Kidney Transplantation

There are over 2,000 kidney transplants performed throughout the Middle East each year. Kidney transplants account for the largest number of the solid organs transplanted and patients with renal failure or kidney diseases can get on the transplant waiting list if their illness requires one. The initial kidney transplant operations were performed in the 1950s. A successful kidney transplant is a more effective treatment for kidney failure than either peritoneal dialysis or haemodialysis. However, not everyone is suitable for transplantation, and not everyone who is suitable is suitable all the time.

Before a transplant can take place, it is necessary to find an appropriate donor kidney, which may not be easy. Transplanted kidneys may come from living donors, including from patients who have been declared brain-stem dead. The transplants from non-living donors are called cadaveric transplants. Such transplants may be arranged in hospital intensive care units, for example following spontaneous brain haemorrhage or a road traffic accident.

The operation itself is straightforward, with a good success rate. After a transplant, patients will need to take drugs (immunosuppressant agents) daily for the rest of their lives to prevent their new kidney from being rejected. There are a number of different immunosupressant agents. Most patients will usually take about three of these. The best combination will be chosen to suit the individual. If a transplant fails, patients can go back to dialysis or possibly have another transplant.

Improved patient management techniques including newer immunosuppressant drugs have led to improved outcomes. In 1985 the survival rate was 70 per cent at one year after the transplant. By 1997 this one-year survival rate was up to 85 per cent. The one-year survival rates for livers, hearts and lungs in 1997 were 75, 84 and 69 percent, respectively, in the UK.

Nowadays, kidney transplant recipients can look forward to many years with the enhanced lifestyle which freedom from dialysis brings. There are many patients whose transplants have survived into their second or even their third decade. Despite the introduction of Donor Cards, the waiting lists for transplants is growing as demand outstrips the supply of organs.

Causes and Risk Factors

The indication for kidney transplantation is end-stage renal failure (ESRF), also called end-stage renal disease (ESRD). End-stage renal failure is reached when the kidneys are functioning at about 10% of the normal level, and the patient is showing the signs and symptoms of uraemia. This level of kidney function is unable to sustain life without artificial support. A wide variety of conditions can result in ESRF. The main ones are Diabetes (more than 30% of cases), Hypertension, Glomerulonephritis and Cystic Kidney diseases.

Diagnosis and Screening

End-stage renal disease (ESRD) occurs when the kidneys are no longer able to function at a level that is necessary for day to day life. It usually occurs as chronic renal failure progresses to the point where kidney function is less than 10% of baseline. At this point, the kidney function is so low that without dialysis or kidney transplantation, complications are multiple and severe, and death will occur from accumulation of fluids and waste products in the body.

Prevention

Treatment of Chronic Renal Failure may delay or prevent progression to ESRD. Some cases may not be preventable.

Signs and tests

the patient usually has a long history of chronic renal failure, which has progressed. The person may have required dialysis to control chronic renal failure. The urine volume may decrease or urine production may stop totally. Signs of complications commonly are present:

• Creatinine level is chronically high.
• Creatinine clearance is very low.

Management

Immunosuppression and transplantation:
The body’s immune system identifies a transplanted organ as foreign and produces an immune response in an attempt to reject it. To manage this, transplant recipients take immunosuppressants (powerful drugs to suppress their immune system) usually for the rest of their lives. Immunosuppressants prevent rejection in 60-90% of all transplant cases.

Though rejection may occur at any time, the risk is highest during the first three months after surgery (acute rejection). Careful post-operative monitoring is required as early signs of rejection may be asymptomatic; when they occur, immunosuppression is increased until the rejection episode is reversed. All acute rejection episodes damage the graft; in some instances, the damage is reversible. This damage may affect the life of the graft.

Apart from organ rejection, there is a long-term risk of complications associated with immunosuppression including infection, hypertension, and renal insufficiency associated with calcineurin inhibitor therapy (a class of immunosuppressive agents).

Acute rejection rates are now less than 20% and as low as 10% in some studies. Thus, medical focus has shifted to improving long-term graft survival and reducing the side effects of immunosuppressive agents. Researchers at Roche are working to develop efficacious and low-toxicity long-term immunosuppressive regimes.

Types of immunosuppressant therapy:
Cortisone was the only available immunosuppressant in 1951. It offered limited efficacy and unpleasant steroidal side effects. Azathioprine, introduced in 1959, was found to be better tolerated and more effective. A combination of azathioprine and the steroid prednisolone became the ‘gold standard’ of immunosuppressant therapy until the late 1970s. However, the use of high doses of prednisolone caused major steroidal side effects such as Cushings disease, loss of bone density, oedema and obesity.

In the 1980s, the introduction of the calcineurin inhibitor (CNI), cyclosporine, was a significant milestone in the evolution of immunosuppressant therapy. By preventing the activation of T cells, cyclosporine improved one-year graft survival rates from 64% to 78%2. By the late 80s and early 90s, tacrolimus was developed with a comparable method of action to cyclosporine.

However, as well as being toxic to the kidneys, patients taking cyclosporine or tacrolimus have been reported to have high incidence of hypertension, hyperlipidaemia and diabetes. The combination of serious side effects and the on going loss of transplanted kidneys led Roche to develop a new immunosuppressant, mycophenolate mofetil, known as CellCept.

CellCept has fewer side effects than azathioprine and is not nephrotoxic like calcineurin inhibitors.