A pair of genetically modified pig kidneys filtered blood and produced urine for 7 days after being transplanted into a brain-dead patient ― marking another important step toward opening up a new supply of much-needed organs for those with end-stage kidney disease.
A team of researchers in Alabama removed a brain-dead person’s own kidneys and transplanted two kidneys that had been taken from a genetically modified pig. The researchers monitored the patient’s response to the organs and tracked the kidneys’ function over a 7-day period. The findings were published today in JAMA Surgery.
During the first 24 hours after transplantation, the pig kidneys made more than 37 liters of urine. “It was really a remarkable thing to see,” lead investigator Jayme Locke, MD, professor of surgery and the Arnold G. Diethelm Endowed Chair in Transplantation Surgery, University of Alabama at Birmingham, said in a press release.
The recipient was given standard maintenance immunosuppression ― tacrolimus, mycophenolate mofetil, and prednisone. The target tacrolimus level (8–10 ng/dL) was reached by postoperative day 2 and was maintained through study completion
At the end of the study, the serum creatinine level was 0.9 mg/dL, and creatinine clearance was 200 mL/min. Creatinine levels are an indicator of kidney function and demonstrate the organ’s ability to filter waste from blood, according to Roger Lord, PhD, senior lecturer (medical sciences) in the School of Behavioural and Health Sciences, Australian Catholic University, who was not involved in the research.
This is the first time that it has been demonstrated that a standard immunosuppression regimen may be sufficient to support xenotransplantation with pig kidneys and in which creatinine clearance was achieved.
The finding comes less than 2 years after the same team published results from a similar experiment. In that transplant, the investigators didn’t observe significant creatinine excretion into the urine.
In the team’s previous attempts, kidney function was delayed because the brain-dead recipients had deteriorated physiologically. This time, the subject was stable, and the team was able to observe urine production within 4 minutes of restoration of blood flow to the transplanted pig organs.
“This new work firmly establishes that the xenografts not only make urine but provide life-sustaining kidney function by clearing serum creatinine,” Locke told Medscape. “This is the first time in history this has been shown.”
The investigators are hoping animal-sourced organs could become an alternative for human transplantations, potentially solving the serious shortage of human organs available for patients on transplant waiting lists.
Organ transplantation can treat patients with advanced kidney disease and kidney failure, but there are not enough human organs available to meet the need. More than 92,000 people in the US are waiting for a kidney, according to the American Kidney Fund.
Organ rejection is a risk with xenotransplants ― animal-to-human organ transplants. Investigators in this study used kidneys from pigs with 10 gene modifications. The modifications were intended to decrease the likelihood of the organs being rejected by a human host.
The kidneys were still viable at the end of the 7-day period. In addition, there was no microscopic blood clot formation, another indicator of normal kidney function, according to Lord, who provided comments to the UK Science Media Centre.
The long-term outcomes of animal-to-human organ transplantation remain unclear. Lord describes the operation as a “first step” to demonstrate that genetically modified, transplanted pig kidneys can function normally so as to remove creatinine over a 7-day period.
Locke and colleagues say: “Future research in living human recipients is necessary to determine long-term xenograft kidney function and whether xenografts could serve as a bridge or destination therapy for end-stage kidney disease.
“Because our study represents a single case, generalizability of the findings is limited. This study showcases xenotransplant as a viable potential solution to an organ shortage crisis responsible for thousands of preventable deaths annually,” they conclude.
JAMA Surg. Published online August 16, 2023. Full text