Received Rabbit Antithymocyte Globulin Induction Research Articles

Subtle Changes in Tacrolimus Levels Have an Impact on Early Donor-Specific Antibodies in Kidney Transplantation.

Introduction: The impact of each immunosuppressive agent on de novo donor-specific antibodies in kidney transplant recipients varies among extant literature. Project aims: Patterns in immunosuppression and the effects on incidence of de novo donor-specific antibodies were evaluated. Design: Adult kidney transplant recipients from 2017 to 2019 without preformed antibodies were sampled. Allograft function, de novo donor-specific antibodies, tacrolimus concentrations, duration of goal-dose antiproliferatives, and steroid doses were recorded. Outcomes included incidence of de novo donor-specific antibodies, and their relation to tacrolimus concentrations, time at goal-dose antiproliferatives, and steroid doses. Results: Recipients (N = 153) were followed for 1 year; all were crossmatch negative and received rabbit antithymocyte globulin induction. Sixteen (10%) recipients developed de novo donor-specific antibodies in a median of 31 days [interquartile range, IQR: 12-67 days], most were Class II antibodies (87.5%). Incidence of de novo donor-specific antibodies did not differ based on induction dosing. Tacrolimus levels in the first month were lower for patients with de novo donor-specific antibodies (8.8 ng/mL vs 10.4 ng/mL, P < .01). There was no difference in time on goal antiproliferative doses, but higher steroid doses (0.4 vs 0.3 mg/kg/d; P = .02) were noted in patients with antibodies. Steroid dosing was likely impacted by baseline risk factors. Conclusion: A significant association was found between lower tacrolimus concentrations early post-transplant and incidence of de novo donor-specific antibodies. This highlighted the importance of clinician attention to subtle changes in tacrolimus and the impact it can have on antibody risk in the early post-transplant period.

Impact of early corticosteroid withdrawal on simultaneous pancreas-kidney transplant long-term outcomes: Single center experience and comparison to the International Pancreas Transplant Registry.

There remains a paucity of modern data comparing early steroid withdrawal (ESW) versus chronic corticosteroid (CCS) immunosuppression in simultaneous pancreas kidney (SPK) transplant recipients with long-term follow-up. Therefore, the purpose of this study is to assess the effectiveness and tolerability of ESW compared to CCS post-SPK. This was a retrospective single-center matched comparison with the International Pancreas Transplant Registry (IPTR). Patients from University of Illinois Hospital (UIH) represented the ESW group and were compared to those matched CCS patients from the IPTR. Included patients were adult recipients of a primary SPK transplant between 2003 and 2018 within the US receiving rabbit anti-thymocyte globulin induction. Patients were excluded if they had early technical failures, missing IPTR data, graft thrombosis, re-transplant, or positive crossmatch SPK. A total of 156 patients were matched and included in the analysis. Patients were predominantly African American (46.15%) males (64.1%) with Type 1 diabetes etiology (92.31%). Overall pancreas allograft survival (hazard ratio [HR] = .89, 95% confidence interval [CI] .34-2.30, p = .81) and kidney allograft survival (HR = .80, 95%CI .32-2.03, p = .64) were similar between the two groups. Immunologic pancreas allograft loss was statistically similar at 1-year (ESW 1.3% vs. CCS 0%, p = .16), 5-year (ESW 1.3% vs. CCS 7.7%, p = .16), and 10-year (ESW 11.0% vs. CCS 7.7%, p = .99). The 1-year (ESW 2.6% vs. CCS 0%, p>.05), 5-year (ESW 8.3% vs. CCS 7.0%, p>.05), and 10-year (ESW 22.7% vs. CCS 9.9%, p = .2575) immunologic kidney allograft loss were also statistically similar. There was no difference in 10-year overall patient survival (ESW 76.2% vs. CCS 65.6%, p = .63). No differences were found between allograft or patient survival post-SPK when comparing an ESW or CCS protocol. Future assessment is needed to determine differences in metabolic outcomes.

Age-related decline in anti-HBV antibodies in vaccinated kidney transplant recipients.

Hepatitis B virus (HBV) vaccination is indicated for all end stage kidney disease patients, including all solid organ transplant candidates. Maintenance of adequate immunity is especially important for immunosuppressed solid organ recipients who are at increased risk for donor or community acquired HBV. The impact of age and immunosuppression on long-term maintenance of HBV immunity postvaccination has not been fully investigated. We performed a single-center retrospective study of 96 kidney transplant recipients, transplanted between July 2012 and December 2020, who had Hepatitis B surface antibody (HBsAb) levels measured pretransplantation and 1-year posttransplantation. We compared the change in HBsAb levels stratified by patient's age (<45, 45-60, and >60) and by whether or not the patient received lymphocyte depleting induction therapy. Our results demonstrate that HBsAb IgG levels vary by age group, decreased significantly at 1-year posttransplant (p < .0001) and were significantly lower in the older cohort (p = .03). Among recipients who received rabbit anti-thymocyte globulin induction (rATG), the log HbsAb levels were significantly lower in the older age group (2.15 in age <45, 1.75 in age 45-60 and 1.47 in age >60, p = .01). Age group (p = .004), recipient HBcAb status (p = .002), and rATG (p = .048) were independently associated with >20% reduction in log HBsAb levels posttransplant. Significant declines in HBsAb levels occur postkidney transplantation, especially in older individuals, thus placing exposed older kidney transplant recipients at greater risk of HBV infection and associated complications.

Lymphopenia at the time of transplant is associated with short-term mortality after deceased donor liver transplantation

Absolute lymphocyte count (ALC) is considered a surrogate marker for nutritional status and immunocompetence. We investigated the association between ALC and post-liver transplant outcomes in patients who received a deceased donor liver transplant (DDLT). Patients were categorized by ALC at liver transplant: low (<500/μL), mid (500-1000/μL), and high ALC (>1000/μL). Our main analysis used retrospective data (2013-2018) for DDLT recipients from Henry Ford Hospital (United States); the results were further validated using data from the Toronto General Hospital (Canada). Among 449 DDLT recipients, the low ALC group demonstrated higher 180-day mortality than mid and high ALC groups (83.1% vs 95.8% and 97.4%, respectively; low vs mid: P = .001; low vs high: P < .001). A larger proportion of patients with low ALC died of sepsis compared with the combined mid/high groups (9.1% vs 0.8%; P < .001). In multivariable analysis, pretransplant ALC was associated with 180-day mortality (hazard ratio, 0.20; P = .004). Patients with low ALC had higher rates of bacteremia (22.7% vs 8.1%; P < .001) and cytomegaloviremia (15.2% vs 6.8%; P = .03) than patients with mid/high ALC. Low ALC pretransplant through postoperative day 30 was associated with 180-day mortality among patients who received rabbit antithymocyte globulin induction (P = .001). Pretransplant lymphopenia is associated with short-term mortality and a higher incidence of posttransplant infections in DDLT patients.

Survival Rate of Renal Transplant and Factors Affecting Renal Transplant Failure.

The most important complication in kidney transplant is acute/chronic rejection. In this study, we investigated the factors affecting kidney rejection and transplant survival. In this survival analysis study, 352 patients (mean follow-up of 12.9 ± 4.4 years) who underwent renal biopsy due to increased creatinine level from 2012 to 2016 were identified by glomerular filtration rate level and rejection. Probable factors affecting renal function and survival rate after transplant rejection were assessed. P < .05 was considered as significant. Among our study patients, 40.9% developed early and 59.1% developed late acute kidney injury. Graft survival rates at 1 and 5 years were 98.9% and 68.5%, respectively, which was significant when rejection type was considered (P = .002). In addition, patient survival rates at 1 and 5 years were 99.7% and 98.6%, respectively. Graft survival at 5 years was significantly lower among older subjects, those with diabetes, those who received deceased donor organs, and those with late acute kidney injury (P < .002). Patient survival was significantly higher among young patients, those with systemic lupus erythematosus, those who received living donor organs, and those without cytomegalovirus infection (P < .003). We observed that recipient age, type of donor, underlying disease, infection, and late acute kidney injury had great negative impacts on renal dysfunction and survival. In our center, because of the large number of kidney transplants from deceased donors, the necessity of antithymocyte globulin induction therapy was considered, since this study showed that patients who received rabbit antithymocyte globulin induction had better outcomes.

Heterogeneous Manifestations of Posttransplant Lymphoma in Renal Transplant Recipients: A Case Series

Posttransplant lymphoproliferative disorder (PTLD) occurs in 1% to 3% of adult renal transplant recipients (RTRs). PTLD has a heterogeneous presentation and is often associated with Epstein-Barr virus (EBV) and immunosuppression. We present a descriptive case series of 16 RTRs who demonstrate a variety of PTLD manifestations. Fifty-six percent received rabbit antithymocyte globulin induction, and 37.5% received basiliximab. Maintenance immunosuppression included glucocorticoids, tacrolimus, and mycophenolate mofetil. Median time from transplantation to PTLD diagnosis was 96.5 months. PTLD involved a single site in 44% of RTRs and multiple sites in 56%. PTLD was localized to the gastrointestinal tract in 9 RTRs, in lymph nodes in 9, central nervous system in 4, bone marrow in 3, skin in 3, lungs in 2, perinephric space in 2, mediastinum in 1, and native kidney in 1. PTLD was EBV positive in 8 RTRs, monomorphic/monoclonal in 14, and of B-cell lineage in 13. Three RTRs had T-cell PTLD. Immunosuppressive agents, except glucocorticoids, were discontinued at diagnosis. Treatment was chemotherapy either alone (in 14 RTRs) or in combination with radiation. Complete remission was achieved in 62.5% of RTRs. Renal dysfunction developed in 62.5% of RTRs, and 4 received dialysis. The overall mortality rate was 62.5%, with median time of death 6.5 months after diagnosis. PTLD that was EBV negative and had T-cell involvement presented with aggressive disease and a higher mortality. Clinicians should be aware of the various PTLD manifestations. Early diagnosis and a multidisciplinary approach to treatment is crucial for improved patient outcomes.

Relationship between rabbit anti-thymocyte globulin and development of PTLD and its aggressive form in renal transplant population

ABSTRACT: Introduction The aim of our study is to explore the relationship of rabbit anti-thymocyte globulin (R-ATG) on development of post-transplant lymphoproliferative disease (PTLD) and its aggressive forms (monomorphic PTLD and Hodgkin lymphoma) in renal transplant recipients. Methodology All patients diagnosed with PTLD post-renal transplant in the United States’ Organ Procurement and Transplantation Network from 2003 till 2013 and followed up till 2017 were retrospectively reviewed. Multi-variable logistic regression analysis assessed association of R-ATG to development of PTLD and its aggressive form. Results Risk of developing PTLD post renal transplant is 1.35%. In comparison to interleukin-2 blocker induction therapy, R-ATG is associated with increased risk of development of PTLD (Odds Ratio = 1.48, confidence interval ranges from 1.04 to 2.11, p = .02) and is associated with higher risk of development of aggressive PTLD (Odds Ratio = 1.83, confidence interval ranges from 1.001 to 3.34, p = .04). Conclusion We conclude that R-ATG induction is associated with a higher risk of PTLD and its aggressive form (monomorphic PTLD and Hodgkin lymphoma). Careful monitoring for development of PTLD in renal transplant recipients receiving R-ATG induction therapy is advised.

Tacrolimus Concentration-to-Dose Ratios in Kidney Transplant Recipients and Relationship to Clinical Outcomes.

One factor impacting tacrolimus interpatient variability is the presence of CYP3A5 polymorphisms. Low tacrolimus concentration-to-dose ratios (CDRs), or rapid metabolizers (RMs), have been associated with poor graft function outcomes and higher biopsy-proven acute rejection (BPAR) rates in a predominantly white population. Pretransplant CYP genotyping is not routinely conducted, and therefore only a small number of studies have assessed the use of tacrolimus CDRs as a surrogate for metabolism. We explored differences in outcomes between patients with low tacrolimus CDRs and high tacrolimus CDRs (i.e., nonrapid metabolizers [NRMs]) in a diverse patient population. To determine the relationship between tacrolimus CDRs and graft and patient outcomes in kidney transplant recipients at a large transplant center between 2006 and 2016. Inclusion criteria consisted of adult kidney transplant recipients who received rabbit antithymocyte globulin induction followed by a maintenance regimen of tacrolimus, mycophenolate, and prednisone. The primary end point was BPAR at 1year. Secondary end points included graft survival, patient survival, and toxicities. Determination of clusters was conducted using the two-step cluster analysis with a defined two-cluster distribution. Kaplan-Meier survival curves were created using the log-rank test. The NRM cluster consisted of 322 patients with a mean CDR of 2.91ng/ml/mg. The RM cluster consisted of 932 patients with a mean CDR of 1.14ng/ml/mg. The BPAR at 1year posttransplant was 3.7% in the NRM cluster and 3.6% in the RM cluster (p=0.95). Death at 5years was higher in the NRM group compared with the RM group for unknown reasons (p=0.03). Differences in the incidence of posttransplant toxicities were not statistically significant at any time point, except for increased rates of cutaneous cancer at 5years and cardiovascular disease overall in the NRM group. Tailoring tacrolimus therapy early posttransplant based on CDR is not supported by the findings in this study.

Kinetic of the CMV‐specific T‐cell immune response and CMV infection in CMV‐seropositive kidney transplant recipients receiving rabbit anti‐thymocyte globulin induction therapy: A pilot study

Some studies have suggested that rATG treatment may be associated with an increased incidence of CMV infection and delayed CMV immune response. However, the evidences supporting this matter are scarce. This study aims to characterize the kinetic of the CMV-specific T-cell immune response before and after rATG induction therapy and the relationship with the development of CMV infection in CMV-seropositive kidney transplant recipients. An observational prospective study of CMV-seropositive kidney transplant patients that received rATG induction therapy was performed. A pretransplant sample was obtained before the surgery to determine the CMV-specific immunity. CMV viral load (by PCR) and CMV-specific T-cell immune response (by flow cytometry) were determined during the follow-up at 0.5, 1, 2, 3, 6, and 12months post transplantation. A total of 23 patients were included in the study. CMV prophylaxis was administrated for a media of 90days after transplantation. At the end of follow-up, 18 (78.3%) patients had CMV-specific immunity with a median value of 0.31% CD8+ CD69+ INF-γ+ T cells at a median of 16weeks post transplantation. Five patients never acquired CMV-specific immunity. No statistically significant association between CMV infection and CMV-specific T-cell immune response (P=.086) was observed. However, patients with positive pretransplant CMV-specific immunity developed earlier immunity and achieved higher levels of CD8+ CD69+ INF-γ+ T-cell post-transplantation than patients with negative pretransplant immunity. CMV-specific immune monitoring in addition to CMV-serology may be useful to stratify patient's risk of CMV infection before transplantation.

Absence of the Effect of Pretransplant Body Mass Index on Post Kidney Transplant Outcomes.

Obesity has been reported as risk factor for reduced posttransplant graft and patient survival and increased delayed graft function (DGF). The purpose of this work is to analyze the effect of body mass index (BMI) on defined transplant outcomes in patients transplanted under defined guidelines in a kidney transplant program. Review of a prospectively collected database in renal transplant recipients receiving rabbit antithymocyte globulin induction, mycophenolate mofetil, tacrolimus, and early corticosteroid withdrawal between 2001 and 2011. This review was conducted in a single abdominal transplant program in the United States. Primary outcome was death-censored graft survival categorized by posttransplant body mass groups. Secondary outcomes included DGF as well as patient survival. Four hundred sixty seven patients were identified. No difference was observed in graft survival or DGF between BMI groups. One-year, death-censored graft survival and patient survival rates ranged from 97.5% to 100% and 96.6% to 100%, respectively. Delayed graft function was uncommon across all BMI groups, ranging from 5.3% to 9.1%, with the lowest incidence in patients with a BMI ≥ 35 kg/m(2). Biopsy-proven acute rejection rates at 1 year were similar across all groups (10.1%-14%) as were estimated glomerular filtration rates were at 1, 3, and 5 years. Our results do not show an effect of BMI on posttransplant outcomes, suggesting that relaxation of BMI criteria may be warranted for recipient selection.

Effects of Ideal Versus Total Body Weight Dosage of Rabbit Antithymocyte Globulin on Outcomes of Kidney Transplant Patients With High Immunologic Risk.

The optimal dose of rabbit antithymocyte globulin induction therapy in kidney transplant recipients with high immunologic risk lacks consensus. The purpose of this study was to evaluate the effect of using ideal body weight rather than total body weight for the weight-based dose calculations in this patient population. Data were retrospectively collected on 89 adult patients who received rabbit antithymocyte globulin induction therapy for high immunologic risk kidney transplant. Hospital protocol changed from the use of cumulative rabbit antithymocyte globulin doses of 7.5 mg/kg total body weight to 7.5 mg/kg ideal body weight in 2009. Patients were separated into 2 cohorts based on the amount of rabbit antithymocyte globulin (in mg/kg total body weight) received. Rate of biopsy-proven acute rejection, patient survival, and allograft function were evaluated at 90 days and 1 year after transplant. Cost of induction therapy was also evaluated. Baseline demographics were predominantly similar between the 2 cohorts. No significant difference in maintenance immunosuppression was identified. Rates of biopsy-proven acute rejection at 90 days and 1 year were similar between ideal and total body weight cohorts (4.2% vs 0% at 90 days, P = .5; 8.7% vs 0% at 1 year, P = .13). Patient survival and allograft function were also similar. Median cost of rabbit antithymocyte globulin induction therapy per patient was lower in the ideal body weight cohort, but this difference was not statistically significant ($17 542 vs $19 934; P = .3). Our results suggest that use of ideal body weight for dose calculations of rabbit antithymocyte globulin induction therapy in high immunologic risk kidney transplant recipients at 7.5 mg/kg results in low rates of acute rejection with a safety profile similar to that shown with a total body weight dosage. Use of ideal body weight for lower cumulative doses may still need further evaluation in this patient population.

Steroid-free Liver Transplantation Using Rabbit Antithymocyte Globulin Induction in 500 Consecutive Patients.

We have previously documented the efficacy of a steroid-free immunosuppression protocol using rabbit antithymocyte globulin (RATG) induction in orthotopic liver transplantation (OLT) with tacrolimus minimization. The purpose of this report is to demonstrate the benefits of this protocol in a large cohort of patients. We evaluated outcomes of 500 consecutive OLT recipients who received RATG induction and a single dose of solumedrol given before the first dose of RATG. Mycophenolate mofetil was initiated postoperatively with delayed initiation of tacrolimus. Sirolimus replaced tacrolimus if serum creatinine remained above 2.0 mg/dL by day 7. Patients were weaned to tacrolimus or sirolimus monotherapy at 3 months. Mean model for end-stage liver disease (MELD) at transplantation was 22 ± 6. Forty-four percent of patients had hepatitis C. Posttransplant creatinine was highest at 1 month (1.43 ± 0.95 mg/dL) and improved to 1.26 ± 0.60 mg/dL (P < 0.05) at 2.5 years. Glomerular filtration rate was lowest at 1 month (65.6 ± 30.0) and improved by 1 year (72.7 ± 28.2, P < 0.01). Tacrolimus was initiated at 4.79 ± 13.3 days with a level of 4.95 ± 2.45 ng/mL at 1 year. One-year patient and graft survival were 92.8% and 89.6%, respectively, with a 3-year patient survival of 82.9%. Rejection occurred in 114 (22.8%) patients, 33 (6.6%) patients requiring steroids. Univariate and multivariate Cox proportional hazard analyses were performed to evaluate the effects of donor and recipient characteristics on patient and graft survivals. Pretransplant creatinine was consistently a statistically significant predictor for patient and graft survival. This is the largest reported series of OLT recipients using a steroid-free protocol with RATG induction demonstrating excellent outcomes, low complication rates, and preservation of renal function.

Antithymocyte Globulin Induction and Rapid Steroid Taper Leads to Excellent Results in Kidney Transplantation With Donation After Cardiac Death Donors: Importance of Rejection and Delayed Graft Function

Recipients of primary transplants from donation after cardiac death (DCD) donors (n = 40) performed from January 2005 to December 2009 were retrospectively reviewed and compared with recipients of primary transplants from donation after brain death (DBD) donors (n = 142). Patients received rabbit antithymocyte globulin induction and rapid steroid taper (RST; steroids stopped 5 days after surgery). Maintenance immunosuppression included tacrolimus and mycophenolate mofetil. Protocol kidney biopsies, creatinine (Cr), and measured glomerular filtration rate (mGFR; determined by cold iothalamate or 24-h creatinine clearance) were obtained at 1, 4, 12, and 24 months. Kidney biopsies for cause were conducted for unexplained elevated Cr, decline in mGFR, or new proteinuria. Biopsies were graded for rejection according to the Banff criteria. Graft survival at 3 years was 90.0% for DCD recipients and 86.6% for DBD recipients (P = NS). Rejection of any grade diagnosed on any biopsy through the first 2 years occurred in 18 DCD (45%) and 50 DBD (35%) recipients. Rejection of a grade more than Banff borderline occurred in 12.5% DCD and 12.7% DBD recipients. At 2 years, the mean ± SEM Cr and mGFR for DCD recipients with rejection were 1.8 ± 0.29 mg/dL and 59.2 ± 8.5 mL/min versus 1.3 ± 0.11 mg/dL and 67.0 ± 7.8 ml/min for those without rejection. For DBD recipients with rejection, Cr and mGFR at 2 years were 1.7 ± 0.12 mg/dL and 54.0 ± 4.4 mL/min versus 1.4 ± 0.11 mg/dL and 66.6 ± 3.3 ml/min for those without rejection (P = NS). Comparing DCD to DBD, there was no statistical difference in mean Cr or mGFR outcomes. Regardless of group, grafts with delayed graft function had lower 3-year survival. DCD primary kidney transplant recipients treated with rabbit antithymocyte induction and RST have short-term graft survival and function equivalent to DBD recipients. RST appears to be acceptable immunosuppression for DCD recipients.

Evaluating Safety and Efficacy of Rabbit Antithymocyte Globulin Induction in Elderly Kidney Transplant Recipients

The optimal immunosuppression regimen for elderly kidney transplant recipients is poorly defined. We sought to evaluate the short-term efficacy and safety of thymoglobulin in geriatric recipients of deceased-donor kidneys. A single-center, retrospective analysis was undertaken between elderly (≥ 65 years) (n=137) and nonelderly (n=276) kidney transplant recipients who received rabbit antithymocyte globulin induction and calcineurin inhibitor, mycophenolic acid, and prednisone maintenance. The mean age was 70 versus 52 years. Fewer elderly patients had an earlier transplant or panel reactive antibodies > 20%, but had more machine perfused, older, and extended criteria donor kidneys. Elderly patients received lower rabbit antithymocyte globulin (5.4 vs 5.6 mg/kg; P = .04) and initial mycophenolic acid doses (1620 vs 1774 mg; P = .002), and experienced less delayed graft function (31.1% vs 50.0%; P < .001). Death-censored graft survival and graft function at 3 years and biopsy-proven acute rejection at 1 year were comparable; however, there was lower 3-year patient survival in elderly patients. Donor age was the only factor associated with reduced patient survival. Rates of malignancy, infection, or thrombocytopenia were similar; however, leukopenia occurred less frequently in elderly patients (11.7% vs 19.9%; P = .038). Elderly kidney transplant recipients receiving rabbit antithymocyte globulin did not experience different short-term graft survival, graft function or rates of infection, malignancy or hematologic adverse reactions than did nonelderly patients; they experienced fewer episodes of delayed graft function, but had lower 3-year patient survival.

A Protocol Biopsy Directed Randomized Trial Comparing Tacrolimus Minimization to Sirolimus Conversion at 3 Months Results in an Equivalent Degree of Histological Injury at 1 Year Yet Equivalent Renal Function at 2 Years

Currently, the primary question facing renal transplantation is how to prolong renal allograft survival. Given the need to balance immunosuppressive requirements and potential drug toxicities, the optimal long-term therapeutic strategy remains uncertain. It is also unclear whether mTOR inhibitors offer unique advantages in maintaining normal allograft structure and function. Methods: In this prospective study, we examined the clinical and histological consequences of converting 63 low-risk adult renal transplant recipients (RTR). Those without subclinical rejection at 3 mos were converted to either low-dose tacrolimus (LoTAC) (4-6 ng/ml) or sirolimus (SLR) (5-10 ng/ml). Demographics for both groups were similar except that the LoTAC group had more ECD transplants (23% vs. 4%, p=0.05) and diabetic RTR (58% vs. 28%, p=0.02). Protocol biopsies were performed at implantation, 3 and 12 mos. All RTR received rabbit anti-thymocyte globulin induction therapy (3-5 mg/kg/total dose) along with standard dose TAC (levels 10-15 ng/ml), EC-MPS (Myfortic) and low-dose prednisone. Results: Seven patients were not randomized due to subclinical rejection present in the 3 mo. biopsy (Gr.1A n=1, Borderline, n= 6) leaving 26 randomized to SLR and 31 to LoTAC. Eight RTR in the SLR group were withdrawn due to adverse events including 1 AHR, 1 ACR, 3 infections, 1 hyperlipidemia and 2 proteinuria, but none had graft loss. Only 2 RTR in the LoTAC arm were withdrawn due to graft loss from BK and non-compliance (p=0.03). EC-MPS dose reductions occurred only in the SRL arm due to infections. Renal function (eGFR ml/min) was equal in the remaining LoTAC and SRL treated RTR (75±14 vs. 65±16 at 1 yr. and 68±17 vs. 67±18 at 2 yrs. respectively). Both groups exhibited equivalent increases in average IF/TA indices (LoTAC 0.09 - 0.58; SRL 0.01 - 0.86) and overall CADI scores (LoTAC 1.1 - 2.16; SRL 1.0 - 2.0) between the 3 and 12 mo. biopsies respectively. Three LoTAC and 4 SRL RTR had subclinical rejection in the 12 mo. biopsy. Conclusion: When combined with EC-MPS and steroids, early conversion to Lo-TAC is better tolerated with equivalent graft function and histology compared to SLR. Protocol biopsies are invaluable for risk assessment when altering or decreasing immunosuppressive therapy.

Thymoglobulin Induction and Sirolimus Versus Tacrolimus in Kidney Transplant Recipients Receiving Mycophenolate Mofetil and Steroids

To define the role of mammalian target of rapamycin inhibitors in kidney transplantation, we compared efficacy and safety of two immunosuppressive regimens-a calcineurin inhibitor-free regimen with depletive induction versus a calcineurin inhibitor-based regimen. De novo renal allograft recipients were randomized before transplantation to receive sirolimus (SRL; n=71, group A) or tacrolimus (n=70, group B). All patients received mycophenolate mofetil and corticosteroids. In group A, patients received rabbit antithymocyte globulin induction. In group B, antithymocyte globulin therapy could be given in case of delayed graft function. The estimated glomerular filtration rate (GFR) (Nankivell's formula) at month 12 was the primary endpoint. GFR showed no significant difference at month 12, with 56.1 in group A versus 58.4 mL/min/1.73 m in group B. In functioning grafts, renal function was significantly better in the SRL group, with higher GFR values at months 1, 2, 3, 6, and 9 (P<0.05). At month 12, patient survival and incidence of biopsy-proven rejection were not different between groups (95.8% vs. 97.1%, and 16.9% vs. 12.9%, respectively). However, proportion of graft loss was higher with SRL at months 6 and 12 (11.3% vs. 0.0%, P=0.004; 14.1% vs. 4.3%, P=0.044, respectively). Adverse events and premature withdrawals were more frequent with SRL (P<0.001 and P<0.05, respectively), whereas cytomegalovirus infections were more frequent with tacrolimus (P<0.001). Patients treated with induction plus SRL, mycophenolate mofetil, and corticosteroids may obtain good renal function but have a higher risk of adverse events, drug withdrawal, and graft loss.

Induction Immunosuppression With Basiliximab in Heart Transplantation

After clinical heart transplantation (HT), it is crucial to use appropriate immunosuppressive agents to prevent rejection. The use of basiliximab or rabbit anti-thymocyte globulin (RATG) for induction therapy has significantly reduced the incidence of acute rejection episodes after kidney transplantation. In this study we sought to examine the effects of basiliximab after HT. From June 2006 to July 2007, we performed 43 HT including patients 18–65 years old undergoing primary HT who were included in this study of basiliximab induction (20 mg intravenous [iv] on days 0 and 4). Cyclosporine and everolimus were given with basiliximab induction. All others received RATG induction (1.5–2.5 mg/kg iv infusion on days 0, 1, and 2) followed by cyclosporine or tacrolimus combined with mycophenolate mofetil. All patients underwent the same operative procedure, steroid-tapering protocol, and postoperative care with protocol endomyocardial biopsy. Basiliximab was well-tolerated and easy to use. There was only 1 operative mortality; the patient died of sepsis due to Enterobacter cloacae. All others survived the operation and are alive and in good health with a 2-year survival rate of 92.86%. No severe adverse events were noted during the first postoperative month. No acute rejection ≥ grade 2R or rejection associated with hemodynamic compromise was noted during the whole course. Basiliximab as induction immunosuppressant was simple, safe, and effective after HT.

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.

Rabbit Antithymocyte Globulin Decreases Acute Rejection After Lung Transplantation: Results of a Randomized, Prospective Study

The efficacy of antithymocyte induction therapy in lung transplantation is controversial, and its use varies from center to center. We hypothesized that rabbit antithymocyte globulin (RATG) induction therapy would decrease acute rejection after lung transplantation, and we designed a single-center, randomized, prospective study to test this hypothesis. A total of 44 single or bilateral adult lung transplant recipients were randomly assigned to receive either RATG induction therapy (dosage, 1.5 mg/kg/d for 3 days) at the time of transplantation, along with conventional immunosuppression (cyclosporine, azathioprine, and prednisone), or conventional immunosuppression alone with no induction therapy. Although a similar number of biopsies were performed in each group, the number of patients experiencing biopsy-proven grade II or greater acute rejection was significantly reduced in the group receiving RATG induction therapy (23% incidence), as compared to the patients treated with conventional immunosuppression alone (55% incidence; p = 0.03). In addition, there was a nonsignificant reduction in the incidence of bronchiolitis obliterans syndrome at the conclusion of the study in patients who received RATG induction (20%), as compared to patients in the control group (38%). The incidence of posttransplant infections and malignancies were similar between the two groups. Induction therapy with RATG significantly reduces the incidence of acute allograft rejection after lung transplantation.