Acute Rejection Rates Research Articles

Target of rapamycin inhibitors (TOR-I; sirolimus and everolimus) for primary immunosuppression in kidney transplant recipients.

Target of rapamycin inhibitors (TOR-I; sirolimus and everolimus) for primary immunosuppression in kidney transplant recipients.

Renal Transplant Outcomes in Spousal and Living-Related Donors in Malaysia

Studies have shown that a compatible human leukocyte antigen (HLA) match can confer a favourable effect on graft outcomes. We examined the outcomes of HLA matching in renal transplant donors in Malaysia. A total of 140 patients who had compatible ABO blood type with negative T-cell lymphocytotoxicity crossmatch were included in the study and 25% of them were spousal transplant donors. No remarkable differences in acute rejection rate, graft survival, patient survival and serum creatinine level were observed between the spousal and living-related donor groups. The spousal donor group had a higher degree of HLA mismatch than the living-related donor group. HLA-A mismatch was associated with increased rejection risk at 6 months (odds ratio [OR], 2.75; P = 0.04), 1 year (OR, 2.54; P = 0.03) and 3 years (OR, 3.69; P = 0.001). It was also observed in the deleterious effects of HLA-B and HLA-DQ loci when the number of antigen mismatches increased. The risk was 7 times higher in patients with ≥1 mismatch at HLA-A, HLA-B and HLA-DR loci than those who did not have a mismatch at these loci at 6 months (P = 0.01), 1 year (P = 0.03) and 3 years (P = 0.003). A good match for HLA-A, HLA-B, HLA-DR and HLA-DQ can prevent acute rejection risk in renal transplant patients. Consequently, spousal donor transplants could be a safe intervention in renal patients.

Long-term outcomes of pediatric kidney transplantation: A single-center experience over the past 34years in Japan.

To evaluate long-term outcomes and risk factors for graft loss in pediatric kidney transplantation over a 30-year period. We retrospectively assessed 400 consecutive kidney transplants carried out in 377 children during 1975-2009. Patients were stratified according to the immunosuppressive regimen (era1: methylprednisolone and azathioprine; era2: calcineurin inhibitor-based therapy, including methylprednisolone and azathioprine or mizoribine; era3: basiliximab induction therapy, including calcineurin inhibitors, methylprednisolone and mycophenolate mofetil). The median age and bodyweight at transplantation were 9.7years and 20.6kg, respectively. In total, 364 (91.0%) children received a living related donor transplantation. The acute rejection rate within 1year post-transplant decreased significantly from 61.0% in era1 to 14.5% in era3 (P<0.001). For transplant eras1-3, 1-year graft survival was 81%, 93% and 95%; 5-year graft survival was 66%, 86% and 93%; and 10-year graft survival was 47%, 79% and 89%, respectively. The overall 5-, 10- and 20-year patient survival rates were 96%, 93% and 88%, respectively. A Cox multivariate analysis identified cold ischemia time (hazard ratio 1.385, 95% confidence interval 1.251-1.603), acute rejection (hazard ratio 1.682, 95% confidence interval 1.547-3.842), re-transplant (hazard ratio 2.680, 95% confidence interval 1.759-3.982) and donor type (hazard ratio 2.957, 95% confidence interval 1.754-4.691) as independent risk factors for graft loss at 10years post-transplant. The progress of immunosuppressive therapy has led to a low incidence of acute rejection and a high graft survival rate across 30years of pediatric transplantation.

Should we use kidneys from donors with acute kidney injury for renal transplantation?

The scarcity of donor organs for transplant results in long waiting times for kidney transplantation and low transplant rate worldwide. Utilization of kidneys from donors with acute kidney injury (AKI) is one of the strategies that has attracted attention recently. This article reviewed the outcomes of transplanted renal allografts from donors with acute kidney injury. Key findings about the transplant outcomes included a higher incidence of delayed graft function and primary non function, but respectable outcomes in the context of similar acute rejection rates, and graft function and graft survival. Against this background and with evidence of high mortality for patients remaining on waiting list of transplant, we advocate consideration of AKI donors for kidney transplantation.

A Comparison of Different Valgancyclovir Formulations in the Universal 6-Month Prophylaxis Against CMV Infection in Renal Transplant Recipients: A Randomized Single-Centre Study.

Cytomegalovirus (CMV) is the most common opportunistic infective pathogen in kidney transplant recipients. Valganciclovir (VAL) is commonly used for prophylaxis, especially in high-risk recipients. Generic VAL formulations have become available, but the data about their safety and efficacy are lacking. Consecutive de novo kidney transplant patients were randomized to generic VAL Valganciklovir Teva® (VT group)(24 patients) or Alvanocyte® (A group), Alvogen (19 patients) or to Valcyte® (V group), Roche (23 patients) in a 18-month open-label study. Universal prophylaxis was used for 6 months after the transplantation. CMV DNA levels were measured at 1,3,6,9,12 and 18 months after the transplantation. All positive measurements of CMV DNA were recorded. Groups did not differ regarding the clinical characteristics or the risk for developing CMV infection in the post-transplant period. CMV replications were most common at 9 months after the transplantation with rates of 9% for the V, 13% for the VT and 26% for the A group (p=0.26). At 12 months, positive CMV DNA was recorded in 22%, 8% and 11 % of patients taking V, VT and A, respectively (p=0.37). Rates of biopsy-proven acute rejection, adverse events, and serious adverse events were similar for all formulations. Lymphocele occurred most commonly in the V group (35%) compared to 17% in VT and 17% in the A group (p=0.23). One patient from each of the A and VT groups developed CMV disease. Additionally, they were the only two patients with CMV DNA copies above 656 IU/ml. Glomerular filtration rates were similar in all groups at all time points, while proteinuria was significantly higher at 12 months in patients who received V 0.32 g/day (0.18 - 0.42), compared to patients on VT 0.2 (0.1 - 0.2), or A 0.2 (0.2 - 0.3), p=0.04. Valgancyclovir efficacy and safety in this limited data set is similar with early administration of V, VT and A after kidney transplantation. Additional studies aimed at elucidating the effectiveness of this treatment regimen in patients who are at high risk for developing CMV infection are necessary to draw further conclusions.

Association of diagnosed obstructive sleep apnea with kidney transplant outcomes.

Obstructive sleep apnea (OSA) is common but underdiagnosed among patients with kidney disease. This study examines whether the diagnosis of OSA in kidney transplant recipients (KTR) affected death, death-censored graft failure (DCGF), and acute rejection (AR). We analyzed the records of KTR who underwent transplant between 2000 and 2015. A total of 4014 kidney transplants were performed during the study period. Of these, 415 (10.3%) had a diagnosis of pretransplant OSA. Pretransplant OSA was associated with a higher risk of death in unadjusted analyses. After adjustment for potential confounders, pretransplant OSA was not associated with risk of death (HR=1.04, 95% CI: 0.80-1.36). Similarly, pretransplant OSA was associated with a slightly higher incidence of DCGF or AR but neither associations were significant (HR: 1.23, 95% CI: 0.85-1.47 for DCGF; HR 1.10, 95% CI: 0.90-1.36 for AR). A total of 117 (3.3%) were diagnosed with de novo OSA after transplant. Similar to the pretransplant OSA, unadjusted HR for death was significantly higher in the de novo OSA group (HR: 1.48, 95% CI: 1.19-1.84); however, after adjustment, de novo OSA was not significantly associated with risk of death (HR: 1.15, 95% CI: 0.92-1.45). Similarly, DCGF and AR rates were not significantly associated with de novo OSA (HR: 1.10, 95% CI: 0.84-1.44 for DCGF; HR 1.10, 95% CI: 0.90-1.33 for AR). Our work did not detect significant associations between OSA and risk of death, graft failure, and rejection but the estimates might be underestimated due to underdiagnosis of OSA.

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.

Kidney transplant outcomes in HIV-positive patients: a systematic review and meta-analysis

BackgroundKidney transplantation is now a viable alternative to dialysis in HIV-positive patients who achieve good immunovirological control with the currently available antiretroviral therapy regimens. This systematic review and meta-analysis investigate the published evidence of outcome and risk of kidney transplantation in HIV-positive patients following the PRISMA guidelines.MethodsSearches of PubMed, the Cochrane Library and EMBASE identified 27 cohort studies and 1670 case series evaluating the survival of HIV-positive kidney transplant patients published between July 2003 and May 2018. The regimens for induction, maintenance therapy and highly active antiretroviral therapy, acute rejection, patient and graft survival, CD4 count and infectious complications were recorded. We evaluated the patient survival and graft survival at 1 and 3 years respectively, acute rejection rate and also other infectious complications by using a random-effects analysis.ResultsAt 1 year, patient survival was 0.97 (95% CI 0.95; 0.98), graft survival was 0.91 (95% CI 0.88; 0.94), acute rejection was 0.33 (95% CI 0.28; 0.38), and infectious complications was 0.41 (95% CI 0.34; 0.50), and at 3 years, patient survival was 0.94 (95% CI 0.90; 0.97) and graft survival was 0.81 (95% CI 0.74; 0.87).ConclusionsWith careful selection and evaluation, kidney transplantation can be performed with good outcomes in HIV-positive patients.

Proceedings From the Clinical and Scientific Innovations in Oral and Maxillofacial Surgery Conference 2019

Proceedings From the Clinical and Scientific Innovations in Oral and Maxillofacial Surgery Conference 2019

High-risk Corneal Transplantation: Recent Developments and Future Possibilities.

Human corneal transplantation (keratoplasty) is typically considered to have superior short- and long-term outcomes and lower requirement for immunosuppression compared to solid organ transplants because of the inherent immune privilege and tolerogenic mechanisms associated with the anterior segment of the eye. However, in a substantial proportion of corneal transplants, the rates of acute rejection and/or graft failure are comparable to or greater than those of the commonly transplanted solid organs. Critically, while registry data and observational studies have helped to identify factors that are associated with increased risk of corneal transplant failure, the extent to which these risk factors operate through enhancing immune-mediated rejection is less clear. In this overview, we summarize a range of important recent clinical and basic insights related to high-risk corneal transplantation, the factors associated with graft failure, and the immunological basis of corneal allograft rejection. We highlight critical research areas from which continued progress is likely to drive improvements in the long-term survival of high-risk corneal transplants. These include further development and clinical testing of predictive risk scores and assays; greater use of multicenter clinical trials to optimize immunosuppressive therapy in high-risk recipients and robust clinical translation of novel, mechanistically-targeted immunomodulatory and regenerative therapies that are emerging from basic science laboratories. We also emphasize the relative lack of knowledge regarding transplant outcomes for infection-related corneal diseases that are common in the developing world and the potential for greater cross-pollination and synergy between corneal and solid organ transplant research communities.

Efficacy of interleukin 10 gene hydrofection in pig liver vascular isolated 'in vivo' by surgical procedure with interest in liver transplantation.

AimLiver transplantation is the only curative strategy for final stage liver diseases. Despite the great advances achieved during the last 20 years, the recipient immune response after transplantation is not entirely controlled. This results in high rates of acute cell rejection and, approximately, 10% of early mortality. Therapeutic treatment could be improved by efficiently transfecting genes that encode natural immunosuppressant proteins, employing safe procedures that could be transferred to clinical setting. In this sense, interleukin 10 plays a central role in immune tolerance response by acting at different levels.MethodshIL10 gene was hydrofected by retrograde hydrodynamic injection in pig liver with complete vascular exclusion mediated by an ‘in vivo’ surgical procedure. Levels of IL10 DNA, RNA and protein were determined within liver tissue 1 and 10 days after the injection and, more frequently, also the interleukin-10 protein in peripheral blood.ResultsThe procedure was safe for the animals and neither hemodynamic parameters nor liver function determinations showed relevant alterations. The hIL10 hydrofection in watertight liver mediated efficient gene transfer and this was transcribed and translated to protein, achieving up to 110 pg/ml of IL10 in peripheral blood. This value is close to that considered able to reduce the activity of TNFα by half (IL10 IC50 for TNFα = 124 pg/ml).ConclusionsResults of this work suggest that IL10 liver hydrofection with vascular exclusion in vivo is a safe and transferable procedure that mediates plasma protein levels with potential clinical interest in immune modulation after transplantation.

232.5: Rate of opportunistic infection within 3 years after renal transplant using induction with alemtuzumab versus basiliximab.

Background: Induction immunosuppression in organ transplantation has yielded improved early graft function and decreased acute-rejection rates. However, infection risk remains a topic of investigation, particularly between different induction agents. The aim of our study was to compare clinical outcomes during the first 3-years after renal transplantation, with the focus on opportunistic infections, in patients who received either alemtuzumab or basiliximab for induction therapy. Methods: We included all renal transplant recipients from our center who received induction with alemtuzumab between 2011 and 2016. These patients were matched 1:2 (by age and date of transplant) to renal transplant recipients who received basiliximab. Electronic medical records were searched for evidence of the following opportunistic infections within the first 3 years after transplant; BK virus, CMV, VZV, HSV, Cryptococcus, and Histoplasma. Continuous variables were compared using t-tests or Wilcoxon rank-sum tests and categorical variables using Fisher’s tests or chi-square tests. Binary outcomes were compared using Cochran-Mantel-Haenszel tests. Time-to-event outcomes were plotted using the Kaplan-Meier method and compared between groups using log-rank tests. Results: Patients’ demographics and select results are presented in the Table. There were no statistically significant differences in delayed graft function (p = 0.76), graft loss (p = 0.99), or rejection (p = 0.2). Opportunistic infection rates were also not significantly different during the first 3-years post-transplantation (p = 0.87). Time-to-infection (Figure 1) (p = 0.67), time-to-death (p=0.21), and time-to-rejection (p = 0.098) were similar in both groups Conclusions: Despite a difference in immunological risk between the 2 groups, we did not detect any significant differences in outcomes at 3-years post-transplantation between higher immunological risk patients receiving alemtuzumab and lower immunological risk patients receiving basiliximab. Despite previous concerns about CMV reactivation with Alemtuzumab use, infection rates were similar between groups. Surprisingly, no fungal infections were detected at 3-years post-transplant, which may represent a delay in detection of any potential risk differences.

Randomized controlled trial assessing the impact of everolimus and low-exposure tacrolimus on graft outcomes in kidney transplant recipients.

This was a single-center, randomized controlled trial assessing the impact of a 3-month (10-16weeks) conversion to everolimus with low-exposure tacrolimus, as compared to remaining on full exposure tacrolimus with mycophenolate (NCT02096107). Adult kidney transplant recipients with a functioning graft were eligible for participation. Goal troughs in the intervention arm were 2-5ng/mL for tacrolimus and 3-8ng/mL for everolimus, with tacrolimus maintained at 5-12ng/mL in the control arm; 60 were randomized (30 in each arm) and were well matched at baseline; mean age was 51years and 57% were African-American. At 12-months, fibrosis scores (27.8% tacrolimus/mycophenolate vs 22.9% tacrolimus/everolimus, P=.391), acute rejection rates (7% tacrolimus/mycophenolate vs 3% tacrolimus/everolimus, P=.554), and graft function (mean eGFR tacrolimus/mycophenolate 56±15 vs tacrolimus/everolimus 59±14mL/min/1.73m2 , P=.465) were similar between arms. The everolimus arm had significantly lower rates of CMV infection, severe BK infection, and improved BK viral clearance kinetics, as compared to the MPA arm. In this population, including a significant number of African-Americans, an immunosuppression regimen of everolimus with low-exposure tacrolimus provided similar efficacy to tacrolimus and mycophenolate, with significantly lower rates of BK and CMV.

Once-daily prolonged-release tacrolimus versus twice-daily tacrolimus in liver transplantation

ObjectiveFor patients who have received a kidney transplant, studies have shown that once-daily prolonged-release tacrolimus (TAC) has similar efficacy and safety to standard twice-daily dosing. The purpose of this study was to perform a meta-analysis to compare the effectiveness and safety of daily TAC (TAC qd) versus standard twice-daily TAC (TAC bid) administration in liver transplantation (LT). DesignMeta-analysis. Setting and participantsWe systematically searched the PubMed/MEDLINE, Web of Science, and Cochrane Library databases for studies comparing outcomes of LT patients who received TAC qd versus TAC bid. Outcome measuresResults were reported as odds ratios (ORs) with 95% CIs. ResultsSix studies, which included 5179 LT recipients (TAC qd = 951; TAC bid = 4228) were included in the analysis. The TAC qd group had a low 1-year graft loss rate (OR 0.70 [95% CI 0.54–0.91], P = 0.008) and lower rate of biopsy-proven acute rejection (BPAR) at 90 days (OR 0.46 [95% CI 0.24–0.89], P = 0.02) compared with the TAC bid group. There was no significant difference in 1-year mortality or the incidence of adverse events after LT between the 2 groups. ConclusionsCurrent evidence suggests that TAC qd is safe and effective for LT patients during the first year after transplantation. Longer-term follow-up studies are necessary to determine if TAC qd is safe and effective beyond the first year after LT.

Anti-IL-2R blockers comparing with polyclonal antibodies: Higher risk of rejection without negative mid-term outcomes after ABO-incompatible kidney transplantation.

There is no recommendation regarding the type of induction therapy to use in ABO-incompatible (ABOi) kidney transplantation. The aim of this retrospective study was to compare the outcome of ABOi living donor kidney transplant (LDKT) recipients who received either polyclonal antibodies or anti-interleukin-2 receptor (IL-2R) blockers as an induction agent. All ABOi HLA-compatible patients that received a LDKT between 03/11 and 03/18 in three French transplantation center (Paris Saint-Louis, Paris Necker, and Toulouse) were included in the study. Fifty-eight patients were given polyclonal antibodies and 39 patients received anti-IL-2R blockers. We identified by a Cox proportional hazard model the use of polyclonal antibodies as a protective factor against acute rejection (HR=0.4, 95%CI [0-0.9], P<.05). However, pathological findings on protocol biopsies at 1year were similar in both groups, as were patient and graft survivals, renal function, and complications. We conclude that the acute rejection rate was significantly higher in patients given anti-IL-2R blockers compared to polyclonal antibodies. However, in our series, there was no negative impact on mid-term outcome.

A Single-Center Experience of the Optimal Initial Immunosuppressive Strategy for Preventing Early Acute Cellular Rejection in Orthotopic Heart Transplantation Associated With Renal Dysfunction.

Renal dysfunction is a common complication following heart transplantation that may be worsened by the early initiation of calcineurin inhibitors. Antithymocyte globulin (ATG) or basiliximab has been used to delay or avoid calcineurin inhibitors. The most effective strategy for preventing early acute cellular rejection in this context is uncertain. We retrospectively reviewed all heart transplant cases between January 2012 and June 2017. The standard therapy consisted of mycophenolate mofetil, prednisolone, and tacrolimus. In patients at high risk of post-transplant renal dysfunction, an early calcineurin inhibitor-free regimen with basiliximab and/or ATG was used. Patients were assigned to cohorts based on the initial immunosuppressive strategy. The primary end point was the freedom rate of acute cellular rejection within 4 weeks post-transplant. Of 93 cases, 21 patients received standard therapy, 64 patients received an initial calcineurin inhibitor-free regimen with basiliximab, and 8 patients received ATG and basiliximab. Freedom from acute rejection was greater in the ATG plus basiliximab group (all rejection free), compared to 40 (63%) of 64 patients treated with basiliximab and 10 (48%) of 21 patients treated with standard therapy (P < .05, log rank test). In patients treated with basiliximab, early administration (<24 hours) was associated with a higher freedom from acute rejection compared to ≥24 hours, (72% vs 29%, P < .05). The combination of ATG and basiliximab was more effective in preventing acute cellular rejection. In those patients treated with basiliximab, rejection rates were no worse than standard therapy; however, it was only effective when administered within 24 hours.

Clinical Significance of Mycophenolate Mofetil Withdrawal in Kidney Transplant Recipients

IntroductionThe most effective immunosuppressant protocol in kidney transplantation (KT) is the combination of a calcineurin inhibitor, steroid, and mycophenolate mofetil (MMF) until now. However, MMF withdrawal (MW) is performed for many reasons, and the clinical course of the KT recipients after MW is not clearly known. The purpose of this study was to investigate the clinical outcomes of KT after MW. Materials and MethodsWe retrospectively analyzed the medical records of 626 KT recipients between 2000 and 2016. We evaluated the incidence of biopsy-proven acute rejection (BPAR), graft and patient survival rates, and risk factors related with graft failure. ResultsThe proportion of MW was 33.2% (208 of 626 patients). The median time between KT and MW was 6.4 months (range, 3.2–32.1 months). The common causes of MW were infection (70.7%), hematologic abnormalities (9.1%), and gastrointestinal trouble (7.7%). The incidence of BPAR was significantly higher in the MW group compared with the MMF continuation group (27.4% vs 8.9%, respectively, P < .001). Death-censored graft survival and patient survival rates were significantly lower in the MW group compared with the MMF continuation group (P < .001; P < .001, respectively). In the multivariate analysis, BPAR after MW was an independent risk factor for graft failure (hazard ratio 6.058, 95% confidence interval, 3.172–11.569, P < .001). ConclusionsThe incidence of rejection, graft failure, and patient mortality in KT were high after MW. Therefore, MW should be considered carefully.

Renal Transplantation in High Immunological Risk Patients: A Single-Center Experience

BackgroundRenal transplantation (RT) in high-risk patients is increasingly performed due to an inadequate organ pool and increased rate of RT after a failed transplantation. Safety and prognosis of RT in such patients with high risk is an ongoing debate. Herein we aimed to present our single-center experience on RT of high-risk patients. MethodsA total of 89 consecutive RT patients were included into this study in a 10-month period. Patients were divided into 3 groups: the low-risk group (n = 47) with negative panel reactive antibody (PRA), medium-risk group (n = 18) with positive PRA but mean fluorescence intensity (MFI) < 2000, and high-risk group (n = 24) with positive PRA and MFI >2000 or donor specific antibody (DSA) positivity. Groups were compared in terms of demographic features, serum creatinine levels, acute rejection rates, delayed graft function (DGF), and patient or graft loss. ResultsAge of the recipients were similar between the groups. Desensitization (7% vs 11% vs 42%, respectively, in low-, medium-, and high-risk groups; P = .001), plasmapheresis (6% vs 11% vs 46%, respectively, P < .001), and rituximab treatments (0% vs 0% vs 25%, respectively, P < .001) were significantly more frequently performed in high-risk patients. Serum creatinine levels at 1 month and 6 months after RT were similar between the groups (P = .43 and P = .71, respectively). Rates of acute rejection (6% vs 6% vs 16%, respectively, P = .52) and DGF (9% vs 11% vs 29%, respectively, P = .15) were similar between the groups. Frequencies of loss of patient or graft were also similar (0% vs 6% vs 4%, P = .15). ConclusionRT may be successfully performed in high-risk patients without an increase in the risk of acute rejection, DGF, or patient/graft loss.

Once- vs Twice-Daily Tacrolimus: Survival Rates and Side Effects: Single-Center Experience

BackgroundThis study aimed to determine whether de novo, prolonged-release tacrolimus- (PR-tacro) based immunosuppressive regimen affected graft and patient survival when compared to an immediate-release, twice-daily, tacrolimus- (IR-tacro) based regimen in kidney transplant recipients. We also aimed to determine the difference between the frequency of side effects, including diabetes control, in study groups. MethodsA total of 115 standard risk kidney transplant recipients were enrolled in this single center, retrospective study. Fifty-two patients received PR-tacro and 63 patients received IR-tacro as a calcineurin inhibitor. The primary outcome measures included incidence of graft loss and delayed graft function (DGF), biopsy-proven acute rejection , graft and patient survival, and creatinine clearance. Secondary outcome measures included the incidence of non-adherence, drug-induced tremor; post-transplant diabetes mellitus diagnosis rate; and control of diabetes in pre-transplant diabetic patients. ResultsBaseline characteristics and mean tacrolimus trough levels were comparable between groups. Incidence of graft loss, DGF, and graft and patient survival were similar between groups (P > .05). Mean creatinine clearance level was also similar (P > .05). Mean serum levels of fasting glucose (P < .05) and A1C (P < .05) were lower in PR-tacro group when compared to IR-tacro group. Post-transplant diabetes mellitus diagnosis rate was also lower in PR-tacro group when compared to IR-tacro group (P = .040). ConclusionThis study suggests that there is no statistically significant difference between PR-tacro and IR-tacro in terms of patient and graft survival, DGF, and biopsy-proven acute rejection rates in kidney transplant recipients. Post-transplant diabetes mellitus frequency is lower in non-diabetic patients, and glucose metabolism control is better in diabetic patients.

Association of Infections in Patients Supported with Left Ventricular Assist Device with Vasoplegia and Post-Cardiac Transplant Outcomes

Background LVAD-specific infections (LSI) are common in patients on LVAD support. The impact of LSI on post-heart transplant (HT) outcomes is not clear. We hypothesized that LSI are associated with higher rates of acute renal failure (ARF), rejection and mortality in the first year post-HT with perioperative vasoplegia serving as a mediating factor. Methods A retrospective analysis at our institution was conducted for all LVAD patients from 10/2012 to 9/2017 who received HT. Total artificial heart patients were excluded. LSI was defined as driveline infection, pump pocket, pump or cannula infection. Vasoplegia was considered present if the following criteria were met: epinephrine/norepinephrine ≥ 150 ng/kg/min, dopamine ≥ 10 ug/kg/min or vasopressin ≥ 4 U/hr at any time point or duration of inotropic support > 14 days with a cardiac index > 2.1 L/min/m2 and systemic vascular resistance less than 15 mmHg), or any use of methylene blue or vitamin B12 complex. The primary outcome was a composite of ARF, rejection (antibody-mediated or acute cellular rejection ≥ 2R or hemodynamic compromise), and mortality in the first year post-HT. Results A total of 105 patients were bridged to HT with LVAD therapy. Of these, 63 (60%) had evidence of an LSI pre-HT with a majority (92%) being driveline-associated. These patients were more likely to be men (85% vs 69%), have higher BSA (2.05 m2 vs 1.89 m2), and be UNOS 1A (97% vs 64%), but no differences were noted in BMI, etiology of cardiomyopathy, device type, duration on LVAD support, or medical therapy. Among patients with LSI, there was an equal distribution of gram positive and negative organisms identified and 56% were on oral antibiotics vs 41% on IV antibiotics. The incidence of vasoplegia in the overall cohort was 12% (13/105), with 16% (10/63) in the LSI group vs 7% (3/42) in the no LSI group (p=0.183). Over half of the patients (56/105) experienced a composite of ARF, rejection or death post HT, 59% (37/63) in the LSI group vs 45% (19/42) in the no LSI group (p=0.175). Similarly, there was no difference in the individual components of the composite outcomes or in the secondary outcome hospital length of stay. Conclusions In our cohort, LSI were common among LVAD patients but not associated with vasoplegia or the clinical outcome of ARF, graft rejection, or mortality in the first year post HT. This may be limited by a small sample size.