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Kidney transplantation
Kidneys are a pair of bean shaped organs that are placed on either side towards the back side of the upper abdomen, partly covered and protected by the rib cage. They play a vital role in maintaining the fluid and electrolyte balance of our body which means that excess water and impurities in the blood are filtered off by kidneys and is expelled as urine through the urinary bladder. There are many disease processes that cause kidneys to malfunction. Many diseases that cause a sudden insult/injury to kidney results in a state called ‘Acute Kidney Injury’. Such situations usually resolve with appropriate treatment and the kidneys would return to a normal functioning state without much sequelae. On the contrary there are diseases which cause a gradual and steady worsening of kidney function resulting in a state called ‘Chronic kidney disease’. This is not reversible and over a period of time, the functioning of kidney decreases to such a level that the body shows up symptoms of kidney disease and may sometimes result in life threatening complications like pulmonary oedema. Once this stage is reached, the kidneys need to be supported which means that the excretory function of kidneys have to performed with the help of machines. This is performed with the help of dialysis machines. This involves circulating the patient’s blood through the dialysis machines which ‘purifies’ it and removes excess water content and waste products from blood. This process would have to be continued regularly, about 2-3 times per week and the patient would be said to be undergoing ‘maintenance hemodialysis’. An alternate to performance of hemodialysis is ‘peritoneal dialysis’ which involves removal of excess water and waste products through the abdomen, utilizing the purifying capability of the peritoneal membrane which is the lining skin of the inside of the abdomen covering internal organs and abdominal wall from inside. Peritoneal dialysis does not involve handling blood or blood products and the patient can be trained to perform this at home itself.

Regular performance of hemodialysis and peritoneal dialysis has its own logistic difficulties and is also detrimental to the overall health of patients over the years. Also there is always the risk of various of complications associated with these. This can be overcome by the performance of kidney transplantation, where in a healthy kidney from a living/ deceased donor is implanted into a patient suffering from kidney failure. Kidney transplantation (also known as renal transplantation) is a surgery by which a kidney (or kidneys) of one person is implanted into another person’s body for therapeutic purposes. The person who receives the kidney is called the recipient and the one who donates is called the donor. The recipient in such a situation would be suffering from kidney failure which has reached an irreversible and severe stage called as End Stage Renal Disease (ESRD).

Kidney transplantation is typically classified as deceased-donor (formerly known as cadaveric) or living-donor transplantation depending on the source of the donor organ. Deceased donors are typically persons who are brain dead – they are considered to be ‘dead by neurological criteria’. Donation after cessation of activity of the heart is logistically difficult, but is being practiced at a few centers in the US and Europe. Living-donor kidney 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.

Indications for Kidney transplantation

Kidney transplantation is undertaken when both the kidneys fail to work and this reaches such a level that the normal body functions are impaired ie the state of ESRD (End Stage Renal Disease) is reached. Common diseases leading to ESRD include renovascular disease, infection, urinary stones, diabetes mellitus, and autoimmune conditions such as chronic glomerulonephritis and lupus nephritis. Genetic causes include polycystic kidney disease and a number of inborn errors of metabolism which are relatively less common. Apart from these, in a significant number of patients, the cause is unknown.

Diabetes is the most common known cause of kidney transplantation, accounting for approximately 25% of patients who undergo kidney transplantation. The majority of renal transplant recipients are on dialysis (peritoneal dialysis or hemodialysis) 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.

Challenges in performing a kidney transplant

The biggest challenge faced by a patient who plans to have a kidney transplant is finding an appropriate donor. Kidney transplantation is a procedure which has medico-legal implications. In our country, organ transplantation is regulated by various legislations, the most important of which is the Transplantation of Human Organs Act (THOA) which was implemented in 1994. There have been various additions and amendments to this act over the years.
The best donor suited for a patient would be a ‘living related donor’, which means that a close, genetically related healthy person such as parent, siblings or children. This stands good for medical as well legal reasons. However, when such a donor is not available, the spouse is also considered as a ‘related donor’ legally. When no relative is available for donation, it is legally permissible to receive a kidney from an ‘unrelated’ donor. How ever this involves stringent scrutiny and approval of the Ethical committee appointed by government to prevent any kind of foul play or financial transactions. It is illegal to have financial gains for donation of organs including kidney. Organ donation is an action with several moral and ethical overtones and is considered to be act of altruism.

The challenge faced by all organ transplants is the chance of rejection of the transplanted organ. This holds good for kidney transplantation also. Any organ from another person is considered as a ‘foreign’ object by the body and various immunological mechanisms come into play, ultimately culminating in the rejection of the transplanted organ. Research in immunology spanning decades have now resulted in the development of powerful immunosuppressant medicines which are capable of suppressing the immunity of the body that is successful in preventing rejection. As a result of this kidney transplantation has become a wide spread therapeutic practice all over the world in the treatment of ESRD. Development of transplantation of other organs such as liver, heart, lungs, pancreas, intestine etc. have also happened parallelly, kidney transplantation being the pioneer in this field.

Magnitude of the problem of ESRD

It is estimated that globally, chronic kidney disease is associated with approximately 735,000 deaths annually. The prevalence of end-stage renal disease requiring transplantation in India is estimated to be between 151 and 232 per million population. If an average of these figures is taken, it is estimated that almost 220,000 people require kidney transplantation in India. Against this, currently, approximately 7500 kidney transplantations are performed at around 250 kidney transplant centers in India. Most of the patients waiting for transplant continue to have dialysis to sustain their life and many succumb to the complications of kidney disease or develop long term complications of dialysis. Several efforts are in play to increase the number of kidney transplants – like promoting cadaveric transplants, swap transplants, domino transplants, motivating healthy volunteers to donate kidneys. However, all transplants that occur are regulated by government. The government directly controls deceased donor transplants, where as transplant centers follow government guidelines for the performance of living donor transplants.

Exchanges and chains are a novel approach to expand the living donor pool. Swap transplants occur when a pair of recipient-donor pairs are identified where in the donor related to a particular recipient does not match, but matches with the recipient in the other pair and vice versa. In similar fashion, in a domino transplant, the donor of particular patient donates to another recipient, the donor of whom would donate to another recipient and this chain goes on. In 2014 the record for the largest swap chain had taken place in the United States involving 70 participants.

In order to circumvent the problem of donor scarcity, donation from deceased donors was initiated. This became popular in the 1980s after the concept of brain death was recognized and legally accepted in many countries. Brain death is said to occur when the brain suffers an irreversible damage that occurs due to accidents, bleeding inside the brain, brain tumors etc. and life is sustained only by life support measures, the withdrawal of which would lead to cessation of the function of the heart. The irreversible nature of brain death is confirmed by several tests by a panel of doctors approved by the government and the person who has sustained the injury is declared as ‘brain dead’. This is synonymous as ‘death by neurologic criteria’. Once a person is declared as ‘brain dead’ and the relatives are willing for donation of organs, further proceedings are taken over by the government machinery. In Kerala, cadaveric donation is managed by the government appointed body called Kerala Network for Organ Sharing (KNOS).

History of Kidney transplantation

Attempts at transplanting the kidney have been happening since 1902, but a truly successful kidney transplant occurred on 23 December 1954 at Brigham Hospital, Boston, USA. The surgery was performed by Joseph Murray, J. Hartwell Harrison, John P. Merrill and team. The procedure was done between identical twins Ronald and Richard Herrick which reduced problems of an immune reaction. For this and later work, Dr. Murray received the Nobel Prize for Medicine in 1990. The recipient, Richard Herrick, died eight years after the transplantation.

However, most of the early attempts to transplant kidneys were not successful because of the issue of immune mediated rejection. Medicines to suppress immunity was introduced in the 1960s which gave life to the budding specialty of transplantation. Most of the early regimes to suppress immunity used high doses of the drug Prednisolone, which was alone not sufficient to prevent rejection. Also, prolonged use of high doses of this medicine which is a corticosteroid has side effects like glucose intolerance and diabetes, weight gain, osteoporosis, muscle weakness, hypercholesterolemia and cataract formation. The introduction of the drug Cyclosporine in the 1970s revolutionized transplantation and it was possible to prevent rejection of transplanted organs.

The first living donor kidney transplantation in India was performed at Christian Medical College, Vellore in 1971. The world’s youngest cadaveric transplant that was successful was performed at Sultan Qaboos University Hospital, Oman in 1994. Kidneys from a newborn of 33 weeks was transplanted to a 17 month old recipient who survived for another 22 years.

Advances in kidney transplantation

There have been many advances in various facets of kidney transplantation. On the surgical front, retrieval of kidneys from a living donor is performed in many centers laparoscopically. This offers the advantage of early post-operative recovery of the donor with the added advantage of decreased pain and discomfort after surgery. The recipient surgery has also been done laparoscopically at a few centers, but this has fallen out of favor due to high technical skill required, potential of complications and suboptimal graft outcome. At several centers where robotic surgery is available, recipient surgeries are performed with assistance of robot.

Research and advances in immunology has lead to practice of accepting donors with incompatible blood group and immunologically incompatible donors. There are several novel practices that have been applied and accepted clinically to prevent rejection in such patients. Pioneering work in this field has been done at Japan. As a result, several centers in our country also practice ABO incompatible kidney transplants and also follow desensitization protocols to prevent rejection in patients who are otherwise found to be immunologically incompatible.

Recent years have seen an explosion of activity in the development of stem cell–based strategies to build new tissues. Because of its structural complexity, the kidney is a relative latecomer to this aspect of regenerative medicine. However, work in the past 5 years has highlighted the feasibility of this approach as a potential long-term solution to the organ shortage crisis, resulting in a surge of research activity. Much research is underway in synthesizing compatible tissue in the laboratory, and when this becomes a reality in clinical practice, the problem of shortage of organs would be addressed to an extent.

Dr. Renu Thomas MS, DNB, MCh(Uro)
Sr. Consultant and Co-ordinator, Transplant Surgeon
Dept of Urology
KIMS HEALTH, Thiruvananthapuram

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