Receiving Antithymocyte Globulin Induction Research Articles

A comparative analysis of kidney allograft outcomes in steroid use versus steroid discontinuation after basiliximab and ATG induction: AUNOS database study.

The relative safety and efficacy of early steroid withdrawal in kidney transplant patients after basiliximab compared to anti-thymocyte globulin (ATG) induction therapy is unknown. We aimed to compare kidney allograft outcomes in steroid use versus steroid discontinuation after basiliximab and ATG induction from the United Network for Organ Sharing (UNOS) database. We conducted a retrospective cohort analysis of the UNOS database and included first kidney transplant recipients who received ATG or basiliximab induction therapy. We compared graft and patient outcomes in those who received steroid maintenance and those who were discharged off steroids. Of 106,061 patients, 25,344 (86.7%) received basiliximab induction and were maintained on steroids (B-Sm), and 3,880 (13.3%) were on a steroid-free regimen (B-Sf). Graft failure rate was significantly higher in the B-Sf compared to B-Sm at 1-year (4.1 vs. 1.8%, p<0.001), 3-year (6.0 vs. 4.3%, p<0.001) and 5-year follow-up (7.7 vs. 6.4%, p=0.0004). The mortality rate was significantly higher in B-Sf at 1-year (3.3 vs. 2.4%, p=0.0005), 3-year (7.6 vs. 5.5%, p<0.001) and 5-year follow-up (11.5 vs. 8.8%, p<0.001) when compared to the B-Sm. 76,837 recipients received ATG induction therapy, 51,745 (72.4%) were on steroid maintenance therapy (A-Sm) and 25,092 (32.6%) were on a steroid-free regimen (A-Sf). The graft failure rate was significantly higher in A-Sf compared to A-Sm at 1-year follow-up (2.6 vs. 2.3%, p=0.0006), however, there was no difference at 3-year (5.0 vs. 5.0%, p=0.53) or 5-year follow-up (7.2 vs. 8.1%, p=0.17). There was no difference in mortality rates between A-Sf vs. A-Sm at 1 year (2.5 vs. 2.4%, p=0.98) and at 3 years (5.5 vs. 5.4%, p=0.45), respectively. Patients who were maintained on steroids after basiliximab induction had better 5-year allograft survival and patient survival compared to those who were not maintained on steroids. However, steroid maintenance conferred no additional benefit after ATG induction and was associated with higher mortality.

#2980 The natural history of urinary tract infections in kidney transplant recipients

Abstract Background and Aims Urinary tract infections (UTIs) can occur following kidney transplantation, but research on infection rates and outcomes is inconclusive. We therefore aimed to provide a comprehensive understanding of the natural history of UTIs and the impact on long-term outcomes. Method We performed a single-centre cohort study of kidney-only transplant recipients at the Glasgow Transplant Unit, UK. A standardised protocol for UTI screening and treatment was in use and only treated UTIs were included. We studied the first two years post-transplant as this is the time when UTIs are most likely to occur. Patients were categorised into 3 groups based on number of UTIs: no UTIs, 1-2 UTIs and ≥3 UTIs. Furthermore, patients with highly recurrent UTIs defined as ≥10 UTIs in the first 2 years were compiled and analysed. Proportional odds logistic regression was performed to identify risk factors for having ≥3 UTIs, with adjustment for age, sex, primary renal diagnosis, donor type (live donor, deceased heart beating, deceased non-heart beating) and induction immunosuppression. Results Amongst 1412 transplant recipients studied over a nine-year period, the mean age was 48 years and 563 (39.9%) were female. 1169 (82.8%) of recipients experienced no UTIs, 180 (12.7%) had 1-2 UTIs, and 63 (4.5%) had ≥3 UTIs (Fig. 1). The key risk factors for developing ≥3 UTIs were female sex: adjusted odds ratio (aOR) 1.50 (95% confidence interval 1.13-1.99), induction with anti-thymocyte globulin (ATG): aOR 6.60 (3.05-14.05), and age: aOR for each one-year increase 1.01 (1.00-1.02). There were no primary renal diagnoses (PRD) that demonstrated a significant association with ≥3 UTIs. However, individuals with tubulointerstitial disease, a group which includes structural abnormalities of the urinary tract and reflux nephropathy as a considerable proportion, showed a trend towards heightened risk: aOR 1.47 (0.97-2.22, reference group glomerulonephritis). Recipients with ≥3 UTIs had lower estimated glomerular filtration rates (eGFRs) at two years compared to the no UTI group (49.7 vs. 59.2mL/min/1.73 m2, respectively). However, there was no significant increase in mortality or graft loss between the three groups. In the group of patients with highly recurrent UTIs, consisting of 14 patients (0.01%), we observed that 3 (21%) had a PRD of reflux nephropathy, while 5 (35%) had underlying structural abnormalities of the native renal tract as a PRD. Further to this 5 (35%) of the patients received ATG induction and 5 (35%) patients had a previous transplant. Conclusion We describe a low rate of UTIs requiring treatment in the first two years after kidney transplantation. Females, older recipients and those given ATG induction were at increased risk of recurrent UTIs. There was no impact of UTIs on graft loss or patient mortality. However, eGFR at two years post-transplant was lower amongst those with recurrent UTIs. We also observed that for the patients with highly recurrent UTIs, ATG induction, previous transplants, reflux nephropathy and structural abnormalities of native renal tract may be a risk factor. Recipients at highest risk of UTIs should therefore be screened for UTIs and interventions to reduce this risk should be considered

Early Blood Transfusion After Kidney Transplantation Does Not Lead to dnDSA Development: The BloodIm Study.

Outcomes after kidney transplantation are largely driven by the development of de novo donor-specific antibodies (dnDSA), which may be triggered by blood transfusion. In this single-center study, we investigated the link between early blood transfusion and dnDSA development in a mainly anti-thymocyte globulin (ATG)-induced kidney-transplant cohort. We retrospectively included all recipients of a kidney transplant performed between 2004 and 2015, provided they had >3 months graft survival. DSA screening was evaluated with a Luminex assay (Immucor). Early blood transfusion (EBT) was defined as the transfusion of at least one red blood-cell unit over the first 3 months post-transplantation, with an exhaustive report of transfusion. Patients received either anti-thymocyte globulins (ATG) or basiliximab induction, plus tacrolimus and mycophenolic acid maintenance immunosuppression. A total of 1088 patients received a transplant between 2004 and 2015 in our center, of which 981 satisfied our inclusion criteria. EBT was required for 292 patients (29.7%). Most patients received ATG induction (86.1%); the others received basiliximab induction (13.4%). dnDSA-free graft survival (dnDSA-GS) at 1-year post-transplantation was similar between EBT+ (2.4%) and EBT- (3.0%) patients (chi-squared p=0.73). There was no significant association between EBT and dnDSA-GS (univariate Cox’s regression, HR=0.88, p=0.556). In multivariate Cox’s regression, adjusting for potential confounders (showing a univariate association with dnDSA development), early transfusion remained not associated with dnDSA-GS (HR 0.76, p=0.449). However, dnDSA-GS was associated with pretransplantation HLA sensitization (HR=2.25, p=0.004), hemoglobin >10 g/dL (HR=0.39, p=0.029) and the number of HLA mismatches (HR=1.26, p=0.05). Recipient’s age, tacrolimus and mycophenolic-acid exposures, and graft rank were not associated with dnDSA-GS. Early blood transfusion did not induce dnDSAs in our cohort of ATG-induced patients, but low hemoglobin level was associated with dnDSAs-GS. This suggests a protective effect of ATG induction therapy on preventing dnDSA development at an initial stage post-transplantation.

Antithymocyte globulin induction therapy and myocardial complement deposition in pediatric heart transplantation.

Antithymocyte globulin (ATG) consists of polyclonal antibodies directed primarily against human T lymphocytes but may contain antibodies with affinity for other tissues in the transplanted organ, resulting in complement (C4d) deposition. This phenomenon has been demonstrated in endomyocardial biopsies (EMBs) of adult cardiac transplants. We examined the relationship of induction immunosuppression with ATG and C4d deposition in EMB of pediatric cardiac transplants. Results of C4d immunohistochemistry were available from all EMB of patients transplanted at our center between June 2012 and April 2018 (n=48) who received induction immunosuppression with either ATG (n=20) or basiliximab (n=28) as the standard of care. C4d deposition in the first year post-heart transplant was more commonly seen among patients who received ATG induction (20% of EMBs in ATG group vs 1% of EMBs in basiliximab group; p<.0001). C4d deposition related to ATG was observed early post-transplant (50% ATG vs 0% basiliximab on first EMB; p<.0001 and 35% ATG vs 0% basiliximab on the second EMB; p=.0012). While this difference waned by the third EMB (5% ATG vs 0% basiliximab; p=.41), positive C4d staining persisted to the sixth EMB in the ATG group only (6%). C4d deposition is common on EMB up to 1year post-pediatric cardiac transplant following ATG induction. This high rate of positive C4d staining in the absence of histologic AMR after ATG induction therapy must be accounted for in making clinical decisions regarding cardiac allograft rejection diagnosis and treatment.

Antithymocyte Globulin Induction is Associated with Complement Deposition in Pediatric Cardiac Transplant Biopsies

Purpose Antithymocyte globulin (ATG) has been increasingly used as a means of induction immunosuppression (I-I) in pediatric cardiac transplantation (PCT). ATG contains polyclonal antibodies directed primarily against human T-lymphocytes and may also contain other antibodies with affinity for endothelial surface antigens and other tissues in the transplanted organ, resulting in complement (C4d) deposition (C4dD). This phenomenon has been demonstrated in endomyocardial biopsies (EMB) of adult cardiac transplants though the effects of C4dD on rejection risk remain unclear. It has been thought that use of basiliximab for induction may avoid the risk of (C4dD) and decrease the risk of rejection. We examined C4dD and incidence of rejection the relationship among children treated with ATG I-I as well as those treated with basiliximab I-I. Methods A retrospective review of charts of patients with PCT performed at our center between June 2012 and April 2018 was performed. Results of C4d immunohistochemistry were available from all EMB of patients (n=56). Results The population was predominantly male (70%) with a median age of 10 years (IQR 2.63 -14.46 years). 28 patients received ATG and 28 patients received basiliximab as induction therapy. Sixty percent (60%) of the ATG patients had C4dD on the 1st biopsy post-transplant and 25% of patients had a persistent C4dD on the next 5 EMB. When C4dD was demonstrated in ATG patients, other markers of significant rejection were rare; only 4% had ACR grade 2 or higher by the revised 2004 ISHLT grading system (historically 3A, 3B and 4 rejection) and/or histologic evidence of AMR. Only 3% of patients receiving basiliximab for induction had C4dD on any EMB in the first year post-transplant. When C4dD was demonstrated in basiliximab patients, other markers of significant rejection were found frequently; 57% had ACR grade 2 or higher by the revised 2004 ISHLT grading system and/or histologic evidence of AMR. Conclusion C4d deposition was more common on EMB up to 1 year post-PCT in patients receiving ATG induction, compared to basiliximab. Despite less C4dD in basiliximab EMBs, these patients had more rejection episodes. The presence of C4dD may thus not be an accurate measure of rejection in PCT patients and should be taken into consideration when reviewing and determining treatment options. Antithymocyte globulin (ATG) has been increasingly used as a means of induction immunosuppression (I-I) in pediatric cardiac transplantation (PCT). ATG contains polyclonal antibodies directed primarily against human T-lymphocytes and may also contain other antibodies with affinity for endothelial surface antigens and other tissues in the transplanted organ, resulting in complement (C4d) deposition (C4dD). This phenomenon has been demonstrated in endomyocardial biopsies (EMB) of adult cardiac transplants though the effects of C4dD on rejection risk remain unclear. It has been thought that use of basiliximab for induction may avoid the risk of (C4dD) and decrease the risk of rejection. We examined C4dD and incidence of rejection the relationship among children treated with ATG I-I as well as those treated with basiliximab I-I. A retrospective review of charts of patients with PCT performed at our center between June 2012 and April 2018 was performed. Results of C4d immunohistochemistry were available from all EMB of patients (n=56). The population was predominantly male (70%) with a median age of 10 years (IQR 2.63 -14.46 years). 28 patients received ATG and 28 patients received basiliximab as induction therapy. Sixty percent (60%) of the ATG patients had C4dD on the 1st biopsy post-transplant and 25% of patients had a persistent C4dD on the next 5 EMB. When C4dD was demonstrated in ATG patients, other markers of significant rejection were rare; only 4% had ACR grade 2 or higher by the revised 2004 ISHLT grading system (historically 3A, 3B and 4 rejection) and/or histologic evidence of AMR. Only 3% of patients receiving basiliximab for induction had C4dD on any EMB in the first year post-transplant. When C4dD was demonstrated in basiliximab patients, other markers of significant rejection were found frequently; 57% had ACR grade 2 or higher by the revised 2004 ISHLT grading system and/or histologic evidence of AMR. C4d deposition was more common on EMB up to 1 year post-PCT in patients receiving ATG induction, compared to basiliximab. Despite less C4dD in basiliximab EMBs, these patients had more rejection episodes. The presence of C4dD may thus not be an accurate measure of rejection in PCT patients and should be taken into consideration when reviewing and determining treatment options.

Incidence of cytomegalovirus in cardiac transplant recipients receiving induction immunosuppression with antithymocyte globulin.

Cytomegalovirus (CMV) is a major cause of morbidity and mortality in cardiac transplant recipients. Use of induction immunosuppression in cardiac transplantation may have an impact on the incidence of CMV, but literature is limited. Single-center, retrospective cohort study comparing the risk of CMV infection and disease in cardiac transplant patients receiving antithymocyte globulin (ATG) induction therapy to those receiving no antibody induction. A total of 75 patients were included in our analysis, 50 who received ATG induction and 25 who did not. CMV infection occurred in 10 (20%) and 5 (20%) patients in the ATG and No ATG groups, respectively (P > 0.99). CMV disease occurred in 10 (20%) and 4 (16%) patients in the ATG and No ATG groups, respectively (P = 0.763). The median time from transplant to CMV infection was 200.0 [142.5, 364.5] days in the ATG group vs 221.0 [192.0, 299.0] days in the No ATG group (P = 0.723). The median time from end of CMV prophylaxis to CMV infection was 94.5 [66.5, 151.0] days in the ATG group vs 53.0 [41.0,149.5] days in the No ATG group (P = 0.202). Freedom from CMV infection was highest in the D+/R+ group and lowest in the D+/R- group. In cardiac transplant recipients, ATG induction was not associated with an increased incidence of CMV infection or disease in the setting of valganciclovir prophylaxis and an initial maintenance immunosuppression regimen of primarily steroids, mycophenolate mofetil, and tacrolimus.

Do Prior Driveline Infections Increase the Risk of Infection in Heart Transplant Patients Treated With Rabbit Antithymocyte Globulin Induction Therapy?

BackgroundThe use of mechanical circulatory support devices (MCSDs) has been increasing over the past several years. Driveline infections (DLIs) are one of the most common complications seen in these patients; reportedly, up to 50% of patients with MCSDs can develop this complication. It is believed that the removal of the driveline results in treatment of the localized infection area. MCSD patients are also known to develop circulating antibodies. These circulating antibodies have been associated with poor outcomes after heart transplantation. The use of rabbit antithymocyte globulin (ATG) as induction therapy reportedly decreases the development of circulating antibodies; it is now commonly used in sensitized patients undergoing heart transplantation. It is unknown whether ATG induction therapy immediate posttransplant will increase the risk of infection of those MCSD patients with DLIs. MethodsBetween 2003 and 2013, we evaluated 57 MCSD patients who subsequently underwent heart transplantation and received ATG induction therapy. Patients were divided into those with previous MCSD DLI and those without, and they were assessed for 1-year freedom from infection (specifically, sternal wound infections). One-year survival and freedom from treated rejection, both cellular and antibody mediated, were also assessed. ResultsMCSD patients with DLIs who received ATG induction did not have a lower freedom from any treated infection and from sternal wound infection posttransplant compared with those MCSD patients without DLIs and not treated with ATG induction. There were also no significant differences between the 2 groups in terms of 1-year posttransplant survival and freedom from treated rejection. ConclusionsThe use of ATG induction in patients with prior DLIs did not seem to increase the risk for posttransplant infection (eg, sternal wound infection). ATG induction can therefore be safely used in this population.

(794) - Rapid Progression of Allograft Coronary Artery Stenosis Is Decreased in Patients Who Received Antithymocyte Globulin Induction at Time of Transplant

(794) - Rapid Progression of Allograft Coronary Artery Stenosis Is Decreased in Patients Who Received Antithymocyte Globulin Induction at Time of Transplant

Immunosuppression Regimen and the Risk of Acute Rejection in HIV-Infected Kidney Transplant Recipients

Kidney transplantation (KT) is the treatment for end-stage renal disease in appropriate HIV-positive individuals. However, acute rejection (AR) rates are over twice those of HIV-negative recipients. To better understand optimal immunosuppression for HIV-positive KT recipients, we studied associations between immunosuppression regimen, AR at 1 year, and survival in 516 HIV-positive and 93,027 HIV-negative adult kidney-only recipients using Scientific Registry of Transplant Recipients data from 2003 to 2011. Consistent with previous reports, HIV-positive patients had twofold higher risk of AR (adjusted relative risk [aRR], 1.77; 95% confidence interval [CI], 1.45-2.2; P<0.001) than their HIV-negative counterparts as well as a higher risk of graft loss (adjusted hazard ratio, 1.51; 95% CI, 1.18-1.94; P=0.001), but these differences were not seen among patients receiving antithymocyte globulin (ATG) induction (aRR for AR, 1.16; 95% CI, 0.41-3.35, P=0.77; adjusted hazard ratio for graft loss, 1.54; 95% CI, 0.73-3.25; P=0.26). Furthermore, HIV-positive patients receiving ATG induction had a 2.6-fold lower risk of AR (aRR, 0.39; 95% CI, 0.18-0.87; P=0.02) than those receiving no antibody induction. Conversely, HIV-positive patients receiving sirolimus-based therapy had a 2.2-fold higher risk of AR (aRR, 2.15; 95% CI, 1.20-3.86; P=0.01) than those receiving calcineurin inhibitor-based regimens. These findings support a role for ATG induction, and caution against the use of sirolimus-based maintenance therapy, in HIV-positive individuals undergoing KT.

Antithymocyte Globulin Induction Therapy Adjusted for Immunologic Risk After Heart Transplantation

IntroductionThe efficacy of antithymocyte globulin (ATG) induction in the therapy of immunologically low- and high-risk patients after heart transplantation is not known. MethodsAll patients who received ATG induction from January 2000 through January 2010 were divided into two groups based on the risk of rejection. A higher-risk group (age younger than 60 years, multiparous females, African Americans, panel-reactive antibody >10%, or positive cross-match) received ATG (1.5 mg/kg) for 7 days (ATG7), and the remaining lower-risk group received ATG for 5 days (ATG5), all followed by calcineurin inhibitor, mycophenolate, and prednisone. Endomyocardial biopsies were performed based a standard protocol for up to 3 years after heart transplantation, and for suspected rejection. ResultsOf 253 heart transplant recipients, 87 received ATG5 and 166 ATG7. Absolute lymphocyte count <200 per microliter was achieved within 10 days in 88% of ATG5 and 86% of ATG7. Baseline creatinine was 1.3 ± 0.8 pre-transplantation, 1.8 ± 0.9 post-transplantation, and 1.0 ± 0.4 mg/dL at discharge (mean ± standard deviation [SD]; P < .001, compared with pre-transplantation). Of 3667 biopsies, 33 (0.90%) had ≥3A/2R cellular rejection (CR). Of 3599 biopsies, 16 (0.44%) had definite antibody-mediated rejection (AMR). At 5 years, freedom from ≥3A/2R CR (94% ± 2.8% vs 83% ± 7.7%; P = .31) and freedom from AMR (95% ± 2.4% vs 90% ± 6.4%; P = .98) were similar between ATG5 and ATG7, respectively. Survival for ATG5 and ATG7 was comparable at one year (94% ± 2.5% vs 93% ± 2.0%), and at 8 years (61% ± 6.9% and 61% ± 4.7%; P = .88). At 5 years, ATG5 and ATG7 were similar in freedom from cytomegalovirus (CMV) infection (92.3% vs 94.3%; P = not significant [NS]), freedom from pneumonia (83.8% vs 82.1%; P = NS), and in rate of malignancy (excluding skin cancer; 8.0% vs 6.0%; P = NS). ConclusionsATG induction therapy (prospectively dose-adjusted for immunologic risk) in low- and high-risk patients results in excellent and equivalent short- and long-term survival rates, with a low incidence of CR and AMR. The use of ATG does not increase rates of CMV infection with appropriate prophylaxis. ATG may benefit renal function by delaying calcineurin inhibitor exposure, and may have a role in the prevention of AMR.

Infection Risk in Kidney Transplantation From Uncontrolled Donation After Circulatory Death Donors

BackgroundUncontrolled donations after circulatory death (DCD) present 2 well-established risk factors for infection after kidney transplantation (KT): greater rates of delayed graft function (DGF) and antithymocyte globulin (ATG)-containing sequential therapies. MethodsWe performed a prospective cohort study of our 291 KT patients between November 2008 and July 2011 to compare the incidences of infection between DCD (n = 87) and donation after brain death (DBD; n = 204) recipients. Most DCD donors were uncontrolled Maastricht categories 1 or 2. Backward stepwise Cox proportional hazards models were used to assess the impact of DCD on the primary study outcome. ResultsAs compared to the DBD group, DCD recipients were younger, less likely to have undergone previous transplantations, exhibited lower dialysis vintage, and displayed a greater incidence of DGF and graft loss, but lower incidence of acute rejection episodes. There were no differences in the non-death-censored graft survival at 2 years (log-rank P = .835). The DCD group showed lower cumulative incidences of overall, bacterial, cytomegalovirus (CMV), and non-CMV viral infections (P < .05 for all). Multivariate analysis, associated DCD with a lower risk of overall infection (hazard ratio: 0.41; 95% confidence interval: 0.28–0.60; P = .012), an effect that remained when the analysis was restricted to patients receiving ATG induction therapy. Finally, there were no differences in the cumulative incidence of overall infection when DCD recipients were compared with age-matched DBD controls: 43.7% vs 47.1% respectively (P = .648). ConclusionDespite the higher rate of DGF and the use of ATG-containing sequential therapy, uncontrolled DCD policies were safe in terms of the risk of post-transplant infection.

Monitoring of CD3+ T-Cell Count in Patients Receiving Antithymocyte Globulin Induction After Cadaveric Renal Transplantation

AimAlthough antithymocyte globulin (ATG) has been used for years, its ideal dose and administration period is obscure. Herein, we sought to use the CD3+ cell count to detect the optimal ATG dosage. Material and MethodsTwenty-one patients who underwent cadaveric donor renal transplantation from January 2009 to January 2012 received a 1 mg/kg ATG initial dose at the time of the operation. Patients were randomized into 2 cohorts. Group 1 (n = 11) received ATG according to the clinical and total lymphocyte count and group 2 (n = 10), the dose was tailored according to the CD3+ cell count. We compared the total and daily ATG dosages, ATG administration period, side effects of ATG, the number of days to a serum creatinine level <2 mg/dL, graft function at 3 months, acute rejection episodes, infection rates, costs of CD3+ analysis, and ATG amounts. ResultsBoth groups showed similar gender, age, and human leukocyte antigen matching data. There was no difference in presensitizing events or panel-reactive antibody class 1 and 2 levels. The number of days to a serum creatinine level of <2 mg/dL was 11 ± 1.5 for group 1 versus 10.4 ± 0.8 for group 2 (P = .45). Between groups 1 and 2, there was a significant difference between the mean total (P = .031) and mean daily ATG dosages (P = .006). We used a total dose of 3800 mg ATG for group 1 and 2200 mg for group 2 and for the group 2 who underwent 43 CD3+ cell counts. The expenditure per patient was 20% higher among group 1 than group 2. ConclusionDetermination of appropriate ATG dosages by CD3+ cell counts was useful, reliable, and cost effective.

ATG Induction Improves Outcome for Sensitized Patients Who Have Undergone Heart Transplantation

Purpose Heart transplant recipients who are sensitized pre transplant are at increased risk for the development of antibody mediated and cellular rejection post transplantation. The use of induction therapy with anti-thymocyte globulin (ATG) may reduce the incidence of antibody mediated rejection (AMR), but this has not been formally studied in a randomized controlled trial. The purpose of this study was to determine the impact of ATG induction on the incidence of AMR in a large single-center experience. Methods and Materials We identified 170 heart transplant (HTx) patients transplanted between January 1994 and October 2011, with pre-transplant panel reactive antibodies (PRA) >10%. Induction therapy was given based on the treating physician’s preference. One-year outcomes were assessed, including the incidence of treated rejection and pathology-defined AMR. Results Of the 170 HTx, 91 received ATG induction and 79 did not. The mean pre-transplant PRA was significantly higher in the ATG group (59 ± 31% vs 43 ± 32%, p=0.0015). In the ATG induction group, there were fewer treated rejection episodes (14% vs 30%, p= 0.01) and fewer pathology-defined AMR episodes (12% vs 26%, p=0.016). There was no difference in the incidence of cellular rejection (12% in both groups). Conclusions ATG induction therapy for sensitized patients results in fewer treated rejection epiosdes and a decreased incidence of pathology-defined AMR. This suggests that ATG induction is beneficial in sensitized patients, and the results should be confirmed with a randomized trial. No ATG (n=79) ATG (n=91) p-value All Treated Rejections, n (%) 24 (30%) 13 (14%) 0.01 Cellular Rejections, n (%) 10 (12%) 11 (12%) 0.74 Any-Treated AMR, n (%) 21 (26%) 11 (12%) 0.02

Preemptive Therapy Versus Valgancyclovir Prophylaxis in Cytomegalovirus-positive Kidney Transplant Recipients Receiving Antithymocyte Globulin Induction

International consensus guidelines on the management of cytomegalovirus (CMV) infections in kidney transplantation recommend the use of universal prophylaxis over preemptive therapy for the highest risk kidney transplant recipients (KTR), namely donor+/recipient – CMV serostatus. However, no universal recommendations have been made for R+ KTR undergoing antithymocyte globulin (ATG) induction. In this retrospective study, we compared 1-year outcomes among 24 R+ KTR who received 3 months of valgancyclovir prophylaxis with 72 R+ KTR who were subjected to a preemptive strategy. All subjects received ATG induction. The incidence of CMV infection was significantly higher among the preemptive subjects versus the prophylaxis group (78% versus 38%, respectively; P = .0003), whereas the incidence of CMV disease was low and did not differ significantly between the cohorts (8% versus 7% respectively, P = .8). Late-onset CMV infections were only observed in the prophylaxis group (25% versus 0%, P = .0001). Finally, the rate of opportunistic infections, acute rejection episodes, and graft/patient survivals at 1 year were also similar between the two groups. In light of this study, preemptive therapy and universal prophylaxis were almost equally effective to prevent CMV infection among R+ KTR receiving ATG induction.

Long-term outcome of ATG vs. Basiliximab induction

An evaluation of the long-term efficacy and incidence of adverse events after induction therapy with antithymocyte globulin (ATG) vs. Basiliximab in renal transplant patients. Sixty recipients receiving ATG induction and a dual immunosuppression with Tacrolimus and steroids were compared retrospectively with 60 patients treated with Basiliximab. The following characteristics were evaluated: concomitant immunosuppression, recipient age, donor age, time on dialysis, cold ischemia time, year of transplantation and HLA mismatches. The 6-year patient survival in the ATG group was 91·7% compared to 85% in the Basiliximab group (not significant, n.s.). Graft survival at 6 years was 89·7% and. 83·6% in the ATG and the Basiliximab group (n.s.), respectively. Incidence of biopsy proven acute rejection episodes (33·3% vs. 26·7%) and delayed graft function (30% vs. 33·3%) were similar in both groups. Kidney function was not significantly different at 1 and 6 years. CMV infections were more prevalent in the ATG arm (22% vs. 5%; P = 0·05), and a significantly higher rate of haematological complications was observed following ATG induction. ATG induction was associated with an improved (but n.s.) trend in patient and graft survival. Patients induced with ATG had a higher rate of CMV infections and haematological complications.

Risk Factors and Consequences of Delayed Graft Function in Deceased Donor Renal Transplant Patients Receiving Antithymocyte Globulin Induction

Induction rabbit antithymocyte globulin (rATG) is largely used in renal allograft recipients at risk for delayed graft function (DGF) and immunologic rejection. The purpose of our study was to characterize risk factors and outcomes associated with DGF when it occurs in recipients undergoing routine rATG induction. We retrospectively reviewed our experience in a predominantly high-risk population receiving modern immunosuppressive regimens. Of 231 deceased-donor transplants, high-risk characteristics included African American race (68%), retransplants (12%), peak panel reactive antibody of atleast 20% (19%), expanded criteria donor kidney (15%), and cold ischemia time exceeding 24 hr (27%). DGF occurred in 29% of patients. rATG was continued to a dose of 7.3 mg/kg in DGF patients and 5 mg/kg in non-DGF patients (P<0.0001). Risk factors for DGF were recipient body mass index greater than 30 kg/m(2) (odds ratio [OR]=1.5, P=0.02), female donor/male recipient pairings (OR=1.5, P=0.033), sirolimus use (OR=1.7, P=0.003), and donor creatinine more than 1.5 mg/dL (OR=1.6, P=0.016). One-year patient survival (99% non-DGF, 91% DGF; P=0.001) and acute rejection incidence through 36 months (11% non-DGF, 22.4% DGF; P=0.025) differed between groups. DGF patients experienced a higher rejection rate during the second and third years posttransplant. Death-censored graft survival was similar throughout 36 months. In kidney transplantation with routine rATG induction, DGF was related to size and gender, donor creatinine, and immunosuppressive protocol. Despite low first-year rejection rates, DGF was associated with inferior patient survival. Importantly, patients with DGF continued to be at risk for rejection beyond the first year. Donor and recipient selection impacts short-term outcomes, and induction alone may not confer a long-term advantage without further modification of baseline therapy.

Antithymocyte Globulin Induction Therapy in Hepatitis C–Positive Liver Transplant Recipients

It is unclear whether antithymocyte globulin (ATG) induction therapy in hepatitis C-positive (HCV-positive) liver transplant recipients influences the risk of developing recurrent HCV disease. Multiple acute rejection episodes and high-dose steroids and/or OKT3 used to treat acute rejection increase the risk of graft loss from HCV. We studied the impact of ATG induction on graft and patient survival in HCV-positive liver transplants performed since 1990. Recipients who died or lost their grafts within 1 month of transplantation were excluded. Second, third, and fourth grafts were excluded, as were patients with stage III or IV hepatocellular carcinoma. There were 443 cadaveric liver transplants in adult recipients, of whom 142 (32%) were HCV positive. The incidence of biopsy-proven acute rejection was less in patients who received ATG induction, 34.2% (ATG induction) versus 66.6% (no ATG induction) (P<or=.01). ATG induction did not influence the risk of graft loss from HCV-related disease (P=.75). When only HCV-related graft loss was considered, 10-year graft survival for HCV-positive recipients was 74% (ATG induction) versus 68.2% (no ATG induction). Whether ATG induction was given or not had no significant impact on either overall graft survival (P=.39) or patient survival (P=.11) in HCV-positive recipients.

Dacluzimab is Comparable to Antithymocyte Globulin (ATG) Induction in Preventing Acute Rejection (AR) Episodes in High Risk Renal Transplant Recipients

577 Dacluzimab has been shown to significantly reduce the incidence of AR in primary cadaveric renal transplants as compared to placebo [cyclosporine (CSA) and prednisone, or CSA, prednisone and azathioprine]. Its role in high risk renal transplant recipients has not been evaluated. Prior to the availability of Dacluzimab, we used ATG induction in these patients. Methods: In this pilot study we used variable doses of Dacluzimab (1-5 doses depending upon the status of graft function) in conjunction with CSA or FK 506, mycophenolate mofetil (MMF) and prednisone in 17 high risk renal transplant recipients. The indications for Dacluzimab induction included primary graft dysfunction in 5, post- transplant graft dysfunction in 4, prolonged cold ischemia time (>24 hours) in 4, and retransplants with high panel reactive antibodies (PRA) in 4. One patient had a combined liver kidney transplant. The number of AR episodes, need for OKT3 treatment, patient and graft survival and serum creatinines at 3 months were compared to 16 retrospective controls who received ATG induction along with CSA or FK 506, MMF and prednisone. The indications for ATG included primary graft dysfunction in 13 and post-transplant graft dysfunction in 3. Results: Both groups were comparable for age, sex, race, HLA mismatches, PRA, primary versus retransplants, cadaver versus living related transplants, number of patients receiving CSA or FK 506, dialysis and duration of dialysis. One patient died in each group (pseudomonas sepsis in the Dacluzimab group and myocardial infarction in the ATG group). The remaining patients are alive with functioning grafts. One patient in ATG group developed cytomegalovirus (CMV) infection. Three patients (17.6%) had AR in the Dacluzimab group. Of these, one had acute vascular rejection on day 3 after transplant and required treatment with OKT3. Four patients (25%) had AR in ATG group. None required treatment with OKT3. The number of Dacluzimab doses ranged from 1-5 (1.8 ± 1.3). The number of ATG doses ranged from 2-14 (8.9 ± 3.5). The length of stay in the hospital was longer in Dacluzimab group 12.6 ± 8.1 versus 8.4 ± 2.8. The difference was due to pseudomonas sepsis, pulmonary hemorrhage, and liver transplant related complications in three patients respectively. Serum creatinines at 3 months were comparable (1.9 ± 1.4 in Dacluzimab group versus 1.7 ± 1.7 in ATG group). The long term data is not yet available. Conclusions: 1) In this pilot study we show that Dacluzimab induction is comparable to ATG in high risk renal transplant recipients in preventing AR. 2) Patient and graft survival, incidence of CMV infections and serum creatinine at 3 months are comparable in both groups. 3) Since the cost of ATG per dose is equivalent to Dacluzimab dose, it is cost effective to use Dacluzimab (2 doses versus 9 doses of ATG). 4) Dacluzimab is also more convenient to administer avoiding a central line essential for ATG. These results need to be validated in a larger multicenter trial.