Kidney transplantation

The donor kidney is typically placed inferior of the normal anatomical location.

Kidney transplantation or renal transplantation is the organ transplant of a kidney in a patient with end-stage renal disease. Kidney transplantation is typically classified as deceased-donor (formerly known as cadaveric) or living-donor transplantation depending on the source of the recipient organ. Living-donor renal transplants are further characterized as genetically related (living-related) or non-related (living-unrelated) transplants, depending on whether a biological relationship exists between the donor and recipient.

History

The first successful kidney transplantations were done in 1954 in Boston and Paris. The transplantation was done between identical twins, to eliminate any problems of an immune reaction. Kidney transplants were slow to catch on, for example the first kidney transplant in the United Kingdom did not occur until 1960 when Michael Woodruff performed one between identical twins in Edinburgh. Until the routine use of medications to prevent and treat acute rejection, introduced in 1964, deceased donor transplantation was not performed. The kidney was the easiest organ to transplant, tissue-typing was simple, the organ was relatively easy to remove and implant, live donors could be used without difficulty, and in the event of failure, kidney dialysis was available from the 1940s. Tissue-typing was essential to the success, early attempts in the 1950s on sufferers from Bright's disease had been very unsuccessful. The transplantation was done by Dr. Joseph E. Murray, who received the Nobel Prize for Medicine in 1990. The donor is still alive as of 2005; the recipient died eight years after the transplantation.

Indications

The indication for kidney transplantation is end-stage renal disease (ESRD), regardless of the primary cause. Common diseases leading to ESRD include hypertension, infections, diabetes mellitus and glomerulonephritis; genetic causes include polycystic kidney disease. The majority of renal transplant recipients are on hemodialysis at the time of transplantation. However, individuals with chronic renal failure who have a living donor available often elect to undergo transplantation before dialysis is needed.

Contraindications

There is little data on transplant recipients over age 80, and many centers will not transplant such patients. However this will likely change soon. Recent cancer, active substance abuse, or failure to adhere to prescribed medical regimens may make someone ineligible for a transplant.

Sources of Kidneys

About half of kidney transplants are from living donors. Since medication to prevent rejection is so effective, donors do not need to be genetically similar to their recipient. The other half are from deceased donors.

Deceased donors can be divided in two groups:

• Braindead (BD) donors
• Non-heart beating (NHB) donors

Although the brain death (or 'heart beating') donors are considered dead, the donor's heart continues to pump and maintain the circulation. This makes it possible for surgeons to start operating while the organs are still being perfused. During the operation, the aorta will be cannulated, after which the patients' blood will be replaced by an ice-cold storage solution, such as UW (Viaspan), HTK or Perfadex (depending on which organs are transplanted, more than one solution may be used simultaneously). Due to the temperature of the solution (and since large amounts of cold NaCl-solution are poured over the organs for a rapid cooling of the organs), the heart will stop pumping.

Non-heart beating donors are patients who do not meet the braindead criteria, but have no chance of recovery whatsoever. In this procedure, the treatment is being abstained (mechanical ventilation is shut off). Usually, a certain amount of minutes after death has been pronounced, the patient is rushed to the operating theatre, where the organs are harvested, after which the storage solution is flushed through the organs itself. Since the blood is no longer being circulated, coagulation must be prevented with relatively large amounts of anti-coagulation agents, such as heparin.

Kidneys from braindead donors are generally of a superior quality, since they have not been exposed to 'warm ischemia' (the time between the stopping and the kidney being cooled).

Compatibility

The donor and recipient have to be ABO blood group compatible, and should ideally share as many HLA and "minor antigens" as possible. This decreases the risk of transplant rejection and need for dialysis and a further transplant. The risk of rejection after transplant may be reduced if the donor and recipient share as many HLA antigens as possible, if the recipient is not already sensitized to potential donor HLA antigens, and if immunosuppressant levels are kept in an appropriate range. In the United States, up to 17% of all deceased donor kidney transplants have no HLA mismatch.

Procedure

Since in most cases the barely functioning existing kidneys are not removed, the kidney is usually placed in a location different from the original kidney (often in the iliac fossa), and as a result it is often necessary to use a different blood supply:

• The renal artery of the kidney, previously branching from the abdominal aorta in the donor, is often connected to the external iliac artery in the recipient.
• The renal vein of the new kidney, previously draining to the inferior vena cava in the donor, is often connected to the external iliac vein in the recipient.

Kidney-pancreas transplant

Also see Pancreas transplantation.

Occasionally, the kidney is transplanted together with the pancreas. This is done in patients with diabetes mellitus type I, in whom the diabetes is due to destruction of the beta cells of the pancreas and in whom the diabetes has caused renal failure (diabetic nephropathy). This is almost always a deceased donor transplant. Only a few living donor (partial) pancreas transplants have been done. For individuals with diabetes and renal failure, the advantages of earlier transplant from a living donor are approximately equal to the risks of continued dialysis until a combined kidney and pancreas are available from a deceased donor.

These procedures are commonly abbreviated as follows::

• "SKP transplant", for "simultaneous kidney-pancreas transplant"
• "PAK transplant", for "pancreas after kidney transplant"

(By contrast, "PTA" refers to "Pancreas transplant alone".)

The pancreas can come from a deceased donor as well as a living one. A patient can either get a living kidney followed by a donor pancreas at a later date (PAK, or pancreas-after-kidney) or a combined kidney-pancreas from a donor (SKP, simultaneous kidney-pancreas.)

Transplanting just the islet cells from the pancreas is still in the experimental stage, but it does show promise. This involves taking a deceased donor pancreas, breaking it down, and extracting the islet cells that make insulin. The cells are then injected through a catheter into the recipient and they generally lodge in the liver. The recipient still needs to take immunosuppressants to avoid rejection, but no surgery is required. Most people need 2 or 3 such injections, and many are not completely insulin-free.

Post Operation

The transplant surgery lasts about 3 hours. The donor kidney will be placed in the lower abdomen. The blood vessels from the donor kidney will be connected to arteries and veins in the recipient's body. When this is complete, blood will be allowed to flow through the kidney again, so the ischaemia time is minimized. In most cases, the kidney will soon start producing urine. Since urine is sterile, this has no effect on the operation. The final step is connecting the ureter from the donor kidney to the bladder.

The new kidney usually begins functioning immediately after surgery, but this may -depending on the quality of the organ- take a few days. Hospital stay is typically for 4 to 7 days. If complications arise, additional medicines may be administered to help the kidney produce urine.

Medicines are used to suppress the immune system from rejecting the donor kidney. These medicines must be taken for the rest of the patient's life. The most common medication regimen today is : tacrolimus, mycophenolate, and prednisone. Some patients may instead take ciclosporin, rapamycin, or azathioprine.

Acute rejection occurs in 10% to 25% of people after transplant during the first 60 days. Rejection does not mean loss of the organ, but may require additional treatment.[1]

Complications

Problems after a transplant may include:

• Transplant rejection (hyperacute, acute or chronic)
• Infections and sepsis due to the immunosuppressant drugs that are required to decrease risk of rejection
• Post-transplant lymphoproliferative disorder (a form of lymphoma due to the immune suppressants)
• Imbalances in electrolytes including Calcium and Phosphate which can lead to bone problems amongst other things
• Other side effects of medications including gastrointestinal inflammation and ulceration of the stomach and esophagus, hirsutism (excessive hair growth in a male-pattern distribution), hair loss, obesity, acne, diabetes mellitus (type 2), hypercholesterolemia and others.
• The average time a kidney will work is 10-15 years. When a transplant fails a patient may opt for a second transplant, and may have to return to dialysis for some time.

Prognosis

Recent studies have indicated that kidney transplantation is a life-extending procedure. The typical patient will live 10-15 years longer with a kidney transplant than if they stay on dialysis. The years of life gained is greater for younger patients, but even 75 year-olds (the oldest group for which there is data) gain an average of 4 years of life with a kidney transplant. People generally have more energy, a less restricted diet, and fewer complications with a kidney transplant than if they stay on dialysis.

Some studies seem to suggest that the longer a patient is on dialysis before the transplant, the less time the kidney will last. It is not clear why this occurs, but it underscores the need for rapid referral to a transplant program. Ideally, a kidney transplant should take place before the patient starts on dialysis (pre-emptive.)

At least three professional athletes have made a comeback to their sport after receiving a transplant—NBA players Sean Elliott and Alonzo Mourning, and New Zealand rugby legend Jonah Lomu.

Kidney transplant requirements

Kidney transplant requirements vary from program to program and country to country. Many programs place limits on age (i.e. the person must be less than 69 years old when put on the waiting list) and require that one must be in good health (aside from the kidney disease).

Significant cardiovascular disease, incurable terminal infectious diseases (i.e. AIDS) and cancer often are transplant exclusion criteria. In addition, candidates are typically screened to determine if they will be compliant with their medications, which is essential for survival of the transplant. People with mental illness and/or significant on-going substance abuse issues may be excluded.

Kidney transplant statistics

Country	Cadaveric transplants	Living donor transplants	Total transplants
Canada	724	388	1,112 (in 2000)	[2]
France	1,991	136	2,127 (in 2003)	[3]
Italy	1,489	135	1,624 (in 2003)
Spain	1,991	60	2,051 (in 2003)
United Kingdom	1,297	439	1,736 (in 2003)	[4]
United States	8,670	6,468	15,138 (in 2003)	[5]
Pakistan - SIUT	1600

Australian Aboriginal activist Charles Perkins, is the longest surviving receiver of a Kidney transplant. living 28 years on his donor organ.

• Sind Institute of Urology and Transplantation(SIUT - www.siut.org) is the only hospital in the world giving free of cost treatment for Transplantation.

References

• Brook NR, Nicholson ML (2003). "Kidney transplantation from non heart-beating donors". Surgeon. 1 (6): 311–22. PMID 15570790.

External links

• MedlinePlus Overview kidneytransplantation
• med/2604 at eMedicine
• Patient-oriented summary at emedicinehealth.com
• Overview at mvm.ed.ac.uk - undergraduate created but high quality
• Kidney transplantation and renal disease
• The Kidney Patient Guide
• Sindh Institute of Urology and Transplantation
• Immune Tolerance Network