Single-Dose Anti-Thymocyte Globulin Compared With Divided-Dose for Induction Therapy in Kidney Transplantation in a Predominantly Black Population

BackgroundThe aim of this study was to compare single-dose rabbit anti-thymocyte globulin (rATG) with a divided dose in kidney transplant recipients within a majority Black patient population.MethodsWe analyzed the outcomes before and after a change in protocol from divided-dose (1.5 mg/kg/day over 4 days) to single-dose (6 mg/kg over 24 hours) rATG in a retrospective cohort study. All patients who received rATG for kidney transplant induction between December 2015 and July 2018 were included.ResultsA total of 197 patients (n = 98 in the divided-dose group, n = 99 in the single-dose group) received rATG. There was no difference in time to rejection at 1 year (P = .82) or incidence of rejection (P = .80). There was also no difference in delayed graft function, serum creatinine, or survival at 1 year. Patients in the single-dose group were more likely to leave the hospital by postoperative day 3 (12% vs 2%, P = .006). The cytomegalovirus infection rate was higher in the single-dose group (P = .031).ConclusionsUse of a single-dose rATG regimen is an acceptable accelerated induction compared with the standard divided dose for induction therapy in kidney transplant in a predominantly Black population.     

5-Year Results of a Prospective,Randomized, Single-Center Study of Alemtuzumab Compared With Rabbit Antithymocyte Globulin Induction in Simultaneous Kidney–Pancreas Transplantation

Introduction

The study purpose was to analyze 5-year outcomes in a prospective, randomized trial of alemtuzumab (ALEM) versus rabbit antithymocyte globulin (rATG) induction in simultaneous kidney–pancreas transplantation (SKPT).

Patients and Methods

From February 2005 through October 2008, a total of 46 SKPTs (45 portal-enteric drainage) were prospectively randomized to receive either single-dose ALEM (30 mg intraoperatively) or multiple-dose rATG antibody induction (starting intraoperatively, minimum of 3 doses administered) with tacrolimus/mycophenolate and/or steroids.

Results

Of 222 kidney transplant patients enrolled in the study, 46 received SKPTs; 28 (61%) received ALEM and 18 (39%) received rATG induction. Follow-up ranged from 54 to 98 months (mean, 69 months). There were no significant differences between the 2 groups in 5-year patient (82% ALEM vs 89% rATG), kidney graft (79% ALEM vs 72% rATG), or pancreas graft (64% ALEM vs 56% rATG) survival rates. Death-censored kidney (90% ALEM vs 75% rATG) and pancreas (71% ALEM vs 56% rATG) graft survival rates were likewise comparable (both, P = NS). Acute rejection (21% ALEM vs 44% rATG; P = .11) and major infection (39% ALEM vs 67% rATG; P = .13) rates were slightly lower in the ALEM group; cytomegalovirus infections were significantly lower (0% ALEM vs 17% rATG; P = .05). The incidence of late acute rejection was low in both groups. There were no differences in early pancreas thromboses (3.6% ALEM vs 11% rATG), postoperative bleeding (11% ALEM vs 0% rATG), other surgical complications, or readmissions between groups. In patients with functioning grafts, 5-year mean serum creatinine (1.4 ALEM vs 1.6 mg/dL rATG), calculated abbreviated Modification of Diet in Renal Disease glomerular filtration rate (55 ALEM vs 52 mL/min/1.73 m² rATG), glycosylated hemoglobin (both 5.4%), and C-peptide (2.2 ALEM vs 2.3 ng/mL rATG) levels were similar.

Conclusions

Single-dose ALEM and multiple dose rATG induction provided similar medium-term patient, kidney, and pancreas graft function and survival rates. ALEM induction may be associated with less acute rejection and major infection over the long term.     

Routine induction therapy in living donor liver transplantation prevents rejection but may promote recurrence of hepatitis C

Background

Routine induction therapy in living donor liver transplantation (LDLT) has not been well described.

Methods

We reviewed outcomes of induction therapy with rabbit antithymocyte globulin (rATG) or basiliximab within 1 year of LDLT.

Results

Between 2002 and 2007, 184 adults underwent LDLT and received induction therapy in addition to standard immunosuppression. Acute cellular rejection (ACR) developed in 17 of 130 patients (13.1%) who received rATG and 13 of 54 patients (24.1%) who received basiliximab (P = .066). The interval between transplantation and rejection as well as rejection severity was similar in patients who received rATG and those who received basiliximab. Hepatitis C (HCV) recurrence requiring initiation of antiviral therapy was more common in patients who received rATG compared with basiliximab (34.5% vs 8.7%; P = .021), and in those who received induction combined with tacrolimus as opposed to cyclosporine (38.5% vs 3.9%; P = .001). rATG and basiliximab were associated with excellent patient and graft survivals well as low rates of opportunistic infections and malignancies.

Conclusion

Induction with rATG or basiliximab was well tolerated and highly effective at preventing ACR within 1 year of LDLT, but may be associated with a higher risk of clinically significant HCV recurrence in some patients.     

Outcomes after anti-thymocyte globulin vs Basiliximab induction before deceased donor kidney transplants

BackgroundDeceased donor kidney transplants represent an important source of renal replacement for the 100 000 patients initiating hemodialysis annually. We compared the association of induction therapy, anti-thymocyte globulin [rabbit] (rATG) or basiliximab, with posttransplant rejection, graft and patient survival.MethodsUsing the United Network for Organ Sharing (UNOS) database, we identified patients that received deceased donor kidney transplants. The outcomes analyzed were 6- month rejection, 1-year rejection, patient survival and graft survival. Multivariate logistic regression models were constructed to understand the association of induction therapy and rejection. Cox-proportional hazards models were constructed to ascertain the association of choice of induction therapy with both patient and graft survival.ResultsOf 45 339 patients, 33 906 patients received rATG induction therapy and 11 433 patients received basiliximab induction therapy. The rATG group were younger (53.44 years vs 55.28 years, P < 0.001), more frequently female (58.74% male vs 66.08%, P < 0.001) and more frequently Black (34.78% vs 25.66%, p < 0.001) compared with patients in the basiliximab group.Rejection was more likely with basiliximab compared with rATG at 6 months(OR = 1.64, P < 0.001; 7.81% Basiliximab vs 5.23% rATG)and at 12 months (OR = 1.56, P < 0.001; 8.81% Basiliximab vs 6.31% rATG). Basiliximab induction therapy was associated with worse patient survival, (HR = 1.05, P = 0.017). Basiliximab induction therapy was associated with worse graft survival, (HR = 1.03, P = 0.037).ConclusionThe analysis of the national experience demonstrated favorable rejection, patient survival, and graft survival with rATG usage. Further prospective data are necessary to provide treatment recommendations.     

Alemtuzumab Induction and Antibody-Mediated Rejection in Kidney Transplantation

BackgroundInduction therapy improves graft outcomes in kidney transplant recipients (KTRs). We aimed to compare the incidences of antibody-mediated rejection (AMR) and acute cellular rejection (ACR) as well as graft and patient outcomes in KTRs who underwent induction with alemtuzumab versus rabbit-antithymocyte globulin (r-ATG).MethodsThis was a single-center retrospective study involving patients who underwent kidney transplantation between January 2009 and December 2011 after receiving induction therapy with either alemtuzumab or r-ATG. Maintenance immunosuppression included tacrolimus and mycophenolate mofetil with early steroid withdrawal. Acute rejection was diagnosed using allograft biopsy.ResultsAmong the 108 study patients, 68 received alemtuzumab and 40 got r-ATG. There was a significantly higher incidence of AMR (15% vs 2.5%; P = .008) and similar incidence of ACR (4.4% vs 10%; P = .69) for alemtuzumab versus r-ATG groups. One-year serum creatinine levels (l.68 ± 0.8 mg/dL vs 1.79 ± 1.8 mg/dL; P = .66) as well as graft (91.1 ± 3.5% vs 94.5 ± 3.8%; P = .48) and patient (93.8 ± 3.0% vs 96.4 ± 3.5%; P = .92) survivals were similar for the alemtuzumab versus the r-ATG groups.ConclusionOur study showed a higher incidence of AMR and similar incidence of ACR in KTRs who underwent induction with alemtuzumab compared with those who received r-ATG and were maintained on tacrolimus and MMF. This was despite a lower HLA mismatch in the alemtuzumab group. One-year graft survival, patient survival, and allograft function were similar. Inadequate B-cell suppression by alemtuzumab as well as altered phenotypic and functional properties of repopulating B cells could be contributing to heightened risk of AMR in these patients.     

Low-dose rabbit antithymocyte globulin versus basiliximab induction therapy in low-risk renal transplant recipients: 8-year follow-up

Antibody induction is effective in preventing acute rejection, but its effects on long-term renal allograft function and survival remain controversial. Moreover, given the risks of antibody induction, full-dose lymphocyte-depleting therapy for low-risk patients is usually avoided. However, the benefit and risks associated with low-dose (Lo) rabbit antithymocyte globulin (rATG; 3-5 mg/kg total) induction in a low-risk population have not been explored. We now report the long-term outcomes in this patient population. We defined low risk as white, panel-reactive antibody < 30%, and non-Donor with Cardiac Death (DCD) recipients. We compared the risk of acute rejection and graft survival for both living donor (LD) and deceased donor (DD) recipients. The average dose of rATG was 3.1 ± 1.2 mg/kg. Forty DD recipients received basiliximab (BSX) and 145 patients were induced with Lo rATG. Twenty LD recipients received BSX and 64 received Lo rATG. The groups did not differ in demographics, donor characteristics, and maintenance immunosuppression. At 8 years, patient survival was higher for LD patients compared to DD recipients (91% vs 45%, P = .004). In recipients of LD kidneys, 8-year patient survivals were not different comparing Lo rATG and BSX groups (92% vs 91%, respectively, P = .55). In LD, 8-year graft survival was excellent irrespective of induction (Lo rATG 100% vs BSX 98%); however, Lo rATG was associated with a lower rate of acute rejection (7.8% vs 35% BSX, P < .01) and better mean serum creatinine at 3 and 5 years (1.2 vs 1.5, P = .02 and 1.18 vs 1.54, P = .04, respectively). For DD, Lo rATG was associated with a better long-term graft survival (86% vs 76% BSX, P = .02). Viral infections and cancer rates were similar for Lo rATG and BSX. Thus, we conclude that Lo rATG induction may add long-term benefit in low-risk patients compared to anti-interleukin-2 receptor therapy without incurring additional risks of infectious or malignant diseases.     

Anti–Angiotensin Type 1 Receptor Antibodies Associated With Antibody-Mediated Rejection in Patients Without Preformed HLA-Donor–Specific Antibody

IntroductionAngiotensin II is a peptide hormone involved in the renin-angiotensin system (RAS). Anti–angiotensin receptor 1 (AT1R) antibodies are implicated in stimulating RAS and are suspected to have some adverse impacts on renal transplantation outcome.MethodsFrom November 2009 to February 2012, 37 remaining sera from renal transplantation recipients with biopsy-proven antibody-mediated rejection (AMR) (n = 6), acute cellular rejection (ACR) (n = 23), and AMR + ACR (n = 8) without preformed human leukocyte antigeon (HLA) antibodies were tested with anti-AT1R antibody assay. Forty-two control patients without rejection also were analyzed.ResultsThe frequency of elevated anti-AT1R antibodies was higher in patients with AMR (n = 14) compared to controls (28.6% vs 4.9%, P = .03, OR = 8.0). It was also higher in patients with AMR + ACR (n=8) (37.5% vs 4.9%, P = .03, OR = 12.0). There was no difference in frequencies of elevated anti-AT1R antibody in patients with ACR.ConclusionAnti-AT1R antibodies were suspected to be associated with occurrence of AMR without preformed HLA antibodies in renal transplantation. Further studies in a larger number of patients are needed.     

Endomyocardial Biopsy and Prevalence of Acute Cellular Rejection in Heart Transplantation

BackgroundPercutaneous endomyocardial biopsy (EMB) remains the criterion standard method for surveillance of allograft rejection after heart transplant (HT). However, data regarding utility of EMBs and prevalence of acute cellular rejection (ACR) in Asian populations are still limited. We aimed to report our experience in the use of EMBs and prevalence of ACR in HT recipients.MethodsWe retrospectively evaluated all EMBs from consecutive HT recipients between January 2008 and December 2018. EMB pathology results were according to International Society for Heart and Lung Transplantation 2004 revision of biopsy grading. We also divided patients into previous era and current era group (underwent HT before and after 2015) to compare prevalence of ACR and survival outcome.ResultsA total of 832 EMBs from 81 HT recipients were included. Pathologic reports revealed ACR grade 1R 22.8%, 2R 4.2%, and 3R 0.6%. At patient level, at least 1 episode of ACR grade 1R, 2R, and 3R were found in 70.6%, 24.7%, and 3.5% of the patients, respectively. When compared between era, frequency of EMB during the first year after HT in current era was significantly higher (9.74 ± 3.38 vs 4.93 ± 3.29, P < .001), but lower frequency of rejection grade ≥ 2R were found (2.3% vs 8.1%, P < .001). However, 1-year survival was not statistically different (76% in previous era vs 80% in current era, P = .37).ConclusionsFrom our study, prevalence of grade ≥ 2R rejection was approximately 5%, which is comparable with previous studies. Further studies are needed to evaluate proper interval and number of EMBs in HT recipients.     

Low-dose thymoglobulin use in elderly renal transplant recipients is safe and effective induction therapy

Current immunosuppressive therapies and protocols have led to significant improvements in early patient and graft survival rates following kidney transplantation. Whether induction therapies such as rabbit anti-thymocyte globulin (rATG) contribute to these improved results remains controversial. Full-dose rATG induction therapy (7-10 mg/kg) has been associated with increased morbidity, which may be especially true in a high-risk population such as the elderly. Therefore, we studied the efficacy and tolerability of a low-dose rATG induction strategy in 45 older recipients (>65 years) compared to 45 concurrently transplanted younger patients (<65 years). Both groups received a similar low-dose of rATG induction therapy (older: 2.96 ± 1.29 vs younger: 3.2 ± 2.11 mg/kg). All patients were maintained on a calcineurin inhibitor, mycophenolic acid, and low-dose prednisone (5 mg/d). To date, none of the older patients experienced acute rejection, whereas one younger patient had an acute rejection episode. Initial hospital stays were equal (older: 7.8 ± 3.2 vs younger: 7.5 ± 4.4 days, P = .35). Within the first 6 months, nine older patients required rehospitalization compared to 15 younger patients (P = .15). Bacterial infections in older and younger recipients were equal including wound (4 vs 0), urine (20 vs 15), lung (1 vs 1), and skin (0 vs 2), respectively. There were two BK viral infections in older patients, whereas there were three viral infections, two cytomegalovirus cases, and one Herpes zoster case in younger patients. Calculated 6-month glomerular filtration rate was equal in both groups (older: 55.7 ± 18.5 vs younger: 52.7 ± 18.5 mL/min). Three-year patient and graft survival rates were equivalent for older and younger patients (86.6% vs 97.6%, respectively). In conclusion, low-dose rATG induction therapy is safe and effective in patients older than 65. When compared to younger patients, low-dose rATG leads to equivalent graft survival and function without incurring excess morbidity in the older population.     

Induction with ATG in DCD kidney transplantation; efficacy and relation of dose and cell markers on delayed graft function and renal function

AimWe aimed to analyse the efficacy of the Thymoglobulin dose used for induction in controlled DCD kidneys, and its initial impact on blood cell and CD3 count, as predictors of efficacy.Methods140 DCD patients who received ATG induction, were analysed. Intended dose was 1.25 mg/kg/day over 5 days, rounded to nearest 25 mg and not exceeding 125 mg/dose. Outcomes included the total dose in relation with rejection, DGF, graft survival, eGFR. The cell count response to ATG was assessed as predictors of outcome.ResultsGraft survival, was 96.2%, 92.4%, 85% at 1, 3 and 5 years. Rejection was 7% at 1 year and associated with eGFR at 3 (p = 0.003) and 5 years. ATG dose was not predictive of rejection but was associated with the day5 leucocyte and lymphocyte count (p < 0.001) and negatively with DGF (p = 0.05). In 31 patients day3 CD3 count was available and it was associated with rejection (p = 0.002), less DGF (p = 0.09), and 3 years eGFR (p = 0.01).ConclusionThymoglobulin provides excellent results in DCD kidneys that do not significantly differ with small dose variations. In higher doses it reduces DGF. Lymphocytes and CD3 count, may be useful surrogate markers of efficacy and outcome.     

Effect of Rabbit Antithymocyte Globulin on Acute and Chronic Active Antibody-Mediated Rejection After Kidney Transplantation

BackgroundRabbit antithymocyte globulin (rATG) induction is associated with reduction in the occurrence of de novo donor-specific antibody (DSA) and antibody-mediated rejection (AMR). Therefore, rATG administration is considered as a treatment for AMR. However, only a few studies have investigated the treatment of AMR with rATG after kidney transplantation.MethodsBetween April 2013 and March 2018, 162 consecutive de novo kidney transplantations were performed with induction immunosuppressive therapy comprising tacrolimus, mycophenolate mofetil, methylprednisolone, and basiliximab. AMR was diagnosed on the basis of the presence of DSA and episode biopsy findings. For DSA-positive recipients, plasmapheresis was performed to remove DSA before rATG administration (1.5 mg/kg for 5 days). Patients treated with rATG against active AMR were retrospectively analyzed for graft function.ResultsA total of 13 kidney transplant recipients developed active AMR within 302 days after transplantation. After rATG administration, the mean serum creatinine and urine protein levels significantly declined from 3.03 mg/dL to 1.68 mg/dL (P = .002) within 46 days and from 3.01 g/gCr to 0.54 g/gCr (P = .006) within 106 days, respectively. The peripheral blood lymphocyte count rapidly decreased after rATG administration and remained low for 12 months. With regard to adverse events, fever (84.6%), cytomegaloviremia (84.6%), thrombocytopenia (61.5%), anemia (30.8%), and neutropenia (15.4%) occurred within 3 months after rATG administration.ConclusionsrATG improved graft function by suppressing peripheral blood lymphocytes in kidney transplant recipients with active AMR. The rATG administration as a treatment for active AMR may contribute to positive graft outcomes after kidney transplantation.     

Calcineurin Inhibitor–Based Maintenance Immunosuppression in Lung Transplant Recipients: Optimal Serum Levels for Managing Acute Rejection and Renal Function

BackgroundAlthough effective for curtailing alloimmune responses, calcineurin inhibitors (CNIs) have an adverse-effect profile that includes nephrotoxicity. In lung transplant (LTx) recipients, the optimal serum levels of the CNI tacrolimus necessary to control alloimmune responses and minimize nephrotoxicity are unknown.MethodsThis retrospective, single-center study reviewed tacrolimus whole blood trough levels (BTLs), grades of acute cellular rejection (ACR), acute rejection scores, and creatinine clearance (CrCl) obtained in LTx recipients within the first year after their transplant procedure. Comparisons were made between the first 90 days post LTx (when tacrolimus BTLs were maintained >10 µg/L) and the remainder of the post-LTX year (when BTLs were <10 µg/L).ResultsDespite tacrolimus mean BTLs being higher during the first 90 days post LTx compared with the remainder of the first post-LTx year (10.4 ± 0.3 µg/L vs 9.5 ± 0.3 µg/L, P < .0001) there was no association with lower grades of ACR (P = .24). The intensity of ACR (as determined by acute rejection scores) did not correlate with tacrolimus mean BTLs at any time during the first posttransplant year (P = .79). During the first 90 days post LTx there was a significant decline in CrCl and a correlation between increasing tacrolimus mean BTLs and declining CrCl (r = −0.26, P = .03); a correlation that was not observed during the remainder of the year (r = −0.09, P = .52).ConclusionsIn LTx recipients, maintaining BTLs of the CNI tacrolimus >10µg/L did not result in superior control of acute rejection responses but was associated with declining renal function.     

Influence of Interferon Gamma +874 T>A (rs2430561) Polymorphism on Renal Allograft Rejection: A Meta-analysis

BackgroundReported associations of the interferon gamma (IFNG) +874T/A (rs2430561) polymorphism with post-kidney transplantation allograft rejection (AR) have been inconsistent, prompting a meta-analysis to obtain more precise estimates.MethodsEighteen articles (22 studies) were included in the meta-analysis. Operating on the hypothesis that IFNG rs2430561 either increases or reduces AR risk, we used a genetic model-free approach to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Subgrouping was based on ethnicity (white, Middle Eastern, black, and mixed) and rejection type (ACR: acute rejection and CHR: chronic rejection). Quality of the associative effects was assessed with sensitivity treatment and test for publication bias.ResultsThe overall analysis in the dominant model indicated increased risk (OR = 1.26; P^a = .02) was validated in the ACR subgroup (OR = 1.29; P^a = .01), which contrasted with the CHR subgroup, with a nonsignificant effect indicating reduced risk (OR = 0.83; P^a = .68). Only the black subgroup showed significant increased risk (OR = 2.87; P^a = .04), but the association was tenuous on account of low sample size (n = 2) and imprecise effect (95% CI, 1.07-7.73).ConclusionsIncreased risk associations (overall and ACR) of IFNG rs2430561 with AR is significant, robust, statistically powered, and lacking bias. Contrasting ACR (1.3-fold increased risk) and CHR (7% protective) effects may be clinically relevant in the genetics of renal transplantation.     

High tacrolimus trough level variability is associated with rejections after heart transplant

Tacrolimus, the major immunosuppressant after heart transplant (HTx) therapy, is a narrow therapeutic index drug. Hence, achieving stable therapeutic steady state plasma concentrations is essential to ensure efficacy while avoiding toxicity. Whether high variability in steady state concentrations is associated with poor outcomes is unknown. We investigated the association between tacrolimus trough level variability during the first year post‐HTx and outcomes during and beyond the first postoperative year. Overall, 72 patients were analyzed for mortality, of whom 65 and 61 were available for rejection analysis during and beyond the first year post‐HTx, respectively. Patients were divided into high (median >28.8%) and low tacrolimus level variability (<28.8%) groups. Mean tacrolimus levels did not differ between the groups (12.7 ± 3.4 ng/mL vs 12.8 ± 2.4 ng/mL, P = .930). Patients in the high variability group exhibited higher long‐term rejection rate (median total rejection score: 0.33 vs 0, P = .04) with no difference in rejection scores within the first year post‐HTx. Multivariate analysis showed that high tacrolimus trough level variability was associated with >8‐fold increased risk for any rejection beyond the first year post‐HTx (P = .011). Mortality was associated only with cardiovascular complications (P = .018), with no effect of tacrolimus through level variability.     

Basiliximab is associated with a lower incidence of De novo donor-specific HLA antibodies in kidney transplant recipients: A single-center experience

PurposeInduction immunosuppression has improved the long-term outcomes after kidney transplant. This study explores the association of different induction immunosuppression medications (Basiliximab vs. Alemtuzumab vs. rabbit Antithymocyte Globulin) used at the time of kidney transplant with the development of de novo donor-specific HLA antibodies (DSA) in the first 12 months post-transplant period.MethodsA total of 390 consecutive kidney transplant recipients (KTR), between 2016 and 2018, were included in the analysis. A 104 (26.6%) received Basiliximab, 186 (47.6%) received Alemtuzumab, and 100 (25.6%) received rabbit Antithymocyte Globulin (rATG) for induction. All recipients had a negative flow cytometry crossmatch before transplant. Serum samples at 4- and 12-months post-transplant were assessed for the presence of de novo HLA DSA. kidney allograft function was compared among the three groups with calculated Creatinine Clearance on 24 h urine collection.ResultsDe novo HLA DSA were detected in total of 81 (20.8%) patients within 12 months post-transplant. De novo HLA DSA were detected in 12/104 (11.5%), 43/186 (23.11%), and 26/100 (26%) KTR that received Basiliximab, Alemtuzumab, and rATG respectively (p = 0.006). KTR that received Basiliximab were significantly older, and the last follow-up creatinine clearance was significantly lower at 42 ml/min compared to KTR that received Alemtuzumab or rATG (p = 0.006).ConclusionInduction immunosuppression utilizing Basiliximab is associated with significant reduction in development of de novo DSA within the first 12-months post kidney transplant but had lower creatinine clearance with long-term follow up.     

Comparison of alemtuzumab vs. antithymocyte globulin induction therapy in primary non‐sensitized renal transplant patients treated with rapid steroid withdrawal

Alemtuzumab and rabbit antithymocyte globulin (rATG) are commonly used for induction therapy in renal transplantation. This retrospective, single‐center, cohort study evaluated cumulative incidence of one‐yr biopsy‐proven acute rejection (BPAR) among 200 consecutive primary non‐sensitized kidney transplant recipients who received either alemtuzumab (n = 100) or rATG (n = 100) induction followed by rapid steroid taper, tacrolimus, and mycophenolate mofetil. Protocol biopsies, plasma and urine BK virus PCR, serum creatinine and iothalamate glomerular filtration rate (iGFR), were obtained at 1, 4, and 12 months from transplantation. The one‐yr BPAR rates were similar between the alemtuzumab and rATG groups; however, rejection Banff IA and higher was more common in the alemtuzumab arm (18% vs. 5%, p = 0.047). After adjusting for confounding variables, alemtuzumab was still associated with Banff IA and higher rejection (adjusted OR: 3.7, CI: 1.2–10.5, p = 0.02). Despite similar rates of BK viremia, more patients in the alemtuzumab arm developed BK nephropathy (16% vs. 3%, p = 0.046). One‐year iGFR (53.4 ± 20.2 vs. 71.9 ± 27.2 mL/min/1.73 m², p = 0.002) and three‐yr graft survival (89.5% vs. 95%, p = 0.05) were lower in the alemtuzumab group. In low immunological risk kidney transplant recipients on steroid‐free immunosuppression, alemtuzumab was associated with more severe rejection and BK nephropathy compared to rATG.     

Effect of everolimus initiation and early calcineurin inhibitor withdrawal on myocardial FOXP3 + regulatory T cells in heart transplantation

BackgroundThrough immunosuppression CD4 + FoxP3 + regulatory T-cells (Tregs) play an indispensable role in allograft rejection. Post-HTx treatment with everolimus is associated with slower progression of cardiac allograft vasculopathy (CAV) – chronic rejection – than CNI based therapy. We hypothesized treatment with everolimus reduced the risk of CAV by modulating myocardial FoxP3 levels.Methods15 patients from the Schedule trial comparing everolimus, MMF, steroid and early CNI (Everolimus, n = 8) withdrawal to conventional CNI based immunosuppression (Controls, n = 7) after de novo HTx were included and FoxP3 + cells were quantified in 56 endomyocardial biopsies, and compared in the two patient groups. CAV was evaluated invasively using coronary intravascular ultrasound (IVUS).ResultsBaseline FoxP3 biopsy levels were similar in the two groups. The Everolimus group showed a significant increase in Foxp3 densities from baseline to time of one-year follow-up (median (IQR) = 4.8 × 10^− 7(20.4) Tregs/μm², P = 0.046) while Controls showed no significant change (median (IQR) = 3.1 × 10^− 7(6.5) Tregs/μm², P = 0.116). At 1-month follow-up FoxP3 densities correlated with the observed change in TAV from baseline to time of 1-year follow-up (r = 0.641, P = 0.034). FoxP3 densities at 1-week predicted acute cellular rejection (ACR) levels at 1 month (P = 0.026). No other correlations with ACR were found.ConclusionEverolimus treatment combined with early CNI elimination is associated with increased densities of Tregs 12-months post-HTx compared to patients receiving CNI based regimen. Furthermore, the density of myocardial FoxP3+ cells early after transplantation appears to predict at least one measure of CAV burden after one year.     

Retreatment by antithymocyte globulin for second kidney transplantation: Efficacy,tolerance and safety

BackgroundIt is unknown whether kidney transplant patients who receive rabbit antithymocyte globulin (rATG) become immunized against rabbit antibodies, leading to reduced efficacy, or are at higher risk of cytomegalovirus infection or post-transplant lymphoproliferative disorder (PTLD) on retreatment. The efficacy and tolerance of rATG when used as induction for the second time in patients undergoing retransplantation have not been evaluated.MethodsIn a retrospective case–control study, 54 retransplanted patients who received rATG (Thymoglobulin) induction for the second time during 2004–2010 were compared to a matched cohort of 108 patients receiving rATG induction for a first kidney transplantation during the same period. Maintenance treatment was similar in both groups.ResultsMedian follow-up was 45.8 months and 47.3 months in the second and first treatment groups, respectively. No differences were observed between the two groups in terms of leukocyte, lymphocyte or platelet depletion. Dose and duration of rATG treatment were similar in both groups, suggesting a similar tolerance profile. Cytomegalovirus infection (including primoinfection and reactivation) occurred in 4/54 retreated patients versus 22/108 controls (p = 0.108). Use of cytomegalovirus prophylaxis was similar between groups. PTLD occurred in one control patient and no retreated patients.ConclusionA second course of rATG induction results in similar lymphocyte depletion and is as well tolerated as a first course. The incidence of cytomegalovirus infection and post-transplant lymphoproliferative disease was not increased during retreatment. Further studies are required to evaluate specific T cell subpopulation depletion and compare long-term outcome in patients receiving a second induction with rATG.     

Impact of Immunosuppressive Strategies on Post–Kidney Transplantation Thrombocytopenia

BackgroundThrombocytopenia after kidney transplantation is a common complication, partly induced by immunosuppressive therapies. Peritransplant thrombocytopenia may cause serious hemorrhages. We assessed the incidence of early posttransplantation thrombocytopenia (defined as a platelet count of <150,000 mm³ or <150 G/L) in de novo kidney transplant recipients (KTRs) across 4 immunosuppressive regimens.MethodsThis was a single-center observational study that included all consecutive KTRs who received either Thymoglobulin (THY) or Grafalon (GRA) and maintenance therapy of either mycophenolate-mofetil (MMF) or everolimus (EVR), associated with tacrolimus/corticosteroids.ResultsBetween July 27, 2016, and September 7, 2018, 237 KTRs were included; 64.6% experienced thrombocytopenia within the first week. Thrombocytopenia was significantly more frequent (P = .004) among GRA-treated patients (73.4%) compared to THY-treated patients (61.3%). These patients also had lower nadir platelet count (120 ± 52 vs 142 ± 48 G/L; P = .002) and lower platelet count at discharge (227 ± 94 vs 243 ± 92 G/L; P = .25). More of the GRA-EVR group had thrombocytopenia (81.0% vs 61.4% in THY-MMF, 60.9% in THY-EVR, and 69.8% in GRA-MMF; P = .081) and a worse nadir platelet count (109 ± 41 in GRA-EVR vs 141 ± 47G/L in THY-MMF, 145 ± 52 G/L in THY-EVR, and 125 ± 56 G/L in GRA-MMF; P = .011) but GRA was the only risk factor for thrombocytopenia in multivariate analyses (P = .002). Rates of hemorrhage, red blood cell transfusions, reoperations needed within the first week, delayed graft function, acute rejection, graft loss, and death did not differ between the groups after a mean follow-up of 25 ± 8 months.ConclusionsGRA associated with EVR led to more frequent and severe thrombocytopenia, although we found no significant clinical consequences.     

Association of the Number of HLA-DR Mismatches With Early Post-transplant Acute Cellular Rejection Among Heart Transplantation Recipients: A Cohort Study in Japanese Population

Background

Although many risk factors are reported about graft rejection after heart transplantation (HTx), the effect of HLA mismatch (MM) still remains unknown, especially in the Japanese population. The aim of the present study was to investigate the influence of HLA MM on graft rejection among HTx recipients in Japan.