Steroid-free Immunosuppression Research Articles

Incidence and Outcomes of BK Virus Nephropathy in Kidney Transplant Recipients With Steroid-Free Maintenance Immunosuppression

BackgroundBK virus nephropathy (BKVN) is a significant complication in kidney transplant recipients, resulting in graft dysfunction and potentially leading to graft loss. This study aims to investigate the incidence and outcomes of BKVN in kidney transplant recipients receiving steroid-free maintenance immunosuppression in a Latin -American cohort. MethodsCase series study of BKVN among kidney transplant recipients who underwent transplantation between 2008 and 2023. The primary outcome was graft loss caused by BKVN, excluding death with function. Secondary outcomes included graft function and acute rejection episodes. The statistical analysis involved descriptive statistics and the Kaplan-Meier (K-M) method to plot the overall probabilities of not initiating dialysis. ResultsDuring the 15-year period, 2236 kidney transplants were performed, BKVN was histologically diagnosed in 38 kidney recipients and 33 cases were analyzed. Median age was 50 years and men were 48.5% of patients. A total of 45.4% of BKVN occurred within the first 12 months of transplant. The incidence of BKVN was 1.6% but it varied by era. The rate of graft loss was 75.7% (25 cases). The K-M graft survival probability at 6 months and 12 months after diagnosis of BKVN was 38.3% (95% CI 24.7–59.4) and 22.3% (95% CI 11.7–42.8), respectively. ConclusionBKVN affected 1.6% of transplant recipients and it was associated with high-rate of graft loss. We observed that significant graft disfunction at the time of diagnosis resulted in worse outcomes with a reduced probability of graft survival.

Chronic Kidney Disease and Growth Failure in Children.

Chronic kidney disease (CKD) is a significant challenge for pediatric endocrinologists, as children with CKD may present a variety of endocrine complications. Growth failure is common in CKD, and its severity is correlated with the degree of renal insufficiency. Management strategies include addressing reversible comorbidities, optimizing nutrition, and ensuring metabolic control. Kidney replacement therapy, including transplantation, determines a significant improvement in growth. According to a recent Consensus Statement, children with CKD stage 3-or on dialysis older >6 months-are eligible for treatment with recombinant growth hormone (rGH) in the case of persistent growth failure. Treatment with rGH may be considered for those with height between the 3rd and 10th percentile and persistent growth deceleration. In children who received kidney transplantation but continue to experience growth failure, initiation of GH therapy is recommended one year post-transplantation if spontaneous catch-up growth does not occur and steroid-free immunosuppression is not an option. In children with CKD, due to nephropathic cystinosis and persistent growth failure, GH therapy should be considered at all stages of CKD. Potential adverse effects and benefits must be regularly assessed during therapy. Treatment with GH is safe in children with CKD. However, its general efficacy is still controversial. All possible problems with a negative impact on growth should be timely addressed and resolved, whenever possible with a personalized approach to the patient. GH therapy may be useful in promoting catch-up growth in children with residual growth potential. Future research should focus on refining effective therapeutic strategies and establishing consensus guidelines to optimize growth outcomes in this population.

Long-term outcomes of two-dose alemtuzumab induction in pediatric kidney transplantation.

Alemtuzumab is a lymphocyte depleting agent used for induction in kidney transplant, but long-term information on its use in pediatric recipients remains sparse. We performed a single-center retrospective cohort study of 57 pediatric kidney transplant recipients receiving alemtuzumab 20 mg/m2/dose ×2 doses for induction immunosuppression. All patients underwent surveillance biopsies, and 91.3% underwent steroid withdrawal by day 4 post-transplant. Outcomes of interest included graft survival, development of donor specific antibodies (DSA), incidence of viremia and PTLD, and duration of lymphopenia. Median follow-up time was 7.9 years (IQR 5-13.6 years). Median graft survival was 16.5 years (95% CI 11.6-unknown). DSA developed in 36.5% at a median of 944 days (IQR 252-2113 days). Incidences of BK polyomavirus DNAemia (BKPyV-DNAemia), CMV DNAemia, and EBV DNAemia were 38.6%, 22.8%, and 14%, respectively; one patient developed PTLD at 13.3 years post-transplant. Median duration of lymphopenia was 365 days (IQR 168-713 days); 19.3% of patients remained lymphopenic at 3 years post-transplant. There was no association between duration of lymphopenia and graft survival, rejection, DSA detection, or viremia. A two-dose alemtuzumab induction protocol can have excellent outcomes with a steroid-free maintenance immunosuppression regimen. More comprehensive, multicenter, comparative studies of pediatric kidney transplant are needed to improve long-term outcomes.

Basiliximab Induction and Postoperative Steroid-free Immunosuppression With Tacrolimus in Pediatric Liver Transplantation: A Randomized Clinical Trial.

Optimizing the immunosuppressive regimen is essential to improve the long-term outcomes of pediatric liver transplant recipients. We conducted a prospective, randomized, open-label study to compare the safety and efficacy of 2 treatment approaches during pediatric liver transplantation: tacrolimus monotherapy following basiliximab induction (the study group) and a dual regimen of tacrolimus plus steroids (the control group). A total of 150 patients were enrolled, with 75 patients allocated to each group. In both groups, recipients achieved graft and recipient overall survival rates exceeding 93%, with no statistically significant differences between them. However, the study group exhibited a significantly lower incidence of acute cellular rejection (ACR), delayed occurrence of ACR, and an improved ACR-free survival rate at 2 y compared with the control group. Notably, the study group also showed a significant reduction in the incidence of de novo donor-specific antibodies at 3-mo and 2-y posttransplant. Furthermore, 6 mo after the transplant, the study group demonstrated significant improvements in weight-for-age Z score and height-for-age Z score. No notable differences were observed in postoperative complications or the incidence of liver fibrosis between the 2 groups. Basiliximab induction combine with tacrolimus (TAC) monotherapy is a safe and effective immunosuppressive regimen to reduce the episodes of ACR without influencing the development of liver fibrosis and graft and recipient survival rate after pediatric liver transplantation.

Pancreatic Exocrine Secretion and Weight Gain After Pancreas Transplantation.

Weight gain after pancreas transplant is a poorly understood phenomenon thought to be related to increased posttransplant insulin production, immunosuppressive medications, and appetite changes. No study has investigated the effect of increased exocrine secretion posttransplant. We hypothesized that exocrine function, measured by fecal elastase-1 (FE-1), was normal posttransplant and not correlated with weight gain. Our primary aim was to investigate changes in FE-1 levels with pancreas transplantation and to correlate this with weight gain. Establishing weight trends and identifying additional correlating factors were secondary aims. Forty-two patients that underwent simultaneous pancreas and kidney or pancreas after kidney transplant at a single center between 2013 and 2021 were included. Fecal elastase was measured prospectively in each patient at a single time point, with >500 µg/g categorized as high. Weight and C-peptide values were obtained. All the patients were on steroid-free immunosuppression. Nineteen patients (45%) had fecal elastase levels >500 µg/g, with a maximum of 3910 µg/g; 43% had levels greater than twice the upper limit of normal. The biggest increase in weight occurred between years 1 and 2, which continued to a median weight gain of 14% at 3 years. There was no correlation between weight gain and FE-1, pretransplant C-peptide levels, or duration of diabetes. This study demonstrated supranormal fecal elastase levels and weight gain posttransplant; however, there was no correlation. Future study with serial FE-1 before and after transplant is needed to better assess its correlation with weight gain.

Feasibility of steroid-free tacrolimus-basiliximab immunosuppression in pediatric liver transplantation and predictors for steroid requirement.

Avoidance of steroids in pediatric liver transplantation may reduce toxicity and morbidity. The aim of this study was to analyze the feasibility of a steroid-free tacrolimus-basiliximab immunosuppression scheme, the risk factors associated with steroid requirement, and safety parameters. Patients who underwent liver transplantation for biliary atresia between 2011 and 2019 were included and followed for 6 months after transplantation. Immunosuppression consisted of tacrolimus-based treatment with basiliximab induction. Steroid-free survival was estimated, and risk factors for steroid requirement were evaluated using multivariate Cox regression analysis. A total of 76 patients were included, of whom 42 (55.3%) required steroids (>14d) due to biopsy-proven acute rejection (47.6%, n = 20), instability in liver function tests (35.7%, n = 15), tacrolimus-related adverse drug reactions (14.3%, n = 6), or other reasons (bronchospasm episode, n = 1). Steroid-free survival was 45.9% (95% CI, 35.9-58.8). Independent factors associated with steroid requirement included tortuosity in tacrolimus trough levels (≥1.76 vs. <1.76: HR 5.8, 95% CI, 2.6-12.7; p < 0.001) and mean tacrolimus trough levels (≥ 6.4ng/mL vs. < 6.4ng/mL: HR 0.4, 95% CI, 0.2-0.7; p = 0.002). The rate of bacterial and viral infections was comparable between patients with and without steroids, although in the former group, cytomegalovirus infection developed earlier ( p = 0.03). Patients receiving steroids had higher total cholesterol, LDL, and HDL levels ( p < 0.05) during follow-up, but no changes in the height Z-score were observed 1 year after transplantation. Basiliximab induction in combination with tacrolimus-based treatment avoided steroid requirements in 45% of the patients. Tacrolimus variability and trough levels below 6.4ng/mL independently increased the risk of steroid requirement. Further efforts should be focused on personalizing immunosuppressive treatment.

#3962 BALANCING THE RISK OF ALLOIMMUNITY WHILE MINIMIZING IMMUNOSUPPRESSIVE THERAPY: A RETROSPECTIVE STUDY OF PAEDIATRIC KIDNEY TRANSPLANT RECIPIENTS

Abstract Background and Aims Kidney transplantation is the best treatment for end-stage kidney disease, but life with a kidney allograft comes with significant challenges. Many paediatric kidney transplant recipients (KTRs) experience side effects from immunosuppressive medication. Reducing the medication is often necessary, but the reduction comes with a risk of inducing alloimmunity. We aimed to describe the alteration in immunosuppressive medication after kidney transplantation, the reasons for the reductions, and the possible impact on alloimmunity. Method 49 paediatric KTRs aged 1-16 years, receiving a kidney allograft from 2009 to 2020 in a Danish single centre were retrospectively studied. The standard protocol for immunologically low risk KTRs was steroid-free immunosuppression with basiliximab as induction, tacrolimus and mycophenolate mofetil (MMF) as maintenance therapy. KTRs were screened for anti-HLA antibodies with mixed and single bead antigen kits. We defined reduced immunosuppression as a KTR receiving one; OR two immunosuppressive medications AND MMF below 600 mg/m2. Results 49 KTRs received a kidney allograft, two were ABO incompatible transplantations and six KTRs had pretransplant donor specific antibodies. The median age of the KTRs was 11 years (IQR 8), with a median follow-up time of 5 years (IQR 5). In total, 78% KTRs received standard immunosuppressive therapy (steroid free). 5-year death censored (one KTR died) graft survival was 88%, and the cumulative incidence of rejection was 4% (95% CI: -1.5; 5.5) within the first year. None of the six graft losses were related to alloimmunity. 11.4% developed de novo donor specific antibodies (dnDSA) within a median of 3.91 years (IQR 2.28; range: 2.22-9.20) from transplantation. At transplantation, 6% received reduced immunosuppressive medication increasing to 74% at year one. Immunosuppression (primarily MMF) remained reduced in most of the KTRs during follow-up (Figure 1). Side effects predominantly to MMF led to the reduction. Leukopenia caused a reduction in 77%, gastrointestinal side effects in 34%, EBV in 19% (two KTRs developed PTLD), CMV in 15%, and BK polyomavirus in 15%. The reduction was significantly more pronounced in KTRs under 11 years (87% vs. 61%, p-0.044). Tacrolimus seemed well tolerated and was sufficiently regulated according to a target through of five microg/L two months after transplantation (Figure 2). Conclusion Despite 74% of the KTRs receiving reduced immunosuppressive medication according to our protocol, the rejection rate was low, the graft survival was comparable to European reports, and only 11% developed dnDSA during follow-up. Scheduled reduction of MMF shortly after transplantation could decrease the adverse side effects and improve the treatment of paediatric KTRs.

Cold Ischemia Time and Graft Fibrosis Are Associated with Autoantibodies after Pediatric Liver Transplantation: A Retrospective Cohort Study of the European Reference Network TransplantChild.

The reported prevalence of autoantibodies (AAB) (ANA, SMA, LKM, SLA) after pediatric liver transplantation (pLTX) varies considerably from 26–75%, but their clinical impact on outcome is uncertain. We aimed to study the prevalence of AAB after pLTX, their association with donor-, transplant-, and recipient-characteristics, and their relation to outcome. In our multicenter retrospective study, we aimed to clarify conflicting results from earlier studies. Six ERN TransplantChild centers reported data on 242 patients, of whom 61% were AAB positive. Prevalence varied across these centers. Independent of the interval between pLTX and AAB analysis, a one-hour increase in CIT resulted in an odds ratio (OR) of 1.37 (95% CI 1.11–1.69) for SMA positivity and an OR of 1.42 (95%CI 1.18–1.72) for ANA positivity. Steroid-free immunosuppression (IS) versus steroid-including IS (OR 5.28; 95% CI 1.45–19.28) was a risk factor for SMA positivity. Liver enzymes were not associated with ANA or SMA positivity. We did not observe an association of rejection activity index with ANA or SMA. However, the liver fibrosis score in follow-up biopsies was associated with ANA titer and donor age. In conclusion, this first multicenter study on AAB after pLTX showed high AAB prevalence and varied widely between centers. Longer CIT and prednisolone-free-IS were associated with AAB positivity, whereas AAB were not indicative of rejection, but instead were associated with graft fibrosis. The detection of AAB may be a marker of liver fibrosis and may be taken into consideration when indications for liver biopsy and immunosuppressive regimes, or reduction of immunosuppression in long-term follow-up, are being discussed. Prospective immunological profiling of pLTX patients, including AAB, is important to further improve our understanding of transplant immunology and silent graft fibrosis.

Outcomes of granulocyte colony-stimulating factor use in pediatric kidney transplant recipients: A Pediatric Nephrology Research Consortium study.

Neutropenia is common in the first year after pediatric kidney transplant and is associated with an increased risk of infection, allograft loss, and death. Granulocyte colony-stimulating factor (G-CSF) increases neutrophil production, but its use in pediatric solid organ transplant recipients remains largely undescribed. We performed a multicenter retrospective cohort study of children with neutropenia within the first 180days after kidney transplant. Multivariable linear regression and Poisson regression were used to assess duration of neutropenia and incidence of hospitalization, infection, and rejection. Of 341 neutropenic patients, 83 received G-CSF during their first episode of neutropenia. Median dose of G-CSF was 5mcg/kg for 3 (IQR 2-7) doses. G-CSF use was associated with transplant center, induction immunosuppression, steroid-free maintenance immunosuppression, hospitalization, and decreases in mycophenolate mofetil, valganciclovir, and trimethoprim-sulfamethoxazole dosing. Absolute neutrophil count nadir was also significantly lower among those treated with G-CSF. G-CSF use was not associated with a shorter duration of neutropenia (p=.313) and was associated with a higher rate of neutropenia relapse (p=.002) in adjusted analysis. G-CSF use was associated with a decreased risk of hospitalization (aIRR 0.25 (95%CI 0.12-0.53) p<.001) but there was no association with incidence of bacterial infection or rejection within 90days of neutropenic episode. G-CSF use for neutropenia in pediatric kidney transplant recipients did not shorten the overall duration of neutropenia but was associated with lower risk of hospitalization. Prospective studies are needed to determine which patients may benefit from G-CSF treatment.

946. Epidemiology and Long-term Outcomes of BK Polyomavirus Nephropathy in Kidney Solid Organ Transplant Recipients at Texas Children’s Hospital

BackgroundBK Polyomavirus (BKPyV) is an important cause of graft dysfunction and premature graft failure in pediatric kidney transplant recipients (PKTR). Contemporary data on BK viral associated nephropathy (BKVAN) in PKTR are limited. We sought to determine the frequency, associations with, and long-term outcomes of BKVAN in PKTR.MethodsA retrospective cohort study of PKTR ≤21 years of age transplanted from 2011-2018 was completed. Primary outcome was BKVAN and secondary outcomes included graft dysfunction and failure. Associations with BKVAN were measured using chi square and Fisher exact tests. Time to BKVAN and graft failure were assessed using Kaplan-Meier plots. ResultsAmong 200 PKTR, 16 (8%) developed BKVAN at a median of 228 days post-transplant. Median (IQR) age at time of transplant for patients with BKVAN was 14 (7-17) years of age. Of those who developed BKVAN, 13/16 (81%) were biopsy proven, 2/16 (13%) were probable and 1/16 (6%) was presumptive. Treatment of BKVAN included reduced immunosuppression (12, 75%), ciprofloxacin (11, 69%), intravenous immunoglobulin (7, 44%), and leflunomide (4, 25%). Simultaneous rejection therapy occurred in two patients (13%). Notably, three patients with BKVAN had negative BKPyV plasma viral loads. Median (IQR) BKPyV viral load in those with positive PCRs was 82,000 (19,315 – 1,106,283) copies/milliliter. Median (IQR) time to clearance of BKPyV from the plasma was 425 (261 – 858) days. There was no association between age at time of transplant, repeat kidney transplant, donor type, underlying diagnosis at time of transplant, HLA mismatch, mode of dialysis, or steroid free immunosuppression and the development of BKVAN. Mean percent change in eGFR yearly post-transplant was -0.066 for those with BKVAN versus -0.091 for those without BKVAN (p=0.35). Graft failure was experienced in 1/16 (6%) PKTR with BKVAN but was not related to BKVAN. There was no difference in time to graft failure (Figure 1, p=0.64) in those who developed BKVAN versus those who did not. ConclusionBKVAN continues to occur in PKTR. No associations were found with the development of BKVAN in our cohort. PKTR with BKVAN did not have an increased rate of eGFR decline nor did they develop graft failure more quickly than those without BKVAN. Disclosures Sarah J. Swartz, MD, Education grant sponsored by Amgen; awarded by Renal Physicians Association (Other Financial or Material Support, Attended Renal Physician Association PAL (Pediatric Advocacy Leadership) Forum in Jun 2019; Program sponsored by Education grant from Amgen, awarded by the Renal Physicians Association for participation)Vifor Fresensius Medical Care Renal Pharma (Scientific Research Study Investigator, Multi-center site PI for phase 3 study to investigate the safety and efficacy of PA21 (Velphoro) and calcium acetate (Phoslyra) sponsored by Vifor Fresensius Medical Care Renal Pharma funded Sept 2016-Oct 2019)

Patient and Graft Survival Outcomes During 2 Eras of Immunosuppression Protocols in Kidney Transplantation: Indiana University Retrospective Cohort Experience

Since 1964 when Indiana University performed its first kidney transplant, immunosuppression protocol was steroid-based until 2004 when steroid-free immunosuppression protocol was adopted. We describe clinical outcomes on our patients administered early steroid withdrawal (ESW) protocol (5 days) compared with our historical cohort (HC), who were on chronic steroid-based immunosuppression. We performed a retrospective study evaluating kidney transplant recipients between 1993 and 2003 (HC, n=1689) and between 2005 and 2016 (ESW cohort, n=2097) at the Indiana University program, with a median follow-up of 10.5 years and 6.1 years, respectively. Primary outcomes were patient and death-censored graft survival at 1, 3, and 5 years in both study cohorts. Secondary outcomes were 1-year rates of biopsy-proven acute rejection; graft function at 1, 3, and 5 years; and risk of post-transplant infection (BK virus and cytomegalovirus) in the ESW cohort. Cox proportional model and Kaplan-Meier estimates were used to estimate survival probabilities. Fisher exact tests were used to compare episodes of acute rejection in the ESW cohort. No difference was observed in patient survival between the ESW and HC cohorts (P=.13). Compared with the ESW cohort, death-censored graft survival was significantly worse in the HC (5 year: 86.4% vs 90.6%, log-rank P < .001). One-year acute rejection reported in the ESW cohort alone was 15.7% and significantly worse in Black patients and younger patients (P < .05). In this sizeable single-center cohort study with significant ethnic diversity, ESW is a viable alternative to steroid-based immunosuppression protocol in kidney transplant recipients.

Steroid-free maintenance immunosuppression using alemtuzumab in pediatric kidney transplantation: Long-term longitudinal follow-up.

There is a scarcity of long-term data on steroid-free immunosuppression using alemtuzumab in pediatric kidney transplantation (KTx). This study examines long-term outcomes with alemtuzumab without steroid maintenance therapy in pediatric KTx. From July 2005 to June 2015, 71 pediatric KTx recipients received alemtuzumab without steroid maintenance. They were followed from 4.1 to 14.1years post KTx. Patient survival: One child expired with a functioning graft from post-transplant lymphoproliferative disorder (PTLD). Patient survival was 98.6%. Graft survival: Eighteen grafts were lost (16 from chronic rejection). Graft survival at 5 and 10years was 92.3% and 61.3%, respectively. Rejection: Twenty-three (32.4%) patients were free from T-cell-mediated rejection (TCMR), 16 (22.5%) had >3 episodes. Sixteen (22.5%) were treated for antibody-mediated rejection (AMR). Infection: Twenty-three children developed Epstein-Barr virus (EBV), 5 developed cytomegalovirus (CMV), and 20 developed BK virus infection. Four (5.6%) developed PTLD. Twenty-two (31.0%) required treatment for neutropenia. Growth parameters: Mean height and weight increased by 0.56 and 0.69 SDS (standard deviation score), respectively. Body mass index increased by 5.1kg/m2 at 10years. Less than 40% required antihypertensive medications at all-time points. Alemtuzumab, without corticosteroid maintenance, offers 98.6% patient survival at 14years with five and 10-year graft survival of 92.3% and 61.3%, respectively. TCMR and AMR requiring treatment were 67.4% and 22.5%, respectively. CMV, EBV, and BK viremia rates were 7.0%, 32.4%, and 28.2%, respectively. Thirty-one percent were treated for neutropenia; 5.6% developed PTLD. There were improvements in growth parameters and blood pressure.

Does steroid-free immunosuppression improve the outcome in kidney transplant recipients compared to conventional protocols?

Steroids continue to be the cornerstone of immune suppression since the early days of organ transplantation. Steroids are key component of induction protocols, maintenance therapy and in the treatment of various forms of rejection. Prolonged steroid use resulted in significant side effects on almost all the body organs owing to the presence of steroid receptors in most of the mammalian cells. Kidney allograft recipients had to accept the short and long term complications of steroids because of lack of effective alternatives. This situation changed with the intro-duction of newer and more effective immune suppression agents with a relatively more acceptable side effect profile. As a result, the clinicians have been contemplating if it is the time to abandon the unquestionable reliance on maintenance steroids in modern transplantation practice. This review aims to evaluate the safety and efficacy of various steroid-minimization approaches (steroid avoidance, early steroid withdrawal, and late steroid withdrawal) in kidney transplant recipients. A meticulous electronic search was conducted through the available data resources like SCOPUS, MEDLINE, and Liverpool University library e-resources. Relevant articles obtained through our search were included. A total number of 90 articles were eligible to be included in this review [34 randomised controlled trials (RCT) and 56 articles of other research modalities]. All articles were evaluating the safety and efficacy of various steroid-free approaches in comparison to maintenance steroids. We will cover only the RCT articles in this review. If used in right clinical context, steroid-free protocols proved to be comparable to steroid-based maintenance therapy. The appropriate approach should be tailored individually according to each recipient immuno-logical challenges and clinical condition.

1396. Live Virus Vaccination Following Pediatric Liver Transplantation: Results from Two Academic Children’s Hospitals

BackgroundGuidelines for immunization following solid organ transplantation discourage live virus vaccination (LVV) in most recipients. Single-center studies support LVV as safe and effective in orthotopic liver transplant (OLT) recipients on steroid-free immunosuppression (IS). We retrospectively evaluated LVV after OLT at 2 pediatric hospitals.MethodsRecords from OLT recipients between Jan 2007 and Dec 2017 at Lurie Children’s (Chicago) and Children’s Hospital of Philadelphia were reviewed. Patients who underwent OLT at either institution, had ≥ 2 years of follow up, and had documentation of vaccination prior to OLT were included. Adverse events (AEs) within two weeks of receipt of LVV were captured. Factors that might influence the selection of patients for LVV were reviewed, including choice, dose, frequency, and levels of IS medications. IS in non-vaccinated patients was compared to vaccinated patients at two year post-transplant follow-up in both groups using Chi-Square and T-test.ResultsData from 249 patients met inclusion criteria. Varicella zoster (VZV) vaccine was given at least once to 92 patients post-transplant, and MMR to 91 (Table 1). Compared to patients who were re-vaccinated after transplant, those who received their first LVV after OLT were transplanted at a younger age (0.8 v 2.2 years) and received LVV sooner post-OLT (649 v 907 days). AEs were rare for either LVV: 2 experienced injection site reaction, 2 localized rash, and 1 had fever. One recipient experienced worsening rejection one month after MMR and received IV steroids and increased IS, but had no clinical findings concerning for viral infection from vaccination. Most LVV recipients were on a single IS agent both at time of LVV and 2 year post-OLT (Table 2), with tacrolimus the most frequent agent. Compared to those that did not received LVV post-OLT, those that did were on one IS agent more often. Tacrolimus levels were similar among patients receiving LVV post-OLT compared with those who did not.Table 1 Table 2 ConclusionIn a series of pediatric OLT recipients, post-OLT LVV was generally safe and well tolerated. Patients who received LVV post-OLT were more often on one IS agent at 2 year follow up compared to those who did not. Our study supports prospective efforts to define guidelines for patients who may safely receive LVV after OLT.DisclosuresKevin J. Downes, MD, Merck, Inc. (Grant/Research Support)

Antithymocyte induction dosing and incidence of opportunistic viral infections using steroid-free maintenance immunosuppression.

Currently, there is limited literature evaluating rATG induction dosing and incidence of opportunistic viral infections when using steroid-free maintenance immunosuppression. This single-center, retrospective, study compared high rATG (>4.5mg/kg) versus low (<4.5mg/kg) induction dosing and the overall incidence of early opportunistic viral infection at 180days in the setting of maintenance immunosuppression consisting of tacrolimus, mycophenolate, rapid steroid withdrawal, and a tiered antiviral prevention strategy based on donor-recipient Cytomegalovirus (CMV) serostatus. A total of 209 patients were included; 76 patients received low-dose and 133 patients received high-dose rATG. Incidence of overall opportunistic viral infection occurred more frequently in patients who received high compared to low dose (29.8% vs 25% p=.030). Incidence of CMV infection was also significantly increased in the high-dose group (31.6% vs 18.4% p=.039). In a multivariable model, rATG dose, as a continuous variable, remained a significant independent predictor of infection along with CMV risk (OR 1.46, 95% CI 1.02-2.09) controlling for age and CMV risk. There were no differences in graft-related outcomes at 180days. Higher cumulative rATG induction dose was associated with increased incidence of opportunistic viral infections, in the setting of a steroid-free maintenance immunosuppression in the early post-transplant period.

Randomized trial of steroid free immunosuppression with basiliximab induction in adult live donor liver transplantation (LDLT)

BackgroundCorticosteroids are an integral part of immunosuppression following solid organ transplantation, despite their metabolic complications. We conducted a randomized trial to evaluate the efficacy of steroid-free immunosuppression following live donor liver transplantation (LDLT). MethodsWe randomized 104 patients stratified based on pre-transplant diabetic status to either a steroid-free arm (SF-arm) (Basiliximab + Tacrolimus and Azathioprine,n = 52) or Steroid arm (S-Arm) (Steroid + Tacrolimus + Azathioprine,n = 52). The primary endpoint was the occurrence of metabolic complications (new-onset diabetes after transplant (NODAT), new-onset systemic hypertension after transplant (NOSHT), post-transplant dyslipidemia) within 6 months after transplant. Secondary endpoints included biopsy-proven acute rejection (BPAR) within six months, patient and graft survival at 6 months. ResultsThe incidence NODAT was significantly higher in S-arm at 3 months (64.5%vs. 28.1%,p-0.004) and 6 months (51.6% vs. 15.6%,p-0.006). Likewise, the incidence of NOSHT (27.8% vs. 4.8%,p-0.01) and hypertriglyceridemia (26.7% vs. 8%,p-0.03) at six months was significantly higher in S-arm. However, there were no differences in BPAR (19.2% vs. 21.2%, p-0.81), time to first rejection (58 vs. 53 days, p-0.78), patient and graft survival (610 vs. 554 days,p- 0.22). ConclusionFollowing LDLT, basiliximab induction with tacrolimus and azathioprine maintenance resulted in significantly lower metabolic complications compared to the triple-drug regimen of steroid, tacrolimus, and azathioprine.

Retraction: Comprehensive Comparison of Three Different Immunosuppressive Regimens for Liver Transplant Patients with Hepatocellular Carcinoma: Steroid-Free Immunosuppression, Induction Immunosuppression and Standard Immunosuppression.

Retraction: Comprehensive Comparison of Three Different Immunosuppressive Regimens for Liver Transplant Patients with Hepatocellular Carcinoma: Steroid-Free Immunosuppression, Induction Immunosuppression and Standard Immunosuppression.

Low-dose Rituximab and Thymoglobulin Induction With Steroid-free Maintenance Immunosuppression and Protocol Biopsies Improves Long-term Patient and Graft Survival After Kidney Transplantation: Survival and Safety Outcomes in More Than 1100 Patients From a Single Center.

Background.Steroid-free maintenance immunosuppression after kidney transplantation provides acceptable patient and graft survival and minimizes steroid-associated side effects among recipients with a low immunological risk. However, the long-term outcomes of such protocols, incorporating low-dose rituximab and thymoglobulin induction along with protocol biopsies, in non-European populations remains underreported.Methods.We retrospectively analyzed 1142 consecutive kidney transplantations conducted at our center from July 2005 to October 2017. Immunosuppression protocol included induction with thymoglobulin and low-dose preoperative rituximab. Maintenance immunosuppression consisted of tacrolimus and mycophenolate mofetil; prednisolone was discontinued on postoperative day 5. Protocol biopsies were carried out at 3 months and at 1, 5, and 10 years after transplantation—in addition to the indicated biopsies. The 12-year patient and graft survival and posttransplantation complications were studied.Results.The analysis of outcomes was conducted for 1111 transplant recipients. Patients (70.59%) remained steroid-free at 12 years after transplantation. The patient survival rates at 1, 5, and 12 years were 97.7%, 94.8%, and 92.4%, respectively. The corresponding graft survival rates were 97.2%, 90.9%, and 86.1%, respectively. Biopsy-proven acute rejection occurred in 12.7% of recipients, including 3.5% subclinical rejections. The cumulative incidence of graft loss was 6.56% at 12.3 years. The overall incidence of death was 5.3%.Conclusions.Steroid-free maintenance immunosuppression was associated with excellent long-term patient and graft survival rates and reduced incidence of prednisolone-related side effects, despite acceptable rejection rates. Low-dose rituximab with thymoglobulin induction with immediate steroid withdrawal and surveillance biopsies resulted in excellent long-term outcomes in our single-center experience.

MTOR Inhibitor in Combination with Cyclosporine as Primary Maintenance Immunosuppression in Combined Kidney/Pancreas Transplant Recipients

We report our experience employing a steroid-free, mammalian target of rapamycin (mTOR) inhibitor–based immunosuppression regimen in pancreas transplantation and review literature germane to the use of this regimen. In our experience, using mTOR inhibitor–based, steroid-free immunosuppression with low-dose cyclosporine and anti-thymocyte globulin (ATG) induction in 309 combined kidney/pancreas transplants resulted in one-year patient survival and death censored graft survivals of 95.8%, 93.5% (pancreas), and 96.1% (kidney). The biopsy-proven acute rejection incidence was 15.2% at 1 year. De novo donor-specific antibodies developed in 9.4% at last follow-up. Little data currently exists reporting steroid-free, mTOR-based immunosuppression in pancreas transplant recipients. Excellent results have been reported in a small cohort of 25 recipients in Germany. Thus, data used in kidney transplant recipients must be extrapolated to pancreas transplantation. There are some data, including our own, that indicate there are good outcomes with this immunosuppression regimen in combined kidney and pancreas recipients. Data suggest that avoidance of steroids and minimizing CNI exposure are desirable attributes to pancreas transplant immunosuppression to optimize post-transplant pancreas function.

Randomised study on steroid free immunosuppression with basiliximab induction vs standard triple drug immunosuppression in adult live donor liver transplantation (LDLT). CTRI/2017/08/009508

Introduction: Although there is data on steroid-free immunosuppression following deceased donor liver transplantation, robust evidence is lacking in LDLT. Our aim was to evaluate the efficacy of steroid-free immunosuppression(basiliximab induction) following LDLT. Method: Out of 95 LDLTs performed in 1 year, after excluding 11 patients(renal dysfunction-3, APOLT-2, Multiorgan transplant-1, ABO incompatable-2, Retransplant-1, Massive bleed-2), 84 patients were randomized either to SF-arm(Basiliximab + Tacrolimus + Azathioprine, n=42) or S-Arm(Steroid + Tacrolimus + Azathioprine, n=42). Primary objective was to compare metabolic complications. Results: Baseline characteristics like age, etiology, comorbidities, MELD score, duration of surgery, blood loss, cold ischemia and GRWR were comparable in both groups. The incidence of new onset diabetes after transplantation(NODAT) was significantly higher in S-arm at 3 months (68.2% vs 21.7%, p-0.002) and at 6 months(54.5% Vs 13%, p-0.003). Likewise incidence of new onset hypertension(32.1% Vs 6.1%, p-0.021), hypertriglyceridemia(27.8% Vs 7.5%, p-0.041) at six months were significantly higher in S-arm. However incidence of biopsy proved rejection (16.7% Vs 21.4 %, p-0.57), time to first rejection (56 vs 44 days, p-0.080), and graft survival(549 Vs 499 days, p- 0.329)(median follow up of 10.7 months), were not different between two groups (SF-arm Vs. S-arm). Interestingly ICU stay was significantly less in SF-arm compared to S-arm(8.8 Vs 10.7 days, p-0.042). There were no differences in renal functions, readmission rates, hospital stay, infectious, biliary and vascular complications.Tabled 1FP05-04 Table [Study End Points]VariableSF-armS-armP-valueNODAT at 3 months5 (21.7%)15 (68.2%)0.002NODAT at 6 months (6M)3 (13%)12 (54.5%)0.008NOSHT at 3 months2(6.1%)9(32.1%)0.021NOSHT at 6 months2(6.1%)9(32.1%)0.021Hypercholesterolemia at 6 months8 (20%)13(36.1%)0.117Hypertriglyceridemia at 6 months3 (7.5%)10 (27.8%)0.041Mean Total cholesterol at 6M171.39 ±35.33187.76 ±56.230.139Mean Triglycerides at 6M101.5 ±45.64124.88 ±62.980.066Biopsy proved rejection (within 6M)7(16.7%)9(21.4%)0.578Time to rejection56.8 ± 15.4744 ±50.180.080Corticosteroid-resistant rejection2 (4.8%)1 (2.4%)1.000Severity of rejection (RAI)5.86 ± 1.065.44 ± 0.880.495Graft & Patient survival (days)549 ± 23.8499.5 ±31.640.329Overall mortality4 (9.5%)7(16.7%)0.51990 - day mortality2 (4.8%)6(14.3%)0.2931-year survival88.5%83.3%Mean eGFR at 3rd month (mL/min)87.25 ±32.3194.20 ±31.720.399Mean eGIFR at 6th month (mL/min)93.96 ± 37.11103.28 ±35.040.124Renal dysfunction(eGFR < 90mL/min) at 3 months24 (60%)18(50%)0.381Renal dysfunction(eGFR < 90mL'min) at 6 months24 (60%)13 (36.1%)0.037Overall Infections12 (28.6%)14(33.3%)0.637Blood borne sepsis8(19%)7(16.7%)0.776Urinary sepsis2 (4.8%)6(14.3%)0.265Abdominal sepsis6(14.3%)7(16.7%)0.763ICU stay8.86 ± 5.7810.76 ±8.640.042Total Hospital stay20.31 ± 10.7720.14 ±9.460.545Hepatic artery thrombosis0 (0%)4 (9.5%)0.124Middle hepatic vein thrombosis3(7.1%)8(19%)0.196Portal vein thrombosis0 (0%)1(2.4%)1.000Bile leak3(7.1%)8(19%)0.196Biliary stricture0 (0%)5(11.9%)0.065Re-admission12 (28.6%)17(40.5%)0.251Re-exploration2 (4.8%)5(11.9%)0.430 Open table in a new tab Conclusions: Steroid-free immunosuppression with basiliximab induction is as effective as the steroid based triple drug regimen with significantly lower metabolic complications.