Rabbit Antithymocyte Globulin Induction Research Articles

Influence of induction therapy and antiretroviral regimen on outcomes in kidney transplant recipients living with human immunodeficiency.

Kidney transplantation has a survival benefit for people with human immunodeficiency virus (HIV) and end-stage kidney disease, however increased rates of rejection remain an issue. Questions remain regarding the impact of induction immunosuppression therapy and antiretroviral (ARV) choice on long-term outcomes. We performed a multicenter retrospective analysis of outcomes in recipients with HIV who received kidneys from donors without HIV transplanted between 2004 and 2019. The association between induction and ARV regimens and long-term outcomes including rejection, graft, and recipient survival over 5 years was investigated using Cox regression modeling. Seventy-eight kidney transplants (KT) performed in 77 recipients at five US transplant centers were included, with median follow up of 7.1 (4.3-10.7) years. Overall recipient and graft survival were 83% and 67%, respectively. Rejection occurred in 37% (29/78). Recipients with rejection were more likely to be younger, recipients of deceased donor organs, and Black. Receipt of rabbit anti-thymocyte globulin (rATG) induction without protease-inhibitor (PI)-based ARVs was associated with 83% lower risk of rejection (adjusted hazard ratio (aHR) 0.17 (95% CI 0.05-0.63), p =.007) and a non-statistically significantly lower risk of graft failure (aHR 0.18 (0.03-1.16), p =.07) when compared to those who received other induction and ARV combinations. In this multicenter retrospective study, we found a trend toward lower rejection and improved graft survival among those who received both rATG for induction and PI-sparing ARVs.

(1114) - Weight-Adjusted Rabbit Antithymocyte Globulin Induction and Outcomes in Heart Transplantation

(1114) - Weight-Adjusted Rabbit Antithymocyte Globulin Induction and Outcomes in Heart Transplantation

Impact of Cumulative 6 mg/kg Antithymocyte Globulin on Early Posttransplant Outcomes in Kidney Transplant Recipients with Delayed Graft Function.

Introduction: Delayed graft function in kidney transplant is associated with an increased risk of rejection and graft loss. Use of rabbit antithymocyte globulin induction in delayed graft function has been correlated with less rejection compared to basiliximab, but optimal dosing remains unknown. Program Evaluation Aims: The purpose of this evaluation was to retrospectively assess the short-term effectiveness and tolerability of a clinical protocol that increased the net state of immunosuppression in delayed graft function kidney transplant recipients using cumulative 6 mg/kg rabbit antithymocyte globulin induction. Design: This retrospective cohort included 88 kidney transplant recipients with delayed graft function, transplanted between January 2017 and March 2021, who either received cumulative 4.5 mg/kg pre-protocol or 6 mg/kg post-protocol rabbit antithymocyte globulin. Outcomes evaluated were biopsy-proven acute rejection and incidence of graft loss, infection, and cytopenia at 6 months. Results: A significant reduction of biopsy-proven acute rejection incidence occurred post-protocol implementation (10/33, 30.3% vs 6/55, 10.9%; P = .04). Of those with rejection, significantly less post-protocol patients were classified as acute cellular rejection (9/10, 90.0% vs 2/6, 33.3%; P = .04). No death-censored graft loss was observed in either group. Rates of cytopenia and infection were similar pre- versus post-protocol implementation. Conclusion: Increasing the exposure to rabbit antithymocyte globulin and maintenance immunosuppression in delayed graft function kidney transplant recipients was tolerable and significantly reduced rejection occurrence at 6 months.

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.

A report of a prospective randomized trial of extended-release tacrolimus versus immediate release tacrolimus after liver transplantation with anti-thymocyte induction in a steroid free protocol.

Our study hypothesis was that once daily dosing of extended-release tacrolimus (XRT) would be a safe and effective immunosuppression (IS) with the potential to decrease adverse events (AEs) associated with immediate release tacrolimus (IRT) after liver transplantation (LT). All patients receiving LT at our center received rabbit anti-thymocyte globulin (RATG) induction therapy. Eligible patients were randomized in a 1:1 fashion to receive either XRT or IRT. Antimicrobial prophylaxis was the same between arms, and both groups received an antimetabolite for the first 6 months following LT. Patients were then followed at pre-determined study intervals for the following year after LT. We administered the RAND-36SF survey to assess patient's health-related quality of life at pre-determined intervals. All analysis was performed with an intention to treat basis. We screened 194 consecutive patients and enrolled 110. Our control and study arms were well matched. Transplant characteristics were similar between groups. At all timepoints, both arms had similar serum creatinine and estimated glomerular filtration rate (eGFR), calculated by MDRD6 equation, with post-transplant GFRs between 60 and 70mL/min/1.73m2 . Tacrolimus trough levels were similar between arms. The XRT arm had fewer AEs (166) and fewer serious AEs (70) compared to IRT (201 and 99, respectively). AEs most commonly were renal, infectious, or gastrointestinal in nature. While not statistically significant, XRT was held temporarily (25vs. 35 cases) or discontinued (3vs. 11 cases) less frequently than IRT and had fewer instances of rejection (7vs. 12 cases). This analysis showed that XRT is safe and effective as de novo maintenance IS in a steroid-free protocol with RATG.

236.9: Does lymphocyte count after rabbit antithymocyte globulin induction therapy matter in pancreas transplantation?

236.9: Does lymphocyte count after rabbit antithymocyte globulin induction therapy matter in pancreas transplantation?

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.

Excellent efficacy and beneficial safety during observational 5-year follow-up of rapid steroid withdrawal after renal transplantation (Harmony FU study).

We previously reported excellent efficacy and improved safety aspects of rapid steroid withdrawal (RSWD) in the randomized controlled 1-year "Harmony" trial with 587 predominantly deceased-donor kidney transplant recipients randomized either to basiliximab or rabbit antithymocyte globulin induction therapy and compared with standard immunosuppressive therapy consisting of basiliximab, low tacrolimus once daily, mycophenolate mofetil and corticosteroids. The 5-year post-trial follow-up (FU) data were obtained in an observational manner at a 3- and a 5-year visit only for those Harmony patients who consented to participate and covered clinical events that occurred from the second year onwards. Biopsy-proven acute rejection and death-censored graft loss rates remained low and independent of RSWD. Rapid steroid withdrawal was an independent positive factor for patient survival (adjusted hazard ratio 0.554, 95% confidence interval 0.314-0.976; P=.041).The reduced incidence of post-transplantation diabetes mellitus in RSWD patients during the original 1-year study period was not compensated by later incidences during FU. Incidences of other important outcome parameters such as opportunistic infections, malignancies, cardiovascular morbidity/risk factors, donor-specific antibody formation or kidney function did not differ during FU period. With all the limitations of a post-trial FU study, the Harmony FU data confirm excellent efficacy and beneficial safety aspects of RSWD under modern immunosuppressive therapy over the course of 5 years after kidney transplantation in an immunologically low-risk, elderly population of Caucasian kidney transplant recipients. Trial registration: Clinical trial registration number: Investigator Initiated Trial (NCT00724022, FU study DRKS00005786).

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.

#3973 EXCELLENT EFFICACY AND BENEFICIAL SAFETY DURING FIVE YEAR FOLLOW-UP OF RAPID STEROID WITHDRAWAL AFTER RENAL TRANSPLANTATION (HARMONY STUDY)

Abstract Background and Aims We previously reported excellent efficacy and improved safety aspects of rapid steroid withdrawal in the randomized controlled one year “Harmony” trial with 587 predominantly deceased-donor kidney transplant recipients randomized either to basiliximab or rabbit antithymocyte globulin induction therapy and compared to standard immunosuppressive therapy consisting of basiliximab, low tacrolimus once daily, mycophenolate mofetil, and corticosteroids. The five-year post-trial follow-up (FU) data reported here were obtained in an observational manner to evaluate, how these excellent short-term surrogate parameters will translate into hard long-term outcome parameters like patient death/graft loss. Method The five-year post-trial follow-up data were obtained in an observational manner at a three and a five-year visit for patients who consented to participate and covered clinical events that occurred from the second year onwards. Results Biopsy-proven acute rejection and death-censored graft loss rates remained low and independent of rapid steroid withdrawal (see Figure 1). Rapid steroid withdrawal was an independent positive factor for patient survival (adjusted hazard ratio 0.554, 95 % confidence interval 0.314 to 0.976; p = 0.041, see Table 1). The reduced incidence of post-transplantation diabetes mellitus in rapid steroid withdrawal patients during the original one-year study period was not compensated by later incidences during follow-up. Incidences of other important outcome parameters such as opportunistic infections, malignancies, cardiovascular morbidity/risk factors, donor specific antibody formation, or kidney function did not differ during follow-up period. Conclusion The Harmony follow-up trial confirms excellent efficacy and beneficial safety aspects of rapid steroid withdrawal under modern immunosuppressive therapy demonstrating for the first time increased patient survival in an immunologically low-risk, elderly population of Caucasian kidney transplant recipients.

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.

Treatment of De Novo Renal Transplant Recipients With Calcineurin Inhibitor-free, Belatacept Plus Everolimus-based Immunosuppression.

Patients who were de novo renal transplant recipients seropositive for Epstein-Barr virus were randomized to receive BELA+EVL or TAC+MMF maintenance therapy after rabbit antithymocyte globulin induction and up to 7 d of corticosteroids. The primary endpoint was the rate of biopsy-proven acute rejection at month 6. Because of an unanticipated BELA supply constraint, enrollment was prematurely terminated at 68 patients, of whom 58 were randomized and transplanted (intention-to-treat [ITT] population: n = 26, BELA+EVL; n = 32, TAC+MMF). However, 25 patients received BELA+EVL' and 33 received TAC+MMF (modified ITT population). In the ITT population, the 6-mo biopsy-proven acute rejection rates were 7.7% versus 9.4% in the BELA+EVL versus TAC+MMF group. The corresponding 24-mo biopsy-proven acute rejection rates were 19.2% versus 12.5% in the ITT population and 16.0% versus 15.2% in the mITT population; all events were Banff severity grade ≤IIA and similar between groups. One patient in each group experienced graft loss unrelated to acute rejection. The 24-mo mean unadjusted estimated glomerular filtration rates were 71.8 versus 68.7 mL/min/1.73 m2 in the BELA+EVL versus TAC+MMF groups. Posttransplant lymphoproliferative disorder was reported for 1 patient in each group. No deaths or unexpected adverse events were observed. A steroid-free maintenance regimen of BELA+EVL may be associated with biopsy-proven acute rejection rates comparable to TAC+MMF.

Complications of rabbit anti-thymocyte globulin induction immunosuppression in HIV-infected kidney transplant recipients.

Kidney transplantation in HIV-infected individuals with end-stage kidney disease is associated with improved survival compared to dialysis. Rabbit anti-thymocyte globulin (rATG) induction in HIV-infected kidney transplant recipients has been associated with a lower risk of acute rejection, but data on the rates of de novo malignancy and BK viremia in these patients is lacking. We performed a single-center retrospective cohort study of adult HIV-infected individuals who underwent kidney transplantation with rATG induction between January 2006 and December 2016. The primary outcome was the development of de novo malignancy. Secondary outcomes included the development of BK viremia, infections requiring hospitalization, HIV progression, biopsy-proven acute rejection, and patient and allograft survival. Twenty-seven HIV-infected individuals with end-stage kidney disease received deceased (n=23) or living (n=4) donor kidney transplants. The cumulative rate of malignancy at five years was 29%, of whom 29% died because of advanced malignancy. BK viremia was detected in six participants (22%), of whom one had biopsy-proven BK virus-associated nephropathy and all of whom cleared the BK viremia. Five-year acute rejection rates, patient survival and death-censored allograft survival were 17%, 85% and 80% respectively. rATG induction in HIV-infected kidney transplant recipients was associated with a low risk of acute rejection, but a potentially higher risk of de novo malignancies and BK viremia in this cohort. Screening strategies to closely monitor for BK virus infection and malignancy post-transplantation may improve outcomes in HIV-infected kidney transplant recipients receiving rATG induction.

316.5: Long Term Outcomes of Low Dose Anti-thymocyte Globulin And Anti-interleukin-2 Receptor Antibody Induction in Kidney Transplantation From Expanded Criteria Donors

Background: Using kidneys from expanded criteria donors (ECD) has been increased due to the shortage of donor organs but seemed to have poorer prognosis. The aim of this study was to evaluate the safety and efficacy of rabbit anti-thymocyte globulin (rATG) induction in kidney transplantation (KT) from ECD compared to anti IL-2 receptor antibody (basiliximab). Methods: We retrospectively analyzed 182 patients who underwent KT from ECDs between April 2004 and December 2020. The patients were categorized into two groups according to induction therapy modality. The basiliximab group (n=43) received basiliximab 20mg/kg on day 0 and 4, while low dose rATG group (n=139) received rATG 1.5mg/kg on day 0, 1, and 2. Both groups received tacrolimus, mycopheonolate, and steroids as maintenance immunosuppressive agents. Results: The mean donor age (60.6 vs 64.3, p = 0.007) and KDPI score (84.4 vs 90.0, p = 0.005) were higher in rATG group. Patients in rATG group showed more delayed graft function (11.6% vs 30.9%, p = 0.021) but no significant difference in biopsy proven acute rejection (41.9% vs 35.3%, p =0.546). However, graft survival rates (p = 0.88) and overall survival rates (p = 0.846) were not significantly different between the two groups. CMV infection rate seemed higher in rATG group, but graft survival rate was not influenced by CMV infection (p =0.677). Conclusion: Low dose rATG induction in KT from ECD resulted in comparable patient and graft survival despite the worse donor and recipient profile comparing to basiliximab induction. Therefore, low dose rATG can be considered as an effective and safe induction therapy in KT from ECD.

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.

Low dose rabbit antithymocyte globulin is non-inferior to higher dose in low-risk pediatric kidney transplant recipients.

Currently, there is no consensus among pediatric kidney transplant centers regarding the use and regimen for immunosuppressive induction therapy. In this single center, retrospective cohort study, pediatric kidney transplant recipients transplanted between 1 May 2013 and 1 May 2018 with rabbit antithymocyte globulin (rATG) induction were included. We stratified patients based on immunological risk, with high risk defined as those with repeat transplant, preformed donor specific antibody, current panel-reactive antibodies > 20%, 0 antigen match and/or African-American heritage. Outcome of interest was the incidence of biopsy proven acute rejection by 1year. A total of 166 patients met inclusion criteria. Age of patients was 12years (11 mo-21 y), (median, range), 21.5% received a living donor transplant and 50.6% were female. Low-immunologic-risk patients were divided into 2 groups, those who received the lower cumulative rATG dose of ≤ 3.5mg/kg (n = 52) versus the higher cumulative dose of > 3.5mg/kg (n = 47). The median total dose in the lower dose group was 3.1 (IQR 0.3) and 4.4 (IQR 0.8) in the higher dose group, P < 0.001. Rejection rate did not differ significantly between the 2 treatment groups (7/52 vs. 6/47). None in the lower dose group developed BK nephropathy versus 3 in the higher dose group. Graft loss due to BK nephropathy occurred in 1 patient in the higher dose group. Graft loss in the whole cohort at 12months was a rare event (n = 1) with 99.5% graft survival and 100% patient survival. Reduced rATG dosing (≤ 3.5mg/kg) when compared to higher dosing (> 3.5mg/kg) is safe and effective in low-risk pediatric kidney transplant recipients without increasing risk of rejection. A higher resolution version of the Graphical abstract is available as Supplementary information.

CTOTC-08: A multicenter randomized controlled trial of rituximab induction to reduce antibody development and improve outcomes in pediatric lung transplant recipients

We conducted a randomized, placebo-controlled, double-blind study of pediatric lung transplant recipients, hypothesizing that rituximab plus rabbit anti-thymocyte globulin induction would reduce de novo donor-specific human leukocyte antigen antibodies (DSA) development and improve outcomes. We serially obtained clinical data, blood, and respiratory samples for at least one year posttransplant. We analyzed peripheral blood lymphocytes by flow cytometry, serum for antibody development, and respiratory samples for viral infections using multiplex PCR. Of 45 subjects enrolled, 34 were transplanted and 27 randomized to rituximab (n=15) or placebo (n=12). No rituximab-treated subjects versus five placebo-treated subjects developed de novo DSA with mean fluorescence intensity >2000. There was no difference between treatment groups in time to the primary composite outcome endpoint (death, bronchiolitis obliterans syndrome [BOS] grade 0-p, obliterative bronchiolitis or listing for retransplant). A post-hoc analysis substituting more stringent chronic lung allograft dysfunction criteria for BOS 0-p showed no difference in outcome (p=.118). The incidence of adverse events including infection and rejection episodes was no different between treatment groups. Although the study was underpowered, we conclude that rituximab induction may have prevented early DSA development in pediatric lung transplant recipients without adverse effects and may improve outcomes (Clinical Trials: NCT02266888).

Belatacept for Simultaneous Calcineurin Inhibitor and Chronic Corticosteroid Immunosuppression Avoidance: Two-Year Results of a Prospective, Randomized Multicenter Trial.

Immunosuppressive therapy in kidney transplantation is associated with numerous toxicities. CD28-mediated T-cell costimulation blockade using belatacept may reduce long-term nephrotoxicity, compared with calcineurin inhibitor-based immunosuppression. The efficacy and safety of simultaneous calcineurin inhibitor avoidance and rapid steroid withdrawal were tested in a randomized, prospective, multicenter study. This study reports the 2-year results of a randomized clinical trial of 316 recipients of a new kidney transplant. All kidney transplants were performed using rapid steroid withdrawal immunosuppression. Recipients were randomized in a 1:1:1 ratio to receive belatacept with alemtuzumab induction, belatacept with rabbit anti-thymocyte globulin (rATG) induction, or tacrolimus with rATG induction. The composite end point consisted of death, kidney allograft loss, or an eGFR of <45 ml/min per 1.73 m2 at 2 years. The composite end point was observed for 11 of 107 (10%) participants assigned to belatacept/alemtuzumab, 13 of 104 (13%) participants assigned to belatacept/rATG, and 21 of 105 (21%) participants assigned to tacrolimus/rATG (for belatacept/alemtuzumab versus tacrolimus/rATG, P=0.99; for belatacept/rATG versus tacrolimus/rATG, P=0.66). Patient and graft survival rates were similar between all groups. An eGFR of <45 ml/min per 1.73 m2 was observed for nine of 107 (8%) participants assigned to belatacept/alemtuzuab, eight of 104 (8%) participants assigned to belatacept/rATG, and 20 of 105 (19%) participants assigned to tacrolimus/rATG (P<0.05 for each belatacept group versus tacrolimus/rATG). Biopsy sample-proven acute rejection was observed for 20 of 107 (19%) participants assigned to belatacept/alemtuzuab, 26 of 104 (25%) participants assigned to belatacept/rATG, and seven of 105 (7%) participants assigned to tacrolimus/rATG (for belatacept/alemtuzumab versus tacrolimus/rATG, P=0.006; for belatacept/rATG versus tacrolimus/rATG, P<0.001). Gastrointestinal and neurologic adverse events were less frequent with belatacept versus calcineurin-based immunosuppression. Overall 2-year outcomes were similar when comparing maintenance immunosuppression using belatacept versus tacrolimus, and each protocol involved rapid steroid withdrawal. The incidence of an eGFR of <45 ml/min per 1.73 m2 was significantly lower with belatacept compared with tacrolimus, but the incidence of biopsy sample-proven acute rejection significantly higher. Belatacept Early Steroid Withdrawal Trial, NCT01729494.

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.

MO982COMPARISON OF BASILIXIMAB AND R-ATG ON ACUTE REJECTION RISK IN HIGH IMMUNOLOGICAL RISK RENAL TRANSPLANT RECIPIENTS

Abstract Background and Aims High Panel Reactive Antibody (PRA) level has been widely accepted as a marker for acute rejection risk following kidney transplantation. PRA&amp;gt;/= 20% is considered a high immunological risk renal transplant. The aim of our study was to assess the risk of acute rejection in kidney transplant recipients (KTR) following Basiliximab induction compared to Rabbit Anti-Thymocyte Globulin (R-ATG) maintained on tacrolimus and mycophenolate mofetil maintenance immunotherapy. Method This was a retrospective observational cohort study using data from the United States Organ Procurement and Transplantation Network, all KTR’s with PRA =/&amp;gt; 20%, who were maintained on tacrolimus and mycophenolate mofetil between September 2017 and September 2019 were included. Follow-up was until September 2020. Data included recipient factors (age, sex, ethnicity, diabetes, body mass index), transplant factors (delayed graft function, cold ischemia time, number of previous transplants, panel reactive antibodies, HLA-mismatches, induction therapy, maintenance immunotherapy and donor factors (donor type, donor age). The cohort were divided into 2 groups; living and deceased donor renal transplants. The groups were further divided by PRA level, each group was divided into 3 subgroups: Group A (low PRA level: PRA range from 20% to 49%), Group B (moderate PRA level: PRA range from 50% to 79%), and Group C (High PRA level: PRA range from 80% to 100%). Multivariable logistic regression models were constructed to assess the effect of induction therapies (Basiliximab versus R-ATG) on acute rejection episodes at 6 months post-transplant. The multivariable model was adjusted for recipient, donor and transplant factors mentioned above. Results Among living donor KTR’s, there was no difference between Basiliximab and R-ATG in acute rejection episodes in any of the three groups, Group A (low PRA level, n=717, OR=1.17, P=0.79, 95%CI:0.34-3.95), Group B (moderate PRA level, n=618, OR=1.51, P=0.58, 95%CI:0.33-6.92) and Group C (high PRA level, n=401, OR=1.17, P=0.85, 95%CI:0.21-6.56) respectively. In contrast, among deceased donor KTR’s R-ATG was associated with lower risk of rejection compared to Basiliximab in all three groups, group A (low PRA level, n=1895, OR=0.52, P=0.03, 95%CI: 0.28-0.94), group B (moderate PRA level, n=1618, OR=0.41, P&amp;lt;0.01, 95%CI: 0.22-0.78) and group C (high PRA level, n=3973, P&amp;lt;0.01, 95%CI: 0.28-0.70). Conclusion This study shows that risk of acute rejection is no different with Basilximab induction compared to R-ATG in high immunological risk living-donor KTR’s at all levels of PRA in the current tacrolimus-mycophenolate mofetil immunosuppression era. However, risk of acute rejection seems to be lower in deceased donor KTR’s having R-ATG induction at all levels of PRA. Delayed graft function is a risk factor for acute rejection, our models did not adjust for dose of R-ATG which may explain the lower risk seen in deceased donor KTR’s, data was not available on donor specific antibodies. In summary, Basiliximab induction has similar acute rejection rates as R-ATG in living donor KTR’s whereas in deceased donor KTR’s R-ATG was found to be better.