Low Renal Function Increases ESRD Risk after Pancreas Transplantation

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QUEBEC CITY, QUEBEC— End-stage renal disease (ESRD) eventually develops in more than half of patients with moderate kidney dysfunction at the time of pancreas transplantation, according to new findings presented at the Canadian Society of Transplantation's 2012 Annual Meeting.

From an analysis of data from the U.S. Scientific Registry of Transplant Recipients (SRTR) and the United States Renal Data System, investigators discovered that patients undergoing pancreas transplantation who had an estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m2 were eight times more likely than patients with normal renal function to develop ESRD within a decade. This relationship had been strongly suspected but never before quantified using such a large dataset, according to the investigators.

“An eightfold increase is almost unheard-of magnitude these days with respect to risk factors,” lead investigator S. Joseph Kim, MD, PhD, of the University Health Network in Toronto, told Renal & Urology News. “The big question is whether one can predict which specific patients will develop ESRD after pancreas transplantation and the appropriate timing of kidney transplantation in this subset of patients.”

Dr. Kim's team studied information from the SRTR on all pancreas transplant recipients in the United States between January 1, 1994 and December 31, 2009. They excluded patients who underwent simultaneous pancreas-kidney transplants, received a pancreas after a kidney, or were younger than 18 years. Their other exclusion criteria were the presence of ESRD prior to transplant, previous pancreas transplant, and not having serum creatinine data available from the time of pancreas transplant.

The investigators focused on differences in patients' outcomes based on whether at the time of pancreas transplant their eGFR (in mL/min/1.73 m2) was below 60, 60-89.9, or above 90, as determined using the Chronic Kidney Disease Epidemiology Collaboration equation. The three categories included 269, 338, and 528 patients, respectively. Overall, the patients' had a mean and median eGFR of 83.3 and 87.1, respectively.

Patients with an eGFR greater than 90 were significantly younger than the others (average 38.5 vs. 43.7 years for those with an eGFR below 60 and 43.6 years for patients with an eGFR of 60-89.9). Furthermore, a smaller proportion was female (52.7% vs. 59.1% and 59.5%), and fewer were white (93.6% vs. 95.5% and 94.4%). Moreover, fewer of the donors to recipients with an eGFR above 90 were female (32.8% vs. 37.2% and 35.2%).

The cumulative incidence of ESRD was significantly higher among patients who at the time of pancreas transplant had an eGFR below 60: about 54% at 10 years post-transplant compared with 30% for recipients with an eGFR of 60-89.9 and 23% for those with an eGFR above 90.

“The survival curve for people in the group with the lowest eGFR at time of transplant is quite different from the curves for the other two groups, with a very statistically significant increase in ESRD incidence over time”, Dr. Kim noted.

Recipients with an eGFR below 60 had an eightfold greater risk of developing ESRD compared with those with an eGFR above 90. Each 10 mL/min/1.73 m2 increase in eGFR at the time of pancreas transplantation was associated with a 20% reduction in ESRD risk. These results remained consistent when the investigators re-analyzed the data using the Modification of Diet in Renal Disease equation for calculating eGFR and used a statistical model that explicitly accounted for the competing risk of death.

Venkatesh Krishnamurthi, MD, Director of the Kidney and Pancreas Transplant Programs at the Cleveland Clinic, said the new findings are robust but do not point to the need for simultaneous kidney-pancreas transplants in people with suboptimal kidney function.

“These are patients who don't need a kidney transplant and they haven't had one before—usually because their diabetes control is very brittle,” Dr. Krishnamurthi said. “There are plenty of patients who need a kidney transplant immediately, so it's not fair to give a kidney instead to someone who might not need one for many years. It's a tough situation due to limited resources.”

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