Simultaneous pancreatic kidney transplants are increasingly being performed in the United States in people with type 2 diabetes who also have chronic kidney disease, with results similar to those in people with type 1 diabetes.
Traditionally, pancreatic transplant recipients have been people with type 1 diabetes who also have either chronic kidney disease (CKD) or hypoglycemic unconsciousness. The former group could have either a simultaneous pancreatic kidney or a pancreas after a kidney transplant, while the latter – if they have normal kidney function – could be eligible for a pancreatic transplant alone.
But in recent years, patients with type 2 diabetes and CKD have increasingly received concurrent pancreatic kidney transplants, with success rates similar to those with type 1 diabetes.
Such candidates are typically reasonably fit, not pathologically obese, and on insulin regardless of their C-peptide status, said Jon S. Odorico, MD, professor of surgery and director of pancreatic and islet transplantation at the University of Wisconsin, Madison’s transplant program .
“One might ask, is it a crazy idea to have pancreatic transplants in people with type 2 diabetes? Based on the known mechanisms of hyperglycemia in these patients, it could look like this, ”he said, noting that people with type 2 diabetes usually have insulin resistance, many also have a relative or absolute lack of insulin production.
“By replacing the beta-cell mass, pancreatic transplantation addresses this beta-cell defect mechanism,” he explained as he discussed the topic during a symposium held on June 26th at the 81st virtual American Diabetes Scientific Sessions Association (ADA) took place.
Among the arguments in favor of concurrent pancreatic kidney transplantation in people with type 2 diabetes and CKD is the fact that type 2 diabetes is the leading cause of kidney disease in the United States – around 50-60% of the candidates also have type 2 diabetes on the kidney transplant waiting list – and that a kidney transplant tends to worsen diabetes control just because of the immunosuppression required.
In addition, waiting times for the former are shorter and kidney quality is generally better than a kidney transplant alone, unless a living kidney donor is available.
And Odorico added, “Adding a pancreas to a kidney transplant does not appear to jeopardize patient survival or the kidney transplant in appropriately selected patients with diabetes.” However, he also noted that due to the heterogeneity of type 2 diabetes, the ideal candidates for a simultaneous pancreatic kidney transplant are not yet clear.
Currently, people with type 2 diabetes make up about 20% of those who receive a pancreatic kidney transplant at the same time, and about 50% of the pancreas after a kidney transplant. Few pancreatic transplants alone are done for type 2 diabetes, as these people rarely experience severe life-threatening hypoglycemia, Odorico explained.
Criteria have shifted over time, C-peptide was removed in 2019
In an interview with Medscape Medical News, symposium moderator Peter G. Stock, MD, PhD, surgical director of the Kidney and Pancreatic Transplant Program at the University of California, San Francisco, agreed that “it’s a surprising trend. It doesn’t make any intuitive sense. In type 1 diabetes, it makes sense to replace the beta cells. But type 2 is due to a whole range of etiologies … Public opinion is that it is not insulin deficiency, but problems with insulin resistance and obesity. So it doesn’t make much sense to give yourself more insulin if it’s a receptor problem. “
But Stock noted that because in the past the type of diabetes was not always rigorously assessed with C-peptide and antibody tests, which most centers measure today, “a number of transplants have been performed in people who were found to be Had type 2. Our perception is that “anyone who has type 2 is obese, but that’s no longer true.”
When it was found that some patients with type 2 diabetes who appeared to be doing well with a pancreatic transplant appeared to be doing well, the United Network for Organ Sharing (UNOS) pancreatic transplant committee set general criteria for the procedure in people with diabetes . You had to take insulin with a C-peptide value of 2 ng / ml or less or insulin with a C-peptide greater than 2 ng / ml and a body mass index less than or equal to the maximum permitted BMI (28 kg / m2 at this point).
Stock, who chaired that committee from 2005 to 2007, said: “We felt it was risky to offer people with type 2 a scarce supply of donor pancreas when we had people with type 1 that we know will benefit them . The committee decided to limit pancreatic transplants to those with type 2 who have relatively low insulin needs and a BMI that is more in the range of people with type 1. Lo and behold, the results were comparable. “
After Stock’s tenure as chairman, the UNOS committee decided that the BMI and C-peptide criteria for the simultaneous pancreatic kidney can no longer be scientifically justified and are potentially discriminatory both for minorities with type 2 diabetes and for people with type 2 diabetes. 1 diabetes with a high BMI so they removed it in 2019.
Individual transplant centers must adhere to the UNOS rules, but can also add their own criteria. Some do not perform concurrent pancreatic kidney transplants at all in people with type 2 diabetes.
At the Odorico center, which began in 2012, nearly 40% of all concurrent pancreatic kidney transplants are in patients with type 2 diabetes. Indications there are age 20-60 years, depending on insulin with a requirement of less than 1 unit / kg / day, CKD stage 3-5, predialysis or dialysis and BMI <33 kg / m2.
“They are highly selected and a fairly appropriate group of patients,” noted Odorico.
Those who don’t meet all of the requirements for a simultaneous pancreatic kidney transplant may still be eligible for a kidney transplant alone, from either a living or deceased donor, he said.
Stock’s criteria at UCSF are even stricter for both BMI and insulin requirements.
SPK results similar for type 1 and type 2 diabetes: new data
Data guiding this area is slowly accumulating. So far, all studies have been retrospective and used variable definitions for type of diabetes and transplant failure. However, they show fairly consistently similar results by type of diabetes and little impact of C-peptide levels on patient survival or kidney or pancreatic transplant survival, especially after adjustment for confounding factors between the two types.
In a study by the Odorico Center with 284 type 1 and 39 type 2 diabetes patients who underwent simultaneous pancreatic kidney transplantation between 2006 and 2017, the BMI and the insulin requirement before the transplantation had no effect on either type aimed at patient or transplant survival. Very high pre-transplant insulin needs (> 75 units / day) were suspected to be at higher risk of post-transplant diabetes, but the numbers were too small to be definitive.
“It is clear that we will have more pancreatic transplants in this patient population in the future and it is ripe for further investigation,” concluded Odorico.
Beta cells for everyone?
Stock added another aspect. While whole organ transplants are naturally limited by the lack of human donors, stem cell-derived beta cells could potentially produce an unlimited amount. Both Stock and Odorico are working on different approaches.
“We’re very close,” he said, noting, “the data we’re getting from people with type 2 diabetes who are undergoing solid pancreatic transplants could also be applied to cell therapy … we need to better understand which ones Patients Will Do This The data we have so far is very promising. “
Odorico is a Scientific Founder, Shareholder, Chairman of the Scientific Advisory Board, and a former Regenerative Medical Solutions grant recipient. He has reported receiving clinical trial support from Veloxis Pharmaceuticals, CareDx, Natera, and Vertex Pharmaceuticals. Stock reported that he is a member of Encellin’s Scientific Advisory Board and is funded by the California Institute of Regenerative Medicine and the National Institutes of Health.
Scientific meetings of the ADA 2021. Presented on June 26th, 2021.
Miriam E. Tucker is a freelance journalist based in the Washington, DC area. She is a regular contributor to Medscape, with other work appearing in the Washington Post, NPR’s Shots blog, and Diabetes Forecast magazine. She’s on Twitter: @MiriamETucker.
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