Outcomes In Transplant Recipients Research Articles

The outcome of thrombotic microangiopathy in kidney transplant recipients

BackgroundThe outcome of kidney transplant recipients with a history of complement-mediated thrombotic microangiopathy (cTMA) and those who develop post-transplant de novo TMA (dnTMA) is largely unknown.MethodsWe retrospectively studied all kidney transplant recipients with end-stage kidney disease secondary to cTMA and those who developed dnTMA, between Jan 2000 and Dec 2020 in our center.ResultsWe identified 134 patients, 22 with cTMA and 112 had dnTMA. Patients with cTMA were younger at the time of TMA diagnosis (age at diagnosis, 28.9 ± 16.3. vs 46.5 ± 16.0 years; P < 0.001). T-cell mediated rejection, borderline rejection, and calcineurin inhibitor toxicity were more prevalent in the first kidney transplant biopsy (P < 0.05) in the dnTMA group, and antibody-mediated rejection was more prevalent in anytime-biopsy (P = 0.027). After adjusting for potential confounders, cTMA was associated with a sixfold increase in the hazard of transplant failure during the first-year post-transplant (adjusted hazard ratio (aHR): 6.37 [95%CI: 2.17 to18.68; P = 0.001]; the aHR decreased by 0.87 (95% CI: 0.76 to 0.99: P = 0.033) per year elapsed since transplantation. Long-term allograft survival was similar in both groups.ConclusionPost kidney transplant TMA is an important cause of poor allograft survival. More studies are needed to enhance our understanding and management of this disorder.

Impact of Ramadan fasting on kidney function and related outcomes in chronic kidney disease and kidney transplant recipients: a systematic review and meta-analysis

ObjectivesRamadan fasting is an Islamic religious practice involving abstinence from food and drink from dawn to sunset. Its consequences on kidney-relevant outcomes in patients with chronic kidney disease (CKD) and...

Impact of Bebtelovimab Treatment Timing on COVID-19 Outcomes in Ambulatory Solid Organ Transplant Recipients.

Outcomes after bebtelovimab treatment for COVID-19 were favorable for most but not all solid organ transplant recipients (SOTRs) during the era of Omicron BA.2 to BA.5, but effects of timing of bebtelovimab administration on these outcomes are unknown. We sought to compare outcomes of SOTR who received early bebtelovimab ("EBT", given ≤2days from diagnosis) versus late bebtelovimab ("LBT", given between Days 3 and 7), versus no bebtelovimab (NBT). This was a retrospective cohort study of SOTRs with mild-to-moderate COVID-19, with endpoint of 30-day COVID-19-related hospitalization. Multivariable logistic regression was performed to determine variables associated with receiving EBT, and to assess impact of EBT on hospitalization. A propensity score (PS) was calculated for EBT versus NBT. Of 297 SOTRs, 162 (58.1%) received EBT, 46 (16.5%) LBT, and 71 (25.4%) NBT. Early bebtelovimab treatment was associated with a lower risk of 30-day COVID-19-related hospitalization compared to NBT (OR, 0.112 [95% CI, 0.018-0.686]; p=0.018). There was no significant difference in hospitalization risk between LBT and NBT, suggesting that delayed administration may not confer additional benefits over no treatment. Early bebtelovimab treatment in outpatient SOTRs was associated with a lower risk of hospitalization compared to no treatment, while late administration did not show a significant advantage over no treatment. Although bebtelovimab is no longer authorized, these findings suggest that the timing of COVID therapies for SOTRs may be important to optimize outcomes.

Precision in Immune Management: Balancing Steroid Exposure, Rejection Risk, and Infectious Outcomes in Adult Kidney Transplant Recipients.

With kidney transplant immunosuppression, physicians must balance preventing rejection with minimizing infection and malignancy risks. Steroids have been a mainstay of these immunosuppression regimens since the early days of kidney transplantation, yet their risks remain debated. Our study looks at the clinical outcomes of patients undergoing early steroid withdrawal (ESW) vs. steroid continuous (SCI) maintenance immunosuppression in adult kidney transplant recipients. A retrospective case-control study, utilizing propensity score-matching, was performed using the US Collaborative Network Database within TriNetX to evaluate renal transplant outcomes at one year in first-time kidney transplant adult patients (>18 years old) who were prescribed an ESW regimen (no steroids after post-transplant day 7 with maintenance tacrolimus [tac] + mycophenolic acid [MMP]/mycophenolate mofetil [MMF]) vs. SCI (tac + MMF/MMP + prednisone). Cohorts were matched on demographics, comorbidities, previously described risk factors for rejection, and induction immunosuppression. Primary outcomes included viral infections, pyelonephritis, and sepsis. Secondary outcomes included renal transplant rejection, death-censored allograft failure (eGFR < 15 mL/min), patient mortality, delayed graft function, and diabetes mellitus. A total of 2056 patients were in each cohort after matching (mean age: 50.7-51 years, 17.9-20.0% African American, 60-60.6% male.) The SCI cohort had a significantly higher cumulative incidence of composite viremia (18 vs. 28.1%, ESW vs. SCI, p < 0.01) driven by CMV, EBV, and BK virus. Post-transplant diabetes mellitus was significantly higher in the SCI cohort (3.21% vs. 5.49%, ESW vs. SCI, p < 0.01). Delayed graft function was also higher in the SCI cohort (19.55% vs. 22.79%, ESW vs. SCI, p < 0.01). Pyelonephritis (2.3 vs. 4.91%, ESW vs. SCI, p < 0.01) and sepsis (2.15 vs. 5.95%, ESW vs. SCI, p < 0.01) were higher in the SCI cohort. Rejection rates were similar between ESW and SCI (29 vs. 31%, ESW vs. SCI, p = 0.41). There were significantly higher incidences of graft failure (4.9 vs. 9.9%, ESW vs. SCI, p < 0.01) and mortality (0.8 vs. 2.1%, ESW vs. SCI, p < 0.01) in the SCI cohort. This well-matched case-control study suggests that ESW is associated with lower infectious outcomes, mortality, and graft failure without increasing rejection risk, supporting the potential benefits of ESW in kidney transplant patients.

Abstract 4136036: Five-year Outcomes of Heart-Kidney Transplant Recipients Bridged with Durable Mechanical Circulatory Support: Less AMR Better Survival?

Introduction: Despite the increased risk of sensitization in patients receiving pre-transplant durable mechanical circulatory support (D-MCS), it has been suggested that removing D-MCS at the time of transplant may lead to a drop in HLA-antibody levels. Whether this may reduce rejection rates and improve long-term outcomes in patients undergoing heart-kidney transplantation (HKTx) has not been widely investigated. Therefore, we aim to investigate the impact of pre-transplant D-MCS on 5-year clinical outcomes of patients undergoing HKTx. Methods: We included 98 patients undergoing HKTx between 2010 and 2018 at a single center. Recipient pre-transplant characteristics and clinical outcomes were compared between patients receiving D-MCS (n=24) versus non-D-MCS patients (n=74). The D-MCS cohort included those who received total artificial heart (n=13), left ventricular assist device (n=8), and biventricular assist devices (n=3). Endpoints included 1- and 5-year survival, 1-year-freedom from acute cellular rejection (defined as grade 2R or 3R), 1-year-freedom from antibody-mediated rejection (AMR, defined as pathologic AMR of grade ≥1), 5-year freedom from cardiac allograft vasculopathy (CAV, stenosis ≥30% by angiography), 5-year freedom from non-fatal major adverse cardiac events (NF-MACE including myocardial infarction, new congestive heart failure, percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, stroke), and 5-year freedom from left ventricular dysfunction (LVEF ≤40). Results: At 1 year, freedom for AMR was numerically higher in the D-MCS group (100 vs. 90.2%, P=0.12). Additionally, the 5-year post-transplant survival rate was higher in the D-MCS group (95.8% vs. 80.8%), but it did not reach statistical significance (P=0.091). Comparable outcomes were noted for other outcomes, including 5-year freedom from CAV, NF-MACE, or LVD (Table 1 ). Conclusion: The current study hints at better 5-year survival in HTKx recipients receiving pre-transplant D-MCS, which could be attributed to lower rates of AMR in this population. Future larger studies are warranted to further validate these findings.

Trends in Kidney Allograft Failure Among First-Time Transplant Recipients in the United States

Rationale & ObjectiveThe management and outcomes of kidney transplant recipients have evolved over the past three decades. This study of U.S patients whose first kidney allograft failed sought to understand long-term trends in subsequent waitlisting, re-transplantation, and all-cause mortality. Study DesignRetrospective cohort study. Setting & ParticipantsPatients recorded in the United States Renal Data System (USRDS) whose first kidney allograft failed between 1990 and 2019. ExposureThe 5-year period in which the allograft failure occurred: 1990-1994, 1995-1999, 2000-2004, 2005-2009, 2010-2014, or 2015-2019. Outcomes1) Waitlisting for re-transplantation, 2) re-transplantation, and 3) all-cause mortality following first allograft failure. Analytical ApproachCompeting risk survival analyses using the approach described by Fine and Gray were used for the outcomes of waitlisting and re-transplantation. Cox proportional hazards models were used for the outcome of all-cause mortality. ResultsThe absolute number of patients whose allograft failed and started dialysis increased from 3,197 in 1990 to 5,821 in 2019. Compared to 1990-1994, the rate of waitlisting for a second transplant increased with each subsequent 5-year period, peaking between 2005-2009 before decreasing again subsequently. The rate of re-transplantation following allograft failure decreased by 9%, 14%, 18%, 7%, and 11% in the sequential 5-year eras; and the mortality rate was 25% lower in 2015-2019 (HR=0.75, 95% CI, 0.72-0.77) compared to 1990-1994. Women had a reduced rate of waitlisting (HR 0.93, 95% CI 0.91-0.95) and lower rate of re-transplantation (HR 0.93, 95% CI 0.91, 0.95) compared to men. Compared to White patients, African-American and Hispanic patients had significantly lower rates of waitlisting, re-transplantation, and mortality. LimitationsRetrospective data that lacks granular clinical information. ConclusionsDuring the past three decades, among patients whose first kidney allograft failed and subsequently initiated dialysis, the rates of waitlisting for re-transplantation increased while the rates of re-transplantation and mortality decreased. Race-, ethnicity-, and sex-based disparities in waitlisting and re-transplantation were observed and warrant further investigation.

Effect of ABO Mismatch and Red Blood Cell Alloimmunization on the Outcome of Hematopoietic Cell Transplantation for Sickle Cell Disease

Hematopoietic stem cell transplantation (HCT) remains the sole well-established curative option for patients with sickle cell disease (SCD). Nonmyeloablative conditioning has been used to improve outcomes and reduce toxicities in adult SCD patients. However, recipient-donor ABO incompatibility and alloimmunization may be significant impediments to successful outcomes of HSCT in SCD patients owing to risks of hemolysis, delayed engraftment, poor graft function, and graft failure (GF). Here we report our experience with allogeneic HCT for SCD and the effects of RBC group mismatch and alloimmunization on the outcome of transplant recipients. We conducted a retrospective analysis of all SCD patients age >14 years who underwent HCT between January 2015 and February 2022 at our center. All patients received i.v. alemtuzumab (1 mg/kg divided over 5 days on days -7 to -3) and 300 cGy total body irradiation on day -2 or -1 for conditioning. Pretransplantation preparation consisted of hydroxyurea at the maximum tolerated dose for 2 to 3 months and 1 session of exchange transfusion. Peripherally mobilized CD34 stem cells targeting 10 × 106 /kg of recipient weight were used. For graft-versus-host disease prophylaxis, sirolimus was started on day -1 and continued for 1 year with tapering if lymphoid chimerism was >50%. For patients with major ABO incompatibility, we administered 2 doses of rituximab (375 mg/m2) and 3 sessions of plasmapheresis before starting the conditioning regimen, targeting an isohemagglutinin titer <1/32. The primary objective was to determine the impact of RBC group mismatch and alloimmunization on the outcomes of the HCT recipients. The secondary objective was to assess the impact of GF on overall survival (OS). Logistic regression was done to evaluate predictors for GF. The Kaplan-Meier method was used for survival analysis. A total of 194 patients were included, with a median age of 26 years. Their median baseline hemoglobin and hemoglobin S values were 93 g/L and 71.3%, respectively. Indications for HCT included recurrent vaso-occlusive crisis in 52.5% of the patients, central nervous system events in 19.6%, and acute chest syndrome in 17%. After a median follow-up of 28.8 months (range, 5 to 83 months), 16 patients (8%) experienced GF (3 with primary GF and 13 with secondary GF). On univariate analysis, ABO minor incompatibility and RBC alloantibodies against donor non-ABO antigens were predictive of GF. On multivariate analysis, RBC alloantibodies against donor non-ABO antigens (odds ratio, 8.29; 95% confidence interval, 2.01 to 34.05; P = .0033) was the sole factor predictive of GF. None of the 16 patients with major ABO incompatibility developed GF. The 2-year OS for all patients was 95%. The 2-year OS was 98% in patients without GF, compared to 74% in patients with GF (P < .0001). In our SCD patients who underwent HSCT, the presence of RBC alloantibodies against donor non-ABO antigens was an independent risk factor for GF. Patients with GF had inferior survival, and strategies for decreasing the risk of GF are needed.

Neighborhood Socioeconomic Deprivation is Associated with Worse Outcomes in Pediatric Kidney Transplant Recipients.

Social determinants of health shape a child's transplant course. We describe the association between neighborhood socioeconomic deprivation, transplant characteristics, and graft survival in US pediatric kidney transplant recipients. US recipients <18 years of age at listing transplanted January 1st, 2010, to May 31st, 2022 (N=9,178) were included from the Scientific Registry of Transplant Recipients. Recipients were stratified into three groups according to Material Community Deprivation Index score, with greater score representing higher neighborhood socioeconomic deprivation. Outcomes were modeled using multivariable logistic regression and Cox proportional hazards models. Twenty-four percent (N=110) of recipients from neighborhoods of high socioeconomic deprivation identified as being of Black race, versus 12% (N=383) of recipients from neighborhoods of low socioeconomic deprivation. Neighborhoods of high socioeconomic deprivation had a much greater proportion of recipients identifying as being of Hispanic ethnicity (67%, N=311), versus neighborhoods of low socioeconomic deprivation (17%, N=562). The hazard of graft loss was 55% higher (aHR 1.55, 95% CI: 1.24, 1.94) for recipients from neighborhoods of high versus recipients from low socioeconomic deprivation neighborhoods when adjusted for base covariates, race and ethnicity, and insurance status, with 59% lower odds (aOR 0.41, 95% CI: 0.30, 0.56) of living donor transplantation and, although not statistically significant, 8% lower odds (aOR 0.92, 95% CI: 0.72, 1.19) of preemptive transplantation. The hazard of graft loss was 41% higher (aHR 1.41, 95% CI: 1.25, 1.60) for recipients from neighborhoods of intermediate versus recipients from low socioeconomic deprivation neighborhoods when adjusted for base covariates, race and ethnicity, and insurance status, with 27% lower odds (aOR 0.73, 95% CI: 0.66, 0.81) of living donor transplantation and 11% lower odds (aOR 0.89, 95% CI: 0.80, 0.99) of preemptive transplantation. Children from neighborhoods of high socioeconomic deprivation have worse graft survival and lower utilization of preemptive and living donor transplantation. These findings demonstrate inequities in pediatric kidney transplantation that warrant further intervention.

Heterologous Versus Homologous COVID-19 Boosters: Immune Response Outcomes in Renal Transplant Recipients.

We aimed to investigate the immune responses to homologous and heterologous COVID-19 booster vaccinations in renal transplant recipients (RTRs) and to identify factors affecting these responses. In this prospective multicenter observational study, we measured the antibody kinetics of 90 RTRs using the chemiluminescent microparticle immunoassay method. The mean age of participants was 45.2 ± 11.4 years, with 35.6% being female. On the 42nd day after the first vaccine dose, the median antibody level was 16.7 (IQR 2.5-249.5) AU/mL, and the seropositivity rate was 60% (n = 36). Mycophenolic acid (MFA) (OR: 0.087, 95% CI: 0.024-0.311) and ACE inhibitor use (OR: 0.203, 95% CI: 0.052-0.794) were identified as independent factors affecting seropositivity. Patients who received the Pfizer/BioNTech booster had significantly higher antibody levels compared to those who received the CoronaVac/Sinovac booster (p = 0.021). Additionally, a significantly higher rate of COVID-19 positivity was observed among patients who received the CoronaVac/Sinovac booster (p = 0.031). Heterologous COVID-19 booster vaccination is significantly more effective than homologous inactivated booster vaccination in enhancing immune responses and preventing new infections in RTRs. MFA and ACE inhibitor usage were independent factors affecting seropositivity. Additional COVID-19 vaccine doses are needed in this patient group.

Post-Transplant Vitamin D Deficiency in Lung Transplant Recipients: Impact on Outcomes and Prognosis.

Despite the recognized clinical significance of vitamin D deficiency in other solid organ transplant recipients, its specific relevance in lung transplantation remains to be fully understood. In this study, we performed a retrospective observational study on the impact of vitamin D deficiency on clinical outcomes and prognosis in 125 lung transplant recipients (LTRs) from October 2014 to March 2020 at a university hospital in Seoul, South Korea. Among 125 LTRs, 51 patients (40.8%) were vitamin D deficient. LTRs in the vitamin D-deficient group exhibited a higher incidence of post-transplant pneumonia and overall mortality than those with normal vitamin D levels during the follow-up period. This trend persisted when subjects were stratified into vitamin D tertiles. Furthermore, post-transplant vitamin D levels and C-reactive protein (CRP) significantly impacted pneumonia incidence and survival outcomes. Prognosis also varied based on cumulative vitamin D supplementation after transplantation, with patients receiving higher cumulative supplementation demonstrating improved prognosis. Our findings underscore the importance of assessing and maintaining optimal vitamin D levels post-transplantation, suggesting a potential avenue for improving outcomes in lung transplant recipients, especially in mitigating infection risk and enhancing long-term survival. Further research into optimal vitamin D levels and supplementation strategies in this population is warranted.

Increased thrombin generation in kidney transplant recipients with donor-specific antibodies directed against human leukocyte antigens.

The development of de novo anti-HLA donor specific antibodies (DSAs) is associated with poor outcomes in kidney transplant recipients. It is surmised that an interaction between DSAs and the graft endothelium cause tissue injury, however, the exact underlying pathomechanism and optimal management of patients with DSAs remain undetermined. We hypothesized that in kidney transplant recipients the presence of DSAs induce hemostasis alterations, including hypercoagulability, as assessed by the thrombin generation assay (TGA). Patients and methods. In this observational cohort study, 27 kidney transplant recipients with DSAs (DSA+ group) and 16 without DSAs (DSA- group) were enrolled. Venous blood samples were obtained, and besides routine laboratory tests, von Willebrand factor antigen (VWF), FVIII activity, soluble E selectin (sEsel), soluble P selectin (sPsel), TGA, clot lysis assay (CLA), complement levels (C3, C4) were measured. To correlate results with potential changes in DSA status over time, patients were followed and reassessed 6 ± 1.5 months later. VWF and sPsel did not differ between groups, but both parameters were increased in the majority of patients. Endogenous thrombin potential (ETP) was significantly higher in the DSA+ group as compared to DSA- patients (median:1666; IQR:1438-2012 vs. 1230; IQR:1097-1659 nM*min, p=0.0019). Follow-up measurements indicated that the observed hemostasis alterations were not transient. CLA parameters, C3 and C4 did not differ between DSA+ and DSA- groups. The extent of anti-HLA II DSA positivity correlated positively with ETP, while tacrolimus levels negatively correlated with ETP and VWF/FVIII levels. In patients with anti-HLA class II DSAs, thrombin generation was significantly increased as compared to DSA- kidney transplant recipients, suggesting that the presence of antibodies is associated with hypercoagulability. Tacrolimus levels were negatively associated with TGA parameters. Hypercoagulability, associated with the presence of DSAs, may potentially contribute to the pathomechanism of antibody-mediated graft injury, warranting future prospective studies.

Immunosuppressive Therapy, Puberty and Growth Outcomes in Pediatric Kidney Transplant Recipients: A Pragmatic Review.

Kidney transplantation in children with end-stage kidney disease significantly enhances survival and quality of life but poses unique challenges related to chronic immunosuppressive therapy. In fact, despite being essential for preventing organ rejection, immunosuppressive therapy can have significant side effects specific to pediatric patients, such as adverse impacts on physiological growth, puberty, and fertility. The resulting short stature and delayed or incomplete pubertal development can profoundly affect young patients' psychological and social well-being, impacting self-esteem and overall quality of life, and may significantly hamper compliance and therapeutic adherence. Most studies on immunosuppression in pediatric kidney transplant recipients focus on general side effects and outcomes like long-term graft survival or acute complications. On the other side, there is limited evidence in the current literature on the specific issues of growth, puberty, and fertility in this patient population. In this pragmatic review, we aimed to summarize the most relevant information available on these critical aspects of post-transplant management in pediatric patients, also providing some practical indications on management strategies for minimizing these often neglected but still important complications.

Impact of Immunosuppressants and Vaccination on COVID-19 Outcomes in Autoimmune Patients and Solid Organ Transplant Recipients: A Nationwide Propensity Score-Matched Study.

This study investigates the impact of varying degrees of immunosuppression on the clinical outcomes of immunocompromised individuals, particularly those with autoimmune diseases or post-solid organ transplant statuses, in the context of COVID-19. By focusing on these highly vulnerable populations, the study underscores the significant health inequalities faced by immunocompromised patients, who experience disproportionately worse outcomes in comparison to the general population. A retrospective cohort analysis of the K-COV-N dataset was conducted, comparing the effects of immunosuppression in autoimmune and transplant groups with matched control groups. Propensity score matching was employed to minimize inequalities in baseline characteristics, ensuring a more equitable comparison between immunocompromised and non-immunocompromised individuals. Outcomes included COVID-19-related in-hospital mortality, 28-day mortality, ICU admissions, and the need for respiratory support among 323,890 adults in the Republic of Korea. Patients with cancer or other immunosuppressive conditions, such as HIV, were excluded. Subgroup analyses assessed the influence of specific immunosuppressive medications and vaccination extent. Significantly elevated in-hospital mortality was found for patients with autoimmune diseases (adjusted Odds Ratio [aOR] 2.749) and transplant recipients (aOR 7.567), with similar patterns in other outcomes. High-dose steroid use and a greater number of immunosuppressant medications markedly increased the risk of poor outcomes. Vaccination emerged as a protective factor, with a single dose substantially improving outcomes for autoimmune patients and at least two doses necessary for transplant recipients. Immunocompromised patients, particularly those with autoimmune diseases and transplant recipients, are highly vulnerable to severe COVID-19 outcomes. High-dose steroid use and multiple immunosuppressants further increase risks. Vaccination significantly improves outcomes, with at least one dose benefiting autoimmune patients and two doses necessary for transplant recipients. Personalized vaccination schedules based on immunosuppression levels are essential to mitigate healthcare inequalities and improve outcomes, particularly in underserved populations, informing both clinical and public health strategies.

Assessing Long-Term Adverse Outcomes in Older Kidney Transplant Recipients: A Propensity Score-Matched Comparison of Early Steroid Withdrawal Versus Continuous Steroid Immunosuppression Using a Large Real-World Database.

Steroids are widely used in maintenance immunosuppression treatment in kidney transplant recipients. Older individuals undergo age-related immunosenescence that consequently decreases their ability to process and evoke a response to foreign antigens. Thus, steroids may not be necessary in preventing allograft rejection and may consequently increase older recipients' risk of long-term steroid-related adverse effects. The objective of this study was to analyze the adverse outcomes of long-term steroid immunosuppression in older kidney transplant recipients using real-world electronic medical record data. The TriNetX database "US Collaborative Network" was utilized to perform a propensity score-matched case-control study comparing 1-year, 3-year, and 5-year adverse effects of steroid immunosuppression in older adults (aged ≥65 years) kidney transplant recipients who underwent either an early-steroid withdrawal (ESW) maintenance regimen or a steroid continuous immunosuppression (SCI) regimen between 31 December, 2010 and 31 December, 2020. Early-steroid withdrawal was defined as tacrolimus plus mycophenolate mofetil maintenance with no prednisone after the seventh day post-transplant. Steroid continuous immunosuppression was defined as tacrolimus plus mycophenolate mofetil plus prednisone maintenance. Cohorts were matched on age, race/ethnicity, and risk factors for adverse steroid-related outcomes and rejection. Outcomes included post-transplant diabetes mellitus, dyslipidemia osteoporosis/fractures, myocardial infarction, glaucoma/cataract, stroke, pulmonary embolism, and malignancy. Secondary outcomes analyzed incidences of infection-related outcomes, graft-related outcomes, and recipient mortality. After matching, there were 304 recipients in each group (ESW, SCI). Mean age at the time of transplant was 69.2±3.7 years (ESW) and 69.2±3.4 years (SCI, p=0.96). The Kaplan-Meier analysis showed recipients who underwent SCI had increased incidences of post-transplant diabetes mellitus at 1 year (22.36% vs 30.37%, p=0.01) and 3 years (34.89% vs 44.29%, p=0.01), but this became non-significant at 5 years post-transplant (41.97% vs 42.6%, p=0.34). Incidences of acute pancreatitis were higher for the SCI cohort at 3 years (p=0.02) as well as incidences of acute myocardial infarction at 5 years post-kidney transplant (6.75% vs 14.39%, p<0.01). No difference was found for other adverse outcomes. Early-steroid withdrawal recipients experienced significantly fewer infection-related outcomes, such as cytomegalovirus, BK virus, sepsis/bacteremia, and fungal infections, compared with SCI recipients. Last, recipients who underwent ESW experienced fewer incidences of rejection and death-censored graft failure at 5 years post-transplant. There is currently no standard maintenance immunosuppression protocol for older kidney transplant recipients. Death-censored graft survival, rejection, and patient survival were improved with ESW. Steroid minimization may be beneficial in this population given that it lowers the risk of drug-induced adverse effects.

Dynamic prediction of kidney allograft and patient survival using post-transplant estimated glomerular filtration rate trajectory.

Allograft loss is the most feared outcome of kidney transplant recipients. We aimed to develop a dynamic Bayesian model using estimated glomerular filtration rate (eGFR) trajectories to predict long-term allograft and patient survivals. We used data from the Australian and New Zealand Dialysis and Transplant registry and included all adult kidney transplant recipients (1980-2017) in Australia (derivation cohort) and New Zealand (NZ, validation cohort). Using a joint model, the temporal changes of eGFR trajectories were used to predict patient and allograft survivals. The cohort composed of 14 915 kidney transplant recipients [12 777 (86%) from Australia and 2138 (14%) from NZ] who were followed for a median of 8.9 years. In the derivation cohort, eGFR trajectory was inversely associated with allograft loss [every 10ml/min/1.73 m2 reduction in eGFR, adjusted hazard ratio [HR, 95% credible intervals (95%CI) 1.31 (1.23-1.39)] and death [1.12 (1.10-1.14)]. Similar estimates were observed in the validation cohort. The respective dynamic area under curve (AUC) (95%CI) estimates for predicting allograft loss at 5-years post-transplantation were 0.83 (0.75-0.91) and 0.81 (0.68-0.93) for the derivation and validation cohorts. This straightforward model, using a single metric of eGFR trajectory, shows good model performance, and effectively distinguish transplant recipients who are at risk of death and allograft loss from those who are not. This simple bedside tool may facilitate early identification of individuals at risk of allograft loss and death.

Evaluating the Impact of Steroid Withdrawal on Outcomes in Kidney Transplant Recipients: A Systematic Review and Meta-Analysis

Evaluating the Impact of Steroid Withdrawal on Outcomes in Kidney Transplant Recipients: A Systematic Review and Meta-Analysis

Donor age over 55 is associated with worse outcome in lung transplant recipients with idiopathic pulmonary fibrosis

BackgroundLung transplantation (LTx) remains the only efficient treatment for selected patients with end-stage pulmonary disease. The age limit for the acceptance of donor organs in LTx is still a matter of debate. We here analyze the impact of donor organ age and the underlying pulmonary disease on short- and long-term outcome and survival after LTx.MethodsDonor and recipient characteristics of LTx recipients at our institution between 03/2003 and 12/2021 were analyzed. Statistical analysis was performed using SPSS and GraphPad software.ResultsIn 230 patients analyzed, donor age ≥ 55 years was associated with a higher incidence of severe primary graft dysfunction (PGD2/3) (46% vs. 31%, p = 0.03) and reduced long-term survival after LTx (1-, 5- and 10-year survival: 75%, 54%, 37% vs. 84%, 76%, 69%, p = 0.006). Notably, this was only significant in recipients with idiopathic pulmonary fibrosis (IPF) (PGD: 65%, vs. 37%, p = 0.016; 1-, 5-, and 10-year survival: 62%, 38%, 16% vs. 80%, 76%, 70%, p = 0.0002 respectively). In patients with chronic obstructive pulmonary disease (COPD), donor age had no impact on the incidence of PGD2/3 or survival (21% vs. 27%, p = 0.60 and 68% vs. 72%; p = 0.90 respectively). Moreover, we found higher Torque-teno virus (TTV)-DNA levels after LTx in patients with IPF compared to COPD (X2 = 4.57, p = 0.033). Donor age ≥ 55 is an independent risk factor for reduced survival in the whole cohort and patients with IPF specifically.ConclusionsIn recipients with IPF, donor organ age ≥ 55 years was associated with a higher incidence of PGD2/3 and reduced survival after LTx. The underlying pulmonary disease may thus be a relevant factor for postoperative graft function and survival.Trial registration number DKRSDRKS00033312.

Drug Development Considerations for Additives to Organ Preservation Solutions.

The addition of a novel therapeutic agent to an organ preservation solution has the potential to address unmet needs in organ transplantation and enhance outcomes for transplant recipients. However, the development expectations for novel therapeutic agents in this context are unclear because of limited precedence and published regulatory guidance documents. To address these gaps, we have articulated a drug development strategy that leverages expectations for parenteral drug products administered via more conventional routes (eg, intravenous) and provided considerations for when deviations may be justified. We have supplemented this strategy with a comparison to available regulatory guidance from the US Food and Drug Administration to highlight potential areas for further clarification. The strategy articulated here is based on Genentech's internal experience for a program intended for use in kidney transplantation.

Impact of waitlist weight change on outcomes in heart transplant recipients: a UNOS database analysis.

While the effect of pre-transplant weight on patient outcomes following heart transplantation (HTx) has previously been studied, data regarding the impact of dynamic weight change prior to HTx are extremely limited. We sought to elucidate the interaction between HTx listing weight and weight change while waitlisted, and explore how that interaction impacts post-HTx survival in a continuous manner. Adult patients listed for HTx from 1987 to 2020 were identified from UNOS database. Three-dimensional restricted cubic spline analysis explored post-HTx survival relative to both changes in BMI/weight and BMI at time of HTx listing. Continuous predictor variables were analyzed with Cox proportional hazards method. 9,628 included patients underwent HTx. Median recipient age was 55 [IQR 46-62] years, and 21% were females. 53% of patients lost while 47% gained weight on the waitlist. Median BMI (27.6kg/m2 [24.3-31.3] vs. 27.4kg/m2 [24.2-30.9], paired p < 0.001) and weight (84.8kg [73.0-98.0] kg vs. 84.4kg [72.6-96.6], p < 0.001) were similar at listing and transplant. One-year survival was 89.3%. Weight loss over 3 BMI points or 10kg was associated with higher hazard of death irrespective of listing BMI. In non-obese patients, some weight gain (1-4 BMI points or 5-15kg) was associated with improved survival. In cachectic patients (BMI < 18.5), failure to gain weight was associated with worse survival. Impact of weight change varies depending on listing BMI. While a survival benefit is seen in non-obese patients who gain some weight, significant weight loss is associated with poorer survival.

Multidisciplinary approach to optimizing long-term outcomes in pediatric kidney transplant recipients: multifaceted needs, risk assessment strategies, and potential interventions.

The post-transplant course of pediatric kidney transplant recipients is marked by a myriad of challenges, encompassing medical complications, recurrent hospitalizations, physical and dietary restrictions, and mental health concerns such as depression, anxiety, and post-traumatic stress disorder. Moreover, pediatric recipients are at risk of neurodevelopmental impairment, which may result in neurocognitive deficits and pose significant psychosocial obstacles. Addressing these multifaceted demands necessitates a multidisciplinary approach to pediatric kidney transplant care. However, the existing literature on the effective implementation of such a model remains scarce. This review examines the psychosocial and neurodevelopmental challenges faced by pediatric kidney transplant recipients and their families, discussing their impact on long-term transplant outcomes. Furthermore, it provides insights into risk assessment strategies and potential interventions within a multidisciplinary framework, aiming to enhance patient care and optimize post-transplant outcomes.