Transplant surgery has come a long way since the first successful attempt in 1954. For ages, surgeons toyed with the idea ofreplacing diseased organs with a healthy one from a donor. However, such a transplanted organwas recognised as a foreign invader by the recipient’s immune system and eventually rejected. Further research enlightened surgeons that an existing genetic compatibility between the donor and recipient tissue did not prompt aggressive response from the recipient’s immune system.
In 1954, a Massachusetts surgeon, Joseph E. Murray of Brigham and Women’s Hospital in Boston, used this principle to successfully transplant a kidney in identical twins. Although this was groundbreaking at that point, it did not offer a solution to the millions who needed organ transplants but did not have an identical twin.
In 1960’s, further research paved a way for surgeons to perform transplants in non-relatives by using drugs to suppress the recipient’s immune system. But these drugs were toxic and required that surgeons not just maintain the transplant, but also treat patients for drug toxicity. Crushed between side effects of immunosuppressant drugs and their toxicity, most patients did not survive long after transplant.
However, with the latest strides in medical technology, organ preservation and the development of more effective drugs to prevent rejection, success rates of transplant surgeries have advanced a great deal.
Renal Or Kidney Transplantation: Definition And Causes
Kidney transplantation or renal transplantation is defined as the organ transplant of a kidney in a patient with end-stage renal disease. Depending on the source of the organ donor, kidney transplantation is typically classified as deceased-donor (formerly known as cadaveric) or living-donor. 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.
A patient is diagnosed with an end-stage renal disease if his filtration rate plummets to 20-25 percent below normal. This rarely occurs as a stand-alone consequence and is more often an aftermath of other diseases like hypertension, infections, inflammation of the kidney, diabetes mellitus, inborn errors of metabolism, and autoimmune conditions.
In renal failure, although long-term dialysis is an option, transplantation offers better survival and quality of life as well as economic advantages.
Kidney Transplant: Statistics
Of the single kidney transplants performed in 2000, 5,293 were from living donors and the rest were from cadaveric donors. In addition, 911 kidneys were transplanted in combination with pancreas transplants. Living donor kidney transplants are increasing – 589 in 2005-2006, 690 in 2006-2007, 831 in 2007-2008 and 927 in 2008-2009 and now represent more than one in three of all kidney transplants.
About 88.3 percent of the kidneys transplanted from cadavers (persons who died recently) are still functioning well at one year after surgery. The results are even better for kidneys transplanted from living donors. One year after surgery, 94 percent of these kidneys were still functioning well.
Latest Advances In Kidney Transplantation
Kidney Transplantation Through ‘Mixed Chimerism’
For David H. Sachs, MD, and Megan Sykes, MD, both at the Massachusetts General Hospital Transplantation Biology Research Center, the successful transplant of the world’s first non-HLA-matched combined kidney and bone marrow was a pivotal moment in their three decades of transplant research.
They devised a method of ‘tricking’ the recipient’s immune system by making it believe that the new organ belonged to its own body and thereby immensely reduce rejection percentage, even without using immunosuppressant drugs. This method of ‘inducing immune tolerance of transplanted organs’, involved the transfer of the donor’s bone marrow along with the kidney to produce a state of ‘mixed chimerism’, wherein the immune system blends elements of both the donor and the recipient, allowing the donated organ to be accepted.
Xenotransplantation
This is the current hot topic in renal transplant research. Xenotransplantation involves the transplantation of nonhuman tissues or organs into human recipients. The concept was pioneered a century ago, when transplanting human organs was considered ethically controversial.
The rationale for xenotransplantation is also driven by demand and supply. Although this approach sounds very promising, inter-species transmission of infectious diseases is a key concern. The more closely related the donor and recipient species, the more likely this is to arise, and research is underway to develop safer ways to make this a feasible choice in transplant surgery.
Reducing ‘Panel Reactive Antibodies’
Some patients test positive on a panel reactive antibody (PRA) blood test, which indicates that these patients had high levels of PRAs, or proteins that attack foreign tissue. Transplant specialists are currently exploring a strategy to lower PRA levels in patients by administering high doses of Intravenous Immunoglobulin (IVIG) before the transplant surgery. IVIG is a drug derived from the pooled blood of hundreds of donors and has been used to treat various immune disorders for at least 30 years.
Improving Efficacy Of Immunosuppressants
With a focus on improving medications that better control high blood pressure (a common cause for kidney failure), new drug combinations are being researched to refine existing immunosuppressant drugs and reduce rate of tissue rejection. According to the National Kidney Foundation, almost 80,000 Americans are currently on a waiting list for a new kidney. Therefore the endeavour here is to allow transplantation without so much of a close tissue type and therefore better address the shortage of suitable kidney donors vs. recipients.
Conclusion
Transplant surgery has become much more common in the last 30 years, which has created the universal problem of a shortage of donated organs. In the USA, where transplants have saved over 300,000 people and are now the most common treatment for many diseases that lead to organ failure, demand outstrips supply several times over.
To overcome this challenge, researchers across the globe are aggressively pursuing answers and looking for innovative solutions to improve transplant options. The results of kidney transplantation have improved considerably over the last 20 years, and will probably continue to improve, with a better understanding and introduction of newer immunosuppressant medicines.
Article by Snigdha Taduri for Biomed-ME