Introduction: Experiences with simultaneous pancreas-kidney transplantation (SPKT) in uremic patients with detectable pretransplant C-peptide (Cp) levels with a “type 2” diabetes mellitus (DM) phenotype have demonstrated survival outcomes equivalent to those with type 1 (Cp negative) DM.  However, few studies have analyzed these outcomes in a case-control fashion. The study purpose was to evaluate outcomes in SPKT recipients according to presence or absence of pretransplant Cp.
Methods:  Selection criteria for Cp positive (Cp+, ≥2.0 ng/ml) were similar to Cp negative (Cp-) patients. We retrospectively analyzed 215 SPKTs performed at our center between 8/02 - 5/19 and identified 41 patients who were Cp+ pretransplant (mean level 5.4 ng/ml) and compared to 41 Cp- (level undetectable) case controls matched for recipient age, gender, race, and date of transplant. All SPKTs were performed as intent to treat with portal-enteric drainage; all patients received depleting antibody induction with FK/MMF ± steroids.  Pancreas graft failure (GF) was defined as return to daily insulin therapy. 
Results: The two groups were well-matched for numerous donor, preservation, recipient, and immunological characteristics. Mean donor (26 Cp+ vs 23 years Cp-) and recipient (both 44 years) ages were similar. Both groups had 21 males/20 females and 19 Caucasian (C)/20 African American (AA) patients. There was one early death secondary to infection in each group. There were no other early (<6 month) kidney GFs in either group. There were 5 other early pancreas GFs, 3 in Cp+ and 2 in Cp- patients. With a mean follow-up of 7.3 years in both groups, 5-year patient survival (PS, 93% vs 95%), kidney graft survival (GS, 73% vs 85%), and pancreas GS (68% vs 85%, p=0.11) rates were slightly lower in Cp+ vs Cp- patients, respectively. Death-censored kidney (69% vs 73%) and pancreas GS (59% vs 81%, p=0.07) rates were also slightly lower in Cp+ vs Cp- patients, respectively.  The Cp+ group had fewer deaths with functioning grafts (9.8% vs 19.5% Cp) but more pancreas GFs (9.8% vs 0 Cp-, p=0.12) due to either insulin resistance (in patients with normal C-p levels and excessive weight gain) or rejection (19.5% vs 12% Cp-, p=NS). There were no differences in outcomes according to gender or race.  Post-transplant weight gain >3 kg occurred in 76% of Cp+ vs 32% of Cp- patients (p=.0001). Mean post-transplant weight gain was 15 kg in Cp+ vs 6.5 kg in Cp- patients (p<.001). In patients with functioning grafts, mean post-transplant Cp (4.9 vs 2.6 ng/ml), HbA1c (5.5 vs 5.2%) and serum creatinine (1.4 vs 1.2 mg/dl) levels were slightly higher in Cp+ patients whereas mean eGFR levels (61 vs 66 ml/min/1.73 m2) were slightly lower compared to Cp- patients.
Conclusions: In this matched case-control study, survival and functional outcomes in Cp+ patients are slightly inferior following SPKT, with post-transplant weight gain and GF due to insulin resistance or rejection accounting for differences in outcomes.