2025’s Turning Point: Gene-Edited Pig Kidneys in Trials

The year pig kidneys moved from headlines to clinics

On January 25, 2025, surgeons at Massachusetts General Hospital implanted a genetically edited pig kidney into 66-year-old Tim Andrews. The hospital announced the success on February 7, reporting that the kidney was working and he was off dialysis. This was not a one-off. It was the second expanded-access pig-to-human kidney transplant at the same center, following the first of its kind there in March 2024. For patients and clinicians who have watched xenotransplantation make periodic splashes over the decades, these cases felt different. The results were not months of speculation around a single heroic attempt, they were steps in a cadence that continued through 2025.

Two regulatory decisions turned that cadence into something predictable. On February 3, 2025, the FDA cleared United Therapeutics to start the first U.S. clinical trial of a gene-edited pig kidney designed for potential registration, with predefined 24-week efficacy and safety endpoints and lifelong follow up for infection surveillance. United Therapeutics outlined these endpoints and the combination Phase 1/2/3 design in its announcement, as detailed in FDA clears UKidney trial design details.

Seven months later, on September 8, 2025, eGenesis announced FDA clearance of its own IND for a Phase 1/2/3 study of EGEN-2784, a gene-edited porcine kidney focused on dialysis-dependent patients age 50 and older on the transplant waitlist. That trial also centers on 24-week outcomes with structured safety surveillance and follows updates from an expanded-access program that produced the January transplant at MGH and a second transplant in June. See the company’s summary in eGenesis IND clearance and study overview.

With those two green lights, plus an April 2025 FDA authorization for a study of external pig-liver support as a bridge for acute liver failure, 2025 is the year xenotransplantation stops being a curiosity and starts to look like a therapeutic category. The center of gravity is the kidney, and the focus is clear: prove 24-week function with rigorous pathogen surveillance, then scale.

Why kidneys are the first longevity lever

Kidney failure is a disease of numbers and age. More than half a million Americans live on dialysis. Waitlists remain long, and older adults often face the longest waits because of blood type, comorbidities, or center-level criteria that prioritize expected graft longevity. Dialysis keeps people alive, yet it extracts a heavy toll: time tethered to treatments, cardiovascular strain, and a five-year mortality that rivals many cancers. For a 60- or 70-year-old with end-stage kidney disease, getting even a few high-quality years off dialysis can mean more independence, fewer hospitalizations, and a meaningful extension of healthy life.

Kidneys are also the most transplantable organ in terms of surgical complexity, postoperative management, and the ability to track success with routine labs. Xenokidneys offer two strategic advantages. First, they can be matched to size and delivered on schedule rather than waiting for an unpredictable human donor. Second, the biology that once made pig organs impossible has been engineered to reduce the triggers that cause immediate rejection and clotting.

These shifts echo other longevity advances that move from hype to scaled care, such as how GLP-1s at scale reshapes prevention and how immune aging is being targeted in restoring immune youth at the source.

The biology behind human-compatible pig kidneys

The main historical barrier to pig-to-human transplantation has been immunology. Human immune systems are primed to attack pig tissues within minutes, largely due to sugars on pig cell surfaces that human antibodies recognize.

Modern xenokidneys meet that challenge with three intertwined genetic strategies.

1) Glycan knockouts to silence the biggest alarms

GGTA1 encodes the enzyme that produces the alpha-gal epitope, a dominant target for preformed human antibodies. Knocking out GGTA1 removes alpha-gal and reduces the risk of hyperacute rejection.
CMAH produces Neu5Gc, a sialic acid humans stopped making over evolutionary time. Humans carry antibodies to Neu5Gc through diet; removing CMAH helps avoid a fast humoral response.
B4GALNT2 drives the Sd(a)-like antigen that can also trigger human antibodies. Deleting B4GALNT2 further lowers immediate antibody binding.

Together, these three deletions reduce the initial complement activation that used to destroy porcine grafts within hours.

2) Human transgenes to make pig endothelium act more like ours

Even with glycan removal, pig vessel linings are not fully compatible with human blood. Seven human genes commonly appear in leading xenokidney donors to address this mismatch.

Complement regulators such as human CD46 and CD55 help blunt complement-driven injury.
Coagulation modulators such as thrombomodulin and endothelial protein C receptor improve the balance between clotting and bleeding at the graft surface.
Anti-inflammatory and immune-modulating genes such as heme oxygenase 1 and TNFAIP3 reduce inflammatory cascades.
A don’t-eat-me signal like human CD47 helps limit macrophage activation.

The effect is to make the porcine endothelium behave more like human endothelium under human blood flow, reducing thrombotic microangiopathy and antibody-mediated injury that undermined earlier attempts.

3) Inactivation of porcine endogenous retroviruses, plus biosecure breeding

Porcine endogenous retroviruses, or PERVs, are viral sequences embedded in the pig genome. They rarely pose a problem in pigs, yet the theoretical risk of cross-species infection makes regulators and clinicians cautious. Using genome editing, developers can inactivate PERV sequences across the donor line. Combined with designated pathogen free facilities, barrier housing, and continuous surveillance, this reduces the risk of zoonotic transmission to very low levels. A key feature of both FDA-cleared kidney trials is not just editing but a plan for lifetime pathogen monitoring in recipients.

What the first U.S. trials will measure

If the field’s story has been one of stunning surgical feats followed by uncertainty, 2025 is when the questions are routinized into endpoints. Both cleared kidney trials share a core logic.

Primary horizon: 24-week graft and patient outcomes. The first milestone is six months of reliable kidney function, measured by survival of the recipient, survival of the xenokidney, change in measured GFR, and quality of life. United Therapeutics describes these endpoints and lifelong surveillance in FDA clears UKidney trial design details.
Safety playbook: layered monitoring. Frequent labs for creatinine, direct or estimated GFR, hemolysis, and clotting markers; protocol biopsies to catch subclinical rejection; PCR and culture-based surveillance for porcine pathogens; and public health safeguards over the long term.
Immunosuppression: targeted and adaptive. Regimens are tailored to blunt antibody-mediated injury without erasing immune surveillance. Costimulation blockade, complement inhibitors, and standard maintenance drugs can be combined and adjusted to keep the graft quiet while reducing infection risk. The precise cocktail varies by center and protocol, which is why multi-center trials matter.

The goal is not perfection on day one. It is reproducibility. If 24-week outcomes look like dependable allografts in the same risk band, the field can move to longer-term durability.

Real-world proof points in 2025

Three developments in 2025 reinforce that the biology is translating into care pathways, not just headlines.

Second expanded-access kidney at a major center. MGH’s January 25 transplant, disclosed February 7, showed a rapid return to kidney function, discharge within a week, and a clean early recovery. By midyear, a second patient at the same center also came off dialysis after a gene-edited pig kidney transplant.
First FDA-cleared kidney trials with registrational intent. United Therapeutics’ trial opens a path to a BLA if data are strong at 24 weeks and beyond, and eGenesis’ IND creates a parallel track focused on older, dialysis-dependent adults.
FDA green light for external pig-liver support. In April 2025, the agency authorized a study that connects a gene-edited pig liver to a patient outside the body, similar to a dialysis circuit for acute liver failure. That decision signals growing comfort with highly engineered porcine organs in tightly monitored human settings and broadens operational experience that kidney teams can leverage.

Risks that still need to be retired

Xenotransplantation is not skipping risk, it is reorganizing it.

Rejection and microvascular injury. Even with three glycan knockouts and multiple transgenes, antibody-mediated rejection remains possible. Thrombotic microangiopathy and complement-driven damage can still occur if immune control slips or if endothelial stress accumulates.
Infection risk, including porcine pathogens. Designated pathogen free herds, PERV inactivation, and serial testing bring risk down, not to zero. Trials build in frequent surveillance for early detection. Recipients will be followed for life.
Immunosuppressive burden. Drugs that protect grafts can predispose to infections and malignancies. Protocols must find a stable trough that preserves host defenses.
Surgical and urologic complications. Ureteral strictures, leaks, or vascular issues can occur, similar to human-to-human transplants. Centers will standardize techniques as experience grows.
Public health and ethics. Regulators require binding agreements from recipients for long-term monitoring and disclosure because theoretical zoonoses are a community risk. Consent must be robust, especially for patients who may feel pressure to accept a scarce lifeline. This conversation is evolving alongside the dog longevity pill precedent.

Despite these risks, the comparison set is not a healthy person. It is a dialysis-dependent older adult who may never receive a human kidney. For many, the trade-offs can be rational and humane if outcomes are predictable and monitoring is reliable.

Can this scale beyond a handful of cases

Scaling is not just more pigs. It is five systems moving in sync.

Biosecure supply. Donor pigs must be bred, housed, and tracked in designated pathogen free facilities with batch records, genetic stability checks, and continuous microbiologic surveillance.
Surgical capacity. Teams must master procurement from engineered donors and implantation in humans, including standardized anastomoses, ureteral management, and perioperative anticoagulation.
Immunology infrastructure. Centers need fast-turn diagnostics for donor-specific antibodies, complement activity, and graft injury markers, plus pharmacy programs that can source and dose specialized agents.
Long-term follow up. Registries, pathogen monitoring networks, and interoperability with public health departments are essential. Trials already require lifelong surveillance; a commercial ecosystem would make this routine.
Payment and policy. Medicare covers dialysis at great cost. If xenokidneys deliver sustained dialysis-free survival, payers will model cost offsets from fewer admissions, better functional status, and reduced dialysis sessions. Coding, coverage policies, and value-based agreements will follow data.

There are constraints. Gene editing must remain precise and stable across generations of donor lines. Even biosecure herds will have capacity limits at first. And because every recipient must be tracked for life, centers will scale deliberately. None of these barriers are conceptually new. They echo the early era of human transplantation, updated with genome engineering and real-time surveillance.

What success would mean for older adults on dialysis

If the 24-week readouts in these trials look like modern allografts, the beneficiaries will be older adults first.

Earlier access. Trial criteria that prioritize patients age 50 and older and those with low chances of receiving a human kidney align with the population carrying the most dialysis burden.
Fewer hours lost to treatment. Even a few years off dialysis translates into hundreds of spared sessions, better appetite and energy, and space for rehabilitation.
Lower cardiovascular stress. Dialysis swings fluids and electrolytes in ways that strain hearts, especially in older patients. A functioning graft smooths those curves.
A different conversation about transplant ethics. Instead of rationing a small number of human kidneys among older adults who are rarely first in line, clinicians can discuss engineered grafts with known monitoring and risk profiles.

Downstream, a consistent xenokidney option would reshape organ-aging care. Nephrology clinics would incorporate transplant education earlier. Rehabilitation and nutrition programs would aim at a predictable transplant date rather than an indefinite wait. Primary care would plan around immune surveillance rather than dialysis logistics. Even palliative care would shift, because some patients will choose comfort over a lifelong monitoring commitment and that choice should be just as supported.

For readers tracking the broader longevity landscape, these shifts mirror the move from mechanism to clinic seen in restoring immune youth at the source and in GLP-1s at scale reshapes prevention.

What to watch next

Enrollment pace and first 24-week data. Early cohorts are small by design. The first durability signals should emerge within months of the initial surgeries in each trial.
Pathogen surveillance reports. Expect protocol-driven updates on testing frameworks, not just negative results. The field advances when methods are transparent.
Immunosuppression optimization. Watch for dose-sparing strategies that maintain graft health while reducing infection risk.
Manufacturing capacity. As trials proceed, look for updates on donor herd capacity and designated pathogen free output. Stability and scale matter if payers are to model affordability.
The external pig-liver study. If a short-term support device shortens ICU stays or improves survival in acute liver failure, it will widen clinical and regulatory comfort with engineered porcine organs.

The bottom line

In 2025, xenotransplantation crossed a threshold. Two FDA-cleared kidney trials, anchored on 24-week function and lifelong safety surveillance, converted a decade of engineering into a clinical agenda. Compassionate-use surgeries showed real-world plausibility, and an external pig-liver support study broadened the organ toolkit. The risks are real and must be managed, yet for older adults on dialysis the alternative risks are already here, measured in hours, heart strain, and years of diminished life. If these trials hit their marks, pig kidneys move from headlines to a new rung on the longevity ladder for aging kidneys, with care pathways that look less like miracles and more like medicine.