Pancreas After Kidney Transplants Research Articles

Pancreas-after-kidney transplantation: an increasingly attractive alternative to simultaneous pancreas-kidney transplantation.

Historically, the clinical acceptability of pancreas-after-kidney (PAK) transplantation has been hampered by relatively high acute rejection rates and lower pancreas graft survival rates when compared with the more commonly performed simultaneous pancreas-kidney (SPK) transplantation. The purpose of this study was to compare PAK transplantation to SPK transplantation in the Thymoglobulin induction era. The authors reviewed all bladder-drained PAK (n=47) transplants receiving rabbit antithymocyte globulin induction from June 1998 to June 2002 and compared them with SPK (n=25) transplants during the same time period at their institution. The authors retrospectively studied data on demographics, patient survival, graft (pancreas and kidney) survival, complications, and biopsy-proven rejection episodes. The actuarial 1-year patient survival was 93% for the PAK group versus 100% for the SPK group (P =not significant [NS]). The actuarial 1-year pancreas graft survival was 87% for the PAK group versus 92% for the SPK group (P =NS). Waiting time for PAK was significantly shorter than for SPK (6.3 +/- 5.2 vs. 16.2 + -13.7 months, P <0.05). Clinical acute rejection rates were similar in the two groups (4.3% for PAK vs. 4.0% for SPK). PAK recipients demonstrated a greater decline in renal function after transplantation compared with SPK. A multivariate analysis failed to elucidate the cause. Newer immunosuppressive regimens allow PAK transplant patients to achieve immunologic outcomes similar to SPK transplant patients. Although the shorter waiting time and the ability to use living-donor kidneys make PAK an increasingly attractive alternative to SPK transplantation, its effect on renal allograft function deserves further attention.

Improving results in solitary pancreas transplantation with portal-enteric drainage, thymoglobin induction, and tacrolimus/mycophenolate mofetil-based immunosuppression

Abstract Advances in surgical techniques and clinical immunosuppression have led to steadily improving results in pancreas transplantation (PTX). The purpose of this study was to analyze retrospectively the outcomes in patients undergoing solitary PTX with portal-enteric (P-E) drainage and contemporary immunosuppression. From June 1998 through December 2000, we performed 28 solitary PTXs with antibody induction and tacrolimus/mycophenolate mofetil maintenance therapy. The first 13 patients Received: daclizumab (DAC) induction, while the next 15 Received: thymoglobulin (rabbit anti-human thymocyte gamma globulin; Thymo) induction. The study group included 13 pancreas alone (PA) and 15 sequential pancreas-after-kidney-transplantation (PAKT). Solitary PTX was performed with P-E drainage in 18 patiens and systemicenteric (S-E) drainage in ten. Patient and pancreas graft survival rates were 96% and 79%, respectively, with a mean follow-up of 22 (range 1–39) months. The 1-year actual death-censored pancreas graft survival rate was 89%. One PAKT patient died with a functioning graft at 1 month; three patients (11%) experienced early graft loss due to thrombosis and were excluded from the immunological analysis, leaving 24 evaluable patients. The incidence of acute rejection was 54%, including 50% in PA and 58% in PAKT recipients (P=NS). In patients receiving Thymo induction, the rate of acute rejection was slightly lower (43% Thymo vs 70% DAC). Moreover. P-E drainage was associated with a slightly lower rate of acute rejection (44% P-E vs 75% S-E; P=NS). In patients with both Thymo induction and P-E drainage (n=11), there was a tendency toward less rejection (the incidence of acute rejection was 36%). Two immunological graft losses occurred (one due to non-compliance), both in patients with P-E drainage. Only one patient had a cytomegalovirus (CMV) infection. Event-free survival (no rejection, graft loss, or death) was slightly higher in patients receiving Thymo (47%) than in those on DAC (23%) induction (P=NS). We can conclude that solitary PTX with P-E drainage and Thymo induction may be associated with improved intermediate-term outcomes and a possible immunological advantage.

Pancreas after kidney transplantation.

After three decades of controversy surrounding the therapeutic validity of pancreas transplantation, the procedure has become accepted as the preferred treatment for patients with insulin-dependent diabetes mellitus (IDDM) and advanced diabetic nephropathy with end-stage renal disease (ESRD) and for

Pancreas after kidney transplants

Background: For certain uremic diabetic patients, a sequential transplant of a kidney (usually from a living donor) followed by a cadaver pancreas has become an attractive alternative to a simultaneous transplant of both organs. The purpose of this study was to compare outcomes with simultaneous pancreas-kidney (SPK) versus pancreas after kidney (PAK) transplants to determine advantages and disadvantages of the two procedures. Methods: Between January 1, 1994, and June 30, 2000, we performed 398 cadaver pancreas transplants at our center. Of these, 193 were SPK transplants and 205 were PAK transplants. We compared these two groups with regard to several endpoints, including patient and graft survival rates, surgical complications, acute rejection rates, waiting times, length of hospital stay, and quality of life. Results: Overall, surgical complications were more common for SPK recipients. The total relaparotomy rate was 25.9% for SPK recipients versus 15.1% for PAK recipients ( P = 0.006). Leaks, intraabdominal infections, and wound infections were all significantly more common in SPK recipients ( P = 0.009, P = 0.05, and P = 0.01, respectively, versus PAK recipients). Short-term pancreas graft survival rates were similar between the two groups: at 1 year posttransplant, 78.0% for SPK recipients and 77.9% for PAK recipients ( P = not significant). By 3 years, however, pancreas graft survival differed between the two groups (74.1% for SPK and 61.7% for PAK recipients), although this did not quite reach statistical significance ( P = 0.15). This difference in graft survival seemed to be due to increased immunologic losses for PAK recipients: at 3 years posttransplant, the incidence of immunologic graft loss was 16.2% for PAK versus 5.2% for SPK recipients ( P = 0.01). Kidney graft survival rates were, however, better for PAK recipients. At 3 years after their kidney transplant, kidney graft survival rates were 83.6% for SPK and 94.6% for PAK recipients ( P = 0.001). The mean waiting time to receive the pancreas transplant was 244 days for SPK and 167 days for PAK recipients ( P = 0.001). Conclusions: PAK transplants are a viable option for uremic diabetics. While long-term pancreas graft results are slightly inferior to SPK transplants, the advantages of PAK transplants include the possibility of a preemptive living donor kidney transplant, better long-term kidney graft survival, significantly decreased waiting times, and decreased surgical complication rates. Use of a living donor for the kidney transplant expands the donor pool. Improvements in immunosuppressive regimens will hopefully eliminate some of the difference in long-term pancreas graft survival between SPK and PAK transplants.

Optimal timing for a pancreas transplant after a successful kidney transplant.

For certain uremic, diabetic patients, a sequential transplant of a kidney (usually from a living donor) followed by a cadaver pancreas has become an attractive option. But how long to wait after the kidney transplant before proceeding with a pancreas transplant is unclear. We studied outcomes in recipients of a pancreas at varying times after a kidney to determine the optimal timing for the second transplant. We compared pancreas after kidney (PAK) transplants performed early (< or =4 months) and late (>4 months) after the kidney transplant to determine any significant differences in surgical complications or outcomes between the two groups. Between January 1, 1994, and September 30, 1998, we performed 123 cadaver PAK transplants. Of these, 25 (20%) were early and 98 (80%) were late. Characteristics of the two recipient groups were similar. We found no significant differences in outcome between the two groups. The incidence of surgical complications (bleeding, leaks, thrombosis, infections) and of opportunistic infections (such as cytomegalovirus) did not significantly differ between the two groups. Graft and patient survival rates were also equivalent (P=NS). The incidence of acute rejection by 3 months posttransplant was 20% in both groups. The timing of the pancreas transplant for PAK recipients does not seem to influence outcome. As long as an acceptable organ is available and the recipient is clinically stable, a PAK transplant can be performed relatively soon after the kidney transplant.

Review of immunosuppressive usage in pancreas transplantation.

Throughout 1997, nearly 10,000 pancreas transplants have been performed worldwide, with 88% being simultaneous kidney transplants (SKPT). The current 1 yr patient survival rate exceeds 90% and pancreas graft survival (complete insulin independence) rate exceeds 80% for SKPT, 70% for sequential pancreas after kidney transplant (PAKT), and 65% for pancreas transplant alone (PTA). According to registry data, rejection accounts for 32% of graft failures in the first year after pancreas transplantation. However, improvements are expected to continue with the evolution of treatment protocols. Most pancreas transplant centers employ quadruple drug immunosuppression with anti-lymphocyte induction with either a monoclonal or polyclonal antibody agent. In recent years, there has been an overall decline in the use of antibody induction therapy from 90% during the period 1987-1993 to 83% of pancreas transplants performed during 1994-1997. Maintenance immunosuppression is triple therapy consisting of a calcineurin inhibitor (cyclosporine or tacrolimus), corticosteroids, and an anti-metabolite (AZA or MMF). Prior to 1995, nearly all pancreas transplant recipients were managed with Sandimmune. In the last 2 yr, tacrolimus-based therapy has been used in approximately 20% of cases and a new microemulsion formulation of cyclosporine (Neoral) has replaced Sandimmune in contemporary post-transplant immunosuppression. In addition, MMF is replacing AZA as part of the standard immunosuppressive regimen after pancreas transplantation. At present, a number of centers are conducting various trials with new drug combinations including either Neoral or tacrolimus in combination with steroids and MMF with or without antibody induction therapy. From 1994 to 1997, the 1 yr rates of immunologic graft loss have decreased to 2% after SKPT, 9% after PAKT, and 16% after PTA. The current array of new immunosuppressive agents are providing more effective control of rejection and permitting solitary pancreas transplantation to become an accepted treatment option in diabetic patients without advanced complications. The apparent potency of new drug combinations has also resulted in a resurgence of interest in steroid withdrawal. Immunosuppressive strategies will continue to evolve in order to achieve effective control of rejection while minimizing injury to the allograft and risk to the patient. In addition, new regimens must not only address the issue of specific drug toxicities but also long-term economic, metabolic, and quality of life outcomes. Pancreas transplantation will remain an important alternative in the treatment of diabetic patients until other strategies are developed that can provide equal glycemic control with less immunosuppression and overall morbidity.

Immunosuppression in pancreas transplantation: progress, problems and perspective

Through 1997, over 10 000 pancreas transplants have been performed world-wide, with 88% being simultaneous kidney-pancreas transplants (SKPTs). Current 1-year patient survival exceeds 90% and pancreas graft survival (complete insulin independence) exceeds 80% for SKPT, 70% for sequential pancreas after kidney transplant (PAKT), and 65% for pancreas transplant alone (PTA). According to Registry data, rejection account for 32% of graft failures in the first year after pancreas transplantation. However, improving outcomes are expected to continue with the evolution of treatment protocols. Most pancreas transplant centres employ quadruple drug immunosuppression with anti-lymphocyte induction, using either a monoclonal or polyclonal antibody agent. In recent years, there has been an overall decline in the use of antibody-induction therapy from 90% during 1987–93, to 83% of pancreas transplants performed during 1994–97. Maintenance immunosuppression is triple therapy consisting of a calcineurin inhibitor (cyclosporine or tacrolimus), corticosteroids, and an anti-metabolite such as azathioprine (AZA) or mycophenolate mofetil (MMF). Prior to 1995, nearly all p ancreas transplant recipients were managed with Sandimmune. Since 1986, tacrolimus-based therapy has been used in approximately 20% of cases, and a new microemulsion formulation of cyclosporine (Neoral) has replaced Sandimmune in contemporary post-transplant immunosuppression. In addition, MMF is replacing AZA as part of the standard immunosuppressive regimen following pancreas transplantation. At present, a number of centres are conducting various trials with new drug combinations including either Neoral or tacrolimus in combination with steroids and MMF, with or without antibody-induction therapy. From 1994 to 1997, the 1-year rates of immunologic graft loss have decreased to 2% after SKPT, 9% after PAKT, and 16% after PTA. The current array of new immunosuppressive agents are providing more effective control of rejection and permitting solitary pancreas transplantation to become an accepted treatment option in diabetic patients without advanced complications. The apparent potency of new drug combinations has also resulted in a resurgence of interest in steroid withdrawal. Immunosuppressive strategies will continue to evolve to achieve effective control of rejection while minimizing injury to the allograft and risk to the patient. In addition, new regimens must not only address the issue of specific drug toxicities, but also long-term economic, metabolic, and quality of life outcomes. Pancreas transplantation will remain an important alternative in the treatment of diabetic patients until other strategies are developed that can provide equal glycaemic control with less immunosuppression and overall morbidity.