received without a lymph node.
Donors 96 cadaver and 4 live donor grafts were carried out. 1 patient received a kidney from his identical twin and 3 patients received a kidney from a parent. The initial warm ischæmia time for cadaver grafts varied from 2-80 minutes; 2 patients received kidneys with 70 minutes warm ischaemia time and 1 a kidney with 80 minutes warm ischænia time. 18 kidneys with a warm ischsemia time of 50 minutes or longer were used. The total ischxmia time varied from 159 to 855 minutes, the longest total ischxmia times being associated with long term good function. None of the 38 local kidneys were taken from heart-beating cadavers, and none received pre-treatment with drugs as preparation for transplantation. The local kidneys - , were perfused manually with fructose/bicarbonate, Gelin’s solution, or Perfudex. Most of the imported kidneys were perfused with Perfudex.
Operation most cases end-to-side arterial and venous anastomoses carried out to the external iliac vessels. In 2 cases a large polar artery was anastomosed to the main renal artery before the anastomosis to the external iliac. A capsulotomy was always done. In the earlier cases the ureter was anastomosed to the bladder by a Leadbetter-Politano mucosal tunnel, without the use of a ureteric splint. Later in the series an on-lay anastomosis through the muscle coat to the vesical mucosa was found simpler and easier.
In
were
Immunosuppressive
and post-transplant
care
The patients given living donor grafts, with the exception of the identical twin, received their first immunosuppression treatment 24 hours before the transplant. Patients receiving cadaver kidneys were given azathioprine, 5 mg/kg bodyweight, and hydrocortisone 200 mg intravenously after being anaesthetised. The hydrocortisone was repeated 6-hourly for3 further doses (800 mg in all). Thereafter azathioprine, 1.5 mg/kg body-weight, and prednisolone 20 mg were given orally everyday until the creatinine clearance exceeded 20 (later ml/min, when the azathioprine was increased to 3 mg/kg bodyweight and continued at this level unless leucopenia supervened. After 6 months prednisolone was reduced gradually to 10 mg daily, this dose being reached sometime during the second year. In many patients developing a Cushingoid appearance the treatment was changed to a double dose of prednisolone on alternate days. Rejection episodes were treated by increasing the dose of prednisolone to 200 mg daily, and then reducing it in 2-5 day steps to maintenance level. At first azathioprine was doubled for 5 days and actinomycin C 400 µg was given once, but this was stopped after 2 patients treated for late rejection episodes died of infection. In some patients an intravenous bolus of methylprednisolone 1 g, repeated at 24-48 hour intervals up to a maximum of 4 doses, was used, but the results were not better than those with the previous method. Frusemide was not given during operation or early in the postoperative period and only a few patients were given it at any time. Heparin, rheomacrodex, antilymphocyte serum. prophylactic antibiotics, and antifungal agents were not used. The operation was carried out in the renal theatre and the
30)
649 patient was isolated in a filtered air environment until the wound healed.4 Considerable care was taken to exclude other causes of a de-
TABLE II—CAUSES OF DEATH RELATED TO KIDNEY TRANSPLANT
graft function before making a diagnosis of rejection. Postoperative oliguria, even if prolonged for 2 weeks or more, was not regarded as a reason for anti-rejection therapy without further evidence. Renography was found valuable. In the early post-transplant period it showed whether the blood supply to chne in
it excluded ureteric obstrucand radiological tests were used in the diagnosis of rejection. At present reliance is placed mainly on a combination of clinical features and laboratory evidence of deteriorating function. Urinary protein and N-acetyl-beta-D-glucosaminidase are checked regularly and care is taken to exclude hyperglycæmia3 and infections, particularly those due to virus.
the
graft
was
intact, and later
on
tion.2 A variety of biochemical,
Method
serological,
of analysis
The data on patient and graft survival were analysed by the life-table method5 and the cumulative survival-rate and its standard error expressed as percentages. The analysis was completed for survival of grafts and patients on 31st Decem-
*cause unknown, suspected association with flurazepam (’Dalmane’) combination flurazepam and diazepam (’Valium’)6 tl at 3 mo, 1 at 9 mo. or
:tat I yr.
ber, 1976.
The fate of all the cadaver grafts is shown in table
73 - 9% of the grafts survive.
RESULTS
76 of the 91
one having returned to await a second haemodialysis graft. The cumulative survival in is shown table I, 80.7% surviving for patient 2 years or longer, with no deaths between 3 and 7 years. 8 of the 15 patients who died had excellent graft function up to the time of death, the graft showing no evidence of rejection or other abnormality at necropsy. The causes of death and status of the graft are shown in Table n. Infection caused no deaths within the first 60 days after transplantation. There were 2 later deaths caused by chest infections subsequent to leucopenia brought about by anti-rejection therapy including high doses (6.mg/kg body-weight) of azathioprine and actinomycin C. There have been no deaths from infection after we started treating rejection episodes by increasing prednisolone, without actinomycin C. 3 of the 4 patients who received living donor grafts survive with functioning grafts.
patients survive,
to
TABLE I-CUMULATIVE
Died II nh functioning graft Not yet completed time mterval.
2 of the 71
ill
surviving grafts
have poor function after 3yyears (serum creatinine 515 and 770 umol/1), one from recurrence of chronic pyelonephritis in the graft,’ one probably from chronic rejection. The other 69 grafts have adequate to excellent function. The survival of the small number of second and third grafts is gratifying, both third grafts surviving. One patient who received 3 grafts, had thrombosis of the first 2 grafts on the third day, but the third graft continues to function after more than 2 years. A second patient received 3 grafts; the first was removed at the primary operation because the middle two-thirds did not become vascularised, the second was rejected at 3 weeks and the third continues to function at 9 months after the
transplant. The cumulative survival of all grafts is 82.1% (S.E.±3.9) for 1-7 years, and of all 91 first grafts is 82.5% (S.E.±4.1) from 1-7 years (table i), including the 4 live donor grafts whose survival does not differ from the cadaver grafts.
SURVIVAL
(PATIENTS AND GRAFTS)
650 TABLE III-FATE OF ALL CADAVER KIDNEY GRAFTS 1
1968-1976
(P 005).
P
72 of the 76 surviving patients are well rehabilitated although not all have been able to find employment. DISCUSSION
Although it is generally accepted that the patient with successful transplant is fitter and has a better quality of life than the patient surviving on regular dialysis, the mortality is thought to be much higher. Home dialysis is considered to give the best survival-rates, the European Dialysis and Transplant Association (E.D.T.A.j’ reporting 93.1% at 1 year, 86.7% at 2 years, and 80.8 at 3 years. The cumulative survival of our patients (86-2% at 1 year, 84.7% at 2 years, and 80.7% from 3-5 years) is not far short of these figures for home dialysis. Infection accounted for 37.5% of all deaths during the first 60 days after transplantation in the E.D.T.A. report.7 None of our patients died from infection during this period. We attribute this result partly to the isolation techniques4 used and partly to the sparing use of steroids. Episodes of high fever were the commonest reason for readmission during the early months and most were due to cytomegalic-virus infection. During the fever the serum urea and creatinine rose in some patients. This rise was not a manifestation of rejection and was not treated with increased steroids. The cumulative survival of first grafts in our patients was 82.5% (s.E.±4-l) from 1-7 years, which compares favourably with the cumulative survival of first cadaver grafts reported by E.D.T.A.7 of 30-1% at 1 year, 43-9 at 2 years, and 39.4% at 3 years. Immediate function of the graft was exceptional in the 96 cadaver grafts and most patients required postoperative dialysis. This did not adversely affect the future function of the graft, even in the 3 patients with the longest warm ischxmia times (2 of 70 and 1 of 80 minutes), similar experiences being reported by White et a
TABLE IV-CAUSE OF LOSS OF GRAFT
*Rejection could be excluded in 1 only, although pathological typical of rejection in others.
appear-
ances not
The cause of loss of graft is shown in table iv. 5 of the graft failures were clearly due to rejection and this may have contributed to 4 of the 5 arterial thromboses although the histological appearances were not typically those of rejection. 8 grafts, although still functioning, were lost because of the death of the patient. The cumulative graft survival of the 19 first grafts without mis-match on the B locus was 94-6% (s.E.±5-3) from 3 months to 7 years, compared with 75% (s.E.±10-8) for the 17 first grafts with 2 mismatches at this locus. These differences were not significant
(p >0.05)survival of the first
graft in
48 3 months, group-0 patients 88-6% (s.E.±4-8) at 1-7 years, compared with 77-4% (s.E.±8-l) at 3 months and 69.3% (s.E.±9.1) at 1-7 years for 28 group-A patients receiving group-A kidneys. These differences were not significant (P>0-05). The blood transfusion history was known accurately for 69 of the patients and is shown in table v, but the small number (6) of patients who did not receive blood precludes statistical analysis. The survival of grafts at 3 months was better in patients dialysed for longer than 9 months than in those dialysed for shorter periods (93.3%, s.E.±3-7 compared with 71-2%, s.E.±3-2). This difference was significant The cumulative
graft
was
93-6% (s.E.±3-6)
at
TABLE V-TRANSFUSIONS BEFORE FIRST TRANSPLANT
*Packed cells or whole blood.
al.8
patients who had bilateral nephrectomy required blood transfusions, and blood transfusion is reported to improve graft survival in man9-11 and in animals.12 The incidence of urinary tract infection is lower in our nephrectomised patients" than in other series. 14, 11 The tissue-match grade was not particularly good in our patients, 35 receiving a first transplant with no or with only one HLA mis-match, and 48 with two or more mis-matches. The survival of our patients is nearly as good as that obtained by home dialysis, and the survival of graftsis well above the European average. With the rising costs of regular dialysis therapy we believe that transplantation offers the only hope of providing treatment for the many who could benefit.16 The scarcity of kidney donors continues and colleagues in other fields need to be convinced that kidney transplantation is worthwhile and capable of returning many patients to full health. Our
more
The following also made valuable contributions during the weight years covered by this paper: Dr Claire Hill, Dr K. V. Rajkumar, Dr S. N. Mehta, Mr R. A. Donaldson, Mr D. Middleton, Ms Kai Maguire, s.R.N., and Mr J. Lyness. We thank the staff of the Laboratories, Belfast City Hospital for constant help, Dr J. Connolly for HBsAg and virological tests. :he
651 staff of the X-rav Department, Prof. D. Gardner, Dr H. Bharucha, and Prof. K. A. Porter for histological examinations, the staffs of the intenme care units of the Royal Victoria Hospital, Craigavon Hospital, Lister Hospital, Mater Hospital, and Altnagelvin Hospital for kidney donors, and Miss A. B. Feely and the staff of the outpatients’ department Generous support has been received from the Northern Ireland Ktdnev Research Fund. Requests for reprints should be addressed to M.G.McG. REFERENCES
Doherty, C. C., O’Connor, F., Buchanan, K. D., Douglas, J. F., McGeown, M G Proc. Eur. Dial. Transplant Ass. (in the press). 2 Doherty, C., Douglas, J. F., McGeown, M. G. Unpublished. 3 Hill, C., Douglas, J. F., Rajkumar, K. V., McEvoy, J., McGeown, M. G. Lancet, 1974, ii, 493. 1
4 Maguire, K., McKnight, R., Johnston, M. A., Corrigan, M., McGeown, M. G. Proc. Eur. Dial. Transplant Nurses Ass. (in the press). 5 Cutler, S. J., Ederer, B. S. J. Chron. Dis. 1958, 8, 699. 6 Taclob, L, Needle, M. Lancet, 1976, ii, 704 7 Gurland, H. J., Brunner, F. P., Chantler, C., Jacobs, C., Schärer, K., Selwood, N H., Spies, G. W., Wing, A. J. Proc. Eur. Dial. Transplant Ass. 1976, 13, 3. 8 White, H. J. D., Evans, D. B., Calne, R. Y. Br. med. J. 1968, iv, 739. 9 Festenstein, H., Sachs, J. A., Paris, A. M. I., Pegrum, G. D., Moorehead, J. F. Lancet, 1976, i, 157. 10 Opelz, G, Terasaki, P. I. ibid, 1976, ii, 380. 11 van Hooff, J P., Kalff, M. W., van Poelgeaste, A. E. Transplantation, 1976, 22, 306 12 van Es, A. A., Marquet, R. L., van Rood, J. J., Kalff, M. W., Balner, H. Lancet,
13
1977, i, 506.
Douglas, J. F., Clarke, S, Kennedy, J. A., McEvoy, J., McGeown,
M. G.
ibid
1974, ii, 1015. 14 Hamshere, R. J., Chisholm, G D., Shackman, R. ibid. 1974, ii, 793. 15
Steen, W., Pedersen, F. B., Vejlsgaard, R. Br. J. Urol. 1975, 47, 513.
16. McGeown, M. G. in Replacement of Renal Function by Dialysis (edited by J F. Maher, F M. Parsons, and W. Drukker). The Hague (in the press).
Points of View JUBILEE BANDWAGONS 1977 has been a right royal year in the United Kingdom, with State trumpetings and martial music justifiably prominent. Unfortunately, however, this seems to have been the signal for noise from an increasing number of bandwagons to reverberate around the medical scene. Those of us who view these activities with scepticism tend to be regarded as a nuisance, and steamroller tactics are usually employed to flatten any opposition. The following comments on some of these bandwagons are a personal cri de coeur which yet may echo the feelings of many of my colleagues at grass-roots level. The Therapeutic Team The team concept has been so enthusiastically espoused in quarters that the role of the doctor in caring for his patient, whether in general or hospital practice, has tended to be undermined. All members of the team claim to have at least equal responsibility with the doctor for the patient’s welfare, and in some cases actually believe they should over-ride the medical view. I do not seek to denigrate the nurse’s role or that of paramedical personnel, but I contend that the doctor must remain, and be seen to remain, the leader of any such team. Abrogation of this responsibility leads to a deterioration m the doctor-patient relationship. Certainly in law the consultant is held to be responsible for the total care of his patient while he remains in hospital. The tendency towards medicine by committee, with all members having an equal vote, must be resisted; it is imperative for the doctor to be the permanent chairman, and to retain the right of veto. some
.tfedicalAudit
Currently it is virtually impossible to open any of the "respectable" medical journals without being subjected to a paper extolling the virtues of medical audit or peer review. Since the
advent of the financial crisis, the clamour has become intense and has been justified on the grounds that we are being helped to make better use of available resources. However, I suspect this concept is not regarded with such widespread enthusiasm as its proponents would like us to believe. Many clinical procedures are still sanctioned by tradition rather than any firm evidence of their effectiveness, but there is a real danger that audit and peer review might induce complacency in those who comply with the norm, and discourage a questioning approach. A few years ago not to give anticoagulants to patients with coronary thrombosis, or not to recommend a low residue diet to patients with diverticular disease, was regarded almost as malpractice. Let us hope that medical men will continue to take what their peers say and do with a handful rather than a pinch of salt.
Postgraduate Education A doctor continues to learn throughout his professional carcan best be helped to continue this process is uncertain. Fashionable at the moment are workshops, symposia, courses, and conferences, often with considerable duplication and all liberally sprinkled with audiovisual aids. The desire of the small-print brigade to expose us all to the flashing-slide darkened-room syndrome seems unbounded. Organisers of such meetings would do well to consider carefully whether the proposed event really has anything much to offer, or whether the real reason for its promotion is not a desire to inflate the ego of the individual or department concerned, with an eye to the subsequent "proceedings", which now drop like confetti from the medical publishers. Unquestionably some meetings are of immense value, but one wonders if the phrenetic, peripatetic existence led by so many really leads to better doctoring. A doctor whose postgraduate diet consists mainly of learning from clinical experience, private study, and attendance at local postgraduate activities, with excursions further afield being the exception rather than the rule, has the great advantage of more time to spend with his patients, and probably functions at least as efficiently as his more widely travelled colleagues.
eer, but how he
Training Programmes Until recently the training of doctors after registration, whether they wished to remain in hospital or general practice, was based largely on the apprenticeship system. With respect to a consultantship, the aspirant was free to choose where, when, and with whom he wished to work-with the result that he often obtained considerable experience at various centres both in this country and abroad. Training schemes have now been introduced both for hospital specialists and for general practitioners, but at a sacrifice of flexibility and scope for individual enterprise and initiative in shaping one’s own training sequence; the system has become increasingly complex, with an organisational superstructure and inspectorate, and it seems doubtful if little more than lip-service is paid to the principle that nonconformists are given a fair hearing. Undoubtedly there was a need to improve training programmes both for hospital specialists and general practitioners, but there is now a danger of patient care being subordinated to this end. There always have been, and there probably always will be, good and bad doctors; training schemes will probably swing the balance towards improvement less than current noise levels in their favour would suggest.
Many similar examples of current fads could have been chosen. Bandwagons have a habit of eventually coming to a halt, with a resultant unseemly scramble by the passengers to dismount as quickly as possible and move away from the scene. Many of us feel it is more appropriate to resist the temptation to climb aboard in the first place. Cumberland Infirmary, Carlisle CA2 7HY
R. H. SALTER
Hospital Practice ONE HUNDRED KIDNEY TRANSPLANTS IN THE BELFAST CITY HOSPITAL MARY G. MCGEOWN W. G. G. LOUGHRIDGE J. A. ALEXANDER
J. A. KENNEDY J. DOUGLAS S. D. CLARKE* J. C. HEWITT‡
J. McEVOY† Belfast City Hospital, Belfast BT9 7AB S. D. NELSON
Craigavon Hospital, Belfast 100 kidney transplants have been carried out on 91 patients (7 had 2 transplants and 2 had 3 transplants). 4 transplants were from living related donors and 96 from cadavers. 76 patients survive, all but one with functioning kidneys. The cumulative survival of patients was 82% at 2 years and 80·7% at 5 years. 8 patients died with functioning grafts, and 2 of the other deaths took place more than 3 months after removal of a rejected kidney and resumption of hæmodialysis. There were no deaths from sepsis in the first 60 days after transplantation. The cumulative survival of all grafts was 82·1% at 2 and 5 years. The cumulative survival of first grafts was 82·5% at 2 and 5 years.
Summary
INTRODUCTION
91 patients received 100 kidney transplants in the Belfast City Hospital between November, 1968, and November, 1976. There were 7 second transplants and 2 third transplants. PATIENTS AND METHODS
the commonest primary diseases treated were glomerulonephritis (48%), chronic pyelonephritis (18%), polycystic disease (16%), and hypoplastic kidneys (16%). The age range of patients was 13 to 53 years; 34 were between 15 and 34 at the time of the first graft, 25 between 41 and 49 and 7 were aged 50 or over. 79 patients were transplanted after hospital haemodialysis, 10 from hospital peritoneal dialysis, and 1 from home haemodialysis. The median time on dialysis was 9 months; 44 patients received a kidney in less than 9 months, 47 after 9 or more months, and 9 patients waited longer than 2 years. All the patients had a micturating cystogram to determine the adequacy of bladder capacity and bladder emptying and the presence or absence of reflux. All had a barium meal. Recently more detailed tests of gastric function have been carried out because it is known that bleeding can take place during dialysis from duodenal ulcers not shown on the barium meal.’ 1 patient had recurrence of bleeding after vagotomy and had a subtotal gastrectomy. 72 patients underwent bilateral nephrectomy before the transplant and 1 patient after the transplant. 1 patient had unilateral nephrectomy before the transplant. The spleen was *Present address: Kuwait Oil Company, Kuwait. †Present address: Department of Internal Medicine, The Christ Hospi tal, Cincinatti, Ohio. ‡Royal Infirmary, Hull.
removed from 1 patient. Only 6 patients did not receive any blood transfusion. Tissue typing was carried out with a standard microlymphocyte toxicity method. 7 transplants were carried out before the tissue typing service was established and these grafts were based on an ABO match only. The donor tissue type was known and was used to select the best matched recipient for the other 93 transplants. The direct cross-match was negative in all except 1 patient where the cross-match was not carried out because the kidney was received without a lymph node.
Donors 96 cadaver and 4 live donor grafts were carried out. 1 patient received a kidney from his identical twin and 3 patients received a kidney from a parent. The initial warm ischæmia time for cadaver grafts varied from 2-80 minutes; 2 patients received kidneys with 70 minutes warm ischaemia time and 1 a kidney with 80 minutes warm ischænia time. 18 kidneys with a warm ischsemia time of 50 minutes or longer were used. The total ischxmia time varied from 159 to 855 minutes, the longest total ischxmia times being associated with long term good function. None of the 38 local kidneys were taken from heart-beating cadavers, and none received pre-treatment with drugs as preparation for transplantation. The local kidneys - , were perfused manually with fructose/bicarbonate, Gelin’s solution, or Perfudex. Most of the imported kidneys were perfused with Perfudex.
Operation most cases end-to-side arterial and venous anastomoses carried out to the external iliac vessels. In 2 cases a large polar artery was anastomosed to the main renal artery before the anastomosis to the external iliac. A capsulotomy was always done. In the earlier cases the ureter was anastomosed to the bladder by a Leadbetter-Politano mucosal tunnel, without the use of a ureteric splint. Later in the series an on-lay anastomosis through the muscle coat to the vesical mucosa was found simpler and easier.
In
were
Immunosuppressive
and post-transplant
care
The patients given living donor grafts, with the exception of the identical twin, received their first immunosuppression treatment 24 hours before the transplant. Patients receiving cadaver kidneys were given azathioprine, 5 mg/kg bodyweight, and hydrocortisone 200 mg intravenously after being anaesthetised. The hydrocortisone was repeated 6-hourly for3 further doses (800 mg in all). Thereafter azathioprine, 1.5 mg/kg body-weight, and prednisolone 20 mg were given orally everyday until the creatinine clearance exceeded 20 (later ml/min, when the azathioprine was increased to 3 mg/kg bodyweight and continued at this level unless leucopenia supervened. After 6 months prednisolone was reduced gradually to 10 mg daily, this dose being reached sometime during the second year. In many patients developing a Cushingoid appearance the treatment was changed to a double dose of prednisolone on alternate days. Rejection episodes were treated by increasing the dose of prednisolone to 200 mg daily, and then reducing it in 2-5 day steps to maintenance level. At first azathioprine was doubled for 5 days and actinomycin C 400 µg was given once, but this was stopped after 2 patients treated for late rejection episodes died of infection. In some patients an intravenous bolus of methylprednisolone 1 g, repeated at 24-48 hour intervals up to a maximum of 4 doses, was used, but the results were not better than those with the previous method. Frusemide was not given during operation or early in the postoperative period and only a few patients were given it at any time. Heparin, rheomacrodex, antilymphocyte serum. prophylactic antibiotics, and antifungal agents were not used. The operation was carried out in the renal theatre and the
30)
649 patient was isolated in a filtered air environment until the wound healed.4 Considerable care was taken to exclude other causes of a de-
TABLE II—CAUSES OF DEATH RELATED TO KIDNEY TRANSPLANT
graft function before making a diagnosis of rejection. Postoperative oliguria, even if prolonged for 2 weeks or more, was not regarded as a reason for anti-rejection therapy without further evidence. Renography was found valuable. In the early post-transplant period it showed whether the blood supply to chne in
it excluded ureteric obstrucand radiological tests were used in the diagnosis of rejection. At present reliance is placed mainly on a combination of clinical features and laboratory evidence of deteriorating function. Urinary protein and N-acetyl-beta-D-glucosaminidase are checked regularly and care is taken to exclude hyperglycæmia3 and infections, particularly those due to virus.
the
graft
was
intact, and later
on
tion.2 A variety of biochemical,
Method
serological,
of analysis
The data on patient and graft survival were analysed by the life-table method5 and the cumulative survival-rate and its standard error expressed as percentages. The analysis was completed for survival of grafts and patients on 31st Decem-
*cause unknown, suspected association with flurazepam (’Dalmane’) combination flurazepam and diazepam (’Valium’)6 tl at 3 mo, 1 at 9 mo. or
:tat I yr.
ber, 1976.
The fate of all the cadaver grafts is shown in table
73 - 9% of the grafts survive.
RESULTS
76 of the 91
one having returned to await a second haemodialysis graft. The cumulative survival in is shown table I, 80.7% surviving for patient 2 years or longer, with no deaths between 3 and 7 years. 8 of the 15 patients who died had excellent graft function up to the time of death, the graft showing no evidence of rejection or other abnormality at necropsy. The causes of death and status of the graft are shown in Table n. Infection caused no deaths within the first 60 days after transplantation. There were 2 later deaths caused by chest infections subsequent to leucopenia brought about by anti-rejection therapy including high doses (6.mg/kg body-weight) of azathioprine and actinomycin C. There have been no deaths from infection after we started treating rejection episodes by increasing prednisolone, without actinomycin C. 3 of the 4 patients who received living donor grafts survive with functioning grafts.
patients survive,
to
TABLE I-CUMULATIVE
Died II nh functioning graft Not yet completed time mterval.
2 of the 71
ill
surviving grafts
have poor function after 3yyears (serum creatinine 515 and 770 umol/1), one from recurrence of chronic pyelonephritis in the graft,’ one probably from chronic rejection. The other 69 grafts have adequate to excellent function. The survival of the small number of second and third grafts is gratifying, both third grafts surviving. One patient who received 3 grafts, had thrombosis of the first 2 grafts on the third day, but the third graft continues to function after more than 2 years. A second patient received 3 grafts; the first was removed at the primary operation because the middle two-thirds did not become vascularised, the second was rejected at 3 weeks and the third continues to function at 9 months after the
transplant. The cumulative survival of all grafts is 82.1% (S.E.±3.9) for 1-7 years, and of all 91 first grafts is 82.5% (S.E.±4.1) from 1-7 years (table i), including the 4 live donor grafts whose survival does not differ from the cadaver grafts.
SURVIVAL
(PATIENTS AND GRAFTS)
650 TABLE III-FATE OF ALL CADAVER KIDNEY GRAFTS 1
1968-1976
(P 005).
P
72 of the 76 surviving patients are well rehabilitated although not all have been able to find employment. DISCUSSION
Although it is generally accepted that the patient with successful transplant is fitter and has a better quality of life than the patient surviving on regular dialysis, the mortality is thought to be much higher. Home dialysis is considered to give the best survival-rates, the European Dialysis and Transplant Association (E.D.T.A.j’ reporting 93.1% at 1 year, 86.7% at 2 years, and 80.8 at 3 years. The cumulative survival of our patients (86-2% at 1 year, 84.7% at 2 years, and 80.7% from 3-5 years) is not far short of these figures for home dialysis. Infection accounted for 37.5% of all deaths during the first 60 days after transplantation in the E.D.T.A. report.7 None of our patients died from infection during this period. We attribute this result partly to the isolation techniques4 used and partly to the sparing use of steroids. Episodes of high fever were the commonest reason for readmission during the early months and most were due to cytomegalic-virus infection. During the fever the serum urea and creatinine rose in some patients. This rise was not a manifestation of rejection and was not treated with increased steroids. The cumulative survival of first grafts in our patients was 82.5% (s.E.±4-l) from 1-7 years, which compares favourably with the cumulative survival of first cadaver grafts reported by E.D.T.A.7 of 30-1% at 1 year, 43-9 at 2 years, and 39.4% at 3 years. Immediate function of the graft was exceptional in the 96 cadaver grafts and most patients required postoperative dialysis. This did not adversely affect the future function of the graft, even in the 3 patients with the longest warm ischxmia times (2 of 70 and 1 of 80 minutes), similar experiences being reported by White et a
TABLE IV-CAUSE OF LOSS OF GRAFT
*Rejection could be excluded in 1 only, although pathological typical of rejection in others.
appear-
ances not
The cause of loss of graft is shown in table iv. 5 of the graft failures were clearly due to rejection and this may have contributed to 4 of the 5 arterial thromboses although the histological appearances were not typically those of rejection. 8 grafts, although still functioning, were lost because of the death of the patient. The cumulative graft survival of the 19 first grafts without mis-match on the B locus was 94-6% (s.E.±5-3) from 3 months to 7 years, compared with 75% (s.E.±10-8) for the 17 first grafts with 2 mismatches at this locus. These differences were not significant
(p >0.05)survival of the first
graft in
48 3 months, group-0 patients 88-6% (s.E.±4-8) at 1-7 years, compared with 77-4% (s.E.±8-l) at 3 months and 69.3% (s.E.±9.1) at 1-7 years for 28 group-A patients receiving group-A kidneys. These differences were not significant (P>0-05). The blood transfusion history was known accurately for 69 of the patients and is shown in table v, but the small number (6) of patients who did not receive blood precludes statistical analysis. The survival of grafts at 3 months was better in patients dialysed for longer than 9 months than in those dialysed for shorter periods (93.3%, s.E.±3-7 compared with 71-2%, s.E.±3-2). This difference was significant The cumulative
graft
was
93-6% (s.E.±3-6)
at
TABLE V-TRANSFUSIONS BEFORE FIRST TRANSPLANT
*Packed cells or whole blood.
al.8
patients who had bilateral nephrectomy required blood transfusions, and blood transfusion is reported to improve graft survival in man9-11 and in animals.12 The incidence of urinary tract infection is lower in our nephrectomised patients" than in other series. 14, 11 The tissue-match grade was not particularly good in our patients, 35 receiving a first transplant with no or with only one HLA mis-match, and 48 with two or more mis-matches. The survival of our patients is nearly as good as that obtained by home dialysis, and the survival of graftsis well above the European average. With the rising costs of regular dialysis therapy we believe that transplantation offers the only hope of providing treatment for the many who could benefit.16 The scarcity of kidney donors continues and colleagues in other fields need to be convinced that kidney transplantation is worthwhile and capable of returning many patients to full health. Our
more
The following also made valuable contributions during the weight years covered by this paper: Dr Claire Hill, Dr K. V. Rajkumar, Dr S. N. Mehta, Mr R. A. Donaldson, Mr D. Middleton, Ms Kai Maguire, s.R.N., and Mr J. Lyness. We thank the staff of the Laboratories, Belfast City Hospital for constant help, Dr J. Connolly for HBsAg and virological tests. :he
651 staff of the X-rav Department, Prof. D. Gardner, Dr H. Bharucha, and Prof. K. A. Porter for histological examinations, the staffs of the intenme care units of the Royal Victoria Hospital, Craigavon Hospital, Lister Hospital, Mater Hospital, and Altnagelvin Hospital for kidney donors, and Miss A. B. Feely and the staff of the outpatients’ department Generous support has been received from the Northern Ireland Ktdnev Research Fund. Requests for reprints should be addressed to M.G.McG. REFERENCES
Doherty, C. C., O’Connor, F., Buchanan, K. D., Douglas, J. F., McGeown, M G Proc. Eur. Dial. Transplant Ass. (in the press). 2 Doherty, C., Douglas, J. F., McGeown, M. G. Unpublished. 3 Hill, C., Douglas, J. F., Rajkumar, K. V., McEvoy, J., McGeown, M. G. Lancet, 1974, ii, 493. 1
4 Maguire, K., McKnight, R., Johnston, M. A., Corrigan, M., McGeown, M. G. Proc. Eur. Dial. Transplant Nurses Ass. (in the press). 5 Cutler, S. J., Ederer, B. S. J. Chron. Dis. 1958, 8, 699. 6 Taclob, L, Needle, M. Lancet, 1976, ii, 704 7 Gurland, H. J., Brunner, F. P., Chantler, C., Jacobs, C., Schärer, K., Selwood, N H., Spies, G. W., Wing, A. J. Proc. Eur. Dial. Transplant Ass. 1976, 13, 3. 8 White, H. J. D., Evans, D. B., Calne, R. Y. Br. med. J. 1968, iv, 739. 9 Festenstein, H., Sachs, J. A., Paris, A. M. I., Pegrum, G. D., Moorehead, J. F. Lancet, 1976, i, 157. 10 Opelz, G, Terasaki, P. I. ibid, 1976, ii, 380. 11 van Hooff, J P., Kalff, M. W., van Poelgeaste, A. E. Transplantation, 1976, 22, 306 12 van Es, A. A., Marquet, R. L., van Rood, J. J., Kalff, M. W., Balner, H. Lancet,
13
1977, i, 506.
Douglas, J. F., Clarke, S, Kennedy, J. A., McEvoy, J., McGeown,
M. G.
ibid
1974, ii, 1015. 14 Hamshere, R. J., Chisholm, G D., Shackman, R. ibid. 1974, ii, 793. 15
Steen, W., Pedersen, F. B., Vejlsgaard, R. Br. J. Urol. 1975, 47, 513.
16. McGeown, M. G. in Replacement of Renal Function by Dialysis (edited by J F. Maher, F M. Parsons, and W. Drukker). The Hague (in the press).
Points of View JUBILEE BANDWAGONS 1977 has been a right royal year in the United Kingdom, with State trumpetings and martial music justifiably prominent. Unfortunately, however, this seems to have been the signal for noise from an increasing number of bandwagons to reverberate around the medical scene. Those of us who view these activities with scepticism tend to be regarded as a nuisance, and steamroller tactics are usually employed to flatten any opposition. The following comments on some of these bandwagons are a personal cri de coeur which yet may echo the feelings of many of my colleagues at grass-roots level. The Therapeutic Team The team concept has been so enthusiastically espoused in quarters that the role of the doctor in caring for his patient, whether in general or hospital practice, has tended to be undermined. All members of the team claim to have at least equal responsibility with the doctor for the patient’s welfare, and in some cases actually believe they should over-ride the medical view. I do not seek to denigrate the nurse’s role or that of paramedical personnel, but I contend that the doctor must remain, and be seen to remain, the leader of any such team. Abrogation of this responsibility leads to a deterioration m the doctor-patient relationship. Certainly in law the consultant is held to be responsible for the total care of his patient while he remains in hospital. The tendency towards medicine by committee, with all members having an equal vote, must be resisted; it is imperative for the doctor to be the permanent chairman, and to retain the right of veto. some
.tfedicalAudit
Currently it is virtually impossible to open any of the "respectable" medical journals without being subjected to a paper extolling the virtues of medical audit or peer review. Since the
advent of the financial crisis, the clamour has become intense and has been justified on the grounds that we are being helped to make better use of available resources. However, I suspect this concept is not regarded with such widespread enthusiasm as its proponents would like us to believe. Many clinical procedures are still sanctioned by tradition rather than any firm evidence of their effectiveness, but there is a real danger that audit and peer review might induce complacency in those who comply with the norm, and discourage a questioning approach. A few years ago not to give anticoagulants to patients with coronary thrombosis, or not to recommend a low residue diet to patients with diverticular disease, was regarded almost as malpractice. Let us hope that medical men will continue to take what their peers say and do with a handful rather than a pinch of salt.
Postgraduate Education A doctor continues to learn throughout his professional carcan best be helped to continue this process is uncertain. Fashionable at the moment are workshops, symposia, courses, and conferences, often with considerable duplication and all liberally sprinkled with audiovisual aids. The desire of the small-print brigade to expose us all to the flashing-slide darkened-room syndrome seems unbounded. Organisers of such meetings would do well to consider carefully whether the proposed event really has anything much to offer, or whether the real reason for its promotion is not a desire to inflate the ego of the individual or department concerned, with an eye to the subsequent "proceedings", which now drop like confetti from the medical publishers. Unquestionably some meetings are of immense value, but one wonders if the phrenetic, peripatetic existence led by so many really leads to better doctoring. A doctor whose postgraduate diet consists mainly of learning from clinical experience, private study, and attendance at local postgraduate activities, with excursions further afield being the exception rather than the rule, has the great advantage of more time to spend with his patients, and probably functions at least as efficiently as his more widely travelled colleagues.
eer, but how he
Training Programmes Until recently the training of doctors after registration, whether they wished to remain in hospital or general practice, was based largely on the apprenticeship system. With respect to a consultantship, the aspirant was free to choose where, when, and with whom he wished to work-with the result that he often obtained considerable experience at various centres both in this country and abroad. Training schemes have now been introduced both for hospital specialists and for general practitioners, but at a sacrifice of flexibility and scope for individual enterprise and initiative in shaping one’s own training sequence; the system has become increasingly complex, with an organisational superstructure and inspectorate, and it seems doubtful if little more than lip-service is paid to the principle that nonconformists are given a fair hearing. Undoubtedly there was a need to improve training programmes both for hospital specialists and general practitioners, but there is now a danger of patient care being subordinated to this end. There always have been, and there probably always will be, good and bad doctors; training schemes will probably swing the balance towards improvement less than current noise levels in their favour would suggest.
Many similar examples of current fads could have been chosen. Bandwagons have a habit of eventually coming to a halt, with a resultant unseemly scramble by the passengers to dismount as quickly as possible and move away from the scene. Many of us feel it is more appropriate to resist the temptation to climb aboard in the first place. Cumberland Infirmary, Carlisle CA2 7HY
R. H. SALTER
