ORGAN TRANSPLANTATION: EVERYTHING YOU NEED TO KNOW!
–Sai Lavanya Patnala, Intern, Apollo Medical College, Hyderabad
WHAT IS ORGAN TRANSPLANTATION?
Organ donation is the donation of biological tissue or an organ of the human body, from a living or dead person to a living recipient in need of a transplantation.
The introduction of antibiotics, massive vaccinations of the general population to prevent infectious diseases, and organ transplantation may be considered the miracles of twentieth century medicine. Organ transplantation is the best therapy for terminal and irreversible organ failure.[3]
Types of Transplant
Autograft: transplantation of organs, tissues from one part of the body to another in the same individual
Allograft: transplant of an organ or tissue between two genetically non-identical members of the same species. Most human tissue and organ transplants are allografts.
Xenograft: transplant of organs or tissue from one species to another. An example is porcine heart valve transplant, which is quite common and successful.[1]
Types of donors
The sources of organs for transplantation, i.e., living donor (related and nonrelated), cadaveric donor, and brain-dead patients.[1]
HISTORY
The idea of transferring body parts appears in ancient mythology of civilizations around the world. Roman, Greek, Indian, Chinese, and Egyptian legends include tales of organ transplants performed by gods and healers using organs from cadaveric and animal origins.[2]
The first written mention of transplant is attributed to the Ebers Papyrus, written circa 1550 bc, which mentioned skin grafting for the treatment of burns. Around 600 bc, the Indian surgeon Sushruta, known as the father of surgery, is credited with performing the first plastic surgery operations, including full-thickness skin grafts [2]
In 1869,Swiss surgeon Jacques-Louis Reverdin demonstrated success with epidermic grafting. [2] In 1905, the first successful cornea transplant was done by Eduard Zirm in Czech Republic.[1]
By the 1950s, basic science had been researching the viability of transplanting organs. Much of early organ transplant research focused on kidneys, since live donors, the only kind at the time, could survive with just one of their own.[2]
The first renal human allograft was performed on April 3, 1933, by Dr. Yurii Voronoy in Ukraine where the patient survived for 2 days and the failure of the case was largely attributed to ABO incompatibility and prolonged warm ischemia time of the kidney. [2]
In 1953, 22-year-old Richard Herrick was discharged from the Coast Guard with chronic nephritis, a then life-threatening diagnosis with no cure. He agreed to undergo an experimental procedure that was performed by Hartwell Harrison and Joseph Murray in Boston, receiving a kidney from his twin. The Herrick brothers underwent surgery without complications.
In 1959, the first kidney transplant in Louisiana was performed at Charity Hospital. This case marked the first successful kidney transplant between individuals not genetically identical. At the time, immunosuppression had not yet been added to transplantation care. Despite a difficult postoperative recovery, the patient continued living an active life and died of cardiac issues 25 years later. This success excited transplant teams across the world.
By the 1960s, it was clear that not all transplants could be from genetically identical or even related donors, so research scientists and physicians delved into immunosuppression to prevent rejection. In 1962, Dr. Roy Calne and his team at Peter Bent Brigham Hospital published findings that 6-mercaptopurine prolonged survival after renal transplant in 104 dogs. In the same year, Murray led the first renal transplant between nonrelated patients with the use of azathioprine. This was also a landmark case, as it was the first successful transplant from a deceased donor.
While the early years of transplantation focused largely on kidneys, by the late 1960s, liver, heart, and pancreas transplants from deceased donors had also been performed successfully. After performing more than 400 lung transplants on dogs, Dr. James Hardy’s team at the University of Mississippi transplanted the first human lung from a non-heart-beating donor in 1963. The recipient died 18 days postoperatively.
In 1967, Dr. Thomas Starzl performed the first liver transplant in a human at the University of Colorado, aided by canine model results and azathioprine and steroid-based immunosuppression. In 1986, the first successful double-lung transplant was performed. Subsequently in 1987, the first successful intestinal transplant was performed. [4]
In 1998, the new immunosuppressants Tacrolimus and Mycophenolate Mofetil improved recipient tolerance of transplants, especially vascularized composite grafts composed of multiple tissues. The same year, Dr. Jean-Michel Dubernard in Lyon, France, performed the first successful hand transplant on a patient with a mid-forearm amputation. Dubernard later performed the first double hand transplant in 2000.
In 2005, Dr. Bernard Devauchelle and Dubernard performed a partial face transplant on Isabelle Dinoire, who had suffered a disfiguring dog attack 7 months earlier and felt she could not return to normal life.[2]
CLINICAL IMPORTANCE
Renal transplantation is considered the best therapeutic option for the treatment of ESRD(End stage renal disease).
Liver transplantation (LT) is the second most frequently performed transplant after kidney transplantation. According to the 2010 report of the European Liver Transplant Registry, the main indications for LT are cirrhosis, cancers , cholestatic diseases, acute hepatic failure, metabolic diseases and other diseases.
Heart transplantation is indicated in patients suffering from refractory cardiac failure owing to cardiomyopathy, coronary artery disease, congenital heart diseases, retransplant because of previous graft failure, valvular heart disease and for other entities.
The main indication for lung transplantation is respiratory insufficiency secondary to idiopathic pulmonary fibrosis, emphysema/chronic obstructive pulmonary disease and cystic fibrosis.
Heart–lung transplantation has remained almost stable in the last three decades and the major indications are congenital heart disease, pulmonary arterial hypertension and cystic fibrosis.(Christie et al. 2012)[8]
PROTOCOL
Transplantation of Human Organs Act (THOA) 1994 was enacted to provide a system of removal, storage and transplantation of human organs for therapeutic purposes and for the prevention of commercial dealings in human organs. THOA is now adopted by all States except Andhra and J&K, who have their own similar laws. Under THOA, source of the organ may be:
- Near Relative donor (mother, father, son, daughter, brother, sister, spouse)
- Other than near relative donor: Such a donor can donate only out of affection and attachment or for any other special reason and that too with the approval of the authorisation committee.
- Deceased donor, especially after Brain stem death. Other type of deceased donor could be donor after cardiac death.[5]
Physicians who participate in transplantation of organs from deceased donors should:
- Avoid actual or perceived conflicts of interest by ensuring that they not directly involved in retrieving or transplanting organs from the deceased donor.
- No member of the transplant team has any role in the decision to withdraw treatment or the pronouncement of death.
- Ensure that death is determined by a physician not associated with the transplant team and in accordance with accepted clinical and ethical standards.
- Ensure that the prospective recipient (or the recipient’s authorized surrogate if the individual lacks decision-making capacity) is fully informed about the procedure and has given voluntary consent in keeping with ethics guidance.
- Except in situations of directed donation, ensure that organs for transplantation are allocated to recipients on the basis of ethically sound criteria, including but not limited to likelihood of benefit, urgency of need, change in quality of life, duration of benefit, and, in certain cases, amount of resources required for successful treatment.
- Refrain from placing transplant candidates on the waiting lists of multiple local transplant centers, but rather place candidates on a single waiting list for each type of organ. [6]
Physicians who participate in donation of nonvital organs and tissues by a living individual should:
- Ensure that the prospective donor is assigned an advocacy team, including a physician, dedicated to protecting the donor’s well-being.
- Avoid conflicts of interest by ensuring that the health care team treating the prospective donor is as independent as possible from the health care team treating the prospective transplant recipient.
- Carefully evaluate prospective donors to identify serious risks to the individual’s life or health, including psychosocial factors that would disqualify the individual from donating; address the individual’s specific needs; and explore the individual’s motivations to donate.
- Obtain the prospective donor’s separate consent for donation and for the specific intervention(s) to remove the organ or collect tissue.
- Ensure that living donors do not receive payment of any kind for any of their solid organs. Donors should be compensated fairly for the expenses of travel, lodging, meals, lost wages, and medical care associated with the donation only.
- Protect the privacy and confidentiality of donors and recipients, which may be difficult in novel donation arrangements that involve many patients and in which donation-transplant cycles may be extended over time (as in domino or chain donation).[6]
PRE AND POST TRANSPLANT MEASURES
Pre-transplant evaluation
Perform a preoperative risk assessment and coordinate perioperative preparation steps (e.g., perioperative antibiotic prophylaxis).
Pre-transplant infectious workup
-Screen both the donor and recipient for infections, including (at a minimum):
- HIV, human T-cell lymphotropic virus
- Herpes simplex virus, varicella zoster virus
- Epstein-Barr virus, cytomegalovirus
- Viral hepatitis panel
- Rapid plasma regain
- Toxoplasma gondii antibody
- Tuberculin skin test or interferon-γ release assay
-Consider serological screening for endemic infections, e.g., Leishmania, Trypanosoma cruzi
-Ensure immunization schedule is completed.
Post-transplant infectious workup
-Monitoring:
- CMV viral loads in blood monthly for a minimum of 12 months
- EBV viral loads in blood monthly for a minimum of 12 months
- In kidney transplant recipients: BK virus viral loads monthly for 6 months, then at 9 and 12 months
-Universal prophylaxis
- PCP prophylaxis with trimethoprim-sulfamethoxazole for a minimum of 6–12 months
- CMV prophylaxis with ganciclovir or valganciclovir for 12–14 weeks
-Specific situations
- Recipients seronegative for T. gondii who receive a heart transplant from a seropositive individual: pyrimethamine with folinic acid for 6 months
- Hematopoietic stem cell transplantation:
-Acyclovir for prophylaxis against HSV and VZV
-12 months post-transplantation: tetanus, diphtheria, H. influenzae, polio, and pneumococcal pneumonia vaccination
-24 months post-transplantation: MMR, VZV, and possibly pertussis vaccination
Post-transplant immunosuppressive therapy
-Intense immunosuppression in the early postoperative period (3–6 months)
-To minimize drug toxicity, use low doses of multiple drugs rather than high doses of a few drugs.
-Avoid excessive immunosuppression that increases the risk of post-transplant infections and post-transplant malignancy.
Post solid organ transplant
-Phase 1: Induction therapy with Anti-T-lymphocyte antibodies
- Non-depleting antibodies (monoclonal): basiliximab
- Lymphocyte-depleting antibodies (polyclonal): thymoglobulin
-Phase 2: Maintenance therapy commonly a triple-drug regimen consisting of:
- Glucocorticoids
- Calcineurin inhibitor (e.g., cyclosporine, tacrolimus)
- Antiproliferative agents (e.g., azathioprine, mycophenolate mofetil, sirolimus)[7]
CONCLUSION
Organ transplantation is one of the major medical achievements of the twentieth century. It is is a revolutionary concept that saves lives in patients affected by terminal organ failures and improve quality of life.[1]
The history of transplantation teaches us how to learn from errors and use modern advancements like new drugs to reduce the incidence of complications.
Nowadays, many diseased organs are being replaced by healthy organs from living donors, cadavers, and from animal source. Successful bone marrow, kidney, liver, cornea, pancreas, heart, and nerve cell transplantations have taken place. The incidence is limited only by cost and availability of the organs. [1]
REFERENCES
- https://www.ncbi.nlm.nih.gov/books/NBK500177/
- Nordham KD, Ninokawa S. The history of organ transplantation. Proc (Bayl Univ Med Cent). 2021 Oct 19;35(1):124-128. doi: 10.1080/08998280.2021.1985889. PMID: 34970061; PMCID: PMC8682823.
- Grinyó JM. Why is organ transplantation clinically important? Cold Spring Harb Perspect Med. 2013 Jun 1;3(6):a014985. doi: 10.1101/cshperspect.a014985. PMID: 23732857; PMCID: PMC3662355.
- https://unos.org/transplant/history/#:~:text=The%20beginning-,In%201954%2C%20the%20kidney%20was%20the%20first%20human%20organ%20to,were%20begun%20in%20the%201980s.
- https://dghs.gov.in/content/1353_3_NationalOrganTransplantProgramme.aspx
- https://www.ama-assn.org/delivering-care/ethics/transplantation-organs-living-donors
- https://next.amboss.com/us/article/gn0Fsg?q=solid%20organ%20transplantation#Zc522e5d8473c2defec88274f7fd123f2
- Grinyó JM. Why is organ transplantation clinically important? Cold Spring Harb Perspect Med. 2013 Jun 1;3(6):a014985. doi: 10.1101/cshperspect.a014985. PMID: 23732857; PMCID: PMC3662355.