Interleukin-2 Receptor Antibody Induction Research Articles

Induction Therapy and Outcomes following Kidney Transplantation in Recipients of Previous Heart or Liver Transplants.

Introduction:Optimal induction for kidney transplantation in patients with previous nonrenal organ transplantation is unclear. We aimed to evaluate the impact of induction therapy on the outcomes following kidney transplantation in patients who underwent prior heart or liver transplantation.Methods:Using the UNOS database, patients who underwent isolated heart or liver transplant from 2000 to 2016 followed by subsequent kidney transplant and maintained on calcineurin inhibitor (CNI)/mycophenolic acid (MPA) regimen were identified and stratified into three groups according to the induction used for kidney transplant: No induction, induction with interleukin-2 receptor antibody (IL-2RA), or T-cell depleting induction with Thymoglobulin. The outcomes were compared between no induction vs. IL-2RA and T-cell depleting induction, and IL-2RA vs. T-cell depleting induction.Results:Adjusted risk for delayed graft function was significantly higher for T-cell depleting vs. no induction (OR 4.56, 95% CI 1.14–18.3, P = 0.03) and trended higher for IL-2RA vs. no induction (OR 2.96, 95% CI 0.84–10.33, P = 0.08) among kidney after heart group and significantly higher for T-cell depleting vs. no induction (OR 2.88, 95% CI 1.40–5.95, P = 0.004) and IL-2RA induction (OR 1.88, 95% CI 1.12–3.17, P = 0.02) among kidney after liver patients. Adjusted graft failure and patient death risks were similar in patients who got IL-2RA or depleting inductions vs. no induction and IL-2RA vs. depleting induction groups in kidney after heart and kidney after liver groups.Conclusions:The use of induction was not associated with graft or patient survival benefits for kidney transplantation in patients who had prior heart or liver transplants and maintained on CNI and MPA regimen.

Reduced calcineurin inhibitor exposure with antibody induction and recurrent hepatocellular carcinoma after liver transplantation

Background Hepatocellular carcinoma (HCC) is a common indication for liver transplantation (LT), but post-LT tumor recurrence remains a concern. Early post-LT immunosuppression is suggested to affect recurrence risk. We evaluated the impact on HCC recurrence of an immunosuppression protocol introduced in 2010 with interleukin-2 receptor antibody (IL-2RA) induction and delayed-introduction of reduced-dose tacrolimus with mycophenolate. Methods We included consecutive HCC patients transplanted 2000–2017 in Gothenburg. The impact on HCC recurrence of IL-2RA induction and mean tacrolimus trough concentration during the first 20 post-LT days was analyzed by multivariable Cox regression and propensity score-adjusted analyses. Results The study comprised 235 patients (mean age 57 yrs, men 80%, mean MELD 13, within Milan criteria 57%). The cumulative 5-yr HCC recurrence rate among patients transplanted before and after 2010 were 28.6% and 19.7%, respectively. IL-2RA induction had no independent effect on HCC recurrence. High tacrolimus exposure (mean 20-day tacrolimus concentration ≥8ng/mL) was associated with increased HCC recurrence risk on univariable analysis (HR 2.22, 95% CI 1.23–4.01, p = .008), but was non-significant on multivariable analysis (p = .17). Outside Milan criteria, high tacrolimus exposure was significant for HCC recurrence (HR 3.68, 95% CI 1.34–10.11, p = .012) independently of tumor characteristics and AFP level. This was confirmed on multivariable propensity score-adjusted analysis. Conclusions Reduced early tacrolimus exposure, facilitated by IL-2RA induction, was associated with reduced risk for HCC recurrence among patients outside Milan criteria. Prospective studies are needed to confirm if early tacrolimus-minimization strategies can help reduce HCC recurrence rates and help extend transplant criteria.

Interleukin-2 receptor antibody induction with early low dose tacrolimus preserves post-liver transplant renal function in at risk individuals

BackgroundRenal dysfunction post liver transplantation (LT) is common. We report our real-world experience of IL2Ra induction with immediate exposure to reduced dose tacrolimus used for patients with chronic kidney disease (CKD) and evolving acute kidney injury (AKI). MethodA single-centre retrospective analysis of elective adult LT from 1/1/17 to 31/12/17. The primary outcome measure was increase in CKD stage at month 6 post-LT, and secondary outcome was early biopsy proven acute rejection (BPAR). Results161 patients were included: 17 planned-IL2Ra for CKD; 38 unplanned-IL2Ra for AKI; and 106 standard immunosuppression. IL2Ra group had lower trough tacrolimus levels till month 3 post-LT. Patients receiving IL2Ra did not have an increased risk of increase in CKD class at month 6 (aOR 0.95, 95% CI 0.34–2.75, P = 0.92), or of early BPAR (aOR 0.53, 95% CI 0.19–1.32, P = 0.19). ConclusionIL2Ra induction with immediate exposure to reduced dose tacrolimus can be given to patients with CKD or early evolving AKI post-LT, with no greater attrition of renal function at 6 months or an increased risk of early BPAR when compared to standard IS. Longer-term outcome data is required, however this regimen can be considered for high risk LT recipients with CKD and AKI.

Effect of Interleukin-2 Receptor Antibody Induction Therapy on Survival in Renal Transplant Patients Receiving Tacrolimus

Background: This study aims to assess outcomes of interleukin-2 (IL-2) receptor blocker induction therapy on allograft and patients’ outcomes in standard risk recipients in the tacrolimus era, analysing data form the British Renal Transplant Registry. Methods: The study population involved all standard-risk renal transplant patients from 2000 till 2015 who were registered in the UK transplant registry and followed up till May 2018. Standard risk transplants were defined as patients with <2DR mismatch, calculated reaction frequency <20%, live donors or donors after brain death and patients with no previous renal transplantation transplant. We used inverse probability weights to adjust different covariates between the groups. Cox regression analysis for adjusted data and treatment effects model were used to assess outcomes. Results: In all, 3,597 renal transplant patients were included in the study. Two groups were identified; induction group (n = 2,858) which included patients who received IL-2 receptor blocker induction therapy and the no-induction group (n = 739). There was no significant difference between both groups in terms of estimated glomerular filtration rate (eGFR) rate at 1-year post-transplant (correlation co-efficient = 1.224, 95% CI ranges from –0.347 to 2.796). Average eGFR was 59.922 mL/min/1.73 m² in the induction group (SD 29.171) and 64.557 mL/min/1.73 m² in the no-induction groups (SD 46.763). There was no significant difference between both groups regarding graft survival at 5 years post-transplant (hazard ratio [HR] 0.944, 95% CI ranges from 0.599 to 1.485, p = 0.804), patient survival at 5 years post-transplant (HR 0.809, 95% CI ranges from 0.477 to1.372, p = 0.433). Conclusion: In the standard risk renal transplant population, the IL2 receptor blocker induction regimen does not affect eGFR at 1 year or renal and graft outcomes at 5 years.

Immunological risk stratification and tailored minimisation of immunosuppression in renal transplant recipients

BackgroundThe efficacy and safety of minimisation of immunosuppression including early steroid withdrawal in kidney transplant recipients treated with Basiliximab induction remains unclear.MethodsThis retrospective cohort study reports the outcomes from 298 consecutive renal transplants performed since 1st July 2010–June 2013 treated with Basiliximab induction and early steroid withdrawal in low immunological risk patients using a simple immunological risk stratification and 3-month protocol biopsy to optimise therapy. The cohort comprised 225 low-risk patients (first transplant or HLA antibody calculated reaction frequency (CRF ≤50% with no donor specific HLA antibodies) who underwent basiliximab induction, steroid withdrawal on day 7 and maintenance with tacrolimus and mycophenolate mofetil (MMF), and 73 high-risk patients who received tacrolimus, MMF and prednisolone for the first 3 months followed by long term maintenance immunosuppression with tacrolimus and prednisolone. High-risk patients not undergoing 3-month protocol biopsy were continued on triple immunosuppression.ResultsSteroid withdrawal could be safely achieved in low immunological risk recipients with IL2 receptor antibody induction. The incidence of biopsy-proven acute rejection was 15.1% in the low-risk and 13.9% in the high-risk group (including sub-clinical rejection detected at protocol biopsy). One- year graft survival was 93.3% and patient survival 98.5% in the low-risk group, and 97.3 and 100% respectively in the high-risk group. Graft function was similar in each group at 1 year (mean eGFR 61.2 ± 23.4 mL/min low-risk and 64.6 ± 19.2 mL/min high-risk).ConclusionsImmunosuppression regimen comprising basiliximab induction, tacrolimus, MMF and prednisolone with early steroid withdrawal in low risk patients and MMF withdrawal in high risk patients following a normal 3-month protocol biopsy is effective in limiting acute rejection episodes and produces excellent rates of patient survival, graft function and complications.

Evidence of Interleukin-2-Receptor-Antibody Induction in Low-Risk Living Donor Kidney Transplantation: A Single-Center Pilot Study

BackgroundThe recommended standard immunosuppressive therapy for renal transplant recipients comprises an initial induction therapy mainly with an interleukin-2-receptor antibody (IL2-RA) and a triple maintenance therapy. With tacrolimus and mycophenolate acid it is unknown whether IL2-RA application affects the short- and long-term results. This question is addressed in the present analysis. MethodsFrom July 2007 to June 2019 a total of 127 living donor kidney transplant recipients meeting the center-specific definition of immunologic low risk situation (first transplantation, HLA-mismatch ≤3, panel reactive antibody ≤10%) were identified. In 83 recipients with a first-degree relationship to the donor we omitted the IL2-RA induction (IL2-RA-). The remaining 44 recipients, mostly not first-degree relatives, served as controls (IL2-RA+). Biopsy-proven acute rejection and long-term patient and graft survival rates were compared. ResultsBiopsy-proven acute rejection rates after 3 months were similar in both groups with 4.8% (IL2-RA-) vs 13.7% (IL2-RA+; P = .0937), including borderline rejection rates of 18.0% (IL2-RA-) vs 18.3% (IL2-RA+; P = 1.000), respectively. Ten-year long-term survival rates were comparable between the IL2-RA- and the IL2-RA+ group with 95.6% vs 93.5% (patient survival; P = .5465) and 92.1% vs 90.6% (death-censored graft survival; P = .8893). ConclusionFor low-risk living donor kidney transplant recipients with first-degree relationship to the donor, it is safe to omit induction therapy with IL2-RA.

Implication of interleukin-2 receptor antibody induction therapy in standard risk renal transplant in the tacrolimus era: a meta-analysis

BackgroundInterleukin-2 (IL-2) antagonist has been used as an induction therapy in many centres in calcineurin inhibitor-sparing regimens. Tacrolimus has overwhelmingly replaced cyclosporine in the maintenance immunosuppressive protocols in many transplant centres. The aim of our study and meta-analysis is to explore the effect of IL-2 induction therapy on the rate of rejection and patient and graft survival in standard-risk renal transplant patients with tacrolimus-based maintenance immunotherapy. Secondary aims included assessment of the effect of IL-2 induction therapy on creatinine change and the risk of cytomegalovirus (CMV) infection.MethodsWe conducted a systematic review in different databases to identify studies and research work that assessed the effect of IL-2 antibody induction therapy on renal transplant outcomes. Inclusion criteria for our meta-analysis were all studies that compared IL-2 induction therapy with placebo or no induction therapy in standard-risk renal transplant recipients on tacrolimus-based maintenance immunosuppressive therapy. Data collected were the name of the first author, journal title, year of publication, country where the study was conducted, number of patients in the IL-2 induction therapy arm and in the placebo arm, number of patients who had biopsy-proven rejection and graft survival in each arm. A random effects model was used for the meta-analysis.ResultsOf the 470 articles found in different databases, 7 were included in the meta-analysis. Forest plot analysis for rate of rejection during the follow-up period post-transplant showed no significant difference between the groups. There was no evidence of heterogenicity between included studies (I2 = 21.8%, P = 0.27). The overall risk difference was −0.02 [95% confidence interval (CI) −0.05–0.01]. A random effects meta-analysis for patient and graft survival was performed using forest plot analysis and showed no significant effect of IL-2 receptor (IL-2R) antibody induction on patient or graft survival compared with placebo. The overall risk difference was −0.01 (95% CI −0.04–0.01) and 0.00 (95% CI −0.00–0.01), respectively. Three of the included studies showed no effect of basiliximab on creatinine change, two showed no effect on risk of CMV infection and two showed less risk of post-transplant diabetes in the basiliximab group.ConclusionIL-2R antibody induction therapy has no significant effect on the rate of rejection or patient or graft survival in standard-risk renal transplant recipients on tacrolimus-based maintenance immunotherapy. More randomized controlled studies are needed.

Risk factors and outcomes of delayed graft function in renal transplant recipients receiving a steroid sparing immunosuppression protocol.

AIMTo analyse the risk factors and outcomes of delayed graft function (DGF) in patients receiving a steroid sparing protocol.METHODSFour hundred and twenty-seven recipients of deceased donor kidney transplants were studied of which 135 (31.6%) experienced DGF. All patients received monoclonal antibody induction with a tacrolimus based, steroid sparing immunosuppression protocol.RESULTSFive year patient survival was 87.2% and 94.9% in the DGF and primary graft function (PGF) group respectively, P = 0.047. Allograft survival was 77.9% and 90.2% in the DGF and PGF group respectively, P < 0.001. Overall rejection free survival was no different between the DGF and PGF groups with a 1 and 5 year rejection free survival in the DGF group of 77.7% and 67.8% compared with 81.3% and 75.3% in the PGF group, P = 0.19. Patients with DGF who received IL2 receptor antibody induction were at significantly higher risk of rejection in the early post-transplant period than the group with DGF who received alemtuzumab induction. On multivariate analysis, risk factors for DGF were male recipients, recipients of black ethnicity, circulatory death donation, preformed DSA, increasing cold ischaemic time, older donor age and dialysis vintage.CONCLUSIONAlemtuzumab induction may be of benefit in preventing early rejection episodes associated with DGF. Prospective trials are required to determine optimal immunotherapy protocols for patients at high risk of DGF.

Immunosuppression in the elderly renal allograft recipient: a systematic review.

The Elderly are the fastest growing part of kidney transplant recipients. The best immunosuppressive strategy is unknown. We performed a systematic search of randomized controlled trials and observational studies focused on safety and efficacy of different immunosuppression strategies in elderly kidney recipients. Data extraction and risk of bias evaluation were systematically performed. Ten studies were included: 2 randomized clinical trials and 8 observational. A marginal benefit was found for early renal function with delayed tacrolimus or complete tacrolimus avoidance using mycophenolate mofetil (MMF). Observational cohort studies looked at different antibody induction strategies, calcineurin-inhibitors based maintenance immunosuppression, calcineurin-inhibitor-free sirolimus-based therapy and use of MMF versus azathioprine. Treatment with interleukin-2 receptor antibody induction, calcineurin-inhibitor minimization with MMF and steroid minimization is advisable in the low immunologic risk elderly recipient, considering the increased risk of toxicities, infection and malignancies. In the high immunologic risk elderly recipient, taking into account the morbid consequences of acute rejection in the elderly, observational studies support antibody induction with depletive antibodies, calcineurin-inhibitor, MMF and steroids; calcineurin-inhibitor-minimization is not recommended. There is very limited evidence for the benefits and harms of different immunosuppression strategies in the elderly. Most of the published literature are observational studies, and randomized controlled trials are urgently needed.

REFINE: A Randomized Trial Comparing Cyclosporine A and Tacrolimus on Fibrosis After Liver Transplantation for Hepatitis C

REFINE was a 12-month, prospective, open-label study in 356 patients receiving de novo liver transplantation for hepatitis C virus (HCV) cirrhosis, randomized to cyclosporine A (CsA) or tacrolimus with (i) no steroids, IL-2 receptor antibody induction and mycophenolic acid, or (ii) slow steroid tapering. The primary analysis population based on availability of liver biopsies comprised 165 patients (88 CsA, 77 tacrolimus). There was no difference in the primary endpoint, fibrosis stage ≥2 at 12 months, which occurred in 63/88 CsA-treated patients (71.6%) and 52/77 tacrolimus-treated patients (67.5%) (odds ratio [OR] 1.11; 95% CI 0.56, 2.21; p = 0.759). Similarly, no significant between-group difference occurred at month 24 (OR 1.15; 95% CI 0.47, 2.80; p = 0.767). Among steroid-free patients, fibrosis score ≥2 was significantly less frequent with CsA versus tacrolimus at month 12 (7/37 [18.9%] vs. 16/38 [42.1%]; p = 0.029). HCV viral load was similar in both the tacrolimus- and CsA-treated cohorts. Mean blood glucose was significantly higher with tacrolimus from day 15 onward. Biopsy-proven acute rejection, graft loss and death were similar. These results showed no differences in posttransplant HCV-induced liver fibrosis between patients treated with CsA or tacrolimus in steroid-containing regimens, whereas CsA in steroid-free protocols was associated with reduced severity of fibrosis progression at 1 year posttransplant.

Three-year outcomes in kidney transplant patients randomized to steroid-free immunosuppression or steroid withdrawal, with enteric-coated mycophenolate sodium and cyclosporine: the infinity study.

In a six-month, multicenter, open-label trial, de novo kidney transplant recipients at low immunological risk were randomized to steroid avoidance or steroid withdrawal with IL-2 receptor antibody (IL-2RA) induction, enteric-coated mycophenolate sodium (EC-MPS: 2160 mg/day to week 6, 1440 mg/day thereafter), and cyclosporine. Results from a 30-month observational follow-up study are presented. Of 166 patients who completed the core study on treatment, 131 entered the follow-up study (70 steroid avoidance, 61 steroid withdrawal). The primary efficacy endpoint of treatment failure (clinical biopsy-proven acute rejection (BPAR) graft loss, death, or loss to follow-up) occurred in 21.4% (95% CI 11.8–31.0%) of steroid avoidance patients and 16.4% (95% CI 7.1–25.7%) of steroid withdrawal patients by month 36 (P = 0.46). BPAR had occurred in 20.0% and 11.5%, respectively (P = 0.19). The incidence of adverse events with a suspected relation to steroids during months 6–36 was 22.9% versus 37.1% (P = 0.062). By month 36, 32.4% and 51.7% of patients in the steroid avoidance and steroid withdrawal groups, respectively, were receiving oral steroids. In conclusion, IL-2RA induction with early intensified EC-MPS dosing and CNI therapy in de novo kidney transplant patients at low immunological risk may achieve similar three-year efficacy regardless of whether oral steroids are withheld for at least three months.

Acute Rejection Characteristics From a Prospective, Randomized, Double-Blind, Placebo-Controlled Multicenter Trial of Early Corticosteroid Withdrawal

This report characterizes acute rejection and rejection outcomes in subjects randomized to continuous corticosteroid therapy (CCS) or early corticosteroid withdrawal (CSWD; 7 days after transplantation) in the Astellas Blinded CSWD Trial. The Astellas Blinded CSWD Trial was a 5-year, prospective, multicenter, randomized, double-blind trial of early CCS withdrawal in 386 kidney transplant recipients (195 CCS and 191 CSWD). Tacrolimus and mycophenolate mofetil were required as well as either rabbit antithymocyte globulin or interleukin-2 receptor antibody induction. Biopsy-confirmed acute rejection (BCAR) was grade 1A or higher by Banff criteria. This report also provides borderline changes (BL) that did not meet Banff grade 1A included with BCAR (BCAR+BL). BCAR+BL was 25 (12.8%) in CCS group and 42 (22.0%) in CSWD group (P=0.022). Early BCAR+BL (first 90 days after transplantation) was less frequent in CCS (n=5 [2.6%]) than in CSWD (n=22 [11.5%]; P<0.001). Among non-African-American subjects, early BCAR+BL occurred more often in CSWD (n=20 [12.7%]) versus CCS (n=2 [1.3%]; P<0.001). Late acute rejection (>2 years) occurred more often in African-American subjects in CCS (n=5 [13.9%]) than in CSWD (n=0; P=0.056). Risk factors were CSWD (hazard ratio [HR], 4.72; P<0.002) and human leukocyte antigen mismatch (HR, 1.48; P<0.005) for early BCAR+BL and CSWD (HR, 1.9; P<0.02), human leukocyte antigen mismatch (HR, 1.2; P<0.01), and age (HR, 0.97; P<0.002) for 5-year rejection. The HR for graft loss associated with BCAR+BL was 8.8. BCAR+BL may occur more frequently during the early period after transplantation under an early CSWD regimen with tacrolimus plus induction compared with CCS, particularly among non-African-Americans.

Steroid avoidance with early intensified dosing of enteric-coated mycophenolate sodium: a randomized multicentre trial in kidney transplant recipients

Short-term intensified dosing using enteric-coated mycophenolate sodium (EC-MPS) reduces rejection after kidney transplantation without compromising safety and may facilitate steroid avoidance. In a 6-month, multicentre open-label trial, 222 de novo kidney transplant recipients at low-immunological risk were randomized to steroid avoidance or maintenance steroids with interleukin (IL)-2 receptor antibody (IL-2RA) induction, EC-MPS (2160 mg/day to Week 6, 1440 mg/day thereafter) and cyclosporine. The primary end point; treatment failure at Month 6 [biopsy-proven acute rejection (BPAR), graft loss, death or loss to follow-up], occurred in 17.9% (20/112) of steroid-avoidance patients and 14.5% (16/110) of controls (difference 3.4%, 95% confidence interval -6.3 to 13.1, P = 0.47 for superiority testing). BPAR occurred in 11.6 and 7.3% of patients in the steroid-avoidance and control arms, respectively (P = 0.27). Creatinine clearance was similar at Month 6 (steroid-avoidance 56 ± 18 mL/min/1.73 m(2), controls 60 ± 22 mL/min/1.73 m(2), P = 0.34). Cytomegalovirus infection, as reported by investigators, occurred in 12.5% of steroid-avoidance patients and 22.7% of controls (P = 0.045). A regimen of early intensified EC-MPS dosing with calcineurin inhibitor and IL-2RA induction permits oral steroid avoidance in adult kidney transplant patients at low-immunological risk without compromising efficacy at 6 months' follow-up.

Effect of interleukin-2 receptor antibody therapy on acute rejection risk and severity, long-term renal function, infection and malignancy-related mortality in renal transplant recipients

In renal transplantation, the use of interleukin-2 receptor antibody (IL-2Ra) has been associated with reduced rejection rates, but the effect of this agent on rejection severity and type, long-term graft function and risk of infection and malignancy-related mortality remains unclear. Using Australia and New Zealand Dialysis and Transplant Registry, all live- and deceased-donor renal transplant recipients in Australia between 2000 and 2006 were included. Of the 3344 renal transplant recipients, 1874 (56.0%) received no induction and 1470 (44.0%) had received IL-2Ra. Compared with no induction, IL-2Ra was associated with reduced rejection risk (relative risk 0.70, 95% CI 0.60, 0.81) and higher estimated glomerular filtration rate at 5 years (difference in means 3.51, 95% CI 0.83, 6.19). Severity and type of rejection were similar in both the groups. The adjusted rate of death attributed to malignancy for no induction and IL-2Ra per 1000 patient-years was 1.48 and 1.63, respectively, whereas death attributed to infection was 2.42 and 2.16 respectively. This registry analysis demonstrates that IL-2Ra induction in kidney transplantation is associated with substantial clinical benefits of reduced risk of acute rejection and improved long-term graft function without an increase in adverse events.

Interleukin-2 receptor antibody does not reduce rejection risk in low immunological risk or tacrolimus-treated intermediate immunological risk renal transplant recipients

The use of interleukin-2 receptor antibody (IL-2Ra) induction has been associated with reduced rejection rates in renal transplant recipients. However, the effect of IL-2Ra induction on graft and patient outcomes in renal transplant recipients with differing immunological risk remains unclear. Using Australia and New Zealand Dialysis and Transplant Registry, renal transplant recipients in Australia between 1995 and 2005 were included. Recipients were stratified into low immunological risk (primary grafts with < or = 2 human leucocyte antigen (HLA)-mismatches and panel-reactive antibody (PRA) < 10%) or intermediate immunological risk (subsequent grafts or >2 HLA-mismatches or PRA > 25%) recipients. Recipients receiving T-cell depletive induction therapy or steroid and/or calcineurin-free inhibitor regimens were excluded. Outcomes analysed included the presence of rejection at 6 months, estimated glomerular filtration rate at 1 and 5 years, graft and patient survival. 218 of 1220 (18%) low-risk and 883 of 3204 (28%) intermediate-risk recipients received IL-2Ra. In intermediate-risk recipients, IL-2Ra induction was associated with a 26% reduction in the incidence of acute rejection; but this benefit was restricted only to recipients initiated on cyclosporine-based immunosuppressive regimens. In contrast, the use of IL-2Ra in low-risk recipients was not associated with reduced rejection risk. There was no association between IL-2Ra induction and other graft or patient outcomes in both low- and intermediate-risk recipients. This registry analysis suggests that IL-2Ra induction may be associated with a reduction in rejection risk in cyclosporine-treated intermediate immunological risk recipients, but not in low-risk renal transplant recipients.

Interleukin-2 Receptor Antibody Reduces Rejection Rates and Graft Loss in Live-Donor Kidney Transplant Recipients

The use of interleukin-2 receptor antibody (IL-2Ra) induction has been associated with reduced rejection rates in both live and deceased donor kidney transplantation. However, the longer term effect of IL-2Ra induction on estimated glomerular filtration rates and graft and patient survival remains unclear. Using Australia and New Zealand Dialysis and Transplant Registry, live donor renal transplant recipients in Australia between 2001 and 2005 were studied (n=1106). Multiple organ graft recipients and those receiving T-cell depletive induction therapy or steroid- or calcineurin-free inhibitor regimens were excluded. Outcomes analyzed included the presence of rejection at 6 months, estimated glomerular filtration rate at 1 and 3 years, 5 years graft and patient survival. A total of 41.7% of live donor renal transplant recipients received IL-2Ra induction. Recipients of IL-2Ra experienced a 51% reduction in the incidence of acute rejection (odds ratio 0.49, 95%CI 0.36-0.67; P<0.001). In addition, the use of IL-2Ra was associated with reduced overall graft loss (hazard ratio 0.58, 95%CI 0.35-0.96; P=0.03) and higher mean estimated glomerular filtration rate at 1 year but not 3 years. There was no association between IL-2Ra induction and death-censored graft loss or death with functioning graft. This registry analysis demonstrates that IL-2Ra induction in live donor kidney transplantation is associated with substantial clinical benefits of reduced risk of acute rejection, improved short-term graft function, and reduced graft loss.

Pancreas Transplantation in African American Patients Using Basiliximab Induction

The long-term outcome of pancreas transplant (PT) in African Americans (AA) using interleukin-2 receptor antibody induction has not been well documented. We retrospectively analyzed the 7-year outcomes of 45 AA and 73 white recipients of primary PT at our center. All PT were performed with enteric-systemic drainage. Basiliximab induction, tacrolimus, mycophenolic acid, and steroid maintenance were used as the primary immunotherapy. There was no difference by Kaplan-Meier analysis in patient (P=0.94), pancreas graft (P=0.76), or death-censored graft survival (P=0.71) over 7 years between the AA and white groups. Clinically treated pancreas rejection episodes were slightly higher in AA than in white patients. Similarly, cytomegalovirus infection rates and comparable quality of graft function were noted in both groups over 7 years. Excellent long-term patient and pancreas graft survivals can be achieved in AA recipients of PT by using interleukin-2 receptor antibody induction and combination of tacrolimus, mycophenolic acid, and steroid maintenance.

Association of Type of Induction with Posttransplant Lymphoproliferative Disorders

Association of Type of Induction with Posttransplant Lymphoproliferative Disorders

Bolus anti-thymocyte globulin induction in renal transplant recipients: a comparison with conventional ATG or anti–interleukin-2 receptor antibody induction

Bolus anti-thymocyte globulin induction in renal transplant recipients: a comparison with conventional ATG or anti–interleukin-2 receptor antibody induction

IL-2 receptor antibody induction increases the risk for chronic rejection after liver transplantation

IL-2 receptor antibody induction increases the risk for chronic rejection after liver transplantation