Kidney transplantation


Kidney transplant or renal transplant is the organ transplant of a kidney into a patient with end-stage kidney disease. Kidney transplant is typically classified as deceased-donor or living-donor transplantation depending on the source of the donor organ. Living-donor kidney transplants are further characterized as genetically related or non-related transplants, depending on whether a biological relationship exists between the donor and recipient. The first successful kidney transplant was performed in 1954 by a team including Joseph Murray, the recipient's surgeon, and Hartwell Harrison, surgeon for the donor. Murray was awarded a Nobel Prize in Physiology or Medicine in 1990 for this and other work. In 2018, an estimated 95,479 kidney transplants were performed worldwide, 36% of which came from living donors.
Before receiving a kidney transplant, a person with ESRD must undergo a thorough medical evaluation to make sure that they are healthy enough to undergo transplant surgery. If they are deemed a good candidate, they can be placed on a waiting list to receive a kidney from a deceased donor. Once they are placed on the waiting list, they can receive a new kidney very quickly, or they may have to wait many years; in the United States, the average waiting time is three to five years. During transplant surgery, the new kidney is usually placed in the lower abdomen ; the person's two native kidneys are not usually taken out unless there is a medical reason to do so.
People with ESRD who receive a kidney transplant generally live longer than people with ESRD who are on dialysis and may have a better quality of life. However, kidney transplant recipients must remain on immunosuppressants for as long as the new kidney is working to prevent their body from rejecting it. This long-term immunosuppression puts them at higher risk for infections and cancer. Kidney transplant rejection can be classified as cellular rejection or antibody-mediated rejection. Antibody-mediated rejection can be classified as hyperacute, acute, or chronic, depending on how long after the transplant it occurs. It is important to regularly monitor the new kidney's function by measuring serum creatinine and other tests; these should be done at least every three months. Donor-derived cell-free DNA blood testing can be done to detect early rejection. If rejection is suspected, a kidney biopsy should be obtained.

History

One of the earliest mentions about the possibility of a kidney transplant was by American medical researcher Simon Flexner, who declared in a reading of his paper on "Tendencies in Pathology" in the University of Chicago in 1907 that it would be possible in the then-future for diseased human organs substitution for healthy ones by surgery, including arteries, stomach, kidneys and heart.
In 1933, surgeon Yuriy Vorony from Kherson in Ukraine attempted the first human kidney transplant, using a kidney removed six hours earlier from a deceased donor to be reimplanted into the thigh. He measured kidney function using a connection between the kidney and the skin. His first patient died two days later, as the graft was incompatible with the recipient's blood group and was rejected.
It was not until 17 June 1950, when a successful transplant was performed on Ruth Tucker, a 44-year-old woman with polycystic kidney disease, by Richard Lawler at Little Company of Mary Hospital in Evergreen Park, Illinois. Although the donated kidney was rejected ten months later because no immunosuppressive therapy was available at the time, the intervening time gave Tucker's remaining kidney time to recover and she lived another five years.
File:Herrick kidney transplant.jpg|thumb|right|Dr. John P. Merrill explains the workings of a then-new machine called an artificial kidney to Richard Herrick and his brother Ronald. The Herrick twin brothers were the subjects of the world's first successful kidney transplant, Ronald being the donor.
A kidney transplant between living patients was undertaken in 1952 at the Necker hospital in Paris by Jean Hamburger, although the kidney failed after three weeks. The first truly successful transplant of this kind occurred in 1954 in Boston. The Boston transplantation, performed on 23 December 1954 at Brigham Hospital, was performed by Joseph Murray, J. Hartwell Harrison, John P. Merrill, and others. The procedure was done between identical twins Ronald and Richard Herrick, which reduced problems of an immune reaction. For this and later work, Murray received the Nobel Prize for Medicine in 1990. Richard Herrick's death eight years after the transplant was unrelated to the transplant.
In 1955, Charles Rob, William Dempster carried out the first deceased donor transplant in United Kingdom, which was unsuccessful. In July 1959, "Fred" Peter Raper performed the first successful deceased donor transplant in the UK. A year later, in 1960, the first successful living kidney transplant in the UK occurred, when Michael Woodruff performed one between identical twins in Edinburgh.
In November 1994, the Sultan Qaboos University Hospital, in Oman, performed the world's youngest cadaveric kidney transplant successfully. The work took place from a newborn of 33 weeks to a 17-month-old recipient who survived for 22 years.
Until the routine use of medication 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. As explained in Thomas Starzl's 1992 memoir, these factors explain why Starzl's team and others began with kidney transplantation as the first type of solid organ transplantation to translate to clinical practice before attempting to move on to liver transplantation, heart transplantation, and other types.
The major barrier to organ transplantation between genetically non-identical patients lies in the recipient's immune system, which would treat a transplanted kidney as a 'non-self' and immediately or chronically reject it. Thus, having medication to suppress the immune system was essential. However, suppressing an individual's immune system places that individual at greater risk of infection and cancer, in addition to the side effects of the medications.
The basis for most immunosuppressive regimens is prednisolone, a corticosteroid. Prednisolone suppresses the immune system, but its long-term use at high doses causes a multitude of side effects, including glucose intolerance and diabetes, weight gain, osteoporosis, muscle weakness, hypercholesterolemia, and cataract formation. Prednisolone alone is usually inadequate to prevent rejection of a transplanted kidney. Thus, other, non-steroid immunosuppressive agents are needed, which also allow lower doses of prednisolone. These include: azathioprine and mycophenolate, and ciclosporin and tacrolimus.

Indications

The indication for kidney transplantation is end-stage renal disease, regardless of the primary cause. This is defined as a glomerular filtration rate below 15 ml/min/1.73 m2. Common diseases leading to ESRD include renovascular disease, infection, diabetes mellitus, and autoimmune conditions such as chronic glomerulonephritis and lupus; genetic causes include polycystic kidney disease, and several inborn errors of metabolism. The most common 'cause' is idiopathic.
Diabetes is the most common known cause of kidney transplantation, accounting for approximately 25% of those in the United States. The majority of renal transplant recipients are on dialysis at the time of transplantation. However, individuals with chronic kidney disease who have a living donor available may undergo pre-emptive transplantation before dialysis is needed. If a patient is put on the waiting list for a deceased donor transplant early enough, this may also occur pre-dialysis.

Evaluation of kidney donors and recipients

Both potential kidney donors and kidney recipients are carefully screened to ensure positive outcomes.

Contraindications for kidney recipients

Contraindications to receiving a kidney transplant include both cardiac and pulmonary insufficiency, as well as hepatic disease and some cancers. 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 age limits and require that one must be in good health. Significant cardiovascular disease, incurable terminal infectious diseases, and cancer are often transplant exclusion criteria. In addition, candidates are typically screened to determine if they will be compliant with their medications, which is essential for the survival of the transplant. People with mental illness and/or significant ongoing 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.

Living kidney donor evaluation

As candidates for a significant elective surgery, potential kidney donors are carefully screened to ensure good long-term outcomes. The screening includes medical and psychosocial components. Sometimes donors can be successfully screened in a few months, but the process can take longer, especially if test results indicate additional tests are required. A total approval time of under six months has been identified as an important goal for transplant centers to avoid missed opportunities for kidney transplant.
The psychosocial screening attempts to determine the presence of psychosocial problems that might complicate donation, such as a lack of social support to aid in their post-operative recovery, coercion by family members, or a lack of understanding of medical risks.
The medical screening assesses the general health and surgical risk of the donor, including conditions that might indicate complications from living with a single kidney. It also assesses whether the donor has diseases that might be transmitted to the recipient, assesses the anatomy of the donor's kidneys, including differences in size and issues that might complicate surgery, and determines the immunological compatibility of the donor and recipient. Specific rules vary by transplant center, but key exclusion criteria often include: