Calcineurin inhibitor avoidance versus steroid avoidance following kidney transplantation: Postoperative complications.

This study compared early postoperative complications in kidney transplant recipients treated with either a sirolimus-based calcineurin inhibitor (CNI)-free regimen or a tacrolimus-based steroid-free regimen. We used a single-center, prospective, sequential but nonrandomized study design. Consecutive recipients of primary cadaveric or non-HLA identical kidney transplant recipients received either a CNI-free regimen, consisting of sirolimus 5 mg daily beginning postoperative day 3, mycophenolate mofetil 1 gm twice a day, and methylprednisolone 500 mg intraoperatively, then prednisone 30 mg daily tapered to 10 mg daily at 3 months, or a prednisone-free regimen, consisting of methylprednisolone 500 mg, 250 mg, and 125 mg from days 0 to 2, then no further steroids, tacrolimus 0.075 mg/kg twice a day, and mycophenolate mofetil 1 g twice a day. All patients received thymoglobulin induction 6 mg/kg total dose. Outcome measures were patient and graft survival, BPAR, surgical and wound complications, viral infections and posttransplant diabetes mellitus (PTDM). Both groups had excellent early outcomes with no significant difference in patient or graft survival, early renal function, BPAR, surgical or wound complications, or viral infections between the two groups. Patients in the sirolimus-based CNI-free group had a significantly higher incidence of PTDM and a trend toward more discontinuation due to drug toxicity. Whether either regimen improves long-term outcomes awaits longer follow-up.

Intestinal function following allogeneic small intestinal transplantation in the rat.

This study tests the hypothesis that small bowel transplantation alters the function of the intestine. The function of the small intestine was investigated after syngeneic (BN----BN or Lew----Lew) and fully allogeneic (BN----Lew) orthotopic total small intestinal transplantation (SIT) using a two-stage model. All animals were treated with cyclosporine A throughout the 60-day study period. Syngeneic transplantation reduced weight gain in the (BN----BN) rats, but not in the (Lew----Lew) animals. Allogeneic transplantation caused a reduction in weight gain for the first 30 days posttransplantation, which may have been associated with graft-versus-host disease. Thereafter, the rate of growth of allogeneic SIT animals was normal. Dietary fat absorption was reduced in all groups of transplanted animals. Intestinal permeability to mannitol and polyethylene glycol 400 (PEG-400) was increased by syngeneic transplantation in all groups, with further permeability increases to mannitol, lactulose, PEG-400, and 51Cr-EDTA after allogeneic SIT. The glucose-stimulated intestinal short circuit current was reduced by both syngeneic and allogeneic SIT, but the maximal active transport rate for glucose uptake was increased, as was the passive uptake of fatty acids. These functional alterations were not associated with changes in intestinal morphology or evidence of rejection. These findings demonstrate that: (1) SIT results in significant changes in the transport characteristics of the bowel, but these have a minimal impact on the well-being of the animal overall; (2) SIT induces an increase in intestinal permeability to mannitol and PEG-400, with a further increase in permeability to all markers following allogeneic SIT; (3) following SIT, and the immune events associated with allogeneic SIT, significant adaptation of the transplanted intestine occurs. We suggest that denervation of the small intestine after SIT is the underlying cause of the changes observed.

A 9-year experience with 126 pancreas transplants with portal enteric drainage.

HYPOTHESIS: A novel technique of pancreas transplantation (PTX) with portal venous delivery of insulin and enteric exocrine drainage (portal enteric) was developed at our center to improve the PTX procedure. DESIGN: Case series. SETTING: Single-center experience at a university hospital. PATIENTS AND INTERVENTION: From October 1990 through December 1999, we performed 126 PTXs with portal enteric drainage, including 90 simultaneous kidney PTXs (SKPT) and 36 solitary PTXs (18 sequential PTXs after kidney transplantation and 18 PTXs alone). MAIN OUTCOME MEASURES: Patient and graft survival rates; medical and surgical morbidity. Three groups, representing 3 eras of immunosuppression, were compared. Thirty patients underwent SKPT with muromonab-CD3 induction and cyclosporine-based therapy in era 1 (October 1990 through June 1995); 42 SKPTs received tacrolimus and mycophenolate mofetil-based immunosuppression without antibody induction in era 2 (July 1995 through May 1998); and 18 SKPTs were performed in era 3 (June 1998 through December 1999) with either basiliximab or daclizumab induction. RESULTS: One-year patient survival rates after SKPT were 77% in era 1, 93% in era 2, and 100% in era 3 (P =.03). The 1-year kidney graft survival rates were 77% in era 1, 93% in era 2, and 94% in era 3 (P =.08). The 1-year pancreas graft survival rates after SKPT were 60% in era 1, 83% in era 2, and 83% in era 3 (P =.06). The incidences of rejection (63% vs. 33% vs. 39%; P<.001) and thrombosis (20% vs. 7% vs. 6%; P<.001) were decreased in eras 2 and 3. CONCLUSION: Simultaneous kidney PTXs with portal enteric drainage can be performed with improved outcomes.

Kidney transplantation in a veterans administration medical center: 40 years' experience.

OBJECTIVES: Advances in immunosuppressive therapy have led to substantial improvements in kidney transplant outcomes in the past 20 years. Kidney transplantation activity started in 1963 at the Veterans Administration Medical Center in Nashville, Tennessee, and continues to grow with increasing numbers of transplants from living-related and unrelated donors. In this study, patient and graft survival rates during 2 different periods were evaluated and compared with non-veterans-administration centers. MATERIALS AND METHODS: Six hundred fourteen kidney transplants were performed between March 1963 and December 2002. For analytic purposes, the 40-year experience was divided into 2 eras based on the immunosuppressive agents used. Azathioprine and prednisone were the immunosuppressive agents used in era 1. A calcineurin-inhibitor-based triple immunosuppressive regimen initially including azathioprine and prednisone and later, mycophenolate mofetil and prednisone, was the preferred immunosuppressive regimen in era 2. RESULTS: In era 1, 1-year patient and graft survival rates were 72.5% and 50%, and 89% and 75% for deceased-donor and living-donor transplants respectively. In era 2, patient survival rates increased to 95.1% and 87.8% for 1 and 3 years respectively, while graft survival increased to 87.6% and 74.9%. Forty-three percent of deceased-donor and 21% of living-donor kidneys were lost owing to rejection in era 1. In era 2, the incidence of acute rejection was 14.5% overall. CONCLUSIONS: Overall, our results are comparable with non-veterans-administration centers and the national average and show that kidney transplantation offers veteran patients with end-stage renal disease a safe and effective treatment with increased quality of life.

A prospective comparison of simultaneous kidney-pancreas transplantation with systemic-enteric versus portal-enteric drainage.

OBJECTIVE: To compare pancreas transplantation with systemic-enteric (SE) versus portal-enteric (PE) drainage in a prospective fashion. SUMMARY BACKGROUND DATA: To improve the physiology of pancreas transplantation, the authors developed a new technique of portal venous delivery of insulin and enteric drainage of the exocrine secretions. METHODS: During a 26-month period, the authors prospectively alternated 54 consecutive simultaneous kidney and pancreas transplants to either SE (n = 27) or PE (n = 27) drainage. The two groups were well matched for numerous characteristics. Maintenance immunosuppression in both groups consisted of tacrolimus, mycophenolate mofetil, and steroids. RESULTS: Patient survival rates were 93% SE versus 96% PE; kidney graft survival rates were 93% in both groups. Pancreas transplantation survival (complete insulin independence) was 74% after SE versus 85% after PE drainage with a mean follow-up of 17 months. The mean length of initial hospital stay was 12.4 days in the SE group and 12.8 days in the PE group. The SE group was characterized by a slight increase in the number of readmissions. The incidences of acute rejection (33%) and major infection (52%) were similar in both groups. The incidence of intraabdominal infection was slightly higher in the SE group. However, the early relaparotomy rate was similar between groups. The composite endpoint of no rejection, graft loss, or death was attained in 56% of SE versus 59% of PE patients. CONCLUSIONS: These results suggest that simultaneous kidney and pancreas transplantation with SE or PE drainage can be performed with comparable short-term outcomes.

Portal-enteric pancreas transplantation at the University of Tennessee, Memphis.

The UT Memphis group has made a number of important contributions to the field of PTX, including: 1) pioneering studies on the effects of PTX on autonomic neuropathy, 2) comprehensive reports dealing with quality of life after PTX, 3) seminal studies on the metabolic effects of PTX with portal venous delivery of insulin, 4) refining and perfecting a novel technique of PTX with portal venous drainage of insulin and primary enteric drainage of the exocrine secretions, 5) describing a safe outpatient percutaneous technique of pancreas allograft biopsy, 6) developing the use of glucose tolerance for rejection surveillance, and 7) managing PTX patients with biopsy-directed immunosuppression and no anti-lymphocyte induction therapy. The P-E technique has the potential to become the standard of care in the near future because it is more physiologic, normalizes carbohydrate and lipid metabolism, and minimizes complications attributed to the transplant procedure. In addition, we have been actively involved in studying new immunosuppressive regimens in order to improve and simplify the care of the PTX recipient. We believe that PTX will remain an important treatment option for IDDM until other strategies are developed that can provide equal glycemic control with less or no immunosuppression and less overall morbidity.

Liver transplantation at king fahad national guard hospital riyadh, kingdom of saudi arabia.

Liver disease is a major medical problem in the Kingdom of Saudi Arabia and is mostly due to viral hepatitis. Liver transplantation is the only option for patients with end-stage liver disease offering good long-term survival. The first liver transplant at the King Fahad National Guard Hospital was performed in February 1994 and since then, 40 liver transplants have been performed on 37 patients. Immunosuppression consisted of prednisone combined with cyclosporin (Neoral) or FK 506. Maintenance immunosuppression was with the use of cyclosporin or FK 506 as monotherapy. All, but one patient, survived the surgical procedure; there were no cases of primary non-function; acute cellular rejection occurred in 12 patients all of whom responded to steroids. Pneumonia and biliary sepsis occurred in 12 patients each. A total of 10 patients died, with sepsis being the leading cause of death. The overall graft survival was 73%. Donor shortage continues to be a major limiting factor.

Evolving experience of hepatitis B virus prophylaxis in liver transplantation.

Passive immunoprophylaxis with hepatitis B immunoglobulin (HBIG) is important to prevent recurrence of hepatitis B virus (HBV) after orthotopic liver transplantation (OLT) for chronic HBV cirrhosis. With availability of lamivudine (3TC), the use of combination prophylaxis with long-term HBIG/3TC has been shown to prevent short-term HBV recurrence. This report compares HBV recurrence rates between groups receiving no/short-term HBIG, long-term HBIG alone, or HBIG/3TC prophylaxis, and describes HBIG requirements during the first 6 and 12 months in the latter two groups. This study involved patients undergoing OLT at the University of Tennessee-Memphis between May 1990 and July 2001. During this period, 388 liver transplants were performed at our center. All hepatitis B surface antigen (HBsAg)-positive recipients (n = 27) were included in this retrospective analysis. The groups were similar with regard to pre-transplant demographic characteristics such as age, gender, weight, and pre-transplant diagnosis. Owing to the retrospective study design, median follow-up was longer for the no-prophylaxis (5.6 years) and the HBIG-alone (6.0 years) groups compared to the HBIG/3TC group (4.2 years). Patient survival was 50% in the no-prophylaxis and 71% in the HBIG-alone groups compared to 100% in the HBIG/3TC group (P = 0.09). When censored for death with a functioning graft, graft survival was 50% in the no-prophylaxis and 86% in the HBIG-alone group compared to 100% in the HBIG/3TC group (P = 0.07). The overall incidence of HBV recurrence in the no-prophylaxis era was 100% and 21% in the HBIG-alone era compared to 0% in the HBIG/3TC era (P < 0.001), despite similar mean and median HBIG trough titers in the HBIG-alone and HBIG/3TC groups. The incidence of HBV recurrence in HBV DNA-positive recipients was 100% in the no-prophylaxis era, 30% in the HBIG-alone era, and 0% in the HBIG/3TC era (P < 0.001). Recipients in the HBIG-alone group had a nearly two-fold increase in HBIG requirement at 6 and 12 months in order to maintain similar HBIG trough titers post-transplant compared to recipients in the HBIG/3TC group despite similar pre-transplant HBV serology. This increased HBIG requirement in the HBIG-alone group resulted in a marked increase in the mean overall cost of HBV prophylaxis in this group ($47,367 US dollars at 6 months; $84,280 US dollars at 12 months) compared to the HBIG/3TC group ($25,931 US dollars at 6 months; $49,599 US dollars at 12 months). These data demonstrate an improvement in patient and graft survival rates in the group receiving combination HBIG/3TC prophylaxis compared to the HBIG-alone and no-prophylaxis groups. There was a significant reduction in HBV recurrence in the group receiving combination HBIG/3TC when compared to the groups receiving HBIG alone or no prophylaxis. Furthermore, we demonstrated that the addition of 3TC to the long-term HBIG regimen led to elimination of the disparity previously described in HBV recurrence rates between HBV DNA-positive and HBV DNA-negative recipients. Importantly, our data demonstrates a complete lack of HBV recurrence in the HBIG/3TC group at a median follow-up of 4.2 years. Additionally, the data show that the addition of 3TC to the post-operative prophylaxis regimen resulted in a reduction in the requirement of HBIG at 6 and 12 months, which markedly reduced the overall cost of post-transplant HBV prophylaxis.

Outcomes of simultaneous kidney-pancreas transplantation in African-American recipients: a case-control study.

INTRODUCTION: Previous studies have suggested that African-American (AA) ethnicity is a risk factor for rejection and graft loss after kidney transplantation. However, little data is available regarding outcomes after simultaneous kidney pancreas transplantation (SKPT) in AA recipients. The objective of this study was to compare the outcomes of SKPT in AA patients to matched Caucasian patients as controls. METHODS: From January 1996 to September 1999, we performed 79 SKPTs, including 10 in AA recipients. Ten Caucasian controls were selected and matched for age, gender, weight, timing and technique of transplantation, and immunosuppressive regimen. Clinical outcomes were collected and compared between the two groups. RESULTS: The two groups were well matched for donor and recipient demographic, immunologic and transplant characteristics, including 2 patients in each group with type 2 diabetes. All patients received tacrolimus (TAC), mycophenolate mofetil (MMF) and steroids, and about half in each group received antibody induction therapy. Patient survival was 100% in both groups with a mean follow-up of 18 months (range 6 47). Kidney and pancreas graft survival rates were both 80% in the AA and 100% in the Caucasian groups, respectively (p = 0.14). All but one kidney (in the AA group) and all pancreas grafts experienced immediate function. There were two immunologic kidney and two immunologic pancreas graft losses in the AA group. No grafts were lost due to technical problems. The mean length of initial hospital stay was 16 d in the AA group compared to 10 d in the Caucasian group (p = 0.07). The AA group had a slight increase in the number of readmissions (mean 2.2 AA vs. 1.6 Caucasian, p = 0.08). The incidence of biopsy-proven pancreas acute rejection was significantly higher in the AA group (50%) compared to the Caucasian group (10%) (p = 0.05). The incidence of either kidney or pancreas acute rejection was also higher in the AA group (60% AA vs. 20% Caucasian, p = 0.06). TAC levels were comparable at specific times after transplantation, al-though there was a trend toward higher doses of TAC in the AA group to achieve therapeutic levels. The incidences of relaparotomy (30% AA vs. 20% Caucasian) and major infection (40% AA vs. 60% Caucasian) were similar between groups. Renal and pancreas allograft functions were comparable between groups at specific times after transplantation. CONCLUSIONS: These results suggest that SKPT in AA recipients may be associated with a higher incidence of rejection and immunologic graft loss compared to matched Caucasian controls.