Piggy Pumps: A New Era in Kidney Transplantation

Oink oink! In a recent groundbreaking medical procedure, surgeons at Massachusetts General Hospital successfully transplanted a genetically engineered pig kidney into 62-year-old patient Richard Slayman, who had kidney failure. 

Kidneys play a key role in maintaining balance within the body. Blood filtration occurs in specialized units in the kidneys called nephrons; blood enters the nephron where waste products, electrolytes, and excess fluid are filtered out to form urine. As nephrons concentrate waste, they also reabsorb essential substances like water in order to maintain optimal hydration and electrolyte levels in the body. This regulation is necessary for nerve function, muscle contraction, and blood pressure stability. 

For Slayman, his history with diabetes and hypertension caused kidney failure. Diabetes causes inflammation and strain in blood vessels, severely damaging nephrons as well as blood vessels in the kidney, leading to declined kidney function or even kidney failure. Hypertension constricts blood vessels, reducing blood flow and causing ineffective filtration. As a result, these symptoms accumulated into chronic, or long-term, kidney disease, a leading cause of death in the U.S. and a disease known to cause dangerous levels of fluids, electrolytes, and wastes to build up in the body, eventually leading to gradual loss of kidney function. 

Kidneys are the most commonly demanded organ. More than 500,000 people in the U.S. suffer from the last stage of long-term kidney disease. While nearly 100,000 people are on waitlists for kidneys, thousands die waiting for one, and only 25,000 kidney transplants are performed annually. Furthermore, the immune system often rejects the transplanted kidney because the recipient’s immune system may recognize the donor kidney as foreign and mount an immune response against it. This initial immune response involves the activation of white blood cells and other immune cells, which may lead to failure in the functionality of the new kidney. 

Xenotransplantation, the implantation of another animal’s organ into a human, has long been proposed as a solution for this organ shortage. There have been many recent scientific advancements that have made this process possible—in September 2021, NYU Langone surgeons attached a pig’s kidney to a brain-dead man and watched his body begin to function again as it made urine. After a human is reported to be brain-dead, their life support machine will keep their heart beating, but they will not regain consciousness or start breathing on their own again. The kidney functioned for more than 32 days, and there were little signs of rejecting the organ. However, due to ethical concerns about how long a brain-dead man can be kept on a ventilator, the study came to an end, meaning researchers could not conclude anything about long term consequences. Then, University of Alabama at Birmingham researchers conducted an extremely similar study where they found that the implanted kidney filtered creatinine, a byproduct of muscle contraction that must be removed from the blood. The combination of these results presented many promising possibilities for the future.

Slayman received a human kidney transplant in 2018 that had quickly failed, resulting in blood clots and heart failure. This ultimately brought him to the operating table in March 2024 where he became the first living person to receive a modified pig kidney transplant.

Pig kidneys are extremely similar to human kidneys, making them optimal for transplantation. Essentially, pig kidneys have demonstrated compatibility with processing human foods and fluids. Their metabolic pathways and activities align closely with those of human kidneys, allowing them to effectively metabolize, balance, and eliminate waste products from dietary intakes. This compatibility reduces the risk of post-transplantation metabolic complications. This compatibility can also be measured in terms of estimated Glomerular Filtration Rate (eGFR), which is a measure of kidney function, reflecting the rate at which the kidneys filter waste products from the blood. After much research, scientists have found that pig kidneys exhibit eGFRs comparable to those of human kidneys, suggesting that pig kidneys can adequately meet the filtration requirements of human recipients.

To the human eye, the pig kidney used for Slayman’s transplant was roughly the same size as a human kidney and was microscopically almost identical as well. This was because scientists at biotech company eGenesis used CRISPR-CAS9 technology to genetically engineer the kidney. A total of 69 edits were made to the mini pig’s genes. Three pig carbohydrates potentially involved in rejection of the kidney, alphaGal, Sd(a), and Neu5gc, were removed, and seven human genes were inserted to enhance compatibility with the rest of the human body. Another 59 edits were made to inactivate porcine endogenous retroviruses, viruses present in the pig’s genome that could infect humans once introduced. Complement inhibitors, proteins that prevent complement activation, a process by which a part of the immune system becomes activated in the presence of pathogens, such as hCD46 and hCD55, were added. Anticoagulants, chemical substances that help to prevent blood clot formation, such as hTHBD and hPROCR, were also added, as well as immune regulators, substances that regulate activity of the immune system: CD47, hHMOX1, and hTNFAIP3.

Following these edits,  a team led by director of kidney transplantation at Massachusetts General Hospital Dr. Leonardo Riella transplanted the kidney into Slayman in a four hour procedure. Two new drugs, Tegoprubart and Ravulizumab, were used during the surgery to suppress the immune system and prevent rejection of the organ. Tegoprubart is an antibody that blocks specific immune cell activation by targeting the CD40L pathway. Ravulizumab is an antibody that works similarly by blocking inflammation and cell lysis, a process when the cell membrane breaks down. 

Despite its bright future, this breakthrough has received much criticism. Critics raise the problem of xenotransplantation becoming another form of animal exploitation, as it would require animals to be kept under unnatural laboratory conditions, and it could essentially be described as using animals for spare parts. 

So far, the results of the surgery are promising, though the long-term results remain unclear. According to Mass General Hospital, it would be considered a success if Slayman doesn’t require dialysis in the future. Up to this point, Slayman’s condition has continued to improve and he has been discharged from the hospital. Dr. Riella hopes that dialysis can now become obsolete and that xenotransplantation can serve “as a bridge to receiving a human kidney or a permanent treatment.”