Prevention and management of hyperglycemia after pancreas transplantation

PURPOSE OF REVIEW: Pancreas transplantation is considered the optimal therapy for patients with insulin-dependent diabetes. Successful pancreas transplantation achieves euglycemia and allows freedom from insulin therapy. Long-term allograft success may be limited by the development of impaired glucose metabolism. The objectives of the present review are to summarize the possible reasons for endocrine pancreatic dysfunction and to focus on its prevention and management and emphasize the role of immunosuppression. RECENT FINDINGS: The diabetogenic effects of current immunosuppressive agents have been well established. Regimens without corticosteroids and calcineurin-inhibitor minimization or avoidance have been promoted. Recent studies have revisited the pathogenesis of type I and type II diabetes and demonstrated common pathways, including apoptosis induction, for the exhaustion and destruction of the pancreatic islets. SUMMARY: The immunosuppressive regimens in pancreatic transplantation should be designed and appropriately modified according to the graft immunological and metabolic conditions. New molecules that are able to preserve islet function and maintain optimal insulin secretion should be considered for pancreas transplant recipients

A Technique for Autologous Priming of the Veno-Venous Bypass Circuit during Liver Transplantation

Orthotopic liver transplantations (OLT) have been associated with significant blood loss and hemodilution, necessitating significant homologous blood component replacement. Increasing administration of homologous blood products has been found to be inversely related to patient and graft survival. Various methods to reduce the amount of blood products patients receive during OLT, such as antifibrinolytic therapy, thromboelastography-guided transfusion, phlebotomy, reduced central venous pressures intraoperatively, and the use of the veno-venous bypass (VVB) circuit, have been explored. The asanguineous priming volume of the VVB circuit increases the likelihood of the patient receiving homologous blood products due to hemodilution. It was reasoned that autologous priming of the VVB circuit in OLT surgery was a plausible adjunctive blood conservation technique given its application to the extracorporeal circuit during cardiac surgery. We describe our technique of modifying the VVB circuit for autologous priming. This technique adds minimal risk and a small amount of cost to the procedure, requires slightly more communication among members of the surgical team, and with proper sequencing, adds no additional length to the surgical procedure. It is recommended that this technique be considered for addition to the arsenal of blood conservation techniques when VVB is used during OLT

Improving medication safety and cardiovascular risk factor control to mitigate disparities in African-American kidney transplant recipients: Design and methods

There is a lack of data analyzing the influence of cardiovascular disease (CVD) risk factor control on graft survival disparities in African-American kidney transplant recipients. Studies in the general population indicate that CVD risk factor control is poor in African-Americans, leading to higher rates of renal failure and major acute cardiovascular events. However, with the exception of hypertension, there is no data demonstrating similar results within transplant recipients. Recent analyses conducted by our investigator group indicate that CVD risk factors, especially diabetes, are poorly controlled in African-American recipients, which likely impacts graft loss. This study protocol describes a prospective interventional clinical trial with the goal of demonstrating improved medication safety and CVD risk factor control in adult solitary kidney transplant recipients at least one-year post-transplant with a functioning graft. This is a prospective, interventional, 6-month, pharmacist-led and technology enabled study in adult kidney transplant recipients with the goal of improving CVD risk factor outcomes by improving medication safety and patient self-efficacy. This papers describes the issues related to racial disparities in transplant, the details of this intervention and how we expect this intervention to improve CVD risk factor control in kidney transplant recipients, particularly within African-Americans

Graft outcomes in pediatric kidney transplantation: Focus on the role of race

While significant racial disparities in graft outcome persist among adult and pediatric kidney transplant recipients in the US, some international studies do not show these diffe-rences. The aim of this study is to examine predictors of graft outcomes and the impact of race in our pediatric kidney transplant cohort. Records of 109 pediatric kidney transplant recipients performed at our institution between 7/99 and 4/07 were studied. Patients were grouped based on race: African-American (AA) vs. non-AA. Fifty-five AA (12 ± 5 years) and 54 non-AA patients (11 ± 6 years) were studied. There were more females, pre-emptive transplants and living donors in the non-AAs. Survival analysis showed significantly higher rejection rates in AAs, P = 0.02, and lower unadjusted graft survival (P = 0.09). Cox Proportional Hazards Survival Regression Analysis revealed biopsy-proven acute rejection and delayed graft function contributed to worse graft survival, while pre-emptive transplantation had a favorable effect. Race was not an independent risk factor for decreased graft survival in the final model. In conclusion, our cohort showed several modifiable risk factors that can partially account for poorer graft survival in pediatric AA kidney transplant recipients

Comparison of efficacy of induction therapy in low immunologic risk African-American kidney transplant recipients

African-Americans (AA) have higher acute rejection rates and poorer long-term graft survival rates when compared with non-AA. It is yet to be demonstrated that the type of induction therapy modifies outcomes in this 'high-risk' population. This retrospective analysis compares the efficacy of induction therapy [antilymphocyte antibodies (ALA) versus interleukin-2 receptor antagonists (IL-2RA)] in the AA population. Some 189 AAs were included. There was no difference in acute rejection at one year between the groups (ALA (12%) or IL-2RA (12%), P = 0.89). Type of induction therapy had no significant effect on death-censored (P = 0.61) or uncensored graft survival (P = 0.32). There was no difference between CMV or BK virus infections between the groups (P = 0.14 and 0.94 respectively). Type of induction therapy does not appear to affect acute rejection rates or long-term graft survival in low-risk AA kidney transplant recipients

Efficacy of induction therapy on acute rejection and graft outcomes in African American kidney transplantation

BACKGROUND: African Americans (AA) have higher rejection rates and poorer graft outcomes compared to non-AAs. Induction therapy is yet unproven in this high risk population. METHODS: This retrospective study compared the efficacy of induction therapy [IL-2 receptor antibodies (IL2RA) or thymoglobulin] vs. no induction. RESULTS: One hundred and seventy-five AA patients were included in this analysis. Patients were well matched for demographic and immunologic characteristics in the non-induction and IL2RA induction groups; the Thymoglobulin induction group had significantly higher risk patients. Significantly fewer episodes of acute rejection occurred at one yr in patients treated with thymoglobulin and IL2RA vs. no induction (18% vs. 47%, p = 0.003, 26% vs. 47%, p = 0.02). Three yr graft survival was significantly improved in the IL2RA group compared to the non-induction group (85% vs. 68%, p = 0.032). Despite the thymoglobulin group being at high risk, they had similar graft survival rates compared to both the IL2RA group (76% vs. 85%, p = 0.18) and the non-induction group (76% vs. 68%, p = 0.48). Multivariate analysis demonstrated that induction therapy (combining IL2RA and thymoglobulin) independently reduced the risk of both acute rejection and graft loss. CONCLUSION: The use and type of induction therapy in AA patients significantly reduces acute rejection rates and may improve long-term graft outcomes in AA patients

Can preemptive cytomegalovirus monitoring be as effective as universal prophylaxis when implemented as the standard of care in patients at moderate risk?

BACKGROUND: Cytomegalovirus (CMV) is a significant cause of morbidity, mortality, and cost in solid organ transplant recipients. This study was conducted to measure both the clinical efficacy and the pharmacoeconomic impact of implementing, as standard of care, an abbreviated preemptive monitoring strategy compared with universal prophylaxis in a large teaching hospital. METHODS: This prospective observational study included only recipients at moderate risk for CMV infection, specifically recipients who were CMV seropositive before transplant. Recipients transplanted between February 2006 and December 2006 received prophylactic valganciclovir for 90 days after transplant, and those transplanted between January 2007 and December 2007 were enrolled in a preemptive monitoring strategy that included no anti-CMV prophylaxis but instead used serial CMV polymerase chain reactions in weeks 4, 6, 8, 10, 12, 16, 20, and 24 to monitor the development of CMV DNAemia. Costs were analyzed from a societal perspective. RESULTS: A total of 130 patients were included in this study. Baseline and transplant demographics are well matched between groups. CMV syndrome occurred in three patients in each group, and one patient in the preemptive group developed CMV disease. Thirty-seven percent of patients in the preemptive group developed CMV DNAemia, 68% of these patients received antiviral therapy. Personnel and laboratory monitoring costs were significantly higher in the preemptive group, whereas medication cost was significantly higher in the prophylaxis group. CONCLUSIONS: Although outcomes and the overall cost of (1) universal prophylaxis and (2) preemptive monitoring are similar, universal prophylaxis places the cost burden on the patient whereas preemptive monitoring shifts the cost burden to the healthcare system