Kidney transplantation
Patient selection
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:
• glomerulonephritis;
• diabetic nephropathy;
• hypertensive
nephrosclerosis;
• renal vascular disease;
• polycystic disease;
• pyelonephritis;
• 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
5
years. 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 (Fig. 11.15a). 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 (Fig.
11.15b). 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 (Fig.
11.16). 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
Urological
complications
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.
Lymphocele
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;
• infection.
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
• 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.