CADAVERIC TRANSPLANTS

By KENNETH OWEN, M.S., F.R.C.S.

St Mary’s Hospital, London

IT is intended in this short paper to discuss some of the problems peculiar to transplantation of cadaveric kidneys and the results obtained in a series of forty-five such transplants at St Mary’s Hospital.

It was decided to use cadaveric kidneys at the beginning of this series in view of the potential risk to live donors and the uncertainty of results. In patients with irreversible renal failure it was felt that the use of cadaveric transplants would stand some chance of success and there would be no regret at the very great sacrifice of a live donor’s kidney in cases that failed. The only other advantage of cadaveric transplants over the use of live donors is that the vascular dissection can include segments of the aorta and vena cava which sometimes facilitates the vascular anastomosis. This is of particular use where double renal arteries arise close together from the aorta, as a segment of aorta can be taken including both vessels and anastomosed as a patch into the recipient iliac artery.

Against these advantages there are a formidable number of disadvantages. The donor is unrelated and therefore offers a reduced chance of genetic similarity to the recipient which is provided by using close blood relatives. Most methods of tissue typing take too long a time to enable this to be done in the short period between a donor becoming moribund and the transplant being performed. There is little opportunity to do detailed renal function tests or to study the renal anatomy of the donor kidney before transplantation. When removing a kidney from a cadaver rapid dissection is necessary, and this does not allow of the meticulous dissection of the delicate ureteric blood supply that is possible when doing a nephrectomy on a live donor. The transplantation must be done as an emergency operation, often at difficult times when it may not be possible to assemble a complete team. The most formidable problem with cadaveric kidneys is the liability to acute tubular necrosis in view of the period of ischamia that must result between the donor’s death and restoration of a vascular supply. The risks of tubular necrosis are also increased by prolonged hypotension and possibly other incidents immediately before death in the donor. The risk of tubular necrosis is lessened by avoiding the use of donors who have had severe hypotension and also by cooling the kidney and using an osmotic diuretic. It is possible that many of the other disadvantages of cadaveric kidneys may be reduced in the future by the development of a satisfactory method of kidney storage and by the detelopment of improved tissue typing techniques. The methods of pre-operative preparation and post- operative treatment have recently been described (Mowbray et af., 1965). The recipients have varied in age from 8 to 46 years and selection has been based upon major blood group compatibility arid exclusion of gross infective lesions which might be potentiated by the azathioprine and steroid regime used in immunosuppression. The patients have usually been maintained on peritoneal dialysis pre-operatively, and also, when necessary because of tubular necrosis, in their post-operative period. Pre-operative nephrectomy has been performed when indicated by uncontrollable hypertension or the presence of large polycystic kidneys which might interfere with the transplantation operation.

Immunosuppression.-The immunosuppressive regime was by azathioprine which was given in small doses (1 to 1.5 mg./kg.) pre-operatively. Immediately after operation the dose was increased to 5 mg. per kg. and increased further on the diagnosis of a rejection episode, when a single injection of 400 pg. of actinomycin C was also given. This regime was supplemented

Read at the Twenty-second Annual Meeting of the British Association of Urological Surgeons at Manchester, June 1966.

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by hydrocortisone at the time of operation and a daily maintenance dose of 20 to 30 mg. of Prednisone, increased to 200 mg. on evidence of rejection.

Donor Kidneys.-The donor kidneys were from patients dying of non-communicable disease in whom there was no evidence of renal disease, prolonged hypotension or other factors which might increase the risk of acute tubular necrosis. The age range was from 15 to 44 years. The majority of the donors have come from a number of sources, mostly neurosurgical units situated some distance from St Mary’s Hospital, a factor influencing the ischamia time and cooling method. Responsibility for deciding upon death or the advisability of continuing resuscitation measures has rested upon the clinician in charge of the patient. Twenty million units of heparin were given immediately after death intravenously and the kidney dissection was then done through an abdominal incision under full asepsis. The ureters were dissected from the pelvic brim upwards with a block of surrounding tissue as a precaution against injury to the blood supply. The removal of the kidneys has taken an average time of eighteen minutes, and immediately after removal they have been put in a sterile nylon bag and immersed in an ice and water mixture for transport to the transplantation theatre, where the recipients have been anasthetised and the iliac vessels exposed.

Operative Procedure.-Some further dissection of the renal vessels has usually been necessary and during this time the kidney is bathed with ice-cold saline. The transplantation is usually done in the now conventional iliac fossa procedure, although end-to-side anastomosis of renal artery to external or common iliac has been used as an alternative to end-to-end anastomosis to the internal iliac artery. Immediately before release of the clamps an injection of mannitol has been given in order to reduce the risk of tubular necrosis. The ureteric anastomosis is made to the bladder either by an oblique tunnel and mucosa-to-mucosa anastomosis, or by pulling the donor ureter through a short lower segment of the recipient ureter and then making the anastomosis at the normal ureteric orifice. This procedure has been used only where the recipient ureter was of adequate size and there had not been evidence of reflux. It has been found necessary to use a polyvinyl tube in the ureter in these patients, as in those cases where any degree of tubular necrosis occurs there is a low rate of urine flow and debris is liable to obstruct the ureter.

Results.-The following are the results of this series :- Cadaver ic Transplants, 1 96 3 - 6 5-

Number of patients . . 45 Number of transplants . . 51 Number alive . . 21 Deaths . . 24

The following are the current follow-up periods for the twenty-one survivors. Over two years . . 3 One to two years . . 4 Under one year . . 14

The three cases surviving over two years all have adequate renal function. Two of them have normal blood urea and a creatinine clearance of over 100 while renal biopsy shows no evidence of late rejection.

Three of the patients who died had a short period of normal life out of hospital after their transplantation operation and the causes of death in these patients, a fulminating pneumonia in one, a renal pelvis leak in another and complications of esophageal stricture in the third, have been thought to be unrelated to the use of a cadaveric donor, and deaths which might have occurred in any transplant series.

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It is difficult to analyse in the limited time available the deaths of the remaining twenty-five cases but in a further four patients the cause of death, while probably potentiated by the drug treatment, and in particular the steroid therapy, would appear to be unrelated to the donor kidney or any rejection phenomenon. These causes have been hyperoxaluria, coronary thrombosis, acute appendicitis, and peritoneal infection following perforation of a peptic ulcer.

The remaining seventeen patients who died had a multiplicity of complications which is difficult to analyse, except that the onset of one serious complication such as acute tubular necrosis, drug toxicity or a surgical complication such as a vessel thrombosis or a ureteric thrombosis, has usually led to a diverse series of major medical and surgical illnesses. The final cause of death in fifteen cases has been infection, the hazards of which have been described in many other series.

These infections have included, besides local staphylococcal and pyocyaneus lesions leading to septicaemia, fungus and virus infections, aspergillosis, candidiasis and cytomegalovirus infection. It is often difficult to determine the starting point of deterioration in these complex illnesses. A ureteric leak for instance may be due to technical failure in removing the donor kidney, or in performing the transplantation because of injury to the blood supply, or a ureteric lesion may be the result of a rejection episode or of localised infection. However, the major common factors which would seem to have been responsible either singly or combined for the unsuccessful results have been severe tubular necrosis in six patients, secondary operations on eleven occasions, vascular thromboses or leaks on six occasions, and ureteric leaks or clot obstruction of the ureter on eight occasions.

Some of these complications are undoubtedly due to the hazards which have been discussed of cadaveric kidneys, but the overall results together with the complete absence of donor risk and the limited ethical problems, provided the transplantation team is not responsible for deciding on the moment of death in the donor, offer a considerable encouragement to the continued use of this procedure. It is probable that improvement in technique, particularly of renal storage, will reduce the hazards. and the limiting factor then is likely to be the supply of suitable kidneys.

REFERENCE

MOWBRAY, J. F., COHEN, S. L., DOAK, P. B., KENYON, J. R., OWEN, K., PERCIVAL, A., PORTER, K. A., and PEART, W. S. (1965). Brit. med. J., 2, 1387.