Low Acute Rejection Rates Research Articles

Preferential Allocation of Marginal Kidney Allografts to Elderly Recipients Combined with Modified Immunosuppression Gives Good Results

There is an increasing tendency to allocate kidneys from marginal donors in older recipients. This combination optimizes the uses of an expanded donor pool but demands attention for the higher nephrotoxic sensitivity of the kidney and the increased immunosuppression vulnerability of the elderly recipients. We aimed to reduce these hazards by means of a calcineurin-free induction therapy followed by a maintenance regimen targeted to minimize/withdraw steroid. Eighty-eight single (43%) or double (57%) transplant recipients (58.4+/-5.7 years) from 88 marginal donors (67+/-8.3 years) received monoclonal anti-IL-2 receptor antibodies, mycophenolate mofetil (MMF), and steroid. When serum creatinine was less than 2.6 mg/dL, tacrolimus was started and MMF was withdrawn when the tacrolimus trough level was above 15 ng/ml. Steroid was tapered to 5 mg at day 45 and then progressively reduced. Overall patient and graft survival at the first and fourth year were respectively 100 and 96%, and 98 and 79%. Acute rejection rate was 13.6% (12/88), creatinine clearance remained stable (48.2 ml/min at the sixth month, 50.9 ml/min at 48th month). At the first, second, third, and fourth years, 23, 69, 80, and 100% of recipients were off steroids. For those on steroids, mean dose was respectively 2.6 mg/day from month 12. No recipient re-assumed steroids In the "old-for-old" allocation, the calcineurin-inhibitor avoidance at induction and the steroid withdrawal/minimization during the tacrolimus-based maintenance regimen allow a low acute rejection rate, a stable renal function, and favorable recipient and graft outcomes.

Immunosuppression in Pediatric Liver and Intestinal Transplantation: A Closer Look at the Arsenal

Immunosuppression in Pediatric Liver and Intestinal Transplantation: A Closer Look at the Arsenal

Kidney Transplantation From Hepatitis C Virus–Positive Donors Into Hepatitis C Virus–Positive Recipients: A Safe Way to Expand the Donor Pool?

Introduction Because the disparity between the number of patients waiting for kidney transplants and the number of available cadaveric renal allografts continues to increase, there is a clear need to review the inclusion criteria for cadaveric donors. Patients and Methods From January 2001 to March 2004, 24 patients with end-stage renal disease and hepatitis C virus (HCV) seropositivity underwent a kidney transplantation. In 10 transplants in HCV-positive recipients, the donor was HCV-positive (D+/R+) and in 14 cases the donor (1 living donor) was HCV-negative (D−/R+). Results Two of 3 HCV-RNA–negative recipients who received a HCV-RNA+ kidney became HCV-RNA+ in the posttransplantation period. There was a low rate of acute rejection (8.3%). One D+/R+ patient experienced an acute vascular rejection, which finally resulted in graft loss, due to the resurgence of severe infectious disease. The serum creatinine levels at 6 months posttransplantation were similar in both groups. Acute liver dysfunction was observed in 1 patient. There was no death in the entire series. Graft survival was 92% and 90% for D+/R+ and D−/R+, respectively.

Mycophenolate mofetil combination therapy improves long‐term outcomes after liver transplantation in patients with and without hepatitis C

To evaluate the impact of mycophenolate mofetil (MMF) on long-term outcomes of tacrolimus and corticosteroids, we analyzed data reported to the Scientific Registry of Transplant Recipients for 11,670 adult patients (3463 with hepatitis C [HCV]) who underwent primary, single-organ, liver transplantation between 1995 and 2001. Patients who were discharged from the hospital on tacrolimus-based immunosuppression with (n = 4466; n = 1323 HCV) or without MMF (n = 7204; n = 2140 HCV) were included in the analysis. Recipients treated at discharge with MMF, tacrolimus, and corticosteroids had significantly increased patient survival (81.0% vs. 77.0% at 4 years, P < 0.0001) and graft survival (76.4% vs. 72.9%, P < 0.0001), and lower rates of acute rejection (29.0% vs. 33.4%, P < 0.001) as compared to recipients treated at discharge with tacrolimus and corticosteroids alone. A trend toward lower rates of death from infection was observed (6.1% at 4 years for MMF vs. 7.1% at 4 years for tacrolimus and corticosteroids, P = 0.0508), but this result did not reach statistical significance. In multiple regression analyses, MMF triple therapy at discharge was associated with a reduced risk of death (hazard ratio [HR] = 0.77, P < 0.001), graft loss (HR = 0.81, P < 0.001), acute rejection (HR = 0.89, P = 0.002), and death from infectious complications (HR = 0.80, P = 0.007). Outcomes were similar for the cohort with HCV.In conclusion, the addition of MMF at discharge to tacrolimus-based immunosuppression is associated with improved long-term outcomes after liver transplantation in patients with and without HCV.

Use of Neoral C2 monitoring: a European consensus

Large-scale clinical trials using C(2) monitoring of cyclosporine (CsA) microemulsion (Neoral) in renal transplant recipients have demonstrated low acute rejection rates and good tolerability with a low adverse event profile in a variety of settings: with or without routine induction therapy; in combination with mycophenolate mofetil; with standard-exposure or low-exposure Neoral; and in patients with immediate or delayed graft function. In liver transplantation, C(2) monitoring significantly reduces the severity and incidence of acute rejection compared with C(0) monitoring, without adverse consequences in terms of renal function or tolerability. Different C(2) targets are appropriate depending on adjunctive immune suppression, level of immunologic risk, CsA tolerability, risk of renal toxicity and time since transplantation. CsA absorption may increase substantially in most patients during the first 1-2 weeks post-transplant, and this should be taken into account to avoid overshooting C(2) target range. A patient with a low C(2) value may be either a low or a delayed absorber of CsA, or be a normal absorber who is receiving too low a dose of Neoral. C(2) monitoring alone is insufficient to differentiate between these types of patients, and measurement of additional timepoints is recommended. Adopting C(2) monitoring in maintenance transplant patients identifies those who are overexposed to CsA. In summary, randomized, prospective, multicenter studies and single-center trials have evaluated Neoral C(2) monitoring within a range of regimens in different organ types, providing a robust evidence base for the benefits of this sensitive monitoring technique.

Kidney-Pancreas Transplants: Is It So Difficult to Start a Program?

Background For selected patients with type 1 diabetes mellitus and end-stage renal failure, simultaneous kidney-pancreas (SKP) or pancreas after kidney (PAK) transplantation is the treatment of choice. However, it is frequently difficult to start a program for fear of serious intraabdominal complications in an immunosuppressed patient. We review our initial experience with these transplantations. Methods Twenty-three patients (20 SKP, 3 PAK) with type 1 diabetes mellitus received transplants between June 2000 and October 2003. All received immunosuppression therapy with thymoglobulin, prednisone, tacrolimus, and mycophenolate mofetil. The operation included portal venous drainage and exocrine enteric drainage. Rejections were biopsy-proved. Cytomegalovirus prophylaxis with gancyclovir was administered. Results The mean follow-up is 13 months (range, 1–30 months) for recipients of mean age 39 ± 7 years (17 men, 6 women). Mean cold ischemia time for kidney was 10.2 ± 3.9 hours, and for pancreas was 10.5 ± 3 hours. The rate of initial graft function was 100%. Graft rejection rate was 8%. The repeat laparotomy rate was 53% (12 patients), with a mean of 0.8 procedures per patient (range, 0 to 5). At the end of follow-up, patient survival was 95%, kidney survival was 85%, and pancreas survival was 83%. Patients with a functioning graft were insulin-free, with a mean fasting glucose concentration of 79 ± 7 mg/dL, hemoglobin A 1C of 4.5% (range, 4% to 4.9%) C-peptide of 5.9 ng/mL (range, 2.1 to 12 ng/mL), and a mean serum creatinine level of 1.6 mg/dL (range, 0.9 to 4.6 mg/dL). There was 1 death, due to posttransplantation lymphoproliferative disease confined to the pancreatic graft and abdominal sepsis at 3 months posttransplantation. Conclusions Our results are similar to those of other series of SPK or PAK transplantations: low acute rejection rates, frequent requirement for repeat laparotomy, and good patient and graft survival, permitting an excellent quality of life.

Cyclosporine C 2 Levels in De Novo Renal Allograft Recipients: A German Multicenter Prospective Observational Study

This ongoing multicenter prospective observational study was undertaken in de novo renal allograft recipients managed with cyclosporine (CsA) trough (C 0) and 2-hour postdose (C 2) level monitoring at defined times so as to assess the risk for an acute rejection episode or allograft dysfunction. The renal transplant recipients ( n = 159) were enrolled at 11 German centers. The 6-month posttransplant data from 138 patients were evaluable for this interim analysis. Mean C 2 levels (ng/mL), which were measured by liquid chromatography-tandem mass spectrometry at a central laboratory, were: days 3 to 5: 873.1 ± 391.9; days 7 to 10: 939.1 ± 422.8; days 14 to 28: 1116.3 ± 497.6; 3 months: 905.0 ± 316.8; and after 6 months: 787.0 ± 276.5. To identify patients at higher risk for acute rejection or allograft dysfunction, we calculated the relative CsA absorption capacity (C 2 [ng/mL]/morning dose [mg/kg]; CsA-Abs), yielding mean values on days 3 to 5: 284.4 ± 115.1; days 7 to 10: 306.7 ± 134.8; days 14 to 28: 382.5 ± 164.7; month 3: 501.5 ± 168.8; month 6: 512.7 ± 176.5. Three groups were distinguished by CsA-Abs at days 7 to 10: low absorbers (CsA-Abs < 200), normal absorbers (CsA-Abs 200 to 350), and high absorbers (CsA-Abs > 350). A between-group comparison of absorption level at 6 months posttransplant revealed the incidences of biopsy-proven acute rejection and Cockcroft-Gault formula-based mean glomerular filtration rates of 23.8% and 54.7 ± 19.0 mL/min, 22.6% and 59.5 ± 20.7 mL/min, and 17.6% and 67.7 ± 23.5, respectively. In conclusion, mean C 2 levels >1000 ng/mL are attained within 2 to 4 weeks, with CsA-Abs increasing continuously over the first 6 posttransplant months. High CsA absorbers show a propensity toward good allograft function and lower acute rejection rates at 6 months after renal transplantation.

Cyclosporine-Based Immunosuppressive Strategies for Kidney Recipients: Interim Analysis of German Data From the Multinational Observational Study (MOST)

Introduction We collected data from kidney recipients with a functioning graft at German kidney transplant centers in order to analyze the efficacy of various cyclosporine (CsA)-based immunosuppressive strategies, the effects of different perioperative and maintenance regimens, and the impact of donor source on clinical outcome. Methods As part of the ongoing prospective Multinational Observational Study in Transplantation (MOST), data for both prospective and retrospective analysis were collected from kidney recipients over 18 years bearing a functioning graft that was transplanted at 21 German kidney transplant centers between 1987 and 2002. Results Data from 1223 renal graft recipients, including their CsA-based immunosuppressive regimens, were stratified as: 402 de novo patients (median 6.8 months posttransplant) and 821 patients on maintenance therapy (median 71 months posttransplant). Triple regimens with CsA + mycophenolate mofetil (MMF) + steroids (Ste) currently comprise the major perioperative immunosuppressive strategies in Germany (de novo 65%). IL-2 receptor antagonist (IL-2Ra) use is increasing (de novo 18%, maintenance 4%), while mono and dual regimen use de novo is declining (de novo 4%, maintenance 20%). Among 689 patients transplanted between 1987 and 2002 with outcome data, the mean incidence of acute rejection during the first posttransplant year was 21.6%. Rejection rates on initial therapy with CsA + MMF + Ste ± antibodies ( n = 517) averaged 17.8%. Conclusions Between 1987 and 2002, CsA-based immunosuppression combined with MMF and Ste became the most commonly used strategy for both initial and maintenance therapy after kidney transplantation in Germany, yielding the low acute rejection rates particularly when combined with IL-2Ra.

Prevention of Cardiac Allograft Vasculopathy With Certican ® (Everolimus): The Stanford University Experience Within the Certican Phase III Clinical Trial

A large Phase III clinical trial with the novel proliferation signal inhibitor, Certican (everolimus), has shown this agent to be associated with lower rates of acute rejection, cardiac allograft vasculopathy (CAV) and cytomegalovirus (CMV) infection when compared with azathioprine (AZA) at 12 months post-transplant. Given that CAV is the main risk factor for mortality after the first year post-transplant, and that acute rejection and CMV infection play a key role in the development of this disease, the findings suggest that everolimus has an important role as part of the primary immunosuppression of this population. Consideration of the presentation and outcome of patients from Stanford University who were enrolled in the pivotal trial with everolimus in heart transplantation has highlighted the efficacy of everolimus in this setting. Analysis of the angiographic outcome data of these patients demonstrates that the efficacy of everolimus observed in the large, multicenter trial involving heart transplant patients was replicated in the findings of a single center. This finding is important for the interpretation of clinical trial data, offering reassurance that data from large trials are applicable to an individual center. The results from Stanford also reveal an important difference between everolimus and AZA with regard to intimal thickening and the incidence of abnormal left ventricular ejection fraction (LVEF), suggesting that everolimus may improve left ventricular function. Because abnormal LVEF has been associated with greater risk of vascular rejection and allograft vascular disease, use of everolimus could well improve long-term outcomes in heart transplant recipients.

A Prospective, Randomized, Multicenter, Double-Blind Study of Early Corticosteroid Cessation Versus Long-Term Maintenance of Corticosteroid Therapy With Tacrolimus and Mycophenolate Mofetil in Primary Renal Transplant Recipients: One Year Report

This report summarizes year 1 blinded data from a 5-year prospective, randomized (1:1, stratified by race and donor type), multicenter, double-blind study comparing treatment failure rates between early cessation of corticosteroid therapy and long-term corticosteroid maintenance therapy in 397 primary renal transplant recipients receiving tacrolimus and mycophenolate mofetil with antibody induction. Sixteen (4.1%) patients died or experienced graft loss during year 1 (9 deaths, 6 graft losses, and 1 death with a graft loss). Fifty-nine (15.3%) patients experienced rejection; 40 (10.4%) of these cases were biopsy-confirmed. Values for 10-year predictive risk of coronary heart disease (CHD) estimated from the Framingham Heart Study scores showed a shift from baseline toward a more favorable risk profile. Renal transplant recipients treated with a tacrolimus-based immunosuppressive regimen and either early cessation or maintenance of corticosteroid therapy experienced excellent patient and graft survival, low acute rejection rates, low rate of posttransplantation diabetes mellitus (9.0%), and improved CHD risk profile at 1 year posttransplantation.

Acute Cellular Rejection Predominated by Monocytes Is a Severe Form of Rejection in Human Renal Recipients With or Without Campath-1H (Alemtuzumab) Induction Therapy

Campath-1H has been used successfully for induction and has resulted in a low rate of acute cellular rejection (ACR) in renal transplantation in combination with various postoperative immunosuppression regimens. This study was undertaken to investigate the extent of monocyte involvement in ACR, with or without Campath-1H induction. We found that monocytes represented the majority of inflammatory cells in grades Ib or higher ACR, but not with Ia type of ACR, regardless of the status of Campath-1H induction. Cases of ACR, following Campath-1H induction, appear to demonstrate a 'pure form' of monocytic ACR, whereas monocytes were mixed with many other types of inflammatory cells in the cases of ACR in the absence of Campath-1H induction. In addition with Campath-1H induction, the cases of monocyte-predominant ACR were found to uniformly exhibit a good response to corticosteroid treatment. We conclude that monocyte-predominate ACR may represent a severe form of rejection, with or without Campath-1H treatment.

Basiliximab lowers the cyclosporine therapeutic threshold in the early post-kidney transplant period

Early adequate cyclosporine exposure has been shown to predict low acute rejection rate in kidney transplantation. The aim of this study is to determine the importance of exceeding the early cyclosporine therapeutic exposure threshold with basiliximab induction. A retrospective analysis of 166 first cadaveric and non-identical live donor transplant recipients treated with or without basiliximab induction, Neoral, mycophenolate mofetil and prednisone, was performed. Adequate exposure was defined as a 2-h post-Neoral dose cyclosporine level (C2) >1700 ng/mL at day 3. The primary outcome was acute rejection within the first 6 months. In the no basiliximab (control) group (n = 74), rejection occurred in 23% (17 of 74) of recipients and was strongly associated with low cyclosporine exposure on day 3. Acute rejection occurred in 38% (11 of 29) with C2 <1700 ng/mL compared with 13% (six of 45) with C2 >/=1700 ng/mL (p = 0.014). In the basiliximab group (n = 92), rejection occurred in only 11% (10 of 92) of recipients and did not correlate with cyclosporine exposure. Acute rejection occurred in 10% (four of 40) with C2 <1700 ng/mL compared with 12% (six of 52) with C2 >/=1700 ng/mL (p = 0.81). Therefore achieving cyclosporine therapeutic targets by day 3 may not be required when anti-IL2 receptor antibody induction is used.

A Multicenter Pilot Study of Early (4-Day) Steroid Cessation in Renal Transplant Recipients Under Simulect, Tacrolimus and Sirolimus

This study presents the first prospective multicenter study assessing sirolimus-based immunosuppression with early (4-day) corticosteroid withdrawal (CSWD) in renal transplantation. Immunosuppression included: anti-IL-2 receptor antibody and tacrolimus/sirolimus. Inclusion criteria included adult primary recipients. Exclusion criteria included: (i) African Americans, (ii) current PRA >50%, (iii) multiple organ transplants, (iv) WBC < 3000 cells/microL and (v) fasting hypercholesterolemia/hypertriglyceridemia. The primary endpoints were acute rejection and the proportion of patients off corticosteroids. Seventy-seven patients were enrolled: mean age of 49.7 +/- 12 years. Transplants included: cadaveric (26%) and living donor (74%). Patient and graft survival were 100%. Biopsy proven acute rejection occurred in 13%; presumptive rejection in 10.5%. Banff grades included: IA (seven patients), IB (one patient), IIA (one patient) and IIB (one patient). Renal function at 1 year: serum creatinine (1.18 +/- 0.06 mg/dL). Mean weight gain was minimal at 1 year: 3 +/- 2 kg/patient. Mild increases in total, LDL and HDL cholesterol were observed and new antilipid agent use occurred in 26 patients. In conclusion, early CSWD under tacrolimus/sirolimus-based immunosuppression in selected, low-risk renal transplant recipients provides: (i) excellent patient and graft survival, (ii) good renal function, (iii) reduced hyperlipidemia and antilipid agent use and (iv) low acute rejection rates.

Cardiovascular risk profile in patients treated with sirolimus after renal transplantation

Renal transplant patients are inherently predisposed to cardiovascular disease (CVD) as a result of prolonged exposure to multiple cardiovascular risk factors. Approximately one half of all late graft losses are due to death with a functioning graft, and CVD is the most frequent cause of death with a functioning graft among these patients. Immunosuppressive therapies associated with a reduced burden of risk for CVD would therefore greatly decrease post-transplantation morbidity and mortality. The nephrotoxic effects observed with the use of calcineurin inhibitors (CNIs), such as cyclosporine (CsA), run counter to the goal of renal transplant therapy. Sirolimus, a more recent immunosuppressive agent with a unique mechanism of action, offers an alternative to CsA. Recent data from a 4-year study investigating early CsA withdrawal from a sirolimus-CsA-steroid (SRL-CsA-ST) combination demonstrated significantly better renal function, lower blood pressure, and improved graft survival after CsA withdrawal. During that trial, the increase in serum lipids induced by sirolimus was generally manageable with lipid-lowering therapy. Further investigation is warranted to evaluate the value of CNI-free therapy compared with CNI-based regimens in reducing cardiovascular risk factors and improving patient and graft survival.

Analysis of cause of death with a functioning graft: A single-center experience

Introduction After the introduction of new immunosuppressants, such as tacrolimus and mycophenolate mofetil, we have achieved excellent results for kidney transplantation with a low acute rejection rate. Currently, nonimmunological factors are considered to be the main cause of graft loss for long-term transplant patients. In this study, we analyzed the cause of death with a functioning graft. Patients and methods We performed 1375 cases of living kidney transplantation (LKT) and 219 cases of cadaveric kidney transplantation (CKT) between January 1983 and December 2002. Of these patients, 86 LKT patients and 19 CKT patients died with a functioning graft. Results The mean duration of graft function was 4.8 ± 4.5 years. The incidence of the causes of death were: infection, 24%; stroke, 17%; cardiovascular disease, 16%; malignant disease, 15%; hepatic failure, 11%; gastric ulcer, 4%; and accident/suicide 2%. Five- and 10-year graft survivals for LKT were 80.2 and 62.0%, respectively. The corresponding values for patients (with the exception of the patients who died with a functioning graft) was 83.0% and 66.1%, respectively. The 5- and 10-year graft survival rates for cadaveric kidney transplants were 70.8% and 48.9%, respectively. The corresponding values for patients (with the exception of the patients who died with a functioning graft) were 75.3% and 52.6%, respectively. Conclusion To prevent death with a functioning graft, management of vascular disorders such as stroke and cardiovascular disease, malignant disease, and infectious disease is crucial for kidney transplant patients.

A MULTICENTER, OPEN LABEL PILOT STUDY OF EARLY (5 DAY) CORTICOSTEROID CESSATION IN DE NOVO RENAL TRANSPLANT RECIPIENTS UNDER SIMULECT, TACROLIMUS, AND SIROLIMUS THERAPY: ONE YEAR RESULTS

O430 Aims: New immunosuppressive regimens that allow early corticosteroid cessation (ECC) are being reported with increasing frequency. However, few prospective multicenter trials exist evaluating ECC. Herein, we report 1 year (yr) results of the first multicenter trial of ECC under tacrolimus/sirolimus based immunosuppression. Methods: This study is a single limb, open label, multicenter study conducted at 8 sites. Primary endpoints included biopsy confirmed acute rejection (AR) and the proportion of patients (pts) off CS at 6 months. Secondary endpoints included: study withdrawal, calculated GFR, serum creatinine, and pt and graft survival. Inclusion criteria included primary renal transplant (Tx) recipients aged 18 or greater. Exclusion criteria included: African American race, WBC < 3000/ul, fasting hypercholesterolemia or hypertriglyceridemia, and PRA > 50%. Immunosuppression included: Simulect (20mg on posttransplant day (PTD) 0 and 4; tacrolimus (target level 6-9 ng/ml), sirolimus (target level 8-15 ng/ml), and solumedrol (PTD 0-4; 250, 250, 125, 65, 30 mg then DC). Results: 77 pts were enrolled with 1 yr followup. Demographics included: 57% male; 79% Caucasian, 14.5% Hispanic, and 6.5% Asian. Median age at Tx was 51 yr (range 22-69). Donor source included 26% cadaver, 35% living unrelated, 39% living related. ESRD etiology included diabetes in 32.5% of pts. At one yr, pt and graft survival were both 100%; AR occurred in 13% (80% of AR occurred in first 6 mos post-Tx). Most AR were mild; Banff criteria: IA (7), IB (1), IIA (1), IIB (1). AR treatment consisted of: steroids (100%) and antilymphocyte antibody (90%). Serum creatinine at 12 mos was 1.49 +/- 0.09 mg/dL with a mean calculated GFR of 67.7 +/- 2.9 ml/min. Study withdrawal occurred in 26%: tacrolimus toxicity (2), poor wound healing (3), lack of efficacy (1), protocol violation (2),oral ulcers (2), marrow suppression (2). PostTx diabetes occurred in 14.4% of pts. PTLD, CMV, and Pneumocystis were not observed. Infections occurred in 59% of pts, with UTI and URI accounting for 60% of infections. DGF occurred in 22% of pts. Mean weight gain was 1.3 kg/pt. 79.2% of pts were off CS at 1 yr. 26% of pts required new antilipid therapy. Conclusions: This pilot analysis demonstrates excellent patient and graft survival with low rates of AR with an acceptable side effect profile. Additional comprehensive studies comparing this to conventional approaches are warranted.

RACIAL IMPACT ON THE RATE OF POST-TRANSPLANT DIABETES MELLITUS IN STEROID-FREE KIDNEY TRANSPLANT RECIPIENTS

P339 Aims: Early steroid withdrawal has been associated with a lower incidence of post transplant diabetes mellitus (PTDM). A retrospective data analysis was done to study the incidence of PTDM, among racial groups, in kidney transplant (KTx) recipients who received early steroid withdrawal. Methods: Between 1/02 and 11/03, 102 consecutive, adult KTx recipients (40 cadaver, 62 live donor), were studied. All received Methylprednisolone intra-operatively. Group A, (N=68), had steroids withdrawn by pod #6. Maintenance immunosupression consisted of Tacrolimus (TAC) and Mycophenolate Mofetil (MMF). African Americans (AA) received Thymoglobulin induction, all others received Simulect. Group B (n=34) patients received the same immunosuppression but were maintained on steroids indefinitely. The two groups were equivalent for demographic data, donor source and risk factor for diabetes. In particular, family history of DM in Group A was 58% and 44% in Group B (p=ns). Patient and graft survival, serum creatinine, incidence of rejection, BMI and incidence of PTDM were recorded at 3, 6 and 12 months. Diabetes was diagnosed using American Diabetes Association guidelines. Results: At 1 yr, patient/graft survival and serum creat. were similar in all groups. Acute rejection rate was 3% in Group A, compared to 12% in Group B (p=ns). BMI increase from baseline at 1 yr was 5.9% in Group A and 9.4% in Group B (p=ns). The incidence of PTDM was lower in Group A (7%) compared to Group B (24%, p=0.07). The risk of PTDM in Group A was limited to Hispanic (Hisp) patients; AA and Caucasians (Cauc) in Group A did not experience PTDM (p=0.005 for AA compared to Group B).FigureConclusions: KTx recipients treated with early steroid withdrawal have a trend for lower rates of acute rejection and similar renal function at 1yr when compared with patients treated with maintenance steroid therapy. Importantly, a steroid free protocol eliminated the incidence of PTDM in AA and Cauc., but had no effect on the development of PTDM in the Hisp. group. Alternative immunosuppression may benefit this population.

CADAVERIC RENAL TRANSPLANTATION AND EXPANDED CRITERIA DONORS: SHOULD WE REASSESS THEIR USE?

O230 Aims: Renal Transplant waiting lists continue to grow. Living donation has helped but is unavailable for many recipients. The use of expanded criteria cadaveric donors may be an alternative. Since 1997 we have liberalized our cadaveric donor criteria and assessed our results using a standard immunosuppression protocol. Methods: Between January 1st, 1997 to September 30th, 2003 we performed 172 cadaveric renal transplants using induction with Thymoglobulin (Thy), Mycophenolate Mofetil (MMF) and Predinisone. Calcineurin inhibitors (80% tacrolimus (TAC), 20% Cyclosporine Neoral (CsA)) were introduced only when serum creatinine was < 250 μmoles/L (3.0mg/dl). We divided the patients into 2 groups according to the scoring system described by Nyberg et al. (American Journal of Transplantation 2003 (2; 3:715) which was based on donor age, history of hypertension, creatinine clearance before procurement, cause of death, and HLA mismatch. Group 1 (optimal donors) had a score of 0-19 and group 2 (extended criteria donors) had a score of 20-39. We compared the 2 groups for graft survival, acute rejection rate (ACR), creatinine at 1year, delayed graft function (DGF= need for hemodialysis or creatinine >250μmol/L on day 5). Death with a functioning graft was considered to be a graft loss. Results:FigureOverall, graft survival for all 172 patients was 92.2 and 81.8% at 1 & 5 years. Patients in Group 2 had a higher rate of DGF and a higher creatinine at 1 year, however graft survival at 5 years was still relatively good (78 vs 83% p=ns). Patients with DGF (n=61) had a lower 1 and 5 year graft survival compared to patients without DGF (86 vs 98 % and 72 vs 88% p<0.004) irrespective of the group they belong to. DGF had an equally bad impact on “ideal” donors and “extended criteria” donors. All patients with DGF had a renal biopsy in the 1st 4 weeks after transplant and none had rejection. Conclusions: A protocol with Thymoglobulin, MMF, Predinisone and TAC or CsA results in very low acute rejection rate and excellent graft survival. Extended criteria donors had a higher risk for DGF. DGF resulted in poorer 5 year graft survival in both groups. Extended criteria donors without DGF had an excellent 5 year graft survival. Extended criteria donors should be used, and strategies to minimize DGF should result in excellent graft survival

MULTICENTER RANDOMIZED HEPATITIS C (HCV) THREE TRIAL POST LIVER TRANSPLANTATION (OLT): A PRELIMINARY REPORT.

O372 Aims: To assess the efficacy and safety of mycophenolate mofetil (MMF) and steroid (Pred)-free immunosuppression (IS) in an effort to minimize HCV recurrence (HCVR), acute rejection (ACR) and adverse events (AE) post OLT. Methods: The trial was designed as an open label, prospective, randomized multicenter study involving adult HCV-OLT recipients (Pt) allocated into 3 IS regimens. Arm 1: tacrolimus (TAC) + Pred; arm 2: TAC + Pred + MMF and, arm 3: TAC + MMF + 3 dose – daclizumab (2 mg/kg), but no steroids. HCV-OLT Pt (n=312) from 18 different institutions were allocated at a 1:1: 2 ratio, respectively. Laboratory data and liver histology (LBx) were evaluated when clinically indicated and, by protocol, at 90, 365 and 730 days (d). HCVR was staged according to Batts and Ludwig. ACR was graded according to Banff criteria. Primary endpoints were clinically significant HCVR (fibrosis stage (Sg) ≥ 2 at d. 90 or 365 and/or ≥ 3 at 730 d.) and/or clinically significant ACR (Banff grade (Gr) 2 + RAI 4). Results: Report is based on the Data Safety Monitoring Board assessment from November 2003, in order to maintain the validity of the trial. Out of 228 patients enrolled, 182 patients had a median follow up of 89 days. The table summarizes the average patient characteristics. Day 90 Lbx were done in 82% Pt. Preliminary information on 98 Pt showed: HCVR (Sg ≥ 2) in 8 Pt (8.2%) who were placed on antivirals (endpoint). ACR were found on 10 Pt (10.2%, Gr 2 (6); Gr 3 (4)) at a median of 13 d. post OLT. Five patients died due to: lung failure + cancer; CVA; idiopathic lung disease; HA thrombosis; sepsis. Study withdrawal: 3 Pt.Figure*HBVSag and cAB donors were excluded; C.I.T.: cold ischemia time (hours). Conclusions: This 90-d preliminary report suggests the safety of the Pred-free IS (TAC+MMF+daclizumab) used in the trial. The initial low HCVR rate found is encouraging and needs further follow up. The very low ACR rate is of significance, since most of ACR occur early post OLT. Enrollment was completed on 4/1/04 (312 Pt) and a first interim analysis of the treatment groups will be available at presentation.

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.