Young Recipients Research Articles

Children after kidney transplantation show severe cardiac alterations

Abstract Sudden cardiac death is among the most common causes of death in patients with chronic kidney diseases (CKD) after pediatric kidney transplantation (KTx), but defined diagnostic procedures identifying children at risk are not established. Echocardiographically detectable damage in the context of CKD has been described, but there are few data after KTx in childhood. The aim was to characterize structural and functional cardiac alterations on cardiac MRI (cMRI) and echocardiography in children after KTx and to elucidate the significance of diastolic dysfunction in this special context. 46 KTx recipients (mean age 16.0±3.5 years) and due to missing reference values 46 age- and sex-matched healthy controls were examined with non-contrast cMRI. Native T1 time (nT1), left ventricular mass z-score (LVMIz), ejection fraction (EF), global longitudinal strain (GLS) were measured. KTx recipients underwent comprehensive echocardiography: EF, mitral inflow (E-, A-wave), TDI e', E/e'-ratio, isovolumetric relaxation time (IVRT), pulmonary venous flow (PVFsys, PVFdia), atrial reversal (PVF-AR) and left atrial volume index (LAVI), left ventricular mass z-score (LVMz). Multivariable linear regression analysis (co-variates: age, sex, height) were used to show associations between cMRI and echo parameters. In cMRI KTx recipients had a siginficant higher nT1 than healthy controls (septal: 1198±49ms vs. 1155±23ms, p<0.0001; lateral: 1141±57ms vs. 1109±37ms, p=0.003). In KTx recipients, LVMIz was higher (0.1±1.1g/m2 vs. -0.3±0.7g/m2; p=0.026), GLS was lower than in healthy controls (-19± 2.1% vs. -20.3±2.7%, p=0.01). While based on cMRI 2 patients were diagnosed with left ventricluar hypertrophy (LVH), 11% (n=5) displayed LVH on echo. EF was preserved in all patients. However, in echocardiography, 90% (n=40) of the KTx recipients showed diastolic parameters out of the age-specific normal range (Fig.1) with changes in two or more diastolic parameters in half of the cohort. Associations with septal nT1 on cMRI could be demonstrated for septal E/e´ (ß=8.415, p=0.042), A-wave (ß=1.037, p=0.045), LAVI (ß=3.347, p=0.002) and PVF-AR (ß=2.945, p=0.021); associations with lateral nT1: septal E/e´ (ß=9.590, p=0.045) and LAVI (ß=3.393, p=0.009) (Fig. 2); 7 (15 %) had an elevated nT1 septal, lateral and E/e´ out of the normal range. Young KTx recipients show a high prevalence of diastolic dysfunction with preserved EF. Impaired diastolic function was associated with structural alterations reflecting myocardial fibrosis. Our findings suggest that a large number of children after KTx suffer from heart failure with preserved EF – an entity not yet defined in children but described for adults, in whom it is associated with sudden cardiac death. Further studies are needed to describe the clinical relevance of these findings, which gain explicit importance, as the prognosis of HFpEF in adults is improved by SGLT2i, a treatment option not yet considered in our high-risk patient group.

Cardiac Comorbidity and Exercise Intolerance in Bilateral Lung Transplant Recipients Followed at a Pediatric Center.

Reduced exercise capacity is common in young bilateral lung transplantation (Bi-LTx) recipients, but longer-term data on cardiac comorbidities are limited. We evaluate potential cardiac contributions to long-term exercise intolerance in this population. All Bi-LTx recipients at a single pediatric center, who completed routine clinical post-transplant cardiac assessment, including echocardiogram, cardiac exam, and cardiopulmonary exercise testing (CPET), were included. Cardiac risk factors (CRFs) were assessed by history and laboratory tests. CPET-derived peak and percent-predicted peak myocardial oxygen consumption (VO2 peak, ppVO2 peak) were used to quantitate exercise capacity. Percent-predicted peak oxygen pulse (pp peak O2 pulse) assessed stroke volume. 15 patients (67% M; median age 21.6years, median follow-up from Bi-LTx 7.0years) were included. Almost all patients (14, 93%) had multiple CRFs; hypertension and hyperlipidemia/dyslipidemia were the most common. On CPET, 93% (n = 14) had abnormal (≤ 85%) ppVO2 peak (median 59%). 73% (n = 11) had abnormal pp peak O2 pulse (median 74%). Ten had blunted heart rate response to exercise. Nine had left ventricular diastolic dysfunction (LV-DD) on echocardiogram. Median percent-predicted forced expiratory volume in one second was 70%. One had severe chronic lung allograft dysfunction. Cardiac risk factors and exercise intolerance are common among young Bi-LTx recipients years post-transplant, even among those without significant pulmonary dysfunction. High prevalence of multiple CRFs, LV-DD, chronotropic dysfunction, and abnormal stroke volume suggest cardiac comorbidities may contribute to intolerance. Medical management of CRFs and tailored exercise may decrease cardiac risk and improve functional capacity for Bi-LTx survivors.

Does old-to-young kidney transplantation rejuvenate old donor kidneys?

The number of older organ donors is increasing due to the aging population. Aged kidneys often face problems such as delayed graft function but previous murine experiments suggested the possibilities of rejuvenation, for example, in a parabiosis setting between old and young mice. To investigate kidney-graft rejuvenation, we compared an old-to-young (O-Y) patient transplantation group and a transplantation group with donors/recipients of approx. the same age (SA) with the renal senescence marker p16 in kidney biopsy samples at baseline and one year post-transplantation. We retrospectively analyzed our hospital's 32 cases of living-donor ABO-compatible transplants performed between 2013-2020. Both the baseline and one-year biopsy (n=9) or only the baseline biopsy (n=32) were analyzed. We divided the nine cases into an O-Y group (donors' median age 68 yrs, recipients 41, difference -27) and an SA group (donors' median age 53 yrs, recipients 51.5, difference -3.5). p16 was stained with the clones JC8 and E6H4 to determine the precise p16-positive rate. The 32 baseline biopsies' p16-positive rate was weakly related to donor age, suggesting that the p16-positive rate can help evaluate kidney senescence. The (n=5) O-Y group's p16-positive rates were at baseline 0.08 and one year 0.12; the (n=4) SA group's rate was 0.03 at both baseline and one year. No kidney rejuvenation was observed, even when old donor kidneys went to young recipients.

Systemic immunostimulation induces glucocorticoid-mediated thymic involution succeeded by rebound hyperplasia which is impaired in aged recipients.

The thymus is the central organ involved with T-cell development and the production of naïve T cells. During normal aging, the thymus undergoes marked involution, reducing naïve T-cell output and resulting in a predominance of long-lived memory T cells in the periphery. Outside of aging, systemic stress responses that induce corticosteroids (CS), or other insults such as radiation exposure, induce thymocyte apoptosis, resulting in a transient acute thymic involution with subsequent recovery occurring after cessation of the stimulus. Despite the increasing utilization of immunostimulatory regimens in cancer, effects on the thymus and naïve T cell output have not been well characterized. Using both mouse and human systems, the thymic effects of systemic immunostimulatory regimens, such as high dose IL-2 (HD IL-2) with or without agonistic anti-CD40 mAbs and acute primary viral infection, were investigated. These regimens produced a marked acute thymic involution in mice, which correlated with elevated serum glucocorticoid levels and a diminishment of naïve T cells in the periphery. This effect was transient and followed with a rapid thymic "rebound" effect, in which an even greater quantity of thymocytes was observed compared to controls. Similar results were observed in humans, as patients receiving HD IL-2 treatment for cancer demonstrated significantly increased cortisol levels, accompanied by decreased peripheral blood naïve T cells and reduced T-cell receptor excision circles (TRECs), a marker indicative of recent thymic emigrants. Mice adrenalectomized prior to receiving immunotherapy or viral infection demonstrated protection from this glucocorticoid-mediated thymic involution, despite experiencing a substantially higher inflammatory cytokine response and increased immunopathology. Investigation into the effects of immunostimulation on middle aged (7-12 months) and advance aged (22-24 months) mice, which had already undergone significant thymic involution and had a diminished naïve T cell population in the periphery at baseline, revealed that even further involution was incurred. Thymic rebound hyperplasia, however, only occurred in young and middle-aged recipients, while advance aged not only lacked this rebound hyperplasia, but were entirely absent of any indication of thymic restoration. This coincided with prolonged deficits in naïve T cell numbers in advanced aged recipients, further skewing the already memory dominant T cell pool. These results demonstrate that, in both mice and humans, systemic immunostimulatory cancer therapies, as well as immune challenges like subacute viral infections, have the potential to induce profound, but transient, glucocorticoid-mediated thymic involution and substantially reduced thymic output, resulting in the reduction of peripheral naive T cells. This can then be followed by a marked rebound effect with naïve T cell restoration, events that were shown not to occur in advanced-aged mice.

Resilience Intervention Improves Stress-Related Gene Expression in Adolescent and Young Adult HCT Recipients

Overactivation of the stress response can influence cancer outcomes through immune-related pathways. Adolescents and young adults (AYAs) undergoing hematopoietic cell transplantation (HCT) are at risk for poor outcomes, yet there are limited behavioral interventions and no psychosocial biomarker data for this population. The Conserved Transcriptional Response to Adversity (CTRA) is an inflammation-related pattern observed in conditions of heightened stress and is associated with HCT outcomes. The objective of the current study was to explore the CTRA gene regulatory impact of Promoting Resilience in Stress Management (PRISM) intervention among AYAs receiving HCT. We hypothesized that patients who received the intervention would have favorable gene expression signatures compared to those in the control arm. This was an ancillary study within a randomized trial testing the PRISM intervention on psychosocial outcomes among AYAs aged 12 to 24 years receiving HCT (NCT03640325). CTRA was quantified through genome-wide transcriptional profiles obtained from whole blood collected at baseline, 1-, and 3-month post-HCT. Group differences in CTRA gene expression were estimated using mixed-effect linear models. There were no baseline group differences in CTRA expression, but PRISM participants showed a greater decline in CTRA at 1 month compared to controls (β -0.301 ± SE 0.114, P = .016), even when controlling for demographic (Group × Time interaction: F(2, 18) = 7.41, P = .004; β -0.386 ± 0.127, P = .007) and clinical covariates (Group × Time interaction: F(2, 20) = 7.03, P = .005; β -0.480 ± 0.144, P = .003). These differences were not detectable at 3 months (β -0.147 ± SE 0.120, P = .235). There was a change in stress-related gene expression among AYAs randomized to a psychosocial intervention. The stress-inflammation axis may be a targetable pathway in the AYA HCT population.

347.7: Illness perceptions, medication beliefs and immunosuppression adherence in young adult kidney transplant recipients: A single-centre cohort study and comparative analysis.

347.7: Illness perceptions, medication beliefs and immunosuppression adherence in young adult kidney transplant recipients: A single-centre cohort study and comparative analysis.

365.10: Assessing readiness for transition among adolescent and young adult kidney transplant recipients.

365.10: Assessing readiness for transition among adolescent and young adult kidney transplant recipients.

Donor and Recipient Age Influence Outcomes Following Orthotopic Heart Transplantation in the 2018 US Heart Allocation System.

This study evaluates the interaction of donor and recipient age with outcomes following heart transplantation under the 2018 heart allocation system. The United Network for Organ Sharing registry was queried to analyze adult primary isolated orthotopic heart transplant recipients and associated donors from August 18, 2018, to June 30, 2021. Both recipient and donor cohorts were grouped according to age: <65 and ≥65 y for recipients and <50 and ≥50 y for donors. The primary outcome was survival. Subanalyses were performed to evaluate the impact of donor age. A total of 7601 recipients and 7601 donors were analyzed. Of these, 1584 recipients (20.8%) were ≥65 y old and 560 donors (7.4%) were ≥50 y old. Compared with recipients <65, recipients ≥65 had decreased 1-y (88.8% versus 92.3%) and 2-y (85.1% versus 88.5%) survival rates (P < 0.001). The association of recipient age ≥65 with lower survival persisted after adjusting for potential cofounders (hazard ratio, 1.38; 95% confidence interval, 1.18-1.61; P < 0.001). Recipients <65 with donors ≥50 had comparable 1-y and 2-y survival rates to recipients <65 with donors <50 (P =0.997). Conversely, transplantation of older allografts was associated with lower 1-y (84.2% versus 89.4%) and 2-y (79.5% versus 85.8%) survival rates in recipients ≥65 (P = 0.025). Recipient age ≥65 continues to be associated with worse survival following heart transplantation in the 2018 heart allocation system compared with younger recipients. Donors ≥50 may be acceptable among recipients <65 with comparable outcomes. However, careful donor age selection should be considered for recipients ≥65, as the use of younger donor allografts appears to improve posttransplantation survival.

The Adolescent Transplant Recipient: An Overview of Neurocognitive Functioning and Implications for Long-Term Outcomes.

Solid organ transplantation (SOT) offers improved long-term survival for youth with end-stage organ disease. From a neurodevelopmental, cognitive, and academic perspective, children with solid organ transplant have a number of unique risk factors. While cognitive functioning may improve post-transplantation, it is important to understand the trajectory of neurocognitive development starting in transplant candidacy to evaluate the implications of early deficits. The aim of this paper is to describe the neurocognitive risks and long-term implications for adolescent transplant recipients. This paper provides an overview of neurocognitive functioning in youth with end-stage organ dysfunction with discussion of implications for adolescent transplant recipients. Post-transplant, adolescent, and young adult solid organ transplant recipients exhibit significant levels of executive dysfunction, with implications for decision-making, regimen adherence, and transition to adult transplant care. Transplantation may reduce the risk for poor long-term neurocognitive effects, yet adolescent transplant recipients remain at increased risk, particularly in executive functioning, which has implications for adherence and transition to adulthood. Baseline and follow-up assessments for youth with end-stage organ disease and transplant are important for the monitoring of neurocognitive development and may be used to mitigate risk for low adherence to post-transplantation treatment regimens and reduce barriers to transitioning to adult transplant care.

Intensive physical activity following total hip arthroplasty increased the revision risk after 15 years: a cohort study of 973 patients from the Geneva Arthroplasty Register.

Younger recipients of total hip arthroplasty (THA) highly prioritize returning to preoperative levels of physical activity (PA). Surgeons have tended to give cautious advice concerning high-impact sports participation, but there have been few long-term studies. The purpose of our study was to investigate the risk of revision arthroplasty in relation to postoperative PA levels. Patients registered in the Geneva Arthroplasty Register (GAR) who had elective THA when they were aged < 65 years were studied. Postoperative PA was collected prospectively 5-yearly using the UCLA activity scale. Cox proportional hazards models were used to estimate associations between PA and risk of revision THA. Amongst 1,370 eligible subjects, median age at THA 58 years (interquartile range 51-61), UCLA scores were available for 973 (71%). During follow-up over 15 years, there were 79 revisions, giving a cumulative risk of 7.4% (95% confidence interval [CI] 5.8-9.4). After adjusting for covariates, we found an increased risk of revision for each unit increase in postoperative PA (HR 1.2, CI 1.1-1.4), and among people performing the most intensive PA (HR 2.7, CI 1.3-5.6) compared with those who were inactive. The overall risk of revision was small but intensive and moderate PA may be associated with an increased risk of revision.

Adult provider role in transition of care for young adult pediatric recipients of liver transplant: An expert position statement.

Health care transition (HCT) is the process of changing from a pediatric to an adult model of care. Young adult pediatric recipients of liver transplant transferring from pediatric to adult health care services are highly vulnerable and subject to poor long-term outcomes. Barriers to successful transition are multifaceted. A comprehensive HCT program should be initiated early in pediatrics and continued throughout young adulthood, even after transfer of care has been completed. It is critical that pediatric and adult liver transplant providers establish a partnership to optimize care for these patients. Adult providers must recognize the importance of HCT and the need to continue the transition process following transfer. While this continued focus on HCT is essential, current literature has primarily offered guidance for pediatric providers. This position paper outlines a framework with a sample set of tools for the implementation of a standardized, multidisciplinary approach to HCT for adult transplant providers utilizing "The Six Core Elements of HCT." To implement more effective strategies and work to improve long-term outcomes for young adult patients undergoing liver transplant, HCT must be mandated as a routine part of posttransplant care. Increased advocacy efforts with the additional backing and support of governing organizations are required to help facilitate these practices.

LCP-Tacrolimus Extended-Release (Envarsus XR) Use in Adolescent and Young Adult Solid Organ Transplant Recipients.

Limited published experience describes once daily, extended-release tacrolimus (LCP-Tac) use in pediatric solid organ transplantation (SOT), particularly nonrenal SOT. LCP-Tac can simplify immunosuppression (IS) regimens, minimize immediate release-tacrolimus (IR-Tac)-associated adverse effects, and promote adherence. This study describes the successful use of LCP-Tac in adolescent and young adult (AYA) SOT populations. A single-center, retrospective chart review of AYA SOT recipients (age < 25 years) converted from IR-Tac to LCP-Tac. Graft survival, biopsy-proven acute rejection (BPAR), infection rates, estimated glomerular filtration rate (eGFR), and pill burden were assessed at five time points postconversion (1, 3, 6, 12, and 24 months). Intrapatient variability of tacrolimus, as assessed by coefficient of variability (CV%), was also analyzed. Twenty-nine AYA SOT recipients (19 heart, 6 kidney, and 4 liver) were converted to LCP-Tac, with a median age of 17.4 years at conversion. Conversion, mainly due to perceived or identified medication nonadherence, occurred at a median of 5.4 years posttransplant. No graft loss occurred within 24 months of conversion, and BPAR incidence rate was consistent with previous reports for these populations. Only one patient experienced CMV infection. Renal function remained stable postconversion. Successful conversion from IR-Tac to LCP-Tac was demonstrated in AYA heart, kidney, and liver transplant recipients. These AYA SOT recipients experienced reduced pill burden and improved tacrolimus trough concentration variability. However, the impact on medication adherence warrants further investigation. Future research should explore the targeted use of LCP-Tac to enhance IS tolerability and medication adherence in young SOT populations.

The Crucial Role of Empowerment in Engaging Adolescents and Young Adults for Independence: Essential Strategies and Skills for a Successful Transition.

An increasing number of pediatric solid organ transplant (SOT) recipients are surviving into adolescence and young adulthood. The transition from pediatric to adult-oriented care occurs during a unique and vulnerable period. Presented here is a structured approach to healthcare transition (HCT) for adolescent and young adult SOT recipients aimed at optimizing independence in order to assist young patients with adherence, self-management, and improved quality of life. Close attention must be paid to neurocognitive development, mental well-being, and social determinants of health. These efforts require a multidisciplinary team approach as well as collaboration between pediatric and adult providers in order to achieve these goals and patient longevity.

The Effect of Life Stages on the Experience of Those Who Have Received an Unexpected and Violent Death Notification: A Qualitative Study.

How individuals are informed of the traumatic loss of a loved one can influence their grieving process and quality of life. This qualitative study aimed to explore, through thematic analysis, how life stages might influence the experience and feelings of those who have received communication of a traumatic death from police officers or healthcare professionals. Recruited through social networks and word of mouth, 30 people participated in the study. Subjects were divided into three groups according to age (Group 1: ten participants aged between 20 and 35 years; Group 2: ten participants aged between 45 and 55 years; and Group 3: ten participants aged 60 and over). Participants completed an ad hoc questionnaire online. Atlas.ti software 8 was used to perform thematic analysis. The three age groups had the following four key themes in common: (a) emotional reactions; (b) subjective valuation of the notification; (c) support; and (d) needs. Subtle differences emerged between age groups; yet the quality of the reactions and main themes did not vary greatly between the groups considered. The communication of an unexpected and violent death seems to provoke rather similar effects in survivors of different life stages. A few differences were noted in sub-themes (increased need for professional training in younger recipients; absence of suicidal ideation in older adults); perhaps quantitative designs could provide further details in future investigations.

Older age is associated with a distinct and marked reduction of functionality of both alloreactive CD4+ and CD8+ T cells.

Older recipient age is associated with a significant decreased risk for rejection after kidney transplantation which is incompletely understood. In a longitudinal study, circulating alloreactive T cells were assessed of young (≤45 years) and older (≥55 years) stable kidney transplant recipients. Alloreactive T-cells were identified by CD137-expression and phenotype, cytokine producing and proliferative capacity, were evaluated using multiparameter flowcytometry. The results show that before transplantation frequencies of alloreactive CD4+ and CD8+ T-cells in older KT-recipients are significantly higher and shifted towards an effector memory-phenotype. However, the frequency of polyfunctional (≥2 pro-inflammatory cytokines) CD4+ T-cells was significantly lower and less IL2 was produced. The frequency of polyfunctional alloreactive CD4+ T-cells and proliferation of alloreactive T-cells donor-specifically declined after transplantation reaching a nadir at 12 months after transplantation, irrespective of age. A striking difference was observed for the proliferative response of alloreactive CD8+ T-cells. This was not only lower in older compared to younger recipients but could also not be restored by exogenous IL2 or IL15 in the majority of older recipients while the response to polyclonal stimulation was unaffected. In conclusion, older age is associated with a distinct and marked reduction of functionality of both alloreactive CD4+ and CD8+ T-cells.

Vaccine-induced Thrombotic Thrombocytopenia and Graft Thrombosis in a Renal Transplant Recipient

Abstract The use of COVID-19 vaccines has been associated with sporadic reports of thrombosis with thrombocytopenia, a complication referred to as vaccine-induced immune thrombotic thrombocytopenia (VITT). Early recognition of this entity before the occurrence of thrombosis detected by imaging is termed as a pre-VITT syndrome. Thrombosis has been reported to occur in the cerebral venous system, splanchnic veins as well as arteries to the lower limbs. We present the case of a young renal transplant recipient who presented with VITT following ChAdOx1 nCoV-19 (Covishield) vaccination; in this case, thrombosis occurred in the intrarenal arteries of the graft kidney.

Modulation of Human Macrophages by Plasma from COVID-19 Patients Following BCG Vaccination: BATTLE Trial.

To analyze the interfering effect of plasma from COVID-19 convalescent adults vaccinated or not with intradermal Bacillus Calmette-Guérin (BCG) on human macrophages. The BATTLE clinical trial (NCT04369794) was initiated in the 2020 SARS-CoV-2 pandemic to study the safety and efficacy of BCG revaccination of COVID-19 convalescent adults. We measured the expression induction of eleven COVID-19-related genes in human macrophages cultured in plasma taken from 22 BCG vaccinated and 17 placebo patients at baseline and 45 days post-intervention. Subgroup analysis was based on gender, age, job type (healthcare worker [HCW] vs non-HCW), and the presence of anosmia/dysgeusia. Compared to plasma from placebo counterparts, the plasma of BCG vaccinated patients increased the expression induction of interferon (IFN)β-1b (p = 0.042) in human macrophages. This increase was more pronounced in females and in healthcare workers (HCW) (p = 0.007 and 0.001, respectively). Interferon-induced transmembrane protein 3 (IFITM3) expression induction was increased by plasma from BCG vaccinated females, young age group, and HCWs (p = 0.004, 0.011, and 0.040, respectively). Interleukin (IL)-10 induction increased by the plasma of young BCG recipients (p = 0.008). Induction of IL-6 expression increased by non-HCW BCG recipients plasma but decreased by HCW BCG recipients plasma (p = 0.005). Baseline plasma of patients who presented with anosmia/dysgeusia at the time of admission induced lower angiotensin-converting enzyme 2 (ACE2) compared to those without the symptom (0.76 vs 0.97, p = 0.004). ACE2 expression induction significantly increased by plasma of BCG recipients if they had anosmia/dysgeusia on admission (p = 0.028). The expressions of IFNβ-1b, IFITM3, IL-6, and IL-10 in human macrophages incubated with the plasma of COVID-19 convalescent patients were modulated by BCG. These modulations depended on subject-specific characteristics, including gender, age, clinical presentation (anosmia/dysgeusia), job type, and previous exposure to mycobacteria.

Donor to recipient age matching in lung transplantation: A European experience

BackgroundThe age profile of organ donors and patients on lung transplantation (LT) waiting lists have changed over time. In Europe, the donor population has aged much more rapidly than the recipient population, making allocation decisions on lungs from older donors common. In this study we assessed the impact of donor and recipient age discrepancy on LT outcomes in the UK and France. MethodsA retrospective analysis of all adult single or bilateral LT in France and the UK between 2010 and 2021. Recipients were stratified into 3 age groups: young (≤ 30 years), middle-aged (30 to 60) and older (≥60). Their donors were also stratified into 2 groups <60, ≥ 60. Primary graft dysfunction (PGD) rates and recipient survival was compared between matched and mismatched donor and recipient age groups. Propensity matching was employed to minimize covariate imbalances and to improve the internal validity of our results. ResultsOur study cohort was 4,696 lung transplant recipients (LTRs). In young and older LTRs, there was no significant difference in 1 and 5-years post-transplant survival dependent on the age category of the donor. Young LTRs who received older donor grafts had a higher risk of severe grade 3 PGD. ConclusionOur findings show that clinically usable organs from older donors can be utilized safely in LT, even for younger recipients. Further research is needed to assess if the higher rate of PGD3 associated with use of older donors has an effect on long-term outcomes.

Preserving active lifestyle: subcutaneous defibrillators in young patients engaged in recreational sports. Insights from a multicenter study

Abstract Background Leading an active lifestyle and participating in recreational sports are crucial for overall well-being and cardiovascular health. Many young patients with implantable defibrillators engage in these activities, but the safety for subcutaneous defibrillator (S-ICD) recipients is unknown. Purpose Evaluate how lifestyle and recreational sports affect the risk of appropriate (AS) and inappropriate shocks (IAS) in S-ICD recipients. Methods We enrolled consecutive young S-ICD recipients (14-65 years) from 19 Italian centers and assessed their physical activity with the International Physical Activity Questionnaire (IPAQ). During follow-up, we analyzed the impact of lifestyle and recreational sports on AS and IAS. Results We enrolled 602 S-ICD recipients (77% males; age: 46±14 years). Common diagnoses included hypertrophic cardiomyopathy (24%), ischemic heart disease (20%), and idiopathic dilated CM (17%). IPAQ was administered 47 months (IQR: 26-68) post-SICD implantation. According to the IPAQ, patients were categorized as inactive subjects (IS; 27.9%), minimally active subjects (MAS; 43.7%), or highly active subjects (HAS; 28.4%). Patients with progressively higher activity levels had, in parallel, younger age (48±14 vs. 45±13 vs. 44±13 years; p=0.02) and higher ejection fraction (EF, %) (46±16 vs. 48±15 vs. 49±16; p=0.09). 163 patients (27.1%) regularly participated in recreational sports, with fitness/gym (25.2%), walking (20.9%), and cycling (14.1%) as the most common choices. As compared to patients not engaged in sports, recreational athletes were younger (43±13 vs 47±14 years; p&amp;lt;0.01) and had higher EF (52±14 vs 46±16; p&amp;lt;0.01). During follow-up (32 months; IQR 19-54), there were 77 discrete VT/VF episodes and 10 storms in 44 patients treated with AS. Also, there were 38 discrete IAS and 7 inappropriate shock storms in 39 patients. IS, MAS and HAS had similar rates of AS (9.5% vs 6.8% vs 5.8%, respectively; p=0.39) and IAS (4.8% vs 6.5% vs 8.2%, respectively; p=0.44). Kaplan-Meier curves showed similar cumulative rate of first AS (p= 0.12) or IAS (p= 0.74) for the 3 groups (Figures 1 and 2). Recreational athletes and non-athletes were propensity matched for age, sex, heart disease, EF, and primary/secondary prevention ICD implantation. Non-athletes and recreational athletes had similar risk of AS (HR: 1.78; 95% CI: 0.75-4.41; p=0.20) and IAS (HR: 1.20; 95% CI: 0.55-2.64; p=0.64). Out of 163 recreational athletes, 7 (4.3%) experienced 12 distinct AS, of which 3 (25%) occurred during sport activities. There were no arrhythmic storms while engaging in sports. Additionally, 15 patients (9.2%) had 17 episodes of IAS, with 3 (17.6%) occurring during sport practice. Conclusions In young S-ICD recipients, those leading more active lifestyle and commonly engaged in recreational sports were not exposed to a higher risk neither of appropriate, nor of inappropriate shocks. However, shocks related to sport practice were not uncommon.AS-free survival according to IPAQIAS-free survival according to IPAQ

#1713 Blood pressure goals in kidney transplant recipients: an analysis of the collaborative transplant study

Abstract Background and Aims Hypertension is an independent risk factor for cardiovascular disease, the leading cause of death in kidney transplant recipients. Because there is no “one size fits all” approach to blood pressure targets, particularly in the heterogenous group of kidney transplant recipients, identification of subgroup-specific targets, considering factors like age and sex, may be appropriate. However, currently available studies are limited because of sample sizes, and no subgroup analyses have been performed examining the effects of different blood pressure targets on allograft and patient survival. The aim of our study was to investigate the impact of different ACC/AHA blood pressure categories on graft survival and patient mortality and to identify subgroup-specific targets. Method This large-scale retrospective study included 1-year blood pressure data from 62, 556 kidney transplant recipients reported to the Collaborative Transplant Study from 209 centers in 39 countries. Hypertension was categorized according to 2017 ACC/AHA guidelines. The primary outcomes were death-censored graft failure and patient mortality during post-transplant year 1 to 6. Multivariable Cox regression analysis was performed to control for immunologic and nonimmunologic confounders. Results One year after transplantation, 77% of kidney transplant recipients had hypertension. Hypertension stages 1 (130–139/80–89 mmHg), 2a (140–159/90–99 mmHg), and 2b (≥160/≥100 mmHg) were associated with an 8%, 34%, and 102% increased risk of death-censored graft failure, respectively, whereas elevated blood pressure levels (120–129/&amp;lt;80 mmHg) did not significantly increase the risk. Patient mortality was only significantly higher in those with hypertension stage 2b with a Hazard Ratio of 1.21 (95% CI, 1.08–1.36; P &amp;lt; .001). In addition, the impact of hypertension stages on death-censored graft failure varied in different subpopulations (Fig. 1). Female recipients, younger recipients, recipients who received kidneys from donors younger than 60 years, re-transplanted recipients, and recipients with pre-transplant HLA antibodies had a significantly increased risk of death-censored graft failure associated with higher blood pressure levels (Fig. 1). Kidney transplant recipients with hypertension stage 2 continued to have an increased risk of graft failure one year after transplantation, even when they achieved normal blood pressure in the second year. Conclusion This study highlights the importance of treating hypertension early after kidney transplantation to improve long-term graft and patient survival. Attention should be paid to female, younger, and sensitized recipients, who may particularly benefit from optimal blood pressure control.