Renal transplantation is the preferred treatment for many patients with end-stage renal disease because it provides a better quality of life for them than dialysis. Transplantation releases patients from the dietary and fluid restrictions of dialysis and the physical constraints imposed by the need to dialyse. It is also more cost-effective than dialysis.
In the UK, around 8 0—100 people per million population develop end-stage renal disease and the incidence increases with age. The causes of end-stage renal disease are numerous and include the following:
• diabetic nephropathy;
• hypertensive nephrosclerosis;
• renal vascular disease;
• polycystic disease;
• obstructive uropathy;
• systemic lupus erythematosus;
• analgesic nephropathy;
• metabolic diseases (oxalosis, amyloid).
Frequently, the primary cause of end-stage renal disease remains uncertain. For renal transplantation, as for other types of organ transplantation, careful patient selection is essential. Before acceptance as suitable candidates on the transplant waiting list, a transplant surgeon and nephrologist should formally assess all patients. A significant number of patients is likely to be considered unsuitable for renal transplantation because of major comorbid disease, especially cardiovascular disease. In the UK around half of the dialysis population are currently on the waiting list for renal transplantation.
The nature of the primary renal disease does not generally affect the decision to proceed to transplantation. Some of the glomerulonephritides (notably focal segmental glomerulosclerosis) may subsequently affect a transplanted kidney but this only occasionally results in failure of the graft in the first
5years. In the case of primary oxalosis, combined kidney and hepatic transplantation is usually undertaken to eliminate the metabolic defect and thereby prevent early graft failure from the formation of further oxalate stones.
The age of patients with end-stage renal failure accepted for dialysis has gradually risen over the last two decades and in the UK the mean age of patients starting dialysis is around 70 years. There is no absolute upper age limit to renal transplantation but inevitably older patients (over the age of 65 years) are less likely to be considered suitable candidates because of major cardiovascular and other comorbid disease.
A careful assessment of comorbid disease that might significantly reduce the chances of successful outcome after transplantation is essential. Rigorous evaluation of the cardiovascular system is particularly important. Cardiovascular disease is very common in the dialysis population, especially those with diabetes, and is the major cause of death after transplantation. Before listing patients for transplantation it is important to ensure that their urinary tract is functional and that there is no need for corrective urological surgery. Only when there is long-standing renal sepsis, or in the case of very large polycystic kidneys which intrude into both iliac fossae, is native nephrectomy required before transplantation can be undertaken. Finally, the prospective transplant recipient must be judged likely to comply with immunosuppressive therapy.
Immunosuppressive therapy increases the risk of infection and malignancy. Consequently, pre-existing malignancy is an absolute contraindication, and even after curative treatment transplantation should not be considered for at least 3 years. Similarly, the presence of active infection is an absolute contraindication to transplantation.
Technique of renal transplantation
The transplant kidney is placed in the iliac fossa, in the retroperitoneal position, leaving the native kidneys in situ. After induction of general anaesthesia a central venous line and a urinary catheter are inserted. It is helpful to distend the bladder with saline containing methylene blue to allow it to be identified with certainty prior to ureteric implantation. A curved incision is made in the lower abdomen and after dividing the muscles of the abdominal wall, the peritoneum is swept upwards to expose the iliac vessels. These are dissected free so that they can be controlled with vascular clamps. The kidney is then removed from ice and the donor renal vein is anastomosed end-to-side to the external iliac vein. The donor renal artery on a Carrel patch of donor aorta is then anastomosed end-to-side to the external iliac artery . If the donor renal artery lacks an aortic patch, as in the case of a living donor transplant, it is usually preferable to anastomose the donor artery end-to-end to the recipient internal iliac artery . While the vascular anastomoses are being undertaken the kidney is kept cold by application of ice. Following completion of the venous and arterial anastomoses the vascular clamps are removed and the kidney is allowed to reperfuse with blood.
The ureter, which is kept reasonably short to avoid the risk of distal ischaemia, is then anastomosed to the bladder. This is most often achieved by direct implantation of the ureter into the dome of the bladder with a mucosa to mucosal anastomosis followed by closure of the muscular wall of the bladder over the ureter to create a short tunnel —the Lich—Gregoire technique. A double-I ureteric stent is often left in situ, especially if there are technical difficulties, and removed after several weeks during cystoscopy. Alternatively, the ureter may be implanted by the Leadbetter—Politano technique where the bladder is opened to allow the creation of a submucosal antireflux tunnel. Before closing the transplant wound it is important to ensure that the kidney is lying in a satisfactory position without kinking or torsion of the vessels. In small children receiving an adult donor kidney the abdomen is opened through a midline incision and the graft is placed intra-abdominally with anastomosis of the renal vessels to the aorta and vena cava.
The incidence of vascular complications after renal trans plantation is quite low. Renal artery thrombosis occurs it approximately 1 per cent of cases. Renal vein thrombosis is more common (up to 5 per cent of cases), and although sometimes owing to technical error, the aetiology is uncertain. It presents as sudden pain and swelling at the sit of the transplant and the diagnosis is confirmed by Doppler ultrasound. Urgent surgical exploration is indicated and it most cases transplant nephrectomy is required. The incidence of renal vein thrombosis can be minimized by giving low dose heparin or aspirin prophylaxis. Renal artery stenosi presents late (often years) after transplantation with increasing hypertension and decreasing renal function. It may occur in up to 10 per cent of grafts, is diagnosed by angiography and is best treated by angioplasty rather than open surgery.
Urological complications occur in up to 10 per cent o patients in the early post-transplant period, but their incidence can be reduced by leaving a temporary ureteric stent b situ. Urinary leaks result from technical errors at the ureteric anastomosis or because of ureteric ischaemia. They present with discomfort and leakage of urine from the wound am usually require surgical intervention and reimplantation o the ureter into the bladder or anastomosis of the transplant ureter to the native ureter. Obstruction of the transplant ureter may occur early or late. Causes of obstruction include technical error, external pressure from a haematoma or lymphocele and ischaemic stricture. It presents with painless deterioration in transplant function and is confirmed by demonstrating hydronephrosis and ureteric dilatation on ultrasound examination. Initial treatment is by percutaneous antegrade nephrostomy and insertion of a stent. Surgical intervention may be needed to treat strictures that are not amenable to correction by ballon dilatation.
Peritransplant lymphoceles are usually asymptomatic, but occasionally they become large enough to cause ureteric obstruction or oedema of the leg. If they persist, surgical intervention may be needed to drain them into the peritoneal cavity. This can often be achieved by an ultrasound-guided laparoscopic approach.
Investigation of graft dysfunction
Graft dysfunction during the early postoperative period is a common problem. Possible causes are:
• acute tubular necrosis;
• arterial/venous thrombosis;
• urinary leak/obstruction;
• calcineurin blocker toxicity;
• hyperacute/accelerated acute rejection.
Delayed graft function as a result of acute tubular necrosis occurs in up to 50 per cent of cadaveric kidney transplants but is uncommon following living donor transplantation. Often the recipient produces significant volumes of urine from their native kidneys, making the diagnosis of delayed function more difficult. The incidence of delayed function can be minimised by optimising donor management before kidney procurement and by reducing the cold ischaemia time by avoiding unnecessary delay before implantation. As a first step in the management of early graft dysfunction, the urinary catheter should be irrigated in case it is occluded by a blood clot. Hypovolaemia, if present, should be corrected with the aid of central venous pressure (CVP) monitoring. A Doppler ultrasound examination of the graft is the single most important investigation as it allows exclusion of vascular thrombosis and urinary obstruction as causes of graft dysfunction. In addition, a renal radionucleotide scan is often performed and provides information on renal perfusion and excretion. If graft dysfunction is still present after several days it is usual to perform an ultrasound-guided needle biopsy of the kidney to ensure that graft rejection is not present. To avoid the risk of nephrotoxicity, calcineurin blockers are often withheld or given in reduced doses until graft function is established. If calcineurin blockers are not withheld, it is important to monitor their blood levels carefully to avoid nephrotoxicity. Acute tubular necrosis usually resolves within the first 4 weeks of transplantation but a small number of grafts suffers primary nonfunction.
Allograft dysfunction developing late (> 1 month after transplant) may be due to:
• acute/chronic rejection;
• drug toxicity;
• ureteric obstruction (lympocoele/ureteric stricture);
• recurrent disease;
Blood levels of cyclosporine or tacrolimus are assessed to ensure that they are not unduly elevated, and ultrasound examination of the graft is performed to determine whether ureteric obstruction is present. If obstruction is detected, it is further investigated by percutaneous antegrade pyelography. Ureteric stenosis may be amenable to balloon dilatation but a long stricture may require reimplantation of the transplant ureter (or renal pelvis) into the bladder or into the native ureter. If there is uncertainty about the cause of graft dysfunction, transplant biopsy should be performed to establish whether allograft rejection is present.
Outcome after transplantation
The results of organ transplantation are generally defined in terms of patient and graft survival. Patient survival after cadaveric renal transplantation is > 90 per cent at 1 year and > 80 per cent at 5 years. Graft survival is around 85 per cent at 1 year and 65 per cent at 5 years. Graft survival after a second transplant is only marginally worse than after a first graft. After living related kidney transplantation, overall graft survival is > 90 per cent at 1 year and > 80 per cent at 5 years. Graft survival after transplantation can also be expressed in terms of the half-life of the graft. The half-life for grafts obtained from living donors is substantially longer than for cadaveric grafts:
• cadaveric grafts — 7 years;
• living unrelated — 9 years;
• living haploidentical — 12 years;
• living identical — 24 years.
If a kidney transplant fails late after transplantation, transplant nephrectomy may be indicated, especially if the graft is causing symptoms. The operation is undertaken via the original wound but the kidney is dissected free from the renal capsule and delivered into the wound. The renal vessels are then ligated and divided, leaving behind the original vascular anastomosis.
In addition to graft survival, it is important to consider the extent to which transplantation improves the physical and mental well-being of the patient, and allows them to lead a satisfactory social life. As other types of solid organ transport, successful kidney transplantation undoubtedly leads to a substantial improvement in quality of life. However, whereas some recipients return to a normal or near-normal life, others fare much less well, and for the group overall the quality of life after transplantation falls short of that seen in normal healthy individuals. Organ transplantation is best regarded, therefore, as an effective form of therapy rather than a complete cure.
No comments yet.