Old kidneys may be a new answer to organ shortage

Transplant centers come up short more often than not when treating patients in need of a kidney, as there is a shortage of donors. Yet kidneys donated by people 65 or older can still function for many years after transplantation, according to a study published Thursday in the Clinical Journal of the American Society of Nephrology. The results suggest that a new source of quality kidneys could be available to patients in need of life-saving transplants.

“Kidneys from an old donor may be favorably used, particularly in an age-matched patient,” said Dr. Luigi Biancone, lead author of the study and associate professor of nephrology at the University of Torino in Italy.

Biancone and his colleagues found similar survival rates for transplanted organs from donors in the age ranges of 50 to 59 years old, 60 to 69 years old, 70 to 79 years old and even 80 years or older.

“Age is not the sole criteria by which the outcomes of an organ or the quality of an organ should be judged,” said Dr. David Klassen, chief medical officer of the United Network for Organ Sharing (UNOS), which operates the Organ Procurement and Transplantation Network – the nation’s transplant system – under a contract with the federal government.

“To exclude an organ just based on age is probably not appropriate,” said Klassen, who was not involved in the new study. He said the new results are “consistent with previous studies suggesting the outcomes for older donors can be quite good.”

An extensive wait list

The kidneys, a pair of bean-shaped organs about 4½ inches long, remove waste from the body and help regulate blood pressure, blood volume and blood composition. Kidney failure, also called renal failure, occurs when they are unable to remove waste and maintain the blood’s chemical balance. Chronic failure can cause fatigue, sluggishness, anemia, decreased urine and complications such as congestive heart failure. According to the UNOS website, if treatment fails, dialysis and transplantation become necessary.

The organ shortage is dramatic, and the numbers tell the story.

Currently, 99,101 people are waiting for kidneys in the United States, according to UNOS, which updates its numbers in real time. Yet only 12,245 transplant operations using kidneys from 8,306 deceased donors have been performed this year, as of November 30.

Although there are nearly “100,000 people waiting for kidney transplants, the other organ waiting lists are not nearly as large,” observed Klassen. This is because people on dialysis can wait for years for a transplant – and often do – but people who need heart, lung or liver transplants cannot wait, because of both the nature of their disease and “the ability of medical science to sustain people.”

“There’s no equivalent of dialysis for lung recipient candidates or liver recipient candidates,” Klassen said.

However, a very common reason for discarding a donated kidney is the older age of a donor.

“There are no restrictions, per se,” Klassen said. The organ network has never established a policy or “mandated restriction that you cannot procure organs from a recipient a certain age. That’s never been the case.”

A potential new source of donor organs

Troubled by the small number of available kidneys and the large number of people waiting, Biancone and his colleagues investigated how the age of a kidney donor affects the long-term functioning of the transplanted organ.

Generally, survival rates after kidney transplants are good: over 95% for patients and around 95% or slightly lower for the kidney itself, according to data from the Organ Procurement and Transplantation Network.

Biancone and his research team analyzed data from kidney transplants performed at the Turin University Renal Transplant Center between 2003 and 2013.

They identified a total of 647 transplants in which the donors were either between 50 and 59 years old with certain risk factors, or older than 60. Patient and kidney survival rates were comparable after an average follow-up period of 4.9 years among all the age groups studied: 50 to 59 years, 60 to 69 years, 70 to 79 years and 80 years and older.

After five years, patient survival rates ranged from 87.8% to 90.1%, while kidney survival rates ranged from 65.9% to 75.2%.

In conclusion, Biancone and his co-authors said their results support the use of older donors – even those older than 80 – if they’ve been accurately selected and managed.

Meanwhile, other researchers continue to explore new ways to expand the donor pool.

New ideas in donation

One area of increased donation has been substantial, if unanticipated.

“There’s the opioid epidemic that’s sweeping across the country, and in fact, many people dying of overdoses have become donors,” Klassen said. “There are parts of the country where the percentage of donors who have died from overdoses is approaching 25% of the donor population, so that has been quite a change.”

Another new avenue that has resulted in more transplants is the HIV Organ Policy Equity, or HOPE, Act, which allows HIV-positive donors for HIV-positive recipients. At least six hospitals in the United States are able to perform such transplants. Johns Hopkins performed the first in March with a kidney and liver transplant.

There are also efforts underway to change the way available organs are allocated based on geography. The proposal for liver transplants “would create eight liver allocation districts nationwide, with district-wide distribution of livers for candidates in the most urgent medical condition … before local matching of less sick candidates,” according to UNOS.

Researchers are hard at work for solutions as well.

Engineering synthetic organs is making progress in laboratories, but that’s long-term research, not a capability that will be available anytime soon. “That’s on the far horizon, not the near horizon,” said Klassen, who is hopeful nevertheless.

“There’s a lot of research these days and actually clinical trials on techniques of organ profusion and organ preservation,” he said. These technologies are changing the way organ preservation is done, allowing for “resuscitation, if you will, of donor organs.”

Researchers are primarily applying these methods to lungs, hearts and livers because these organs are really limited by how long they can be out of the body, Klassen explained.

“A kidney can be out of the body and in cold storage for up to 48 hours. That’s not a rare event,” he said. “With hearts and lungs, we’re talking four, six, eight hours.”

Though there may be a more pressing need to explore this technique on other organs, Oxford University researchers have begun to study the effects of a process called normothermic perfusion on kidneys.

Before transplantation, scientists flush the donated kidney with oxygenated blood to revive the organ and repair any damage caused by cold storage. Additionally, the kidney is pumped with drugs, including anti-inflammatory agents, to prime it for surgery. Normothermic profusion also enables a surgeon to test kidney function, ultimately lowering the discard rate.

By contrast, other researchers are investigating new ways to preserve kidney function in patients with polycystic kidney disease, which causes small cysts to form in the kidneys. Over time, patients with this genetic disease may develop kidney scarring, which can lead to organ failure, requiring a transplant.

One researcher at University College London Medical School has begun to explore the possibility of blocking an enzyme that contributes to kidney scarring with drugs. This would keep the kidneys working and so prevent the need for a transplant.

At Wake Forest Institute for Regenerative Medicine, scientists are investigating how to engineer replacement kidneys using either human or pig kidneys as scaffolds. All original cells would be removed and replaced with a patient’s own cells, according to Karen Richardson, a spokeswoman for the institute.

Pigs, with their human-sized organs, serve scientists at other institutions around the world that are using these animals as biological incubators for human organs. Transplanting nonhuman organs into human recipients is known as xenotransplantation.

Concerns raised by the FDA include the potential for “cross-species infection by retroviruses, which may be latent and lead to disease years after infection.” Additionally, the FDA fears previously unseen infections that cannot be detected by existing clinical tools.

Wake Forest scientists are also exploring 3-D printing replacement kidneys, commonly referred to as bioprinting. To bioprint an organ, scientists would feed stem cells into a 3-D printer and then program the cells to differentiate into the types necessary to construct an organ. Meanwhile, other Wake Forest researchers are looking into cell therapy to improve kidney function.

Though these treatments inspire hope, “all are experimental and not yet ready for patients,” Richardson said.