[Show abstract][Hide abstract] ABSTRACT: This article reviews the outcome of pancreas transplantations in diabetic recipients according to risk factors, surgical techniques, and immunosuppression management that evolved over the course of a decade at Wake Forest Baptist Medical Center. A randomized trial of alemtuzumab versus rabbit anti-thymocyte globulin (rATG) induction in simultaneous kidney-pancreas transplantation (SKPT) at our institution demonstrated lower rates of acute rejection and infection in the alemtuzumab group. Consequently, alemtuzumab induction has been used exclusively in all pancreas transplantations since February 2009. Early steroid elimination has been feasible in the majority of patients. Extensive experience with surveillance pancreas biopsies in solitary pancreas transplantation (SPT) is described. Surveillance pancreas biopsy-directed immunosuppression has contributed to equivalent long-term pancreas graft survival rates in SKPT and SPT recipients at our center, in contrast to recent registry reports of persistently higher rates of immunologic pancreas graft loss in SPT. Furthermore, the impact of donor and recipient selection on outcomes is explored. Excellent results have been achieved with older (extended) donors and recipients, in recipients of organs from donation after cardiac death donors managed with extracorporeal support, and in African-American patients. Type 2 diabetics with detectable C-peptide levels have been transplanted successfully with outcomes comparable to those of insulinopenic diabetics. Our experiences are discussed in the light of findings reported in the literature.
The Review of Diabetic Studies 01/2011; 8(1):17-27. DOI:10.1900/RDS.2011.8.17
[Show abstract][Hide abstract] ABSTRACT: Background: Increased risk of infectious complications (ICs) after kidney (K) and pancreas (P) transplant (Tx) is a major concern when using lymphocyte depleting antibody induction agents such as alemtuzumab (Alem) and rabbit anti-thymocyte globulin (rATG).
Methods: We conducted a prospective, randomized trial comparing single dose Alem (30 mg) to alternate day rATG (1.5 mg/kg) induction in adult KTx and PTx patients (pts). Maintenance therapy was tacrolimus, mycophenolic acid, and risk stratification to determine early steroid elimination. Infection prophylaxis was given for fungal (1 month KTx; 2 month PTx), pneumocystis (12 month), and CMV (3 months; 6 months for primary CMV exposure). ICs were graded according to NIH Clinical Toxicity Criteria (CTCAE version 3.0).
Results: Between 2/1/05 and 8/31/08 (median follow-up 24 months), 222 pts were enrolled (113 randomized to Alem,109 to rATG induction). Demographics were similar between groups and 52 pts (23%) were age >60. Overall pt, KTx, and PTx survival rates were 95%, 90%, and 85%, respectively, and were comparable between groups (p=NS). Incidence of biopsy proven acute rejection (BPAR) was lower in the Alem (16%) vs rATG group (26%, p= 0.03). A total of 125 ICs occurred in Alem vs 154 ICs in rATG pts (p=NS). Of 113 Alem pts, 61 (54%) developed ICs compared to 81 (74%, p=.002) in the rATG group. Grade 2 (moderate) ICs occurred in 62 (55%) Alem vs 75 (69%, p=.04) rATG pts. Grade 3 (serious) ICs occurred in 52 (46%) Alem vs 75 (69%,p=.0007) rATG pts, whereas Grade 4 (life-threatening) ICs occurred in 8 (7%) Alem vs 1 (1%, p=.04) rATG pts. There was 1 Grade 5 (death) IC in each group. The incidence of polyoma (BK) viral infection was 1.8% in Alem vs 8% (p=.03) in rATG pts. CMV viremia occurred in 9 (8%) Alem vs 19 (17%, p=.04) rATG pts, and was more frequent with D+/R- (23%) and D+/R- (15%) serostatus. 11 fungal infections occurred in each group. Pts >60 did not exhibit a higher risk of infection, whereas the presence of BPAR increased the overall risk of ICs from 41% to 72% (p<.001).
Conclusion: Alem is associated with a lower incidence of BPAR and ICs compared to rATG induction regardless of pt age.
[Show abstract][Hide abstract] ABSTRACT: Background. Alemtuzumab and rabbit antithymocyte globulin (rATG) are commonly used for induction of immunsuppression for kidney and pancreas transplantation, but the two agents have not been compared directly.
Methods. We conducted a prospective randomized single-center trial comparing alemtuzumab and rATG induction in adult kidney and pancreas transplantation in patients treated with similar maintenance immunosuppression.
Results. Between February 1, 2005, and September 1, 2007, 222 patients randomly received either alemtuzumab (n=113) or rATG (n=109) induction; 180 (81%) underwent kidney alone, 38 (17%) simultaneous pancreas-kidney, and 4 (2%) pancreas after kidney transplants. Of 180 kidney-alone transplants, 152 (84%) were from deceased donors, including 61 (34%) from expanded criteria donors. Retransplantation, human leukocyte antigen match, antibody titer, expanded criteria donors, race, cytomegalovirus status, delayed graft function, and immunologic risks were similar between the two induction groups. With a median follow-up of 2 years (minimum 1 year), overall patient, kidney, and pancreas graft survival rates were 96%, 89%, and 90%, respectively. Survival, initial length of stay, and maintenance immunosuppression (including early steroid elimination) were similar between alemtuzumab and rATG groups, but biopsy-proven acute rejection (BPAR) episodes occurred in 16 (14%) alemtuzumab patients compared with 28 (26%) rATG patients (P=0.02). Late BPAR (>12 months after transplant) occurred in 1 (8%) alemtuzumab patient and 3 (11%) rATG patients (P=NS). Infections and malignancy were similar between the two induction arms.
Conclusion. Alemtuzumab and rATG induction therapies were equally safe, but alemtuzumab was associated with less BPAR.
[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to review the incidence, risk factors, and impact of bacteremia after pancreas transplantation (PTX).
We performed a retrospective analysis of consecutive simultaneous kidney-pancreas transplantations (SKPTs) and solitary PTXs from January 2002 through April 2007. Positive blood cultures were correlated with other coexisting infections and parameters.
One hundred ten PTXs with enteric drainage included 80 SKPTs and 30 solitary PTXs. Mean follow-up was 32 months. Bacteremia occurred in 29 (26%) patients with 5 (17%) being recurrent; it was seen during the first month after transplantation in 13 (12%), between 1 and 3 months in 12 (11%), between 3 and 12 months in 3 (3%), and after the first year in 3 cases (3%). Typical organisms were as follows: MRSE, MSSE, Klebsiella, Escherichia coli, vancomycin-resistant enterococci (VRE), and Acinetobacteri. Bacteremia was associated with coexisting site infection in 20 cases (69%): deep abdominal wound (31%); line (31%); urinary tract (34%); and pulmonary (7%). Similar bacterial species in blood and a coexisting site occurred in 15 cases (52%). No correlation was seen with cytomegalovirus (CMV) infections. In the first year, bacteremia was associated with more acute rejection episodes (32% vs 17%; P = .09), surgical complications (54% vs 42%; P = .267), mortality (11% vs 4%; P = .15), and death-censored pancreatic (14% vs 9%; P = .39) and kidney (4% vs 0; P = .08) graft loss. Fewer patients with bacteremia received alemtuzumab compared with rATG induction (14% vs 39%; P = .04).
Bacteremias were common within 3 months of PTX. A significant number (39%) were multidrug resistant. The majority were accompanied by abdominal, urinary, or line infections. Bacteremias were associated with slightly higher incidences of rejection, mortality, and graft loss.