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George W Burke

Publications and source records attributed to George W Burke.

At least 19 recordsLinked to original sources
PubMed2006

A randomized long-term trial of tacrolimus/sirolimus versus tacrolimums/mycophenolate versus cyclosporine/sirolimus in renal transplantation: three-year analysis.

BACKGROUND: We report three-year (interim) effects of combining sirolimus (Siro) vs. mycophenolate mofetil (MMF) as adjunctive therapy with calcineurin inhibitors (CI) in renal transplantation in the three different CI-based regimens. METHODS: Between May 2000 and December 2001, 150 recipients of deceased donor (DD) and living donor (LD) kidney transplants were randomized into three groups (n=50/group): Group A (Tacro/Siro), Group B (Tacro/MMF) and Group C (CsA/Siro). This report details drug dosing and monitoring, protocol discontinuance, biopsy-proven rejection, graft failure, other adverse events, and death at 36 months postoperatively. RESULTS: Actual patient and graft survival respectively in Group A was 90% and 82%, in Group B was 92% and 88%, and in Group C was 96% and 88% (not significant). Biopsy-confirmed acute rejection incidents showed a trend in favor of Group B (10%) vs. Group A (26%) and Group C (20%) combined (P=0.07). The geometric mean */SE serum creatinine concentration and arithmetic mean +/- SE Cockroft-Gault creatinine clearance calculations, respectively, were 1.39*/1.1 and 72.8+/-4.3 for Group A, 1.36*/1.1 and 72.1+/-4.1 for Group B, and 1.60*/1.1 and 61.8+/-3.8 for Group C, a statistically favorable difference for Group B over Group C (P=0.04). There was also less de novo development of posttransplant diabetes mellitus and lipid disorders in Group B vs. A and C (P<0.04). CONCLUSIONS: This three-year (interim) analysis has indicated a trend towards better graft function, fewer endocrine disorders, and fewer acute rejection episodes comparing adjunctive MMF and Tacro vs. Siro and Tacro or Siro and CsA, in the dosages used.

Adolescent↗
PubMed2006

Bone marrow-induced tolerance in the era of pancreas and islets transplantation.

Enormous progress has been made in the field of solid organ adaptation recently because of the improvement in immunosuppression. Although powerful immunosuppressive drugs decrease the rate of acute rejection significantly, the long-term functional graft survival and tolerance induction remains poor. Chronic rejection is the main cause of graft failure. An electronic search was performed for articles on chimerism, tolerance, and immunologic perspectives of islet and pancreas transplantation along with referrals to our experience. Infusion of donor bone marrow-derived cells to create a chimeric state continue to be tested in clinical protocols intended to induce specific immunologic tolerance. The proposed mechanisms of immunologic engagement and the emergence of a tolerant state through mixed chimerism include central depletion of alloreactive cells, induction of T-cell anergy, and generation of suppressor cells by interactions between donor and host cells. In this setting, depletion of recipient T cells by different strategies and subsequent repopulation by donor hematopoietic cells after donor bone marrow infusion are prerequisites for tolerance induction. Many efforts have aimed to establish mixed chimerism along with tolerance in solid organ transplantation including pancreas and islets to facilitate engraftment. A review of the more important advances in the field and the future prospects combined with our experience to induce tolerance in the clinic and the laboratory is presented in this article.

Animals↗
PubMed2006

Efficacy of alemtuzumab in organ transplantation: current clinical status.

An overview of the past 5 years of clinical renal transplantation would include progress in (i) the development of protocols with new induction agents (non-depleting versus depleting monoclonal and polyclonal antibodies) designed to reduce the incidence and severity of acute rejection, (ii) the attempt to reduce calcineurin inhibitor short- and long-term nephrotoxicity, and (iii) the attempt to reduce immunosuppression overall if an immunoregulatory state ('tolerance') against donor alloantigens could be achieved. One such induction agent is the humanized anti-CD52 monoclonal antibody alemtuzumab (Campath-1H), which depletes T cells (most potently), as well as B cells and other lymphoid subsets, and may decrease the dosage or need for concurrent maintenance immunosuppressive agents.

Alemtuzumab↗
PubMed2005

A randomized trial of three renal transplant induction antibodies: early comparison of tacrolimus, mycophenolate mofetil, and steroid dosing, and newer immune-monitoring.

BACKGROUND: New trends in immunosuppression in clinical transplantation include the use of antibody induction agents in protocols that emphasize reduction or avoidance of steroids and calcineurin inhibitors. METHODS: In a randomized trial using three different antibody induction agents in 90 first renal transplant recipients from cadaver donors, group A received Thymoglobulin, group B received Alemtuzumab, and group C received Daclizumab. Maintenance immunosuppression included tacrolimus and mycophenolate in all three arms, and methylprednisolone in groups A and C only (standard clinical institutional practice). The targeted trough level of tacrolimus was between 8 and 10 ng/mL for groups A and C, respectively, with a targeted mycophenolate dose of 1 g twice daily. However, in group B, the target tacrolimus trough level was 4 to 7 ng/mL to reduce long-term nephrotoxicity, with 500 mg twice-daily doses of mycophenolate, without steroid maintenance. RESULTS: In this 15-month median postoperative interval report, there were no notable differences in demographics and patient and graft survivals. Acute rejection rates at 1 year were equivalent, that is, 5 of 30 in all three groups (16.6%). In group B, there was slightly lower renal function at 1 month, but no difference at 1 year. There was also significantly more leukopenia, but a greater percentage of T-regulatory cells and number of Fox-P3 mRNA copies by flow cytometry and semiquantitative polymerase chain reaction analysis, respectively, in group B. CONCLUSIONS: This preliminary analysis indicates that 80% of the patients in group B remained steroid-free 1 year postoperatively, with lower tacrolimus trough levels and no difference in other adverse events.

Adult↗
PubMed2005

Campath-1H does not alter bone marrow cell regulatory function.

We have previously reported in laboratory volunteers (in vitro) and renal transplant recipients (ex vivo) that bone marrow cells (BMC) are potent downregulators of the immune response. Also, the use of alemtuzumab (Campath-1H, C1H) for immunodepletion is associated with the most potent lasting effects yet seen on T-cell immunity in renal transplantation. We questioned whether the administration of C1H to kidney allograft recipients of donor bone marrow cell (DBMC) infusions would lead to stronger or weaker immunoregulatory effects. Human BMC depleted of T cells (nT-BMC) were either untreated or treated with C1H and rabbit complement and compared for their ability to downregulate autologous or allogeneic T-cell responses and to generate T regulatory (T reg) cells. The proliferative responses to anti-CD3 monoclonal antibody of T cells derived from cocultures with C1H-treated or untreated autologous nT-BMC were equally suppressed, i.e., an equivalent alteration in CD3 complex signaling, not regained by the addition of interleukin 2. Adenosine triphosphate levels were also markedly reduced in T cells both from C1H-treated and untreated nT-BMC cocultures. The ability of C1H-treated or untreated nT-BMC to suppress autologous T-cell cytotoxic function was also equivalent, with a marked, but equivalent, capacity to induce CD4/CD25(high) T regs from CD3(+) cells, which effectively downregulated cytotoxic T cells. To mimic the clinical infusion of DBMC into (allogeneic) recipients, peripheral blood mononuclear cells were also cultured with allogeneic C1H-treated and untreated nT-BMC. T cells derived from these cultures secondarily stimulated with the same-donor mature antigen-presenting cells exhibited suppressed cytotoxicity by 85% and 54%, respectively. These in vitro studies suggest that C1H does not abrogate BMC immunoregulation and thus may allow its lympho-depleting effect to be synergistic.

Alemtuzumab↗
PubMed2005

Arterial reconstruction with donor iliac vessels during pancreas transplantation: an intraoperative approach to arterial injury or inadequate flow.

BACKGROUND: Outcome of pancreas transplantation (PTX) has improved because of use of novel immunosuppression and advances in surgical technique. It is not uncommon for severe atherosclerosis in patients with type 1 insulin-dependent diabetes mellitus or the presence of a previously transplanted organ to limit the options for vascular anastomosis. Herein we report the novel application of donor iliac arterial interposition grafts for arterial reconstruction in patients with severe iliac artery arteriosclerosis, and/or previous transplant who develop an arterial injury or stenosis during surgery. METHODS: In five patients undergoing PTX, the external iliac artery was severely atherosclerotic and/or occupied by a previous vascular anastomosis. In four of the five patients, an arterial intimal dissection became apparent. The external iliac artery was excised and reconstructed with donor iliac artery interposition graft (end-to-end anastomosis). Pancreas or kidney was engrafted onto this arterial interposition graft (end-to-side anastomosis). RESULTS: There was no operative morbidity related to this surgical approach. All grafts functioned well after transplantation. Distal lower extremities have no evidence of vascular insufficiency with mean follow-up of 26 months (7-45 months). CONCLUSION: This surgical technique is an acceptable option during PTX for the patient with severe iliac artery arteriosclerosis with intraoperative intimal dissection or stenosis, or perhaps those with challenging arterial access.

Adult↗
PubMed2004

Donor bone marrow infusion in deceased and living donor renal transplantation.

The infusion and persistence in a transplant recipient of donor-derived bone marrow cells (DBMC) of multi-lineage can lead to a state of permanent chimerism. In solid vascular organ transplantation, the donor bone marrow lineage cells can even be derived from the transplant organ, and these cells can be detected in very small numbers in the recipient. This has been called microchimerism. Much controversy has developed with respect to the function of chimeric cells in organ transplantation. One idea is that the occurrence of these donor cells found in microchimerism in the recipient are coincidental and have no long-term beneficial effect on engraftment. A second and opposing view, is that these donor cells have immunoregulatory function that affect both the acute and chronic phases of the recipient anti-donor responses. It follows that detecting quantitative changes in chimerism might serve as an indication of the donor-specific alloimmune or regulatory response that could occur in concert with or independent of other adaptive immune responses. The latter, including autoimmune native disease, need to be controlled in the transplant organ. The safety and immune tolerance potential of DBMC infusion with deceased and living donor renal transplants was evaluated in a non-randomized trial at this center and compared with non-infused controls given identical immunosuppression. Overall DBMC infusions were well tolerated by the recipients. There were no complications from the infusion(s), no episodes of graft-vs-host disease (GVHD) and no increase infections or other complications. In the deceased DBMC-kidney trial, actuarial graft survival at 5 years was superior especially when graft survival was censored for recipient death. Acute rejections were significant reduced in patients given two DBMC infusions, and chronic rejection was dramatically reduced in all DBMC treated patients. The most interesting finding was that the degree of microchimerism slowly increased over the years the DBMC group that had exhibited no rejection episodes. In the DBMC-living related trial, the incidence of acute rejection did not differ between groups. However, DBMC chimerism in recipient iliac crest marrow had increased more rapidly than might be predicted from results previously seen in the cadaver group, despite four times fewer DBMC infused, with the generation of T- regulartory cells in-vitro assays.

Bone Marrow Transplantation↗
PubMed2004

The use of Campath-1H as induction therapy in renal transplantation: preliminary results.

BACKGROUND: In an attempt to reduce both initial and long-term (nephrotoxic) calcineurin inhibitor maintenance dosage and totally eliminate maintenance corticosteroids, alemtuzumab (Campath-1H) was used as induction therapy in first cadaver and non-HLA-identical living donor renal transplantation. METHODS: Forty-four de novo renal allograft recipients were treated with Campath-1H (0.3 mg/kg) on days 0 and 4 postoperatively, preceded by methylprednisolone boluses. Maintenance target 12-hr tacrolimus trough levels of 5 to 7 ng/mL were operational from the outset as well as (reduced) mycophenolate mofetil dosage of 500 mg twice daily. No corticosteroids were planned to be given after the first week postoperatively. RESULTS: With a median follow-up of 9 (range, 1-19) months, patient and graft survival rates are each at 100%. Biopsy-proven acute rejection was diagnosed in four patients. Infections requiring hospitalization developed in four patients. Thirty-eight recipients remain without the need for long-term corticosteroid therapy. CONCLUSIONS: In an early assessment, the combination of Campath-1H, low dosing of tacrolimus and mycophenolate mofetil, and avoidance of maintenance corticosteroid use seems to be safe and effective for kidney transplant recipients. Long-term outcomes will be reported in the future.

Alemtuzumab↗
PubMed2004

Advances in pancreas transplantation.

Despite early obstacles impacting the success of pancreatic transplantation, the introduction of new procedures and new immunosuppressive therapies during the past 2 decades has improved outcomes for pancreatic transplant recipients. For example, the use of bladder drainage and better human leukocyte antigen matching has helped overcome some of the early obstacles of pancreatic transplantation. In addition, the introduction of tacrolimus in 1994 and mycophenolate mofetil in 1996 has helped lower rates of acute rejection and increase graft survival, with less nephrotoxicity than treatment with cyclosporine. Regimens allowing the tapering of corticosteroids have also helped reduce the rates of acute pancreas rejection. To further improve therapeutic options for patients with type 1 diabetes or end-stage renal disease, pancreatic islet transplantation and organ and islet xenotransplantation should be further explored.

Diabetes Mellitus, Type 1↗
PubMed2004

Prospective, randomized trial of the effect of antibody induction in simultaneous pancreas and kidney transplantation: three-year results.

BACKGROUND: Historically, antibody induction has been used because of the higher immunologic risk of graft loss or rejection observed in simultaneous pancreas and kidney (SPK) transplantation compared with kidney transplantation alone. This trial was designed to assess the effect of antibody induction in SPK transplant recipients receiving tacrolimus, mycophenolate mofetil, and corticosteroids. Induction agents included T-cell-depleting and interleukin-2 receptor antibodies. METHODS: A total of 174 SPK transplant recipients were enrolled in a prospective, open-label, multi-center study. They were randomized to induction (n=87) or non-induction (n=87) groups and followed for 3 years. RESULTS: At 3 years, actual patient (94.3% and 89.7%) and pancreas (75.9% and 75.9%) survivals were similar between the induction and non-induction groups, respectively. Actual kidney survival was similar at 1 and 2 years, but at 3 years, it was significantly better in the induction group compared with the non-induction group (92% vs. 81.6%; P =0.04). At 3 years, median serum creatinine and hemoglobin A1C were similar between the induction and non-induction groups (1.35 mg/dL and 1.20 mg/dL, 5.4% and 5.5%, respectively). Three-year cumulative incidence of biopsy-confirmed, treated acute kidney rejection in the induction and non-induction groups was 19.5% and 27.5% (P =0.14), respectively, with odds 4.6 times greater in African Americans regardless of treatment (P =0.004). Significantly higher rates of cytomegalovirus (CMV) viremia and CMV syndrome occurred in those receiving T-cell-depleting antibody induction (36.1%) when compared with those receiving anti-interleukin-2 receptor antibodies (2%) and non-induction (8.1%) (P <0.0001). CONCLUSIONS: Tacrolimus, mycophenolate mofetil, and corticosteroids resulted in excellent safety and efficacy in SPK transplant recipients. Actual 3-year kidney survival was significantly better in the induction group; however, CMV viremia and CMV syndrome rates were significantly higher in the T-cell-depleting antibody group. African Americans demonstrated a significantly greater risk of acute rejection despite antibody induction. Decisions regarding the use of induction therapy must weigh the risk of kidney graft loss or rejection against the risk of infection.

Antibodies, Monoclonal↗
PubMed2004

A randomized long-term trial of tacrolimus and sirolimus versus tacrolimus and mycophenolate mofetil versus cyclosporine (NEORAL) and sirolimus in renal transplantation. I. Drug interactions and rejection at one year.

BACKGROUND: To reduce long-term nephrotoxic calcineurin inhibitor dosage, adjunctive sirolimus or mycophenolate mofetil (MMF) was used in a 150-patient, randomized, three-armed trial in cadaveric or human leukocyte antigen non-identical living-donor first renal transplant recipients (n=50/group). METHODS: Group A received tacrolimus and sirolimus. Target tacrolimus trough levels postoperatively were 10, 8, and 6 ng/mL at 1 month, 6 months, and 1 year, respectively. Group B received tacrolimus and MMF. Target tacrolimus trough levels were 10 and 8 ng/mL at 1 month and 1 year, with a targeted dose of MMF of 1 g twice daily. Group C received cyclosporine A (CsA) (Neoral, Novartis, Basel, Switzerland) and sirolimus with target CsA trough levels of 225 and 175 ng/mL at 1 month and 1 year. Maintenance sirolimus target trough levels were 8 ng/mL in groups A and C. Each group received daclizumab induction and methylprednisolone maintenance. This first of two companion 1-year reports details demographics, drug-dosing interactions, and rejection. RESULTS: There were no notable differences in group demographics, but a somewhat less favorable course occurred in group C, despite higher bioavailability of sirolimus in group C versus group A (P<0.001). Acute rejection rates were lower in groups A (4%) and B (4%) combined versus group C (14%) (P=0.03). Histopathologic findings were supported by comparing perioperative with 1-year postoperative protocol biopsies. CONCLUSIONS: This 1-year interim analysis indicates that a decreasing dosage of tacrolimus with either adjunctive sirolimus or MMF may optimize future graft survival versus a less favorable outcome using a similar algorithm with CsA and sirolimus.

Adult↗
PubMed2004

A randomized long-term trial of tacrolimus/sirolimus versus tacrolimus/mycophenolate mofetil versus cyclosporine (NEORAL)/sirolimus in renal transplantation. II. Survival, function, and protocol compliance at 1 year.

BACKGROUND: In an attempt to reduce chronic calcineurin inhibitor induced allograft nephropathy in first cadaver and human leukocyte antigen non-identical living-donor renal transplantation, sirolimus (Siro) or mycophenolate mofetil (MMF) was tested as adjunctive therapy, with planned dose reductions of tacrolimus (Tacro) over the first year postoperatively. Adjunctive Siro therapy with a similar dose reduction algorithm for Neoral (Neo) was included for comparison. METHODS: The detailed dose reduction plan (Tacro and Siro, group A; Tacro and MMF, group B; Neo and Siro, group C) is described in our companion report in this issue of Transplantation. The present report documents function, patient and graft survival, protocol compliance, and adverse events. RESULTS: As mentioned (in companion report), group demographics were similar. The present study shows no significant differences in 1-year patient and graft survival but does show a trend that points to more difficulties in group C by way of a rising slope of serum creatinine concentration (P=0.02) and decreasing creatinine clearance (P=0.04). There were more patients who discontinued the protocol plan in group C. Thus far, no posttransplant lymphomas have appeared, and infectious complications have not differed among the groups. However, a greater percentage of patients in group C were placed on antihyperlipidemia therapy, with an (unexpected) trend toward a higher incidence of posttransplant diabetes mellitus in this group. Group A required fewer, and group B the fewest, antihyperlipidemia therapeutic interventions (P<0.00001). CONCLUSIONS: This 1-year interim analysis of a long-term, prospective, randomized renal-transplant study indicates that decreasing maintenance dosage of Tacro with adjunctive Siro or MMF appears to point to improved long-term function, with reasonably few adverse events.

Creatinine↗
PubMed2004

Antigen presentation and immune regulatory capacity of immature and mature-enriched antigen presenting (dendritic) cells derived from human bone marrow.

Several reports including those from this laboratory have demonstrated that bone marrow cells (BMC) downregulate in vitro both mixed leukocyte reaction and cytotoxic T lymphocyte reactions. We consequently hypothesized that a general property of immature cells of hematopoietic organs is their ability to suppress immune reactivity. As one of these suppressive activities, the lack of costimulatory molecules was proposed as a mechanism by which immature antigen presenting cells of the bone marrow might be involved. In the present report, we used two culture environments, each of which would regulate a different maturation pattern of human bone marrow-derived enriched dendritic antigen presenting cells (DC or APC) to determine the respective effects on in vitro immune regulatory function. Human BMC depleted of CD3+ cells were cultured with either: interleukin-4 (IL-4) and granulocyte macrophage-colony stimulating factor (GM-CSF), to maintain DC-enriched populations in an immature state (iAPC); or an interferon-gamma (IFNgamma), tumor necrosis factor alpha (TNF-alpha), GM-CSF, LPS, and IL-6 cocktail to promote the maturation of DC-enriched APC (mAPC). These iAPC and mAPC were, respectively, phenotypically characterized and also tested in vitro for the following: (1) both direct and indirect-antigen presentation functions; (2) immune regulatory functions on the response of autologous and allogeneic peripheral blood lymphocytes (PBL); and (3) Western blot analysis determining the levels of both major histocompatibility complex (MHC) class I related cytoplasmic transporter molecules associated with antigen processing (TAP1) and as well as proteasome activator molecules (PA28alpha). The iAPC population expressed fewer dendritic cell markers (CD83 and DCsign), and costimulator molecules (CD86 and CD40) than the mAPC, such that there was an approximate threefold increase in expression of CD83, 2.5-fold increase in DCsign, and a threefold increase in CD40 and CD86 on mAPC than on iAPC (p=0.005 for CD83; p=0.001 for DCsign; p=0.001 for CD86; and p=0.001 for CD40). In lymphoproliferative assays, indirect and direct alloantigen presentation by iAPC was weaker than by mAPC (p=0.05 and 0.04). In addition, iAPC were able to downregulate allogeneic CTL responses. Also, after pulsing with Epstein-Barr virus (EBV) protein antigens, the iAPC were less efficient in their presentation to autologous EBV-specific T-cell lines, and caused an inhibition of EBV-CTL generation. The expression of TAP1 and PA28alpha was reduced in iAPC in comparison to mAPC. These findings support the notion that a maturation state of BMC-derived APC correlates with their capacity to present antigen. The observed in vitro deficiency of this function by immature bone marrow cells may therefore contribute to the immune downregulatory capacity seen in the BMC compartment.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Vascular complications of pancreas transplantation.

OBJECTIVE: The purpose of our study was to focus on the early diagnosis and treatment of vascular complications after simultaneous pancreas-kidney (SPK) transplantation. Description of the technique for salvage of the graft after venous thrombosis (VT) is also provided. METHODS: From July 1994 to December 2002, 14 patients of 206 SPK transplant recipients had partial VT. Partial splenic VT (PSVT) was documented in 10 patients (4.8%), two had complete thrombosis of the splenic vein, one partial superior mesenteric thrombosis, and one developed partial thrombosis of the splenic and superior mesenteric vein. Four patients developed complete VT of the pancreas allograft and one superior mesenteric artery thrombosis. Our experience with four arteriovenous fistulae is also reported. The immunosuppression included tacrolimus, steroids, and monoclonal antibody to the IL-2 receptor. Thymoglobulin was introduced in June 2000 in our protocol combined with rapamycin or mycophenolate mofetil. These cases were identified following the intravenous (iv) use of tacrolimus with or without anti-IL-2R therapy. One case of complete VT is also reported one month following transplantation in a recipient with high rapamycin levels. Diagnosis was established during routine color Doppler ultrasonography. RESULTS: Partial VT was effectively treated with anticoagulation. Complete VT required surgical thrombectomy. In our series, the pancreas was salvaged successfully in all patients with the technique described here. CONCLUSION: Early diagnosis of vascular complications after pancreas transplantation is of paramount importance for the appropriate treatment with organ salvage. Based on our experience, we suggest that VT can be effectively treated with anticoagulation. Aspirin is sufficient for PSVT.

Adult↗
PubMed2004

Cytomegalovirus prophylaxis with valganciclovir in kidney, pancreas-kidney, and pancreas transplantation.

Cytomegalovirus, seen in more than 50% of solid organ transplant recipients, is responsible for numerous direct and indirect consequences, including infection with opportunistic pathogens and allograft rejection. Prophylaxis with intravenous ganciclovir has been the gold standard for prevention; however, intravenous treatment is expensive and carries risks of its own. Oral ganciclovir, to be effective, must be given in large, divided doses. Valganciclovir, the valine ester of ganciclovir, at 900 mg/day, provides oral bioavailability equivalent to that of intravenous ganciclovir and superior to that of oral ganciclovir. This retrospective study assessed the efficacy of 3 months prophylaxis with valganciclovir in kidney, simultaneous pancreas-kidney, and pancreas transplantation. Of 161 patients, all of whom received potent immunosuppressive regimens and were followed for a mean of 440 days, only one developed cytomegalovirus infection, at 120 days post-transplantation. Two patients died, and two others lost their grafts. There were seven incidents of acute rejection. Only seven patients discontinued treatment early, five because of leukopenia. These results suggest that prophylaxis with 900 mg/day of valganciclovir for at least 3 months safely and effectively prevents cytomegalovirus infection in kidney, simultaneous pancreas-kidney and pancreas transplant recipients on highly potent immunosuppression.

Adolescent↗
PubMed2004

Hypercoagulable state associated with kidney-pancreas transplantation. Thromboelastogram-directed anti-coagulation and implications for future therapy.

BACKGROUND: The clinical consequences of type 1 diabetes mellitus (IDDM) include diabetic triopathy: retinopathy, nephropathy, and neuropathy, as well as microangiopathy, accelerated atherosclerotic disease, and hypercoagulability. The etiology of the hypercoagulability is multifactorial, involving various clotting factors or pathways (for example platelets, fibrinogen, individual components of the clotting system and/or fibrinolysis in different studies). The development of end-stage renal disease (ESRD), with the uremia-related platelet effect has the potential to protect from the existing hypercoagulable state. This has important implications for surgery, particularly simultaneous pancreas-kidney (SPK) transplantation, where the pancreas has historically been prone to thrombosis. This has led us to perform intra-operative thromboelastograms (TEG's) to evaluate the patient's current coagulation status. METHODS: A TEG was performed in 85 SPK recipients along with a control group of 54 non-diabetic kidney transplant (KT) recipients. RESULTS: For each of the 4 TEG coagulation parameters, the SPK recipients were significantly more hypercoagulable than the non-diabetic KT recipients. The use of intra-operative heparin is based on the degree of hypercoagulability by TEG and degree of operative hemostasis. There has been one PT lost to thrombosis (1%) in the first week following transplantation during this time. CONCLUSION: The use of TEG is a helpful adjunct to SPK surgery, demonstrating the patient's current coagulation status. Nearly all SPK recipients (type 1 IDDM with ESRD) have been demonstrated to be hypercoagulable. The TEG allows the judicious use of anti-coagulation at the time of surgery, and beyond.

Anticoagulants↗