Simultaneous kidney-pancreas transplant patients may be at risk for long-term kidney dysfunction if they continue to meet criteria for metabolic syndrome 1 year after the procedure, according to a prospective study.
The risk of long-term kidney dysfunction was especially high if patients had both metabolic syndrome and pancreas graft failure 1 year after transplantation. Poor selection of the pancreas graft or technical failures during surgery may contribute to pancreas graft loss and incomplete correction of metabolic syndrome in patients, according to surgeons who were interviewed.
In the study, Dr. Jeffrey Rogers, then at the Medical University of South Carolina, Charleston, and his colleagues used data from 241 insulin-dependent (mostly type 1) diabetic patients who were participating in a randomized, double-blind trial that tested different dosing regimens of daclizumab after simultaneous kidney-pancreas transplantation (Transplant. Proc. 2005;37:3549–51).
The incidence of metabolic syndrome in the patients decreased from 59% pretransplantation to 19% 1 year after the procedure.
But all of the patients could have potentially been free from metabolic syndrome had they received adequate pancreas grafts, Dr. David Sutherland said in an interview.
Two scenarios could explain why these patients developed metabolic syndrome, suggested Dr. Sutherland, director of the Diabetes Institute for Immunology and Transplantation at the University of Minnesota, Minneapolis. Some patients may have had a severe form of metabolic syndrome in which their insulin resistance or need for insulin was so high that even a normal pancreas could not have reduced their blood glucose level. Other patients may have had a form of metabolic syndrome that could have been reversed by receipt of a normal, healthy pancreas. Imperfect testing of deceased donors may be the reason these patients continued to have metabolic syndrome after transplant, he said.
Brain-dead donors on life support often have hyperglycemia because they receive drugs that raise blood glucose levels, such as steroids, Dr. Sutherland said. At the University of Minnesota, donors are given insulin so that hyperglycemia doesn't damage the beta islet cells of the pancreas. Donors who require hundreds of units of insulin to decrease their blood glucose level have extreme insulin resistance but may actually have a good pancreas, he said.
One can be more certain that donors who require 4 or 5 units of insulin to reduce their blood glucose level have a bad pancreas because the organ was not able to produce that amount of insulin itself.
Yet “most people think the opposite,” Dr. Sutherland said. “If it takes 4 to 5 units for blood glucose to come down, they think, 'Oh, good, we'll use the pancreas.' Actually, that's the one I wouldn't use.”
One can be “absolutely sure” that a pancreas is healthy when a donor does not need any insulin and has a normal blood glucose level despite the stress of brain death, he said.
Data on the donors were not provided in the current study.
Many of the donors were likely hyperglycemic when the organs were procured, and probably little attention was paid to how much insulin it would take to correct hyperglycemia in those donors, Dr. Sutherland surmised.
None of the patients with metabolic syndrome who developed pancreas graft failure at 1 year had a prior documented episode of kidney or pancreas rejection. Pancreas graft failure in these patients did not develop secondary to rejection of the organ.
“To me, that means that they got bum pancreases to begin with,” Dr. Sutherland said.
In the study, the presence of metabolic syndrome in patients after 1 year was significantly associated with several changes 3 years after transplant, including decreased glomerular filtration rate, increased HbA1c levels, a lower rate of pancreas graft survival, and a higher rate of acute pancreas graft rejection.
When rejection is diagnosed in one graft in simultaneous kidney-pancreas recipients, most of the time rejection is present in the other grafts as well, Dr. Rogers said in an interview. But in the current study, metabolic syndrome patients with and without pancreas graft failure at 1 year had similar rates of kidney rejection, which suggests that kidney rejection did not play a role in the difference in kidney function.
Pancreas grafts probably failed early in patients with metabolic syndrome because of thrombosis or other technical problems, said Dr. Rogers, who is now in the surgery department at Wake Forest University, Winston-Salem, N.C.
Dr. Rogers suggested using low-dose anticoagulation postoperatively, and being cautious about using pancreases that are fatty, are from older donors, or are from donors who died of a stroke.