Pretransplant C-peptide Levels and Pancreas Transplant Outcomes: Risk and Reward.

Abstract

We read with interest the report by Parajuli et al1, chronicling the University of Wisconsin experience in simultaneous pancreas-kidney transplantation (SPKT) according to the pretransplant fasting serum C-peptide levels. The authors demonstrated that higher pretransplant C-peptide levels predicted the risk of a composite outcome (combination of pancreas graft failure according to the United Network for Organ Sharing definition and pancreas graft dysfunction defined as initiation of any antidiabetic agent) posttransplant in patients with a type 2 diabetes phenotype.1,2 Recipients were categorized into 3 groups based on pretransplant fasting serum C-peptide levels: low (≤2 ng/mL, n = 14), medium (>2–8 ng/mL, n = 47), and high (>8 ng/mL, n = 15). The uncensored composite outcome of pancreas graft failure or dysfunction occurred in 0% in the low, 23% in the medium, and 33% of patients in the high C-peptide groups, respectively, suggesting that higher levels of pretransplant C-peptide are associated with inferior posttransplant outcomes. These findings confirm our recent report based on a case-controlled, single-center, retrospective study of 46 SPKT patients with pretransplant fasting serum C-peptide levels ≥2.0 ng/mL compared with 46 control patients (C-peptide level <0.5 ng/mL) matched for recipient age, gender, race, and transplant date.3 In our study, we likewise reported inferior mid-term outcomes in the group with higher pretransplant C-peptide levels. In our overall SPKT experience, we have 205 patients with a minimum of 5-y follow-up. Using the above C-peptide categories as per the Wisconsin study, we identified 166 patients in the low, 32 patients in the medium, and 7 patients in the high C-peptide groups. Five-y actual (uncensored) patient and graft survival rates were as follows: patient (91% low versus 93.8% medium versus 85.7% high) and kidney (80.7% versus 71.9% versus 71.4%), respectively. Using the composite end point of pancreas graft failure or dysfunction, pancreas outcomes were 25.3% low versus 34.4% medium versus 71.4% high C-peptide (P = 0.10). Similar to the Wisconsin study, we are limited by the small sample size in the high pretransplant C-peptide group but the findings indicate a trend toward a greater need for supplemental antidiabetic therapy in patients with higher pretransplant C-peptide levels. Unfortunately, what is missing from these studies is a better characterization of patients with partial pancreas allograft function (dysfunction) who continue to be free from wide glycemic excursions and do not experience hypoglycemia (despite the need for antidiabetic therapy) because of preserved counterregulatory function of the pancreas allograft.4 In our experience, we identified posttransplant weight gain, insulin resistance, and rejection as potential mitigating factors to explain these inferior outcomes. Consequently, we recommend greater emphasis on weight management strategies, behavioral modification, nutritional counseling, structured physical training programs, timely adjustments in (and use of less diabetogenic) immunosuppression, more intense long-term monitoring by the transplant center, and increased use of novel antidiabetic agents such as Glucagon-like peptide 1 receptor agonists and Sodium-glucose cotransporter-2 inhibitors when indicated in this unique population. We congratulate the authors on this excellent study and agree that these findings should not be an impetus to limit access to pancreas transplantation but rather help guide clinical decision-making and optimize posttransplant management.