1-year Acute Rejection Research Articles

A2/A2B Deceased Donor Kidney Transplantation Using A2 Titers Improves Access to Kidney Transplantation: A Single-Center Study

Rationale and ObjectiveThe option for A2/A2B deceased donor kidney transplantation was integrated into the kidney allocation system in 2014 to improve access for B blood group waitlist candidates. Despite excellent reported outcomes, center uptake has remained low across the United States. Here we examined the effect of implementing an A2/A2B protocol using a cut off titer of ≤ 1:8 for IgG and 1:16 for IgM on blood group B kidney transplant recipients at a single center. Study DesignRetrospective observational study. Setting& Participants: Blood group B recipients of deceased donor kidney transplants at a single center from January 1, 2019 to December 2022. ExposureRecipients of deceased donor kidney transplants were analyzed based on donor blood type: A2/A2B vs. blood group compatible. Outcomes1 year patient survival, death censored allograft function, primary non-function, delayed graft function, allograft function as measured by serum creatinine and eGFR at 1 year, biopsy proven rejection, and need for plasmapheresis. Analytical ApproachComparison between the A2/A2B and compatible groups were performed using the Fisher test or the Chi-Square test for categorical variables and the nonparametric Wilcoxon Rank-Sum Test for continuous variables. ResultsA total of 104 blood type B patients received a deceased donor kidney transplant at our center during the study period, 49 (47.1%) of which received an A2/A2B transplant. Waiting time was lower in A2/A2B recipients compared to blood group compatible recipients (57.9 months vs. 74.7 months, p=0.01). A2/A2B recipients were more likely to receive a donor after cardiac death (24.5% vs 1.8%, p<0.05) and experience delayed graft function (65.3% vs. 41.8%). There were no observed differences in the average serum creatinine or eGFR at 1-month, 3-months, and 1-year post kidney transplantation, acute rejection, or primary non-function. LimitationsSingle center study. Small cohort size limiting outcome analysis. ConclusionsImplementation of an A2/A2B protocol increased transplant volumes of blood group B waitlisted patients by 83.6% while decreasing the waiting time for transplantation by 22.5% with similar transplant outcomes.

Outcomes of Kidney Transplantation Among COVID-19 Recovered Patients in a Single Transplant Center

The COVID-19 pandemic significantly lowered kidney transplantation (KT) rates worldwide, and studies regarding outcomes of patients who developed COVID-19 infection before KT are limited, especially in low to middle-income countries. To determine the 1-year graft and patient survival of kidney transplant recipients who recovered from COVID-19 infection before KT. We retrospectively reviewed all adult end-stage renal disease patients who underwent KT at the National Kidney and Transplant Institute from June 2020 through October 2021. Transplant parameters, graft and patient survival, pretransplant COVID-19 infection, and post-KT infectious complications were recorded. Data was analyzed using two-tailed descriptive statistical tests. Of the 219 recipients, 23 (11%) had COVID-19 infection within 1 to 16 months before KT. The mean age of KT recipients was 36 years (range, 25-57), and 61.9% had chronic glomerulonephritis as primary renal disease. The mean duration from COVID-19 recovery to KT was 79 days (range, 21-207). There was no significant difference in the 1-year biopsy-proven acute rejection in the 2 groups, at 4.5% vs 12.5% for the COVID-19 and non-COVID-19 group, respectively. Both the 1-year graft and patient survival were similar in the COVID-19 and non-COVID-19 groups at 98.4% vs 100% and 100% vs 98.44%, respectively. There was no significant difference in biopsy-proven acute rejection, 1-year graft, and patient survival among patients who had a prior COVID-19 infection vs those who did not. Kidney transplantation appears safe when performed at least 1 month from COVID-19 infection.

Improved outcomes of kidney after liver transplantation after the implementation of the safety net policy.

The number of kidney after liver transplants (KALT) increased after the implementation of the United Network of Organ Sharing (UNOS) safety net policy, but the effects of the policy on KALT outcomes remain unknown. Using the UNOS database, we identified KALT between 60 and 365 days from liver transplant from January 1, 2010, to December 31, 2020. The main outcome was 1- and 3-year patient, liver, and kidney graft survival. Secondary outcomes included 6-month and 1-year acute rejection (AR) of liver and kidney, and 1-year kidney allograft function. Of the 256 KALT, 90 were pre-policy and 166 post-policy. Compared to pre-policy, post-policy 1- and 3-year liver graft survival was higher (54% and 54% vs. 86% and 81%, respectively, p <0.001), while 1- and 3-year kidney graft survival (99% and 75% vs. 92% and 79%, respectively, p =0.19), and 1- and 3-year patient survival (99% and 99% vs. 95% and 89%, respectively, p =0.11) were not significantly different. Subgroup analysis revealed similar trends in patients with and without renal failure at liver transplant. Liver AR at 6 months was lower post-policy (6.3% vs. 18.3%, p =0.006) but was similar (10.5% vs. 13%, p =0.63) at 1 year. Kidney AR was unchanged post-policy at 6 months and 1 year. Creatinine at 1 year did not differ post-policy versus pre-policy (1.4 vs. 1.3mg/dL, p =0.07) despite a higher proportion of deceased donors, higher Kidney Donor Profile Index, and longer kidney cold ischemia time post-policy ( p <0.05 for all). This 3-year follow-up after the 2017 UNOS policy revision demonstrated that the safety net implementation has resulted in improved liver outcomes for patients who underwent KALT with no increased AR of the liver or the kidney allografts.

Pretransplant erythroferrone levels are predictive of 1-year all-cause mortality or acute rejection after heart transplantation

Abstract Background/Introduction Heart transplantation (HTx) remains the treatment of choice for selected advanced heart failure (HF) patients. Iron deficiency is a significant factor in the prognosis of HF, and iron metabolism may play a role after HTx since pretransplant hemoglobin levels predict posttransplant 1-year all-cause mortality. In addition, iron deficiency (ID) is known to impact antigen-specific immune response. Purpose The aim of this study was to quantify the impact of pretransplant iron metabolism components on the primary composite outcome 1-year all-cause mortality (ACM) or 1-year acute cellular rejection. Methods This prospective Swiss national cohort study included consecutive patients with HTx between 2008 to 2017. Iron metabolism was assessed measuring plasma iron, ferritin, erythroferrone (ERFE), hepcidin and interleukin-6 immediately before transplant surgery. Endomyocardial biopsies were procured in accordance with the common national posttransplant surveillance protocol. Acute cellular rejection was defined as histological 2R or 3R rejection according to the ISHLT nomenclature 2004 in the diagnosis of heart rejection. Results A total of 276 HTx recipients were included, median age was 52 [IQR 41;59] years, 24.6% (n=68) were females. HTx recipients with incident combined endpoint (n=118, 42.8%) were not significantly different from controls for demographic or transplant operation parameters, donor/recipient gender or HLA mismatch, ferritin, hepcidin (0.5 [IQR 0.5-1.5] vs. 0.5 [IQR 0.5-1.2]; p=0.382) µg/L), interleukin-6, and most biological parameters associated with posttransplant risk. However, participants with incident combined endpoint had lower haemoglobin levels (125 [IQR 102-134] vs. 128 [IQR 114-141 ] g/L; p=0.004), lower Na+ levels (137.5 [IQR 135-139 ] vs. 138 [IQR 136-140] mmol/L; p=0.017), and higher ERFE levels (1.40 [IQR 0.84-1.84 ] vs. 1.19 ng/mL [IQR 0.91-2.92]; p=0.013) compared to those without the endpoint (n=158, 57.2%). The incidence of the combined endpoint was higher in patients presenting with ERFE levels above the third quartile (&amp;gt;2.25 ng/mL; p=0.003). Multivariable analysis using stepwise backward elimination (table) showed that ERFE levels &amp;gt;2.25 ng/mL predicted the incidence of the combined endpoint with an OR of 2.17 (95% CI: 1.19-3.94) (p=0.011). Conclusion The study demonstrates that increased pretransplant ERFE levels are independently associated with 1-year posttransplant all-cause mortality and 1-year acute cellular rejection. This association is in line with results from chronic kidney disease indicating association of ERFE levels with cardiovascular outcome and studies showing iron-induced immune cell activation. In fact, ERFE reduces hepcidin expression as shown in the present and other studies. Thereby, intestinal iron uptake increases resulting in immune cell activation which may explain the higher incidence of heart rejection observed in the present study.FigureTable

#5509 LOW DOSE THYMOGLOBULIN-BASILIXIMAB INDUCTION PROTOCOL ON INCIDENCE OF ACUTE REJECTION AND POSTTRANSPLANT NEOPLASIA: AN OBSERVATIONAL RETROSPECTIVE STUDY

Abstract Background and Aims Induction therapy plays a key role in the prevention of 1-year acute rejection in kidney transplantation. Several studies suggest that depleting drugs, including thymoglobulin (ATG), are superior to anti-CD25 antibodies in reducing the incidence of acute rejection. However, large retrospective investigations demonstrate a close and significant association between the use of depleting agents and the development of post-transplant neoplasia, in particular post-transplant lymphoproliferative disease. Thus, in the attempt to improve the risk/benefit profile of antibody therapy, we implemented an induction protocol based on low-dose ATG and anti-CD25 blocker basiliximab (Bas). The aim of the present study was to evaluate the efficacy and safety of this approach compared to standard dose ATG alone and basiliximab alone. Method This is a an observational, retrospective, single center study including 957 patients receiving a single kidney transplant the Gemelli kidney transplant center from January 2000 to February 2022 The primary efficacy outcome was biopsy proven acute rejection and the primary safety outcome was the development of post-transplant neoplasia. Patients in the ATG group received a cumulative dose of 7mg/kg in the first week after transplantation; patients in the Bas group were administered the anti-CD25 antibody at a dose of 20 mg before surgery and 20 mg 4 days after transplantation. Finally, patients in the ATG-Bas group received ATG at a cumulative concentration of 3mg/kg over the first 6 days after transplantation and Bas at a dose of 20 mg before surgery and 20 mg 4 days after transplantation. Results In our study population we evaluated 154 patients in the standard ATG group, 492 patients in the low AATG-Bas group and 311 patients in the Bas group. No statistical difference for age, mismatches, donor type, donor age, pre-transplant PRA was observed among groups. Use of mTOR inhibitors was more frequent in the standard ATG and low ATG-Bas groups compared to Bas group (80/154, 155/492, 76/311, respectively, p&amp;lt;0.001). We did not observe any significant difference in the use of other maintenance immunosuppressive drugs. Multivariate analysis (Cox model, including number of mismatches, presence of DSA at transplantation and use of mTOR inhibitors) demonstrated that only low ATG-Bas treatment (HR 0.509 95%CI 0.344-0.754, p&amp;lt;0.001), but not standard ATG (HR 0,819 95%CI 0.472-1.423, p = 0.5), was able to reduce the risk for acute rejection compared to Bas alone. On the other hand, multivariate analysis (Cox model including acute rejection, age, use of mTOR inhibitors) demonstrated that standard ATG induction (HR 1.677 95%CI 1.035-2.717, p = 0.03), but not low ATG-Bas (HR 1,324 95%CI 0,930-1,884, p = 0.1), significantly increased the risk for the development of post-transplant neoplasia compared to Bas alone. Conclusion In this retrospective analysis we demonstrated that low ATG-Bas protocol was the most effective treatment in preventing biopsy-proven acute rejection. In addition, on the contrary of standard ATG dose protocol it did not increase the risk of post-transplant neoplasia compared to Bas alone induction therapy.

Comparing outcomes of third and fourth kidney transplantation in older and younger patients

Performing third or fourth kidney transplantation (3KT and 4KT) in older patients is rare due to surgical and immunologic challenges. We aimed to analyze and compare the outcomes of younger (18–64 years) and older (≥65 years) recipients of 3KT and 4KT. Between 1990 and 2016, we identified 5816 recipients of 3KTs (153 were older) and 886 recipients of 4KTs (18 were older). The incidences of delayed graft function (24.3% vs. 24.8%, p = .89), primary non-function (3.2% vs. 1.3%, p = .21), 1-year acute rejection (18.6% vs. 14.8%, p = .24), and 5-year death censored graft failure (DCGF) (24.8% vs. 17.9%, p = .06) were not different between younger and older recipients of 3KT. However, 5-year mortality was higher in older recipients (14.0% vs. 33.8%, p < .001) which remained significant after adjustment (aHR = 3.21, 95% CI: 2.59–3.99). Similar patterns were noted in the 4KT cohort. When compared with waitlisted patients, 3KT and 4KT are associated with a lower risk of mortality; aHR = 0.37, 95% CI: 0.33–0.41 and aHR = 0.31, 95% CI: 0.24–0.41, respectively. This survival benefit did not differ by recipient age (younger vs. older, p for interaction = 3KT: .49 and 4KT: .58). In the largest cohort described to date, we report that there is a survival benefit of 3KT and 4KT even among older patients. Although a highly selected cohort, our results support improving access to 3KT and 4KT.

Prediction of outcomes after heart transplantation by machine learning models

Abstract Background Models based on traditional statistics for the prediction of outcomes after heart transplantation (HT) have moderate accuracy. We sought to develop and validate state-of-the-art machine learning (ML) models to predict mortality and acute rejection after contemporary HT. Methods We included adult HT recipients from the UNOS database between 2010–2018 using solely pre-transplant clinical and laboratory variables. The study cohort was randomly split in a derivation and a validation cohort with a 3:1 ratio. An effective feature selection algorithm was used to identify strong predictors of 1-year mortality and rejection in the training cohort. Results were used to train the ML models, which were then internally tested using the validation cohort. LIME explainability analysis was used for the best performing ML model. A similar subgroup analysis was performed for 3- and 5-year survival. Results The study cohort comprised of 18,625 patients (53±13 years, 73% males). At 1-year after cardiac transplant, there were 2,334 (12.5%) deaths. Out of a total of 134 pre-transplant variables, 39 and 27 were selected as highly predictive of 1-year mortality and acute rejection respectively, and were used in the ML models. Areas under the curve for the prediction of 1-year survival were 0.689, 0.642, 0.649, 0.637, 0.526 for the Adaboost, Logistic Regression, Decision Tree, Support Vector Machine and K-nearest neighbor models respectively, whereas the IMPACT score had an AUC of 0.569. For the prediction of 1-year acute rejection, Adaboost achieved the highest predictive performance (AUC 0.629). LIME explainability analysis identified the relative impact of the 10 strongest predictors of 1-year mortality and acute rejection. Subgroup analysis using a similar methodology for 3- and 5-year survival yielded AUC of 0.609 and 0.610 using 31 and 91 selected variables respectively. Conclusion ML models created and validated using a contemporary cohort of the UNOS database showed improved accuracy in predicting survival and acute rejection after HT. Funding Acknowledgement Type of funding sources: None.

Ambient air pollution and posttransplant outcomes among kidney transplant recipients

Fine particulate matter (PM2.5 ), a common form of air pollution which can induce systemic inflammatory response, is a risk factor for adverse health outcomes. Kidney transplant (KT) recipients are likely vulnerable to PM2.5 due to comorbidity and chronic immunosuppression. We sought to quantify the association between PM2.5 and post-KT outcomes. For adult KT recipients (1/1/2010-12/31/2016) in the Scientific Registry of Transplant Recipients, we estimated annual zip-code level PM2.5 concentrations at the time of KT using NASA's SEDAC Global PM2.5 Grids. We determined the associations between PM2.5 and delayed graft function (DGF) and 1-year acute rejection using logistic regression and death-censored graft failure (DCGF) and mortality using Cox proportional hazard models. All models were adjusted for sociodemographics, recipient, transplant, and ZIP code level confounders. Among 87 233KT recipients, PM2.5 was associated with increased odds of DGF (OR=1.59; 95% CI: 1.48-1.71) and 1-year acute rejection (OR= 1.31; 95% CI: 1.17-1.46) and increased risk of all-cause mortality (HR=1.15; 95% CI: 1.07-1.23) but not DCGF (HR=1.05; 95% CI: 0.97-1.51). In conclusion, PM2.5 was associated with higher odds of DGF and 1-year acute rejection and elevated risk of mortality among KT recipients. Our study highlights the importance of considering environmental exposure as risk factors for post-KT outcomes.

Induction therapy with mesenchymal stromal cells in kidney transplantation: a meta-analysis

ObjectiveThe aim of this meta-analysis was to evaluate the therapeutic effects of mesenchymal stromal cells (MSCs) versus traditional regimens for induction therapy in kidney transplantation (KT), especially the safety of MSC infusion, practicability of MSCs as induction therapy agents, and posttransplant complications.MethodsPubMed, Embase, EBSCO, Ovid, and the Cochrane Library were searched for prospective clinical trials that compared MSCs with traditional regimens for induction therapy in KT.ResultsFour trials were included, including a total of 197 patients. The pooled results revealed that MSC therapy had a lower 1-year infection rate than did the traditional therapies (RR = 0.65, 95% CI: 0.46–0.9, P = 0.01). There were no significant differences between the two protocols regarding the 1-year acute rejection (AR) rate (RR = 0.77, 95% CI: 0.41–1.45, P = 0.42), 1-year graft survival rate (RR = 0.99, 95% CI: 0.95–1.03, P = 0.74), delayed graft function (DGF) rate (RR = 0.54, 95% CI: 0.21–1.38, P = 0.2) and renal graft function at 1 month (MD = −1.56, 95% CI: − 14.2–11.08, p = 0.81), 3 months (MD = 0.15, 95% CI: − 5.63–5.93, p = 0.96), 6 months (MD = − 1.95, 95% CI: − 9.87–5.97, p = 0.63), and 12 months (MD = − 1.13, 95% CI: − 7.16–4.89, p = 0.71) postsurgery. Subgroup analysis demonstrated that the 1-year AR rate, 1-year graft survival rate, DGF rate, and renal graft function at 12 months postsurgery did not significantly differ between the low-dose calcineurin inhibitor (CNI) group and the standard-dose CNI group, indicating the potential benefits of successful CNI sparing in combination with MSC treatment. Moreover, when MSCs were applied as an alternative therapy rather than an additional therapy or allogeneic MSCs were utilized instead of autologous MSCs, all of the outcomes mentioned above were comparable.ConclusionInduction therapy with MSCs is safe and has similar immune response modulation effects to those of traditional regimens in the short term in KT recipients. However, regarding the long-term effects, as suggested by the 1-year infection rate and the potential of CNI sparing, MSC therapy has significant advantages. However, these advantages should be further verified in more well-designed, multicenter randomized controlled trials (RCTs) with large sample sizes and long follow-up periods.

Outcomes of kidney retransplantation in recipients with prior posttransplant lymphoproliferative disorders: An analysis of the 2000-2019 UNOS/OPTN database.

This study utilized the UNOS database to assess clinical outcomes after kidney retransplantation in patients with a history of posttransplant lymphoproliferative disease (PTLD). Among second kidney transplant patients from 2000 to 2019, 254 had history of PTLD in their first kidney transplant, whereas 28,113 did not. After a second kidney transplant, PTLD occurred in 2.8% and 0.8% of patients with and without history of PTLD, respectively (p=.001). Over a median follow-up time of 4.5years after a second kidney transplant, 5-year death-censored graft failure was 9.5% vs. 12.6% (p=.21), all-cause mortality was 8.3% vs. 11.8% (p=.51), and 1-year acute rejection was 11.0% vs. 9.3% (p=.36) in the PTLD vs. non-PTLD groups, respectively. There was no significant difference in death-censored graft failure, mortality, and acute rejection between PTLD and non-PTLD groups in adjusted analysis and after propensity score matching. We conclude that graft survival, patient survival, and acute rejection after kidney retransplantation are comparable between patients with and without history of PTLD, but PTLD occurrence after kidney retransplantation remains higher in patients with history of PTLD.

Extracorporeal membrane oxygenation bridge to heart transplant: Trends following the allocation change.

This study compared outcomes of patients bridged with extracorporeal membrane oxygenation (ECMO) to orthotopic heart transplantation (OHT) following the recent heart allocation policy change. The United Network of Organ Sharing Registry (UNOS) database was queried to examine OHT patients between 2010 and 2020 that were bridged with ECMO. Waitlist outcomes and 1-year posttransplant survival were compared between patients waitlisted and/or transplanted before and after the heart allocation policy change. Secondary outcomes included posttransplant stroke, renal failure, and 1-year rejection. A total of 285 waitlisted patients were included, 173 (60.7%) waitlisted under the old policy and 112 (39.3%) under the new policy. New policy patients were more likely to receive OHT (82.2% vs. 40.6%), and less likely to be removed from the waitlist due to death or clinical deterioration (15.0% vs. 41.3%; both p < .001). A total of 165 patients bridged from ECMO to OHT were analyzed, 72 (43.6%) transplanted during the old policy and 93 (56.3%) under the new. Median waitlist time was reduced under the new policy (4 days [interquartile range {IQR}: 2-6] vs. 47 days [IQR: 10-228]). Postoperative renal failure was higher in the new policy group (23% vs. 6%; p = .002), but rates of stroke and 1-year acute rejection were equivalent. One-year survival was lower the new policy but was not significant (79.8% vs. 90.3%; p = .3917). The UNOS heart allocation policy change has resulted in decreased waitlist times and higher likelihood of transplant in patients supported with ECMO. Posttransplant 1-year survival has remained comparable although absolute rates are lower.

PANEL REACTIVE ANTIBODY AND THE ASSOCIATION OF EARLY STEROID WITHDRAWAL WITH KIDNEY TRANSPLANT OUTCOMES

Introduction: Early steroid withdrawal (ESW) is a viable maintenance immunosuppression strategy in certain low-risk kidney transplant recipients. A low panel reactive antibody (PRA) may indicate low-risk condition amenable to ESW. We aimed to identify the threshold value of PRA above which ESW may pose additional risk, and to compare the association of ESW with transplant outcomes across PRA strata. Materials and Methods: Using the US national registry data, we studied 121,699 deceased-donor kidney-only recipients in 2002-2017. Using natural splines and ESW-PRA interaction terms, we explored how the associations of ESW with transplant outcomes change with increasing PRA values, and discovered rapid exacerbation in PRA>60 (Figure 1). Then, we assessed whether PRA>60 modifies the associations of ESW with 1-year acute rejection, death-censored graft failure, and death.Results: Among PRA≤60 recipients, ESW was associated with a minor increase in rejection (aOR=1.001.051.10) and with a tendency of decreased graft failure (aHR=0.910.971.03; Table 1). However, among PRA>60 recipients, ESW was associated with a substantial increase in rejection (aOR=1.191.271.36; interaction p<0.001) and with a tendency of increased graft failure (aHR=0.981.081.20; interaction p=0.028). The association of ESW with death was similar between PRA strata (PRA≤60, aHR=0.910.961.01; and PRA>60, aHR=0.900.991.09; interaction p=0.5).Conclusion: The associations of ESW with rejection and graft failure were significantly more adverse in recipients with high PRA, especially those above 60. PRA should be considered in the risk assessment for ESW tailoring. American Society of Nephrology. National Institutes of Health.

Degree of Glomerulosclerosis in Procurement Kidney Biopsies from Marginal Donor Kidneys and Their Implications in Predicting Graft Outcomes.

Background: This study aimed to assess the association between the percentage of glomerulosclerosis (GS) in procurement allograft biopsies from high-risk deceased donor and graft outcomes in kidney transplant recipients. Methods: The UNOS database was used to identify deceased-donor kidneys with a kidney donor profile index (KDPI) score > 85% from 2005 to 2014. Deceased donor kidneys were categorized based on the percentage of GS: 0–10%, 11–20%, >20% and no biopsy performed. The outcome included death-censored graft survival, patient survival, rate of delayed graft function, and 1-year acute rejection. Results: Of 22,006 kidneys, 91.2% were biopsied showing 0–10% GS (58.0%), 11–20% GS (13.5%), >20% GS (19.7%); 8.8% were not biopsied. The rate of kidney discard was 48.5%; 33.6% in 0–10% GS, 68.9% in 11–20% GS, and 77.4% in >20% GS. 49.8% of kidneys were discarded in those that were not biopsied. Death-censored graft survival at 5 years was 75.8% for 0–10% GS, 70.9% for >10% GS, and 74.8% for the no biopsy group. Among kidneys with >10% GS, there was no significant difference in death-censored graft survival between 11–20% GS and >20% GS. Recipients with >10% GS had an increased risk of graft failure (HR = 1.27, p < 0.001), compared with 0–10% GS. There was no significant difference in patient survival, acute rejection at 1-year, and delayed graft function between 0% and 10% GS and >10% GS. Conclusion: In >85% KDPI kidneys, our study suggested that discard rates increased with higher percentages of GS, and GS >10% is an independent prognostic factor for graft failure. Due to organ shortage, future studies are needed to identify strategies to use these marginal kidneys safely and improve outcomes.

Early Conversion to Tacrolimus Vs Cyclosporine Continuation in Normally Functioning Kidney Allograft: A Single-Center Study.

This study evaluated the effectiveness of early pre-emptive conversion from cyclosporine to tacrolimus in kidney transplant patients with normal graft function and in the absence of adverse effects of the initial cyclosporine. A historical cohort study of 166 patients who received deceased-donor kidney transplant between 2011 to 2017 was conducted. All the patients had been treated with cyclosporine (Sandimmune®) during their immediate post-transplantation period. At the time of hospital discharge, the patients were divided into 2 groups: patients with continued cyclosporine (Sandimmune®) treatment (n = 125) and the patients whose treatments converted from cyclosporine to tacrolimus (Prograf®) at discharge (n = 41). The 1-year graft function (p = 0.074), acute rejection (p = 0.566), and graft loss (p = 0.566) were not significantly different between two groups. The patients on tacrolimus had lower levels of cholesterol (p = 0.002) and diastolic blood pressure (p = 0.015). The long-term follow-up showed no significant difference in graft loss (p = 0.566). The patients received tacrolimus had higher all-cause mortality within the first year posttransplantation (p = 0.002) as well as long-term follow-up (p = 0.001). The continuation of initial cyclosporine might be a good option when the graft function is acceptable and the adverse effects are absent.

Combination of calcineurin and mTOR inhibitors in kidney transplantation: a propensity score analysis based on current clinical practice.

The TRANSFORM study demonstrated that an immunosuppression based on a combination of calcineurin inhibitors and de-novo mTOR inhibitors (mTORi) is safe and effective in kidney transplant recipients. However, data that validate this approach in clinical practice are currently missing. Analysis of 401 kidney transplant recipients transplanted from June 2013 to December 2016. All patients received tacrolimus with prednisone in combination with either mycophenolate (n = 186) or mTORi (either everolimus or sirolimus, n = 215). A propensity score to receive mTORi was calculated based on the inverse probability of treatment weighting (IPTW) from the following parameters: age and sex of donor and recipient, BMI, previous transplants, diabetes, cPRA, dialysis before transplantation, dialysis vintage, type of donor, ABO-incompatibility, HLA-mismatches, induction and ischemia time. Median follow-up was 2.6 [1.9; 3.7] years. Cox-regression analysis suggests good results for mTORi versus MPA in terms of 1-year biopsy-proven acute rejection (BPAR, P = 0.063), 1-year graft loss (P = 0.025) and patient survival (P < 0.001). Results observed for BPAR and graft failure were largely attributed to those patients that would have been excluded by the TRANSFORM because of some exclusion criteria (52.9% of the population, P = 0.003 for 1-year BPAR and P = 0.040 for graft loss). In patients who met selection criteria for TRANSFORM, no effect of treatment for BPAR or graft failure was observed, while the beneficial effect on overall survival persisted. In a real-life setting, a protocol based on de-novo mTORi with tacrolimus and prednisone could be employed as a standard immunosuppressive regimen and was associated with good outcomes.

Induction type and outcomes for kidney graft and patient survival in recipients with prior lung transplantation in the United States

Induction immunosuppression regimens for kidney transplants in lung transplant recipients vary widely. We studied the impact of induction types for kidney after lung transplant recipients. Using the Scientific Registry of Transplant Recipients database between 1994 and 2015, we studied outcomes of patients and kidney grafts for 330 kidney after lung transplant recipients for whom induction before kidney transplant included depletional (n = 115), non-depletional (n = 170), or no induction (steroids only; n = 45). We studied risk factors for recipient and graft survival using Cox proportional hazards model adjusted for kidney and lung induction, kidney donor type, dialysis status, recipient and donor ages, time from lung to kidney transplant, cause of lung disease, bilateral vs single lung transplant, diabetes, and human leukocyte antigen mismatches before kidney transplant, with transplant center as a random effect. There was no difference between groups in patient survival or death-censored kidney allograft survival. The 1-year kidney acute rejection rates were 15.5%, 7.14%, and 0% in depletional, non-depletional, and no induction groups, respectively. In the Cox model for patient survival, living kidney donor recipients and bilateral lung transplant recipients were favorable predictors. For death-censored graft survival, kidney induction type did not predict graft survival. Results did not change when models only included recipients on tacrolimus and mycophenolate based maintenance. The type of kidney induction did not influence patient or kidney graft survival following kidney transplants for those with previous lung transplants. No induction may be the preferred choice for kidney after lung transplant because of the lack of benefits from biologic induction in this large cohort.

National Trends in Liver Transplantation in Older Adults.

To explore trends in liver transplantation (LT) and outcomes for older recipients for evaluation, counseling, and appropriate referral of this vulnerable group of older adults. Prospective national cohort study. Scientific Registry of Transplant Recipients (January 1, 2003-December 31, 2016). Older (aged ≥ 65) deceased donor liver-only transplant recipients (n=8,627). We evaluated temporal changes in recipient, donor, and transplant characteristics and post-LT length of stay (LOS), acute rejection, graft loss, and mortality using logistic regression and Cox proportional hazards. LT in older adults almost quadrupled, from 263 in 2003 (9.5% of total LTs that year) to 1,144 in 2016 (20.7% of total LTs). Recent recipients were more likely to be female and African American and have a higher body mass index and Model for End-Stage Liver Disease score. Hepatitis C, nonalcoholic steatohepatitis, and hepatocellular carcinoma were the most common indications for LT in recent recipients. Odds of LOS longer than 2 weeks decreased 34% from 2003-06 to 2013-16 (adjusted odds ratio (aOR)=0.66, 95% confidence interval (CI)=0.57-0.76, P < .001), 1-year acute rejection decreased 30% (aOR=0.70, 95% CI=0.56-0.88, P = .002), all-cause graft loss decreased 54% (adjusted hazard ratio (aHR)=0.46, 95% CI=0.40-0.52, P < .001), and mortality decreased 57% (aHR=0.43, 95% CI=0.38-0.49, P < .001). Despite the substantial increase in the number of older adults undergoing LT and the severity of their condition, LOS, rejection, graft loss, and mortality have significantly decreased over time. These trends can help guide appropriate LT referral and counseling in older adults with end-stage liver disease. J Am Geriatr Soc 66:2321-2326, 2018.

Comparative efficacy and safety of antibody induction therapy for the treatment of kidney: a network meta-analysis

To evaluate the efficacy and safety of antibody induction therapies in kidney transplantation. Systematic literature searches were undertaken using MEDLINE, Embase, and Cochrane Library database from 1980 to 2016. Randomized controlled trials (RCTs) comparing three antibody induction therapies (alemtuzumab, interleukin-2 receptor antibodies and antithymocyte globulin) between each other were identified. Bayesian network meta-analysis was used to combine both the direct and indirect evidence on treatment efficacy and its safety. Antibody induction therapy studies, comprising of 18 RCTs (3444 kidney transplant recipients), were included. Overall, alemtuzumab treatment was superior to the ATG group (OR: 0.49, 95% CI: 0.32 to 0.71) and IL-2RAs group (OR: 0.36, 95% CI: 0.25 to 0.52) for reducing the 1-year acute rejection in kidney transplant recipients. Although alemtuzumab treatment was nearly same with ATG group and IL-2RAs group in improving patient survival and renal function, it can reduce the adverse effects of cytomegalovirus infection more efficiently than ATG group (OR: 0.59, 95% CI: 0.32 to 0.95) and IL-2RAs group (OR: 1.08, 95% CI: 0.61 to 1.73). Alemtuzumab was not associated with increased other adverse effects. Alemtuzumab treatment is safe and effective for kidney transplant recipients. No serious adverse effects were observed in trials or in general populations.

Analysis of Risk Factors for Kidney Retransplant Outcomes Associated with Common Induction Regimens: A Study of over Twelve-Thousand Cases in the United States.

We studied registry data of 12,944 adult kidney retransplant recipients categorized by induction regimen received into antithymocyte globulin (ATG) (N = 9120), alemtuzumab (N = 1687), and basiliximab (N = 2137) cohorts. We analyzed risk factors for 1-year acute rejection (AR) and 5-year death-censored graft loss (DCGL) and patient death. Compared with the reference, basiliximab: (1) one-year AR risk was lower with ATG in retransplant recipients of expanded criteria deceased-donor kidneys (HR = 0.56, 95% CI = 0.35–0.91 and HR = 0.54, 95% CI = 0.27–1.08, resp.), while AR risk was lower with alemtuzumab in retransplant recipients with >3 HLA mismatches before transplant (HR = 0.63, 95% CI = 0.44–0.93 and HR = 0.81, 95% CI = 0.63–1.06, resp.); (2) five-year DCGL risk was lower with alemtuzumab, not ATG, in retransplant recipients of African American race (HR = 0.54, 95% CI = 0.34–0.86 and HR = 0.73, 95% CI = 0.51–1.04, resp.) or with pretransplant glomerulonephritis (HR = 0.65, 95% CI = 0.43–0.98 and HR = 0.82, 95% CI = 0.60–1.12, resp.). Therefore, specific risk factor-induction regimen combinations may predict outcomes and this information may help in individualizing induction in retransplant recipients.

Outcomes Associated with Steroid Avoidance and Alemtuzumab among Kidney Transplant Recipients.

Alemtuzumab is a humanized anti-CD52 monoclonal antibody used as induction in kidney transplantation (KTX) since 2003. Few studies have evaluated long-term outcomes of this agent or changes in outcomes over time. A retrospective cohort study was performed examining United States registry data from 2003 to 2014 of primary KTX recipients receiving induction with alemtuzumab (AZ; n=5521) or antithymocyte globulin (ATG; n=8504) and maintenance immunosuppression with tacrolimus and mycophenolate mofetil and early withdrawal of steroids. The primary outcome was overall death-censored graft survival (DCGS), and secondary outcomes were overall patient survival and 1-year acute rejection. Multivariate models were fit with donor, recipient, and transplant covariates. Because poorer outcomes with AZ may occur from a learning curve impact with the use of a new medication, transplant year was categorized into three time periods to evaluate outcomes over time (2003-2005, 2006-2008, ≥2009), and an interaction term of induction type with transplant year category was included in all models to test for era impacts. On multivariate analysis of DCGS there was a significant interaction between AZ and era (P<0.001). AZ was significantly associated with inferior DCGS in the earliest 2003-2005 era (adjusted hazard ratio [aHR], 2.21; 95% confidence interval [95% CI], 1.72 to 2.84) but not in the middle 2006-2008 era (aHR, 1.14; 95% CI, 0.96 to 1.36) or the most recent 2009-2014 era (aHR, 1.08; 95% CI, 0.90 to 1.29) compared with ATG. Risk-adjusted patient survival (aHR, 1.32; 95% CI, 1.08 to 1.61; aHR, 1.26; 95% CI, 1.09 to 1.46; and aHR, 1.10; 95% CI, 0.93 to 1.29 by era, respectively) and acute rejection (adjusted odds ratio [aOR], 1.17; 95% CI, 0.96 to 1.42; aOR, 0.94; 95% CI, 0.82 to 1.07; aOR, 0.89; 95% CI, 0.81 to 0.98 by era, respectively) with AZ was comparable with ATG in the most recent era; however, there was no significant interaction with time (P=0.13 and P=0.06, respectively). Current alemtuzumab utilization is associated with comparable graft and patient survival and acute rejection compared with ATG. Graft survival with alemtuzumab has improved over time.