ORIGINAL ARTICLES
LIVING RELATED RENAL TRANSPLANTATION: EXPERIENCE IN 22 CASES NAPIERM. THOMSON'.DAVIDF. SCOTT^, VERNON c. MARSHALL3AND ROBERT c. ATKINS4 Department of Nephrology, Prince Henry's Hospital, a n d Department of Surgery, Monash University, Melbourne.
Twenty-two living related ren Itr nspl nt operations have been performed at Prince Henry's Hospital over the last seven years. Donors have been accepted for nephrectomy only after exhaustive examination of their health and search for renal disease. The one and three year graft survival rates have been 85% and 64% respectively. Only two recipients have died, and recipient morbidity has been low. Donors have not suffered any serious complication from nephrectomy. It is concluded that living related renal transplantation has many advantages over cadaveric renal transplantation and is a relatively safe procedure for the donor, provided that rigid criteria are used in donor selection.
RENAL transplantation using living related donors is widely practised throughout the world and in several areas, particularly Japan and South East Asia, the living related donor isvirtuallytheonlysource of kidneys for transplantation. In Europe 14% of renal allografts come from living related donors (Brunner et alii, 1979) and 28% in the U.S.A. (Advisory Committee 1977). In Australia and New Zealand only 84 living related renal transplants have been performed in the 16 years 1963-1978, representing 2.6% of all renal transplants performed in that period (3,176 transplants). Twenty six of the 84 living donor transplants have been performed in the year from November 1977 to October 1978, reflecting the increased interest in this form of donor in Australasia (2nd report of the Australian and New Zealand Combined Dialysis and Transplant Registry, 1979). 1. Deputy Director. Department of Nephrology. Prince Henry's Hospital. 2 Surgeon, Department of Nephrology; Senior Lecturer, Departmentof Surgery, Monash University. 3 Professor of Surgery, Monash University. 4 Director, Department of Nephrology, Prince Henry's Hospital.
Reprints: Dr N. M. Thomson. Department of Nephrology. Prince Henry's Hospital, St Kilda Road, Melbourne, VIC 3004. Australia.
608
Living related transplantation has several advantages over cadaveric transplantation and as there is still a considerable lack of cadaver donors in Victoria, we have actively encouraged living related transplantation at this hospital. The major concern in living related transplantation is the possibility of inducing morbidity in an otherwise healthy donor. In this paper we report our experience with 22 living related renal transplants (38% of all living related transplants in Australasia) performed in the years 1972 to 1979, with particular examination of the consequences to the donor. Our technique of donor selection and evaluation is also discussed. METHODS
Patients- In the years 1971 t o 1979 we have performed 139 renal transplants in 117 patients accepted into our dialysis and transplantation programme. Of these 139 transplants, 22 (16%) have been from living related donors. Twelve of the recipients were Australian residents, whilst the remaining ten recipients came from Malaysia or Fiji. The mean age of the living related graft recipients was 32.2 years (range 18 to 60 years). Five recipients had previously received a cadaveric graft. AUST. N.Z. J. SURG.VOL. 49 - No. 6, DECEMBER, 1979
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Selection of living related donors. - Prior to entry to our end-stage renal failure treatment programme, the patients and their relatives have been made aware of the types of treatment available, viz., haemodialysis, peritoneal dialysis, cadaveric donor transplantation, and living related transplantation. The positive advantages of living related transplantation have been discussed, but no pressure ha5 been brought to bear on relatives to donate kidneys. The donors of all the Australian recipients have spontaneously volunteered to donate. Although the offer to donate from Malaysian or Fijian donors was ostensibly spontaneous, it hasoften been difficult to determine if this was really so, given the very different family relationships and responsibilities in these countries. Once an offer to donate was received, the potential donor was interviewed b y a senior member of the Department of Nephrology and fully instructed in the requirements for donation, chances of rejection, and possible morbidity to donor and recipient. The potential donor was given every opportunity to withdraw his or her offer if he or she wished, at this initial and all subsequent consultations. The potential donor was then thoroughly investigated for a r y evidence of renal disease or other significant disorder. The investigations performed are outlined in Table 1. Potential donors and recipients were interviewed by a psychiatrist so that TABLE1 Assessmen1 of Pofenfial Living Relafed Renal Donors 1. Comprehensive clinical assessment history and examination
2 Investigations: Blood group, Serum electrolytes. urea. creatinine x 2. Creatinine clearance x 3, Twenty-four hour urine protein, calcium, phosphate, urate excretion x 3, Micro-urine and culture x 3. Serum calcium, phosphate, uric acid: Liver function tests and prothrombin time. Full blood examination including ESR. platelet count. Hepatitis B antigen, CMV + herpes simplex antibodies; Chest X-ray examination: E.C.G : Intravenous pyelogram, Tissue typing, M L C
3. Social and psychiatric assessment 4 Renal angiography
- only if donor is acceptable on all other grounds. -~
~-
motives behind donation could be assessed and to detect any significant psychiatric disorder (Ironside, 1979). When more than one potential donor existed, priority was given to a potential donor who was identifical on tissue matching or had minimal family responsibilities. Tissue matching. - Tissue typing for HLA A.B.C. and more recently D Loci was performed on donor and recipient peripheral blood leucocytes, and AUST. N.Z. J. SURG.VOL. 49
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where possible other members of the family were also typed for more accurate genotypes. Mixed lymphocyte culture was also performed. A negative Tcell crossmatch between donor leucocytes and recipient serum was mandatory before transplantation. lmmunosuppressive regime. - Azathioprine in a dose of 2-3 mg per Kg body weight was commenced 48 hours prior to transplantation and continued i n the same dose after transplantation, depending on the peripheral leucocyte count. Prednisolone in a dose of 200 mg per day was commenced 24 hours before transplantation, reducing to a maintenance dose of 10 mg per day by six to nine months after transplantation. The postoperative regime was the same as that used for cadaveric donor transplantation. Rejection episodes were treated with a course of methylprednisolone given as an intravenous bolus of 1 g per day for up to three days. In general, no more than two such courses of methylprednisolone were given. SURGERY IN LIVING RELATED TRANSPLANTATION Donor nephrectomy and recipient transplant operations have generally been performed by two surgical teams in adjacent operating theatres. The timing of the surgery has been such that the recipient team has had the vessels prepared for the transplant by the time the donor kidney was removed. This coordination resulted in a total ischaemta time for the kidney of 30 minutes or slightly less. In preparing the donor for surgery it has been our practice to administer two litres of saline intravenously overnight, so that the patient is normally hydrated at the time of surgery. All donors have had an aortogram as the final part of their preoperative assessment. If both kidneys had singlearteries, then the left kidney was removed for transplantation, as the longer left renal vein facilitated the transplant. If the renal arteries were multiple on the left side but single on the right, then the right kidney was used. On two occasions when there have been double arteries on both sides, we have proceeded with nephrectomy and anastomosed the lesser renal artery to the major renal artery prior to transplantation. The kidney for donor nephrectomy is approached by a loin incision in the bed of the 12th rib. If the rib is very short then the 11th rib approach is used. Care is taken to avoid entry into the pleural cavityand peritoneal cavity. The kidney is fully mobilized, clearing the fat from the renal capsule except in the hilar reg ion. The adrenal gland is dissected off the upper pole and left in situ. The renal artery and renal vein are 609
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fully dissected out to the aorta and vena cava. On the left the gonadal vein and adrenal vein need t o be ligated between ligatures. The ureter is mobilized from the lower pole of the kidney to the point where it crosses the distal common iliac artery, and is ligated and transected. In dissecting out the ureter care is taken to preserve the longitudinal vascular anastomoses along the ureter, as it will be dependent on a blood supply from the renal artery on transplantation. Before clamping of the renal arteryand vein, urine should be seen flowing from the ureter. If the kidney feels soft, and there is no urineoutput, this indicates vasospasm in the kidney. If this is not corrected prior to nephrectomy, delayed renal function and even tubular necrosis may occur in the recipient. Vasospasm is prevented or minimized by preoperative saline infusion of the donor and gentle handling of the kidney during the dissection. Once it occurs it can usually be reversed by further intravenous saline administration, frusemide 40 mg given intravenously, or mannitol 25 g in 100 ml, and leaving the kidney undisturbed for 10 to 15 minutes. Once the urine flow is established the nephrectomy is completed. Transplantation in the recipient is a standard technique as for cadaveric transplantation, anastomosing the renal artery end-to-end to the internal iliac artery and the renal vein end-to-side to the external iliac vein, and the ureteroneocystostomy is created near the base of the bladder using the Leadbetter-Politano technique. One expects urine to be excreted within five minutes of the completion of the vascular anastomosis. Occasionally if the recipient has a depleted extracellular volume, urine output may be delayed until this is recognized and corrected. In our patients all kidneysfunctioned within one to two hours, and generally a marked diuresis of 0.5-2 litres per hour occurred during the first 12 hours after operation. Close supervision is required to maintain fluid balance and prevent hypokalaemia. Postoperative assessment of donors. - As well as receiving the standard postoperative care, all donors have been seen at six-monthly to yearly intervals and thoroughly assessed for hypertension, renal disease and renal function. RESULTS
Donors. - All living related donors wereassessed as being in excellent health, with normal renal function. During the period covered by this survey, twelve other potential donors were also assessed and not accepted for donation because of ABO blood group incompatability, hypertension, single kidney, significant renal abnormality, or family 610
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responsibilities and work commitments. Potential donors who were CMV or herpes simplex antibody positive were also excluded if the potential recipient was antibody negative. The mean age of the donors was44.1 years (range 19 to 67 years). Nine donors were over the age of 50 years, and three were older than 60 years. Ten donors were siblings of the recipients, eleven were parents, and one was an offspring (a nun aged 32 years). Five of the siblings were HLA identical and MLR non-stimulatory t o their respective recipients. All other donors shared one HLA haplotype with the recipients. Graft and patient survival. - Graft survival at one, two and three years post-transplantation was 85%, 72% and 64% respectively. The longest graft survival is seven years, and the graft is still functioning. Only five grafts have been lost through rejection, none before three months after transplantation and none from sibling donors. All grafts functioned immediately. Two recipients have died, one from myocardial infarction and one from opportunistic lung infection, one and two years after transplantation respectively. Both patients died with normal renal function. The one, two and three year patient survival rates were loo%, 93% and 82% respectively. Patient morbidity. - Necrosis of the lower end of the ureter developed in one patient, but was successfully treated by reimplantation. No patient developed significant wound infection. The mean admission period for the transplantation procedure was 17.1 days (range 8 to 58 days). This short initial admission period was largely the consequence of immediate graft function and a low incidence of rejection and surgical complications. The incidence of subsequent illness in the recipients was low in that only 2.2% of the time at risk was spent as a hospital in-patient (i.e., eight days per patient year). A large proportion of this time spent in hospital was accounted for by three non-Australian recipients who developed pulmonary tuberculosis. Donor morbidity. - Neither death nor serious complication occurred in any donor. The mean time spent in hospital for donor nephrectomy was 10.2 days (range 7 to 16 days). Minor basal pulmonary atelectasis with fever occurred in six donors, and two developed superficial wound infections. One donor (aged 67 years) developed carcinoma of the larynx eighteen months after nephrectomy. Significant psychosocial problems have not been encountered. All Australian donors have been reviewed annually since nephrectomy. In all donors creatinine clearances at one year have exceeded 65% of prenephrectomy clearances (range 66% to 89%). This increase in single kidney glomerular filtration AUST. N.Z. J. SURG.VOL. 49 - No. 6, DECEMBER, 1979
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rate was evident as early as one week after nephrectomy. Hypertension and urine infection have not developed in any donor. DISCUSSION
Living related renal transplantation has many advantages over cadaveric donor transplantation. '(1) The operation is elective, allowing conditions for the recipient to be optimal; (2) Immediate graft function occurs in virtually all recipients; (3) There is superior graft survival; (4) Recipient morbidity and mortality are reduced; and (5) There is increase in thesize of the pool of kidneys available for transplantation. The disadvantage of living related transplantationlies in the potential complications of an operation and loss of one kidney by an otherwise healthy donor. Our study reflects all the advantages of living related renal transplantation. Graft survival (85% at one year) is significantly greater than for any reported series of cadaveric grafts. The current one year graft survival for all cadaveric grafts in Australia and New Eealand is 55% (Report, 1979) and for Europe 48% (Brunner et alii, 1979). The thirteenth report from the American renal transplant registry indicates a 73% one year survival for living related grafts compared with 47% for cadaveric grafts (Advisory Committee, 1977). Living related transplantation was also associated with a significantly greater patient survival. The one and three year survival of our patients of 100% and 82% respectively contrasts with the Australasian cadaveric transplant recipient survival of 76% and 66% at one and three years (Report, 1979). Improved patient survival with living related transplantation is likely to be due to immediate and better graft function, less aggressive immunosuppression, and optimal health of the recipient at the time of transplantation. For similar reasons we have had a low incidence of morbidity in our living related graft recipients. One of the major problems associated with cadaveric renal transplantation is the short time between selection of the recipient and the transplant operation. The recipient's health is often less than optimal, immediate dialysis may be required before operation, and the uncertainty associated with hospital admission and preparation for operation is often very disturbing to the patient. The elective nature of living related transplantation has allowed our patients to be in an optimal stateof health at the time of operation and undergo dialysis on the day prior to AUST. N.Z. J. SURG.VOL. 49 - No. 6, DECEMBER, 1979
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the procedure. Moreover, immediate function seen in all living related recipients has obviated the need for dialysis in the first few postoperative days, thus removing the potential dangers of anticoagulation and vascular volume reduction in this period. Throughout Australia there has been a progressive increase in the pool of patients awaiting transplantation from 231 in 1971 to 1,092 in 1978. However, the annual rate of transplantation has only increased from 14.5 per million population to 21 per million in the same period (Report, 1979). The transplantation rate in Victoria has actually fallen in the last three years. I n our hospital, living related donors have helped to reduce this shortfall in available kidneys. Sixteen per cent of our transplants have come from living related donors, compared with an average rate of 1.5% for the rest of Australasia. At least 6,000 living related renal transplants have been performed throughout the world, including over 4,000 in the United States of America (Advisory Committee, 1977). However, only rarely has adonor death been reported. In six reported series (Bennett and Harrison, 1974; McLoughlin, 1976; Penn et alii, 1970; Smith, 1973, Smith et alii, 1973; Spanos etalii, 1974), totalling 1,110 donors, only one death occurred ( halothane hepatitis). All authors stressed in these reports that this very low mortality rate is probably the consequence of very careful donor assessment. Major postoperative complications in the same series of patients were also rare (18 patients - 1.6%). The main problem (14 patients) was severe pneumonia, but in twelve of these patients preexisting chronic lung disease was present. This latter finding again emphasizesthe need to reject potential donors with significant preexisting disease. The reported incidence of minor postoperative complications varies from 28% (Spanos et alii, 1974) to 47% (Penn et alii, 1970). The incidence would seem to be high. However, most problems were easily correctable and shortlived. The majority of minor complications were respiratory disease (basal atelectasis with fever, pneumonia, pleural effusion, pneumothorax), urinary tract infection, and superficial wound infection. Acute psychiatric disturbance was rare. Our incidence of minor complications was 36%, and serious complication or death was not seen. Again this reflects the high standards we demand of donor health. We have not accepted an absolute upper age limit for donors, and two of our donors were 67 and 68 years old respectively. Late complications of donor nephrectomy are rare. Individual cases of the development of glomerulonehphritisrulonephritis (Spanos et alii, 1974), haemolytic uraemic syndrome (Bergstein et alii, 61 1
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1974), chronic pyelonephritis (Bennett and Harrison, 1974), and severe depression (Smith, 1973) have been reported. Significant long-term psychiatric disturbances have not been reported. Smith (1973) reported that all except one of 132 donors were still pleased with their donation one year after nephrectomy. Marshall (1977) reported similar findings ten years after nephrectomy. Significant psychosocial complications in donors or recipients have not been seen in our patients, even after graft failure. We have found psychiatric interviews of potential donors and recipients of considerable value in detecting potential psychiatric problems, false motives and misunderstandings about living related transplantation (Ironside, 1979): Counselling has also been available to donors after transplantation, especially if graft rejection has occurred. The loss of one kidney has not adversely affected renal function or induced hypertension in any of our donors. Single kidney GFR has increased in all donors, as has been reported in other series (Davison et alii, 1976, Donadio et a/;/, 1967, Penn et alii, 1970, Simmons et alii, 1976). This increase in GFR has been shown to occur within the first two to three weeks after nephrectomy with little subsequent increase (Krohn et ah, 1966).The degree of increase is m inverse proportion to the age of the donor. Potential long-term hazards to the living related donor kidney could be renal stones, cancer of the kidney, and trauma to the solitary kidney. We believe the risk of these occurring is acceptably remote. There is noevidence that people with a single kidney have a reduced life expectancy. In our experience and in other reported series of living related transplant subjects, the advantages of the procedure outweigh the potential harm done to the donor. In practical terms, living related transplantation can only be an adjunct to cadaveric transplantation, as not all patients have potential related donors. We believe that every attempt should be
612
made to make potential transplant recipients and their families aware of living related transplantation so that it may bediscussed within the family and, it is hoped, lead to a spontaneous offer of donation. ACKNOWLEDGEMENT
We are very grateful to Professor Wallace lronside of the Department of Psychological Medicine, Monash University, for the in-depth psychiatric assessments of all living related donors and recipients. REFERENCES Advisory Committee to the Renal Transplantation Registry (1977), Transplant Proc., 9: 9. BENNETT,A. H. and HARRISON,J. H. (1974). Surg. Gynec. Obstet., 139: 894. BERGSTEIN, J., MICHAEL.A,, KJELLSTRANT, C., SIMMONS,R. and NAJARIAN,J. (1974), Transplantation, 17: 487. F. P.. BRYNGER, H., CHANTLER, R. A., DONCKERWOICKE, BRUNNER. R. A.. HATHWAY,R . A., JACOBS, C., SELWOOD. N. H.,WING. A. J. (1979) Dialysis. Transpl. Nephrol. 16: In Press. J. M., ULDALL,P. R. and WALLS,J. (1976). Brit. med. J., DAVISON. 1: 1050. C D..HUNT,J. C., TAUXE, N., HALLENDONADIO,J. V., jr, FARMER, BECK, G. A. and SHORTER. R. G. (1967), Ann. intern. Med., 66: 105. IRONSIDE, W. (1979). Opuscula rned. Tech. Lund., 20: 68. KROHN. A. G.. ODGEN.D.A and HOLMES,J. H. (1966), J. Amer. rned. Ass., 196: 322. MCLOUGHLIN,M. G. (1976), J. Urol. (Baltimore), 116: 304. MARSHALL, J. R. 1977. Am. J. Psychiaf. 134: 5. OGDEN,D A. (1967). Ann. intern. Med., 67: 998. PENN,I., HALGRIMSON, C. G.. ODGEN,0.and STARZL, T. E. (1970) Arch. Surg. 101: 226. Report of the Australia and New Zealand Dialysis and Transplant Registry (1979). private publication'. J., KJELLSTRAND, C. M.. YUNIS, E. J., SIMMONS. R. L. THOMSON, CONDIE. R. M., MAUER,S. M., BUSELMIER, J. J. and 321. NAJARIAN, J. S. (1976), Lancet, 1: SMITH,M. J. V. (1973), J. Urol. (Baltimore), 110: 158. SMITH,R. B., WALTON,K.. LEWIS, E. L., PERDUE,G. D., jr and HERNDON, E. G. (1972) J. surg. Res., 3: 199. SPANOS,P. K., SIMMONS,R. L., LAMPE,E., RATTAZZI. L. G.. KJELLSTRAND. C. M., GOETZ.F. C. and NAJARIAN,J. S (1974). Surgery, 76: 741 'Report obtainable trom Dr A P. S Bhsnsy. Hon. Sec.. Australia and New Zealand Dialysis and Transplant Registry, The Queen Elizabeth Hospital,Woodville. South Australia. 5011
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LIVING RELATED RENAL TRANSPLANTATION: EXPERIENCE IN 22 CASES NAPIERM. THOMSON'.DAVIDF. SCOTT^, VERNON c. MARSHALL3AND ROBERT c. ATKINS4 Department of Nephrology, Prince Henry's Hospital, a n d Department of Surgery, Monash University, Melbourne.
Twenty-two living related ren Itr nspl nt operations have been performed at Prince Henry's Hospital over the last seven years. Donors have been accepted for nephrectomy only after exhaustive examination of their health and search for renal disease. The one and three year graft survival rates have been 85% and 64% respectively. Only two recipients have died, and recipient morbidity has been low. Donors have not suffered any serious complication from nephrectomy. It is concluded that living related renal transplantation has many advantages over cadaveric renal transplantation and is a relatively safe procedure for the donor, provided that rigid criteria are used in donor selection.
RENAL transplantation using living related donors is widely practised throughout the world and in several areas, particularly Japan and South East Asia, the living related donor isvirtuallytheonlysource of kidneys for transplantation. In Europe 14% of renal allografts come from living related donors (Brunner et alii, 1979) and 28% in the U.S.A. (Advisory Committee 1977). In Australia and New Zealand only 84 living related renal transplants have been performed in the 16 years 1963-1978, representing 2.6% of all renal transplants performed in that period (3,176 transplants). Twenty six of the 84 living donor transplants have been performed in the year from November 1977 to October 1978, reflecting the increased interest in this form of donor in Australasia (2nd report of the Australian and New Zealand Combined Dialysis and Transplant Registry, 1979). 1. Deputy Director. Department of Nephrology. Prince Henry's Hospital. 2 Surgeon, Department of Nephrology; Senior Lecturer, Departmentof Surgery, Monash University. 3 Professor of Surgery, Monash University. 4 Director, Department of Nephrology, Prince Henry's Hospital.
Reprints: Dr N. M. Thomson. Department of Nephrology. Prince Henry's Hospital, St Kilda Road, Melbourne, VIC 3004. Australia.
608
Living related transplantation has several advantages over cadaveric transplantation and as there is still a considerable lack of cadaver donors in Victoria, we have actively encouraged living related transplantation at this hospital. The major concern in living related transplantation is the possibility of inducing morbidity in an otherwise healthy donor. In this paper we report our experience with 22 living related renal transplants (38% of all living related transplants in Australasia) performed in the years 1972 to 1979, with particular examination of the consequences to the donor. Our technique of donor selection and evaluation is also discussed. METHODS
Patients- In the years 1971 t o 1979 we have performed 139 renal transplants in 117 patients accepted into our dialysis and transplantation programme. Of these 139 transplants, 22 (16%) have been from living related donors. Twelve of the recipients were Australian residents, whilst the remaining ten recipients came from Malaysia or Fiji. The mean age of the living related graft recipients was 32.2 years (range 18 to 60 years). Five recipients had previously received a cadaveric graft. AUST. N.Z. J. SURG.VOL. 49 - No. 6, DECEMBER, 1979
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Selection of living related donors. - Prior to entry to our end-stage renal failure treatment programme, the patients and their relatives have been made aware of the types of treatment available, viz., haemodialysis, peritoneal dialysis, cadaveric donor transplantation, and living related transplantation. The positive advantages of living related transplantation have been discussed, but no pressure ha5 been brought to bear on relatives to donate kidneys. The donors of all the Australian recipients have spontaneously volunteered to donate. Although the offer to donate from Malaysian or Fijian donors was ostensibly spontaneous, it hasoften been difficult to determine if this was really so, given the very different family relationships and responsibilities in these countries. Once an offer to donate was received, the potential donor was interviewed b y a senior member of the Department of Nephrology and fully instructed in the requirements for donation, chances of rejection, and possible morbidity to donor and recipient. The potential donor was given every opportunity to withdraw his or her offer if he or she wished, at this initial and all subsequent consultations. The potential donor was then thoroughly investigated for a r y evidence of renal disease or other significant disorder. The investigations performed are outlined in Table 1. Potential donors and recipients were interviewed by a psychiatrist so that TABLE1 Assessmen1 of Pofenfial Living Relafed Renal Donors 1. Comprehensive clinical assessment history and examination
2 Investigations: Blood group, Serum electrolytes. urea. creatinine x 2. Creatinine clearance x 3, Twenty-four hour urine protein, calcium, phosphate, urate excretion x 3, Micro-urine and culture x 3. Serum calcium, phosphate, uric acid: Liver function tests and prothrombin time. Full blood examination including ESR. platelet count. Hepatitis B antigen, CMV + herpes simplex antibodies; Chest X-ray examination: E.C.G : Intravenous pyelogram, Tissue typing, M L C
3. Social and psychiatric assessment 4 Renal angiography
- only if donor is acceptable on all other grounds. -~
~-
motives behind donation could be assessed and to detect any significant psychiatric disorder (Ironside, 1979). When more than one potential donor existed, priority was given to a potential donor who was identifical on tissue matching or had minimal family responsibilities. Tissue matching. - Tissue typing for HLA A.B.C. and more recently D Loci was performed on donor and recipient peripheral blood leucocytes, and AUST. N.Z. J. SURG.VOL. 49
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where possible other members of the family were also typed for more accurate genotypes. Mixed lymphocyte culture was also performed. A negative Tcell crossmatch between donor leucocytes and recipient serum was mandatory before transplantation. lmmunosuppressive regime. - Azathioprine in a dose of 2-3 mg per Kg body weight was commenced 48 hours prior to transplantation and continued i n the same dose after transplantation, depending on the peripheral leucocyte count. Prednisolone in a dose of 200 mg per day was commenced 24 hours before transplantation, reducing to a maintenance dose of 10 mg per day by six to nine months after transplantation. The postoperative regime was the same as that used for cadaveric donor transplantation. Rejection episodes were treated with a course of methylprednisolone given as an intravenous bolus of 1 g per day for up to three days. In general, no more than two such courses of methylprednisolone were given. SURGERY IN LIVING RELATED TRANSPLANTATION Donor nephrectomy and recipient transplant operations have generally been performed by two surgical teams in adjacent operating theatres. The timing of the surgery has been such that the recipient team has had the vessels prepared for the transplant by the time the donor kidney was removed. This coordination resulted in a total ischaemta time for the kidney of 30 minutes or slightly less. In preparing the donor for surgery it has been our practice to administer two litres of saline intravenously overnight, so that the patient is normally hydrated at the time of surgery. All donors have had an aortogram as the final part of their preoperative assessment. If both kidneys had singlearteries, then the left kidney was removed for transplantation, as the longer left renal vein facilitated the transplant. If the renal arteries were multiple on the left side but single on the right, then the right kidney was used. On two occasions when there have been double arteries on both sides, we have proceeded with nephrectomy and anastomosed the lesser renal artery to the major renal artery prior to transplantation. The kidney for donor nephrectomy is approached by a loin incision in the bed of the 12th rib. If the rib is very short then the 11th rib approach is used. Care is taken to avoid entry into the pleural cavityand peritoneal cavity. The kidney is fully mobilized, clearing the fat from the renal capsule except in the hilar reg ion. The adrenal gland is dissected off the upper pole and left in situ. The renal artery and renal vein are 609
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fully dissected out to the aorta and vena cava. On the left the gonadal vein and adrenal vein need t o be ligated between ligatures. The ureter is mobilized from the lower pole of the kidney to the point where it crosses the distal common iliac artery, and is ligated and transected. In dissecting out the ureter care is taken to preserve the longitudinal vascular anastomoses along the ureter, as it will be dependent on a blood supply from the renal artery on transplantation. Before clamping of the renal arteryand vein, urine should be seen flowing from the ureter. If the kidney feels soft, and there is no urineoutput, this indicates vasospasm in the kidney. If this is not corrected prior to nephrectomy, delayed renal function and even tubular necrosis may occur in the recipient. Vasospasm is prevented or minimized by preoperative saline infusion of the donor and gentle handling of the kidney during the dissection. Once it occurs it can usually be reversed by further intravenous saline administration, frusemide 40 mg given intravenously, or mannitol 25 g in 100 ml, and leaving the kidney undisturbed for 10 to 15 minutes. Once the urine flow is established the nephrectomy is completed. Transplantation in the recipient is a standard technique as for cadaveric transplantation, anastomosing the renal artery end-to-end to the internal iliac artery and the renal vein end-to-side to the external iliac vein, and the ureteroneocystostomy is created near the base of the bladder using the Leadbetter-Politano technique. One expects urine to be excreted within five minutes of the completion of the vascular anastomosis. Occasionally if the recipient has a depleted extracellular volume, urine output may be delayed until this is recognized and corrected. In our patients all kidneysfunctioned within one to two hours, and generally a marked diuresis of 0.5-2 litres per hour occurred during the first 12 hours after operation. Close supervision is required to maintain fluid balance and prevent hypokalaemia. Postoperative assessment of donors. - As well as receiving the standard postoperative care, all donors have been seen at six-monthly to yearly intervals and thoroughly assessed for hypertension, renal disease and renal function. RESULTS
Donors. - All living related donors wereassessed as being in excellent health, with normal renal function. During the period covered by this survey, twelve other potential donors were also assessed and not accepted for donation because of ABO blood group incompatability, hypertension, single kidney, significant renal abnormality, or family 610
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responsibilities and work commitments. Potential donors who were CMV or herpes simplex antibody positive were also excluded if the potential recipient was antibody negative. The mean age of the donors was44.1 years (range 19 to 67 years). Nine donors were over the age of 50 years, and three were older than 60 years. Ten donors were siblings of the recipients, eleven were parents, and one was an offspring (a nun aged 32 years). Five of the siblings were HLA identical and MLR non-stimulatory t o their respective recipients. All other donors shared one HLA haplotype with the recipients. Graft and patient survival. - Graft survival at one, two and three years post-transplantation was 85%, 72% and 64% respectively. The longest graft survival is seven years, and the graft is still functioning. Only five grafts have been lost through rejection, none before three months after transplantation and none from sibling donors. All grafts functioned immediately. Two recipients have died, one from myocardial infarction and one from opportunistic lung infection, one and two years after transplantation respectively. Both patients died with normal renal function. The one, two and three year patient survival rates were loo%, 93% and 82% respectively. Patient morbidity. - Necrosis of the lower end of the ureter developed in one patient, but was successfully treated by reimplantation. No patient developed significant wound infection. The mean admission period for the transplantation procedure was 17.1 days (range 8 to 58 days). This short initial admission period was largely the consequence of immediate graft function and a low incidence of rejection and surgical complications. The incidence of subsequent illness in the recipients was low in that only 2.2% of the time at risk was spent as a hospital in-patient (i.e., eight days per patient year). A large proportion of this time spent in hospital was accounted for by three non-Australian recipients who developed pulmonary tuberculosis. Donor morbidity. - Neither death nor serious complication occurred in any donor. The mean time spent in hospital for donor nephrectomy was 10.2 days (range 7 to 16 days). Minor basal pulmonary atelectasis with fever occurred in six donors, and two developed superficial wound infections. One donor (aged 67 years) developed carcinoma of the larynx eighteen months after nephrectomy. Significant psychosocial problems have not been encountered. All Australian donors have been reviewed annually since nephrectomy. In all donors creatinine clearances at one year have exceeded 65% of prenephrectomy clearances (range 66% to 89%). This increase in single kidney glomerular filtration AUST. N.Z. J. SURG.VOL. 49 - No. 6, DECEMBER, 1979
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rate was evident as early as one week after nephrectomy. Hypertension and urine infection have not developed in any donor. DISCUSSION
Living related renal transplantation has many advantages over cadaveric donor transplantation. '(1) The operation is elective, allowing conditions for the recipient to be optimal; (2) Immediate graft function occurs in virtually all recipients; (3) There is superior graft survival; (4) Recipient morbidity and mortality are reduced; and (5) There is increase in thesize of the pool of kidneys available for transplantation. The disadvantage of living related transplantationlies in the potential complications of an operation and loss of one kidney by an otherwise healthy donor. Our study reflects all the advantages of living related renal transplantation. Graft survival (85% at one year) is significantly greater than for any reported series of cadaveric grafts. The current one year graft survival for all cadaveric grafts in Australia and New Eealand is 55% (Report, 1979) and for Europe 48% (Brunner et alii, 1979). The thirteenth report from the American renal transplant registry indicates a 73% one year survival for living related grafts compared with 47% for cadaveric grafts (Advisory Committee, 1977). Living related transplantation was also associated with a significantly greater patient survival. The one and three year survival of our patients of 100% and 82% respectively contrasts with the Australasian cadaveric transplant recipient survival of 76% and 66% at one and three years (Report, 1979). Improved patient survival with living related transplantation is likely to be due to immediate and better graft function, less aggressive immunosuppression, and optimal health of the recipient at the time of transplantation. For similar reasons we have had a low incidence of morbidity in our living related graft recipients. One of the major problems associated with cadaveric renal transplantation is the short time between selection of the recipient and the transplant operation. The recipient's health is often less than optimal, immediate dialysis may be required before operation, and the uncertainty associated with hospital admission and preparation for operation is often very disturbing to the patient. The elective nature of living related transplantation has allowed our patients to be in an optimal stateof health at the time of operation and undergo dialysis on the day prior to AUST. N.Z. J. SURG.VOL. 49 - No. 6, DECEMBER, 1979
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the procedure. Moreover, immediate function seen in all living related recipients has obviated the need for dialysis in the first few postoperative days, thus removing the potential dangers of anticoagulation and vascular volume reduction in this period. Throughout Australia there has been a progressive increase in the pool of patients awaiting transplantation from 231 in 1971 to 1,092 in 1978. However, the annual rate of transplantation has only increased from 14.5 per million population to 21 per million in the same period (Report, 1979). The transplantation rate in Victoria has actually fallen in the last three years. I n our hospital, living related donors have helped to reduce this shortfall in available kidneys. Sixteen per cent of our transplants have come from living related donors, compared with an average rate of 1.5% for the rest of Australasia. At least 6,000 living related renal transplants have been performed throughout the world, including over 4,000 in the United States of America (Advisory Committee, 1977). However, only rarely has adonor death been reported. In six reported series (Bennett and Harrison, 1974; McLoughlin, 1976; Penn et alii, 1970; Smith, 1973, Smith et alii, 1973; Spanos etalii, 1974), totalling 1,110 donors, only one death occurred ( halothane hepatitis). All authors stressed in these reports that this very low mortality rate is probably the consequence of very careful donor assessment. Major postoperative complications in the same series of patients were also rare (18 patients - 1.6%). The main problem (14 patients) was severe pneumonia, but in twelve of these patients preexisting chronic lung disease was present. This latter finding again emphasizesthe need to reject potential donors with significant preexisting disease. The reported incidence of minor postoperative complications varies from 28% (Spanos et alii, 1974) to 47% (Penn et alii, 1970). The incidence would seem to be high. However, most problems were easily correctable and shortlived. The majority of minor complications were respiratory disease (basal atelectasis with fever, pneumonia, pleural effusion, pneumothorax), urinary tract infection, and superficial wound infection. Acute psychiatric disturbance was rare. Our incidence of minor complications was 36%, and serious complication or death was not seen. Again this reflects the high standards we demand of donor health. We have not accepted an absolute upper age limit for donors, and two of our donors were 67 and 68 years old respectively. Late complications of donor nephrectomy are rare. Individual cases of the development of glomerulonehphritisrulonephritis (Spanos et alii, 1974), haemolytic uraemic syndrome (Bergstein et alii, 61 1
THOMSON ET ALll
LIVING RELATED RENAL TRANSPLANTATION
1974), chronic pyelonephritis (Bennett and Harrison, 1974), and severe depression (Smith, 1973) have been reported. Significant long-term psychiatric disturbances have not been reported. Smith (1973) reported that all except one of 132 donors were still pleased with their donation one year after nephrectomy. Marshall (1977) reported similar findings ten years after nephrectomy. Significant psychosocial complications in donors or recipients have not been seen in our patients, even after graft failure. We have found psychiatric interviews of potential donors and recipients of considerable value in detecting potential psychiatric problems, false motives and misunderstandings about living related transplantation (Ironside, 1979): Counselling has also been available to donors after transplantation, especially if graft rejection has occurred. The loss of one kidney has not adversely affected renal function or induced hypertension in any of our donors. Single kidney GFR has increased in all donors, as has been reported in other series (Davison et alii, 1976, Donadio et a/;/, 1967, Penn et alii, 1970, Simmons et alii, 1976). This increase in GFR has been shown to occur within the first two to three weeks after nephrectomy with little subsequent increase (Krohn et ah, 1966).The degree of increase is m inverse proportion to the age of the donor. Potential long-term hazards to the living related donor kidney could be renal stones, cancer of the kidney, and trauma to the solitary kidney. We believe the risk of these occurring is acceptably remote. There is noevidence that people with a single kidney have a reduced life expectancy. In our experience and in other reported series of living related transplant subjects, the advantages of the procedure outweigh the potential harm done to the donor. In practical terms, living related transplantation can only be an adjunct to cadaveric transplantation, as not all patients have potential related donors. We believe that every attempt should be
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made to make potential transplant recipients and their families aware of living related transplantation so that it may bediscussed within the family and, it is hoped, lead to a spontaneous offer of donation. ACKNOWLEDGEMENT
We are very grateful to Professor Wallace lronside of the Department of Psychological Medicine, Monash University, for the in-depth psychiatric assessments of all living related donors and recipients. REFERENCES Advisory Committee to the Renal Transplantation Registry (1977), Transplant Proc., 9: 9. BENNETT,A. H. and HARRISON,J. H. (1974). Surg. Gynec. Obstet., 139: 894. BERGSTEIN, J., MICHAEL.A,, KJELLSTRANT, C., SIMMONS,R. and NAJARIAN,J. (1974), Transplantation, 17: 487. F. P.. BRYNGER, H., CHANTLER, R. A., DONCKERWOICKE, BRUNNER. R. A.. HATHWAY,R . A., JACOBS, C., SELWOOD. N. H.,WING. A. J. (1979) Dialysis. Transpl. Nephrol. 16: In Press. J. M., ULDALL,P. R. and WALLS,J. (1976). Brit. med. J., DAVISON. 1: 1050. C D..HUNT,J. C., TAUXE, N., HALLENDONADIO,J. V., jr, FARMER, BECK, G. A. and SHORTER. R. G. (1967), Ann. intern. Med., 66: 105. IRONSIDE, W. (1979). Opuscula rned. Tech. Lund., 20: 68. KROHN. A. G.. ODGEN.D.A and HOLMES,J. H. (1966), J. Amer. rned. Ass., 196: 322. MCLOUGHLIN,M. G. (1976), J. Urol. (Baltimore), 116: 304. MARSHALL, J. R. 1977. Am. J. Psychiaf. 134: 5. OGDEN,D A. (1967). Ann. intern. Med., 67: 998. PENN,I., HALGRIMSON, C. G.. ODGEN,0.and STARZL, T. E. (1970) Arch. Surg. 101: 226. Report of the Australia and New Zealand Dialysis and Transplant Registry (1979). private publication'. J., KJELLSTRAND, C. M.. YUNIS, E. J., SIMMONS. R. L. THOMSON, CONDIE. R. M., MAUER,S. M., BUSELMIER, J. J. and 321. NAJARIAN, J. S. (1976), Lancet, 1: SMITH,M. J. V. (1973), J. Urol. (Baltimore), 110: 158. SMITH,R. B., WALTON,K.. LEWIS, E. L., PERDUE,G. D., jr and HERNDON, E. G. (1972) J. surg. Res., 3: 199. SPANOS,P. K., SIMMONS,R. L., LAMPE,E., RATTAZZI. L. G.. KJELLSTRAND. C. M., GOETZ.F. C. and NAJARIAN,J. S (1974). Surgery, 76: 741 'Report obtainable trom Dr A P. S Bhsnsy. Hon. Sec.. Australia and New Zealand Dialysis and Transplant Registry, The Queen Elizabeth Hospital,Woodville. South Australia. 5011
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