First Gene-Edited Pig Kidney Functioned Until Recipient’s Death

The world’s first recipient of a gene-edited pig kidney died from cardiac causes within 2 months, but there was no evidence of xenograft rejection, a brief report detailed.

After undergoing the xenotransplant in March 2024, 62-year-old Richard ‘Rick’ Slayman had sustained kidney function but then died suddenly on day 52 from severe coronary artery disease and ventricular scarring, reported Tatsuo Kawai, MD, PhD, of the Transplant Center at Massachusetts General Hospital in Boston, and colleagues in the New England Journal of Medicine.

“There was no evidence of acute myocardial infarction, pulmonary embolism, pneumonia, inflammation in other organs, or drug toxicity,” they wrote. “We concluded that the patient had probable sudden cardiac death caused by dysrhythmia in the context of severe ischemic cardiomyopathy.”

“With such severe ischemic heart disease, the risk of sudden death from dysrhythmia remains substantial in any patient, especially after a major surgical procedure,” they added. “However, we cannot exclude the possibility that frequent fluctuations in intravascular volume, possibly caused by a dysfunctional RAAS [renin-angiotensin-aldosterone system] in the pig kidney, may have increased the risk of cardiac dysrhythmia in a patient with severe ischemic heart disease.”

Kawai simultaneously presented the case at the International Society of Nephrology World Congress in New Delhi, India.

Slayman, who underwent the 4-hour procedure at Massachusetts General Hospital, had end-stage kidney disease (ESKD) caused by type 2 diabetes and had “exhausted nearly all viable vascular access for dialysis,” according to the authors. He had a history of myocardial infarction, severe vasculopathy, heart failure, and total parathyroidectomy. He received a deceased donor kidney in 2018 but returned to hemodialysis after a graft failure associated with BK virus infection and recurrent diabetic nephropathy in May 2023.

“His chance of receiving a transplant within 5 years was only 16%, with a 76% likelihood of dying or becoming too ill to receive a transplant,” Kawai and co-authors noted.

He received a gene-edited porcine kidney with 69 genomic edits, including deletion of three glycan antigens, inactivation of porcine endogenous retroviruses, and insertion of seven human transgenes. The xenograft functioned immediately, resulting in a prompt and progressive drop in creatinine levels, and dialysis was no longer needed.

On day 8, the patient experienced a 0.7-mg/dL increase in plasma creatinine level, fever, allograft tenderness, and decreased urine output. “The pattern and timing of rejection in this patient suggested that early subtherapeutic levels of tacrolimus and mycophenolic acid may have contributed to the development of T-cell-mediated rejection,” Kawai’s group wrote. An intensified immunosuppression regimen with methylprednisolone and tocilizumab reversed rejection.

On day 34, a xenograft biopsy was performed due to an increase in creatinine of 1.9 to 2.65 mg/dL. The biopsy showed resolution of the T-cell-mediated rejection but with C3 deposition, focal interstitial fibrosis, and tubular atrophy without evidence of antibody-mediated rejection or thrombotic microangiopathy. Creatinine decreased with hydration, and anti-porcine antibody titers remained lower than values in human serum controls.

Kawai and co-authors said that although kidney dysfunction on day 34 was reversed with hydration, more studies are needed to assess possible differences in the hemodynamic regulation of glomerular filtration by pig kidneys transplanted to humans.

Despite the short 52-day observation period, this was the first case to demonstrate that a gene-edited pig kidney could provide life-supporting kidney function in a living human, said Kawai and colleagues. “Xenotransplantation offers a potential solution to the organ shortage crisis,” they added.

Since this case, other successful gene-edited pig kidney xenotransplants have been performed. In April 2024, a 54-year-old New Jersey woman became the first-ever patient to undergo combined mechanical heart pump and gene-edited pig kidney transplant surgery at NYU Langone Health in New York City. She died on July 7.

In December 2024, 53-year-old Towana Looney was able to go off dialysis after receiving a gene-edited pig kidney transplant at NYU Langone Health. As of January 25 — 61 days after surgery — Looney achieved the milestone of being the longest living recipient of a pig organ transplant.

Most recently, 66-year-old Tim Andrews underwent transplant on Jan. 25, and is recovering well, according to Massachusetts General Hospital.

Earlier this week, the FDA cleared eGenesis (who made Slayman’s pig kidney) and United Therapeutics Corporation to begin clinical trials of gene-edited pig kidney transplants for patients with kidney failure. The eGenesis clinical trial will reportedly start with three patients living with kidney failure who are unlikely to receive a human organ within 5 years. United Therapeutics Corporation will enroll an initial six patients with ESKD and expand to up to 50 participants.

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