Indications

The indication for kidney transplantation is end-stage renal disease (ESRD), regardless of the primary cause. This is defined as a glomerular filtration rate <15ml/min/1.73 sq.m. Common diseases leading to ESRD include malignant hypertension, infections, diabetes mellitus, and focal segmental glomerulosclerosis; genetic causes include polycystic kidney disease, a number of inborn errors of metabolism, and autoimmune conditions such as lupus. Diabetes is the most common cause of kidney transplantation, accounting for approximately 25% of those in the US. The majority of renal transplant recipients are on dialysis (peritoneal dialysis or hemofiltration) at the time of transplantation. However, individuals with chronic renal failure who have a living donor available may undergo pre-emptive transplantation before dialysis is needed.

Contraindications and requirements

Contraindications include both cardiac and pulmonary insufficiency, as well as hepatic disease. Concurrent tobacco use and morbid obesity are also among the indicators putting a patient at a higher risk for surgical complications.

Kidney transplant requirements vary from program to program and country to country. Many programs place limits on age (e.g. the person must be under a certain age to enter the waiting list) and require that one must be in good health (aside from the kidney disease). Significant cardiovascular disease, incurable terminal infectious diseases 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.

HIV was at one point considered to be a complete contraindication to transplantation. There was fear that immunosuppressing someone with a depleted immune system would result in the progression of the disease. However, some research seem to suggest that immunosuppressive drugs and antiretrovirals may work synergistically to help both HIV viral loads/CD4 cell counts and prevent active rejection.

Deceased donors

Deceased donors can be divided in two groups:

• Brain-dead (BD) donors
• Donation after Cardiac Death (DCD) donors

Although brain-dead (or "beating heart") 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 donor’s 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, the heart will stop pumping.

"Donation after Cardiac Death" donors are patients who do not meet the brain-dead criteria but, due to the unlikely chance of recovery, have elected via a living will or through family to have support withdrawn. In this procedure, treatment is discontinued (mechanical ventilation is shut off). After a time of death has been pronounced, the patient is rushed to the operating room where the organs are recovered. Storage solution is flushed through the organs. Since the blood is no longer being circulated, coagulation must be prevented with large amounts of anti-coagulation agents such as heparin. Several ethical and procedural guidelines must be followed; most importantly, the organ recovery team should not participate in the patient’s care in any manner until after death has been declared.

Compatibility

If plasmapheresis or IVIG is not performed, the donor and recipient have to be ABO blood group compatible. Also, they should ideally share as many HLA and "minor antigens" as possible. This decreases the risk of transplant rejection and the need for another transplant. The risk of rejection may be further reduced if the recipient is not already sensitized to potential donor HLA antigens, and if immunosuppressant levels are kept in an appropriate range. The level of sensitization to donor HLA antigens is determined by performing a panel reactive antibody test on the potential recipient. In the United States, up to 17% of all deceased donor kidney transplants have no HLA mismatch. However, HLA matching is a relatively minor predictor of transplant outcomes. In fact, living non-related donors are now almost as common as living (genetically)-related donors.

In the 1980s, experimental protocols were developed for ABO-incompatible transplants using increased immunosuppression and plasmapheresis. Through the 1990s these techniques were improved and an important study of long-term outcomes in Japan was published ([1]). Now, a number of programs around the world are routinely performing ABO-incompatible transplants.^[19]

Procedure

In most cases the barely functioning existing kidneys are not removed, as this has been shown to increase the rates of surgical morbidities. Therefore, the kidney is usually placed in a location different from the original kidney, often in the iliac fossa, so 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.

There is disagreement in surgical textbooks regarding which side of the recipient’s pelvis to use in receiving the transplant. Campbell’s Urology (2002) recommends placing the donor kidney in the recipient’s contralateral side (i.e. a left sided kidney would be transplanted in the recipient’s right side) to ensure the renal pelvis and ureter are anterior in the event that future surgeries are required. In an instance where there is doubt over whether there is enough space in the recipient’s pelvis for the donor’s kidney the textbook recommends using the right side because the right side has a wider choice of arteries and veins for reconstruction. Smith’s Urology (2004) states that either side of the recipient’s pelvis is acceptable, however the right vessels are “more horizontal” with respect to each other and therefore easier to use in the anastomoses. It is unclear what is meant by the words “more horizontal”. Glen’s Urological Surgery (2004) recommends putting the kidney in the contralateral side in all circumstances. No reason is explicitly put forth; however, one can assume the rationale is similar to that of Campbell’s—to ensure that the renal pelvis and ureter are most anterior in the event that future surgical correction becomes necessary.

Post operation

The transplant surgery takes about three hours. The donor kidney will be placed in the lower abdomen and its blood vessels connected to arteries and veins in the recipient’s body. When this is complete, blood will be allowed to flow through the kidney again. The final step is connecting the ureter from the donor kidney to the bladder. In most cases, the kidney will soon start producing urine.

Depending on its quality, the new kidney usually begins functioning immediately. Living donor kidneys normally require 3–5 days to reach normal functioning levels, while cadaveric donations stretch that interval to 7–15 days. Hospital stay is typically for 4–7 days. If complications arise, additional medications (diuretics) may be administered to help the kidney produce urine.

Immunosuppressant drugs 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 a cocktail of tacrolimus, mycophenolate, and prednisone. Some patients may instead take cyclosporine, sirolimus, or azathioprine. Cyclosporine, considered a breakthrough immunosuppressive when first discovered in the 1980s, ironically causes nephrotoxicity and can result in iatrogenic damage to the newly transplanted kidney. Blood levels must be monitored closely and if the patient seems to have declining renal function, a biopsy may be necessary to determine whether this is due to rejection or cyclosporine intoxication.

Postoperative diet

Kidney transplant recipients are discouraged from consuming grapefruit, pomegranate and green tea products. These food products are known to interact with the transplant medications, specifically tacrolimus, cyclosporin and sirolimus; the blood levels of these drugs may be increased, potentially leading to an overdose.

Acute rejection occurs in 10–25% of people after transplant during the first 60 days. Rejection does not necessarily mean loss of the organ, but it may necessitate additional treatment and medication adjustments.

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 among 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 osteoporosis.

A patient’s age and health condition before transplantation affect the risk of complications. Different transplant centers have different success at managing complications and therefore, complication rates are different from center to center.

The average lifetime for a donated kidney is ten to fifteen years. When a transplant fails, a patient may opt for a second transplant, and may have to return to dialysis for some intermediary time.

Infections due to the immunosuppressant drugs used in people with kidney transplants most commonly occurs in mucocutaneous areas (41%), the urinary tract (17%) and the respiratory tract (14%). The most common infective agents are bacterial (46%), viral (41%), fungal (13%), and protozoan (1%). Of the viral illnesses, the most common agents are human cytomegalovirus (31.5%), herpes simplex (23.4%), and herpes zoster (23.4%). Infection is the cause of death in about one third of people with renal transplants, and pneumonias account for 50% of the patient deaths from infection.

Prognosis

Kidney transplantation is a life-extending procedure. The typical patient will live 10 to 15 years longer with a kidney transplant than if kept on dialysis.The increase in longevity is greater for younger patients, but even 75-year-old recipients (the oldest group for which there is data) gain an average four more years of life. People generally have more energy, a less restricted diet, and fewer complications with a kidney transplant than if they stay on conventional dialysis.