Early Steroid Withdrawal Group Research Articles

Safety and efficacy of early corticosteroid withdrawal in liver transplant recipients: A randomized controlled trial.

Prolonged use of steroids after liver transplantation (LT) significantly increases the risk of diabetes or cardiovascular disease, which can adversely affect patient outcomes. Our study evaluated the effectiveness and safety of early steroid withdrawal within the first year following LT. This study was conducted as an open-label, multicenter, randomized controlled trial. Liver transplant recipients were randomly assigned to one of the following two groups: Group 1, in which steroids were withdrawn two weeks posttransplantation, and Group 2, in which steroids were withdrawn three months posttransplantation. This study included participants aged 20 to 70 years who were scheduled to undergo a single-organ liver transplant from a living or deceased donor at one of the four participating centers. Between November 2012 and August 2020, 115 patients were selected and randomized into two groups, with 60 in Group 1 and 55 in Group 2. The incidence of new-onset diabetes after transplantation (NODAT) was notably higher in Group 1 (32.4%) than in Group 2 (10.0%) in the per-protocol set. Although biopsy-proven acute rejection, graft failure, and mortality did not occur, the median tacrolimus trough level/dose/weight in Group 1 exceeded that in Group 2. No significant differences in safety parameters, such as infection and recurrence of hepatocellular carcinoma, were observed between the two groups. The present study did not find a significant reduction in the incidence of NODAT in the early steroid withdrawal group. Our study suggests that steroid withdrawal three months posttransplantation is a standard and safe immunosuppressive strategy for LT patients.

Impact of early corticosteroid withdrawal on simultaneous pancreas-kidney transplant long-term outcomes: Single center experience and comparison to the International Pancreas Transplant Registry.

There remains a paucity of modern data comparing early steroid withdrawal (ESW) versus chronic corticosteroid (CCS) immunosuppression in simultaneous pancreas kidney (SPK) transplant recipients with long-term follow-up. Therefore, the purpose of this study is to assess the effectiveness and tolerability of ESW compared to CCS post-SPK. This was a retrospective single-center matched comparison with the International Pancreas Transplant Registry (IPTR). Patients from University of Illinois Hospital (UIH) represented the ESW group and were compared to those matched CCS patients from the IPTR. Included patients were adult recipients of a primary SPK transplant between 2003 and 2018 within the US receiving rabbit anti-thymocyte globulin induction. Patients were excluded if they had early technical failures, missing IPTR data, graft thrombosis, re-transplant, or positive crossmatch SPK. A total of 156 patients were matched and included in the analysis. Patients were predominantly African American (46.15%) males (64.1%) with Type 1 diabetes etiology (92.31%). Overall pancreas allograft survival (hazard ratio [HR] = .89, 95% confidence interval [CI] .34-2.30, p = .81) and kidney allograft survival (HR = .80, 95%CI .32-2.03, p = .64) were similar between the two groups. Immunologic pancreas allograft loss was statistically similar at 1-year (ESW 1.3% vs. CCS 0%, p = .16), 5-year (ESW 1.3% vs. CCS 7.7%, p = .16), and 10-year (ESW 11.0% vs. CCS 7.7%, p = .99). The 1-year (ESW 2.6% vs. CCS 0%, p>.05), 5-year (ESW 8.3% vs. CCS 7.0%, p>.05), and 10-year (ESW 22.7% vs. CCS 9.9%, p = .2575) immunologic kidney allograft loss were also statistically similar. There was no difference in 10-year overall patient survival (ESW 76.2% vs. CCS 65.6%, p = .63). No differences were found between allograft or patient survival post-SPK when comparing an ESW or CCS protocol. Future assessment is needed to determine differences in metabolic outcomes.

P0879EARLY STEROID WITHDRAWAL HAS A POSITIVE EFFECT ON BONE KIDNEY TRANSPLANT RECIPIENTS: A PROPENSITY SCORE STUDY WITH INVERSE PROBABILITY-OF-TREATMENT WEIGHTING

Abstract Background and Aims Long-term corticosteroid use after kidney transplantation is associated with a decrease in bone mineral density and a high fracture risk. We hypothesized that patients with early steroid withdrawal (ESW) would display a gain in bone mineral density in the year following kidney transplantation, when compared with patients on long-term corticosteroid therapy (LTCT). Method In a cohort of kidney transplant recipients, 317 patients were included between 2012 and 2018. Dual-energy X-ray absorptiometry was performed 1 and 12 months after transplantation. The data were analyzed using linear regression with inverse probability-of-treatment weighting based on a propensity score. Results One year after transplantation, the gain in bone mineral density was significantly greater in recipients with ESW than in recipients on LTCT for the lumbar spine (+0.027 g/cm, P < 0.001) and the femoral neck (+0.021 g/cm, P = 0.035). Among patients with ESW, (i) none had osteoporosis, (ii) the percentage with normal bone mineral density increased from 35.0% at month 1 to 56.4% at month 12, and (ii) the percentage with osteopenia fell from 52.5% to 43.6%. In patients undergoing LTCT, the fracture incidence was 14.5 per 1000 person-years. None of the patients in the ESW group experienced a fracture. Cardiovascular risk factors were more prominent in the LTCT group relative to the ESW group: patients in LTCT group (i) were more likely to have high blood pressure (p<0.001), (ii) gained more weight gain (p=0.032) and (iii) displayed a greater increase in serum triglyceride levels (p=0.004).The acute rejection rate was similar in the two groups. Conclusion Early steroid withdrawal is associated with a spontaneous increase in bone mineral density at 12 months post-transplantation (relative to patients on long-term steroid therapy), with a reduction in several cardiovascular risk factors and does not appear to harm the graft.

Early steroid withdrawal has a positive effect on bone in kidney transplant recipients: a propensity score study with inverse probability-of-treatment weighting.

Background:Long-term corticosteroid use after kidney transplantation is associated with a decrease in bone mineral density (BMD) and a high fracture risk. We hypothesized that patients with early steroid withdrawal (ESW) would display a gain in BMD in the year following kidney transplantation, when compared with patients on long-term corticosteroid therapy.Methods:In a cohort of kidney transplant recipients, 356 patients were included between 2012 and 2019. Dual-energy X-ray absorptiometry was performed 1 and 12 months after transplantation. The data were analyzed using linear regression with inverse probability-of-treatment weighting (based on a propensity score).Results:At 1 year after transplantation, the gain in BMD was significantly greater in recipients with ESW than in recipients on long-term corticosteroid therapy for the lumbar spine (+0.036 g/cm2, p < 0.001) and the femoral neck (+0.020 g/cm2, p = 0.035). Among patients with ESW, (i) none had osteoporosis, (ii) the percentage with normal BMD increased from 33.3% at month 1 to 54.4% at month 12, and (iii) the percentage with osteopenia fell from 56.2% to 45.6%. In patients undergoing long-term corticosteroid therapy, the fracture incidence was 13.5 per 1000 person-years. None of the patients in the ESW group experienced a fracture.Conclusion:ESW has a positive effect on bone in kidney transplant recipients.

Early Steroid Withdrawal Compared With Standard Immunosuppression in Kidney Transplantation - Interim Analysis of the Amsterdam-Leiden-Groningen Randomized Controlled Trial.

BACKGROUNDThe optimal immunosuppressive regimen in kidney transplant recipients, delivering maximum efficacy with minimal toxicity, is unknown.METHODSThe Amsterdam, LEiden, GROningen trial is a randomized, multicenter, investigator-driven, noninferiority, open-label trial in 305 kidney transplant recipients, in which 2 immunosuppression minimization strategies—one consisting of early steroid withdrawal, the other of tacrolimus minimization 6 months after transplantation—were compared with standard immunosuppression with basiliximab, corticosteroids, tacrolimus, and mycophenolic acid. The primary endpoint was kidney function. Secondary endpoints included death, primary nonfunction, graft failure, rejection, discontinuation of study medication, and a combined endpoint of treatment failure. An interim analysis was scheduled at 6 months, that is, just before tacrolimus minimization.RESULTSThis interim analysis revealed no significant differences in Modification of Diet in Renal Disease between the early steroid withdrawal group and the standard immunosuppression groups (43.2 mL/min per 1.73 m2 vs 45.0 mL/min per 1.73 m2, P = 0.408). There were also no significant differences in the secondary endpoints of death (1.0% vs 1.5%; P = 0.737), primary nonfunction (4.1% vs 1.5%, P = 0.159), graft failure (3.1% vs 1.5%, P = 0.370), rejection (18.6% vs 13.6%, P = 0.289), and discontinuation of study medication (19.6% vs 12.6%, P = 0.348). Treatment failure, defined as a composite endpoint of these individual secondary endpoints, was more common in the early steroid withdrawal group (P = 0.027), but this group had fewer serious adverse events and a more favorable cardiovascular risk profile.CONCLUSIONSBased on these interim results, early steroid withdrawal is a safe short-term immunosuppressive strategy. Long-term outcomes, including a comparison with tacrolimus minimization after 6 months, will be reported in the final 2-year analysis.

A Comparative Effectiveness Analysis of Early Steroid Withdrawal in Black Kidney Transplant Recipients.

There is continued debate whether early steroid withdrawal is safe to use in high-immunologic risk patients, such as blacks. The goal of this study was to use comparative effectiveness methodology to elucidate the safety of early steroid withdrawal in blacks with kidney transplants. Our cohort study used United Network of Organ Sharing data including all adult black kidney transplant recipients from 2000 to 2009 followed through 2014. Propensity score matching was used to equalize baseline risk between continued steroid and early steroid withdrawal groups. Interaction terms were used to assess if the effect of early steroid withdrawal on outcomes varied by baseline and post-transplant factors. Of 26,582 eligible black patients with kidney transplants (5825 [21.9%] with early steroid withdrawal), 5565 patients with early steroid withdrawal were matched to 5565 blacks on continued steroid use. Black patients with early steroid withdrawal had similar risk of graft loss (hazard ratio, 0.98; 95% confidence interval, 0.92 to 1.04; P=0.42) and lower risk of death (hazard ratio, 0.91; 95% confidence interval, 0.84 to 0.99; P=0.02), primarily driven by a late mortality advantage (>4 years post-transplant). Delayed graft function, cytolytic induction, tacrolimus, and mycophenolate significantly modified the effect of early steroid withdrawal on outcomes (P<0.05). Acute rejection rates were slightly higher in the continued steroid group (13.0% versus 11.3%, respectively; P<0.01), but this was not associated with graft or patient survival. Overall, early steroid withdrawal in black kidney transplant recipients was not associated with graft loss but seemed to be associated with better long-term patient survival. Early steroid withdrawal in blacks not receiving cytolytic induction, tacrolimus, and mycophenolate or those with delayed graft function was associated with higher risk of graft loss and death.

Human Leukocyte Antigen Mismatch and Steroid Maintenance in Kidney Transplantation

BackgroundThis study aimed to analyze the impact of chronic steroid maintenance (CSM) vs early steroid withdrawal (ESW) in kidney transplant recipients (KTRs) stratified by the level of human leukocyte antigen (HLA) mismatch. MethodsAdult KTRs between 2001 and 2011 who received antibody induction followed by calcineurin inhibitor (CNI)/mycophenolate mofetil (MMF) maintenance with or without steroid were identified from the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) database. Using multivariate analysis, graft and patient outcomes were compared for CSM vs ESW in KTRs stratified by HLA mismatch levels separately for depleting and nondepleting antibody-induced patients. ResultsAmong 43,096 study patients, 26,582 received depleting induction (zero HLA mismatch = 5324 [CSM = 3416; ESW = 1908]; 5–6 HLA mismatch = 21,258 [CSM = 13,739; ESW = 7519]) and 16,514 patients received nondepleting induction (zero HLA mismatch = 4109 [CSM = 3453; ESW = 656]; 5–6 HLA mismatch = 12,405 [CSM = 10,890; ESW = 1515]). Adjusted graft failure risks for CSM vs ESW groups for zero HLA mismatch patients were as follows: HR 1.13, P = .07 (depleting induction); HR 1.30, P = .01 (nondepleting induction). Graft outcomes were similar for CSM vs ESW in 5–6 HLA mismatch groups for both induction types. Adjusted patient death risks were significantly higher for CSM vs ESW with depleting (HR 1.3, P = .003) and nondepleting (HR 1.45, P = .006) induction in zero HLA mismatch patients and only with depleting induction in 5–6 HLA mismatch groups (HR 1.16, P < .001). ConclusionOur study supports the feasibility of ESW regardless of the level of HLA mismatch in KTRs selected for antibody induction and CNI/MMF maintenance.

Role of steroid maintenance in sensitized kidney transplant recipients.

To evaluate whether there is a threshold sensitization level beyond which benefits of chronic steroid maintenance (CSM) emerge. Using Organ Procurement and Transplant Network/United Network of Organ Sharing database, we compared the adjusted graft and patient survivals for CSM vs early steroid withdrawal (ESW) among patients who underwent deceased-donor kidney (DDK) transplantation from 2000 to 2008 who were stratified by peak-panel reactive antibody (peak-PRA) titers (0%-30%, 31%-60% and > 60%). All patients received perioperative induction therapy and maintenance immunosuppression based on calcineurin inhibitor (CNI) and mycophenolate mofetil (MMF). The study included 42851 patients. In the 0%-30% peak-PRA class, adjusted over-all graft-failure (HR 1.11, 95%CI: 1.03-1.20, P = 0.009) and patient-death (HR 1.29, 95%CI: 1.16-1.43, P < 0.001) risks were higher and death-censored graft-failure risk (HR 1.06, 95%CI: 0.98-1.14, P = 0.16) similar for CSM (n = 25218) vs ESW (n = 7399). Over-all (HR 1.04, 95%CI: 0.85-1.28, P = 0.70) and death-censored (HR 0.97, 95%CI: 0.78-1.21, P = 0.81) graft-failure risks were similar and patient-death risk (HR 1.39, 95%CI: 1.03-1.87, P = 0.03) higher for CSM (n = 3495) vs ESW (n = 850) groups for 31%-60% peak-PRA class. In the > 60% peak-PRA class, adjusted overall graft-failure (HR 0.90, 95%CI: 0.76-1.08, P = 0.25) and patient-death (HR 0.92, 95%CI: 0.71-1.17, P = 0.47) risks were similar and death-censored graft-failure risk lower (HR 0.84, 95%CI: 0.71-0.99, P = 0.04) for CSM (n = 4966) vs ESW (n = 923). In DDK transplant recipients who underwent perioperative induction and CNI/MMF maintenance, CSM appears to be associated with increased risk for death with functioning graft in minimally-sensitized patients and improved death-censored graft survival in highly-sensitized patients.

G377(P) Early renal transplant biopsies in children: rejection or calcineurin inhibitor toxicity?

AimsAn increase in transplant biopsy rate in the first month following renal transplantation (RT) was observed in our centre following implementation of an early steroid withdrawal (ESW) immunosuppression (IS) protocol...

The Impact of Early Corticosteroid Withdrawal on Graft Survival in Liver Transplant Recipients

BackgroundThere has been increased interest in recent years in reducing or eliminating steroids from the immunosuppression regimen of transplant recipients to reduce adverse effects associated with their use. The purpose of this study was to compare clinical outcomes between early versus late steroid withdrawal after liver transplant to determine the optimal duration of steroid use in this population. MethodsThis large-scale, retrospective analysis of liver transplants occurred at our institution between 2000 and 2009. Patients were excluded if they were <18 years old, received a multiorgan transplant, or remained on steroids for >1 year. The early steroid withdrawal group had steroids eliminated by 3 months posttransplant; late steroid withdrawal patients had steroids withdrawn between 3 and 12 months posttransplant. ResultsA total of 586 liver transplants occurred during the study period; 330 patients were included in the analysis. Graft survival was significantly lower in the early steroid withdrawal group. There was no difference in patient survival or overall acute rejection. However, the late steroid withdrawal group had a significantly higher rate of early acute rejection episodes. There was no difference with regard to new-onset diabetes after transplant, hyperlipidemia, or cardiovascular events between groups. ConclusionThe results of this study suggest that late corticosteroid withdrawal is associated with better long-term graft survival without increasing the rates of diabetes, hyperlipidemia, or cardiovascular events in liver transplant recipients. A prospective study is warranted to confirm these findings.

Early Steroid Withdrawal in Adult Kidney Transplantation at a Single Center

BackgroundBeneficial effects of protocols using minimal steroid exposure have been recently reported. The purpose of this study was to evaluate the outcomes of kidney transplantation recipients who received immunosuppression protocols with early steroid withdrawal (ESW) at our center. MethodsWe retrospectively studied 84 kidney transplant recipients who had received ESW immunosuppressive protocols at our center from March 2005 to December 2010. The immunosuppressive regimen was a combination of calcineurin inhibitors (tacrolimus/cyclosporine), methylprednisolone, which was tapered and discontinued within 2 months, mycophenolate mofetil, and basiliximab (postoperative days 0 and 4). We compared the outcomes of our ESW recipients with those of a historical control group (February 2003 to January 2005; n = 18). ResultsClinical acute rejection episodes were observed in 15 (17.9%) and 5 (27.8%) cases in the ESW and control groups, respectively. Cytomegalovirus infection occurred in 12 (14.3%) and 5 (27.8%) cases in the ESW and control groups, respectively. The creatinine levels at 1 year after transplantation were 1.3 ± 0.4 mg/dL and 1.3 ± 0.5 mg/dL in the ESW and control groups, respectively. In the ESW group of 84 recipients, actuarial patient survival at 1 year was 94.0%. In the historical group of 18 recipients, the actuarial patient survival at 1 year was 100% (P = .76). In the ESW group the graft survival rate at 1 year was 95.2%. In the historical group, graft survival rate at 1 year was 100% (P = .65). There were no significant differences in the parameters between the groups. ConclusionsThe outcomes from this study were considered to be acceptable; however, the possibility of improving the protocols exists.

Early Steroid Withdrawal in Repeat Kidney Transplantation

Kidney re-transplantation (KRT) candidates are considered at high risk for graft failure. Most of these patients are kept on a chronic steroid maintenance (CSM) regimen. The safety of early steroid withdrawal (ESW) remains unanswered in KRT. This study was aimed at comparing the outcomes of ESW and CSM in KRT. Retrospective analysis of 113 KRT patients (ESW, n=59; CSM, n=54) was performed. All patients received rabbit anti-thymocyte globulin/steroid induction and were maintained on mycophenolate/tacrolimus (±steroids). One- and 5-year patient survival for the ESW and the CSM group were not significantly different (98 versus 96% and 91 versus 88%, respectively; P=0.991). No significant difference was seen in the graft survival for both groups at 1 and 5 years (98 versus 93% and 80 versus 74%, respectively; P=0.779). Mean 1- and 5-year estimated GFR was not statistically different between the groups (P=0.773 and 0.790, respectively). The incidence of acute rejection at 1 year was 17 and 22% in ESW and CSM patients, respectively (P=0.635). Compared with the ESW group, patients in the CSM group were more likely to be hyperlipidemic (P=0.044), osteoporotic (P=0.010), post-transplant diabetics (P=0.051) and required more medications to control BP (P=0.004). ESW seems to be a reasonable approach in KRT recipients because the short and intermediate patient survival, graft survival, and graft function is comparable to CSM immunosuppression.

Short-Term Experience with Early Steroid Withdrawal in African-American Renal Transplant Recipients

There are limited data on the results of early steroid withdrawal (ESW) in African-American (AA) renal allograft recipients. We examined short-term transplant outcomes in a retrospective, non-concurrent cohort study of 40 AAs who did not (ESW group), and 33 who did [steroid maintenance (SM) group] receive maintenance steroids after day 4 post-transplant. Patients received thymoglobulin (ATG) induction, mycophenolate mofetil, and tacrolimus or sirolimus. Data were analyzed using survival analysis methods and regression models. Patients in the ESW group were older, had lower current panel reactive antibody and fewer re-transplants, and received fewer doses of ATG. One-year graft survival and acute rejection (AR) rates were 100% and 13% in the ESW group and 97% and 15% in the SM group. After controlling for confounders, at 1 year, ESW was not associated with higher risk of graft loss, AR, or worse graft function, but was associated with less weight gain. The SM group had higher cholesterol levels at 3 months and higher risk of post-transplant diabetes mellitus. We did not observe any cases of subclinical rejection. This study suggests that ESW under modern immunosuppression is safe over the short term in at least a subset of AA recipients with risk profiles similar to those studied herein, and could be associated with improved outcomes.