Outcomes In Transplant Recipients Research Articles

Low Mean Perfusion Pressure Indexed to Body Surface Area is a Powerful Predictor of Poor Outcomes After Heart Transplantation in Patients With High Pre-Transplant Venous Pressure: A Clinical Study With Physiological Insights From Mathematical Modelling of Biventricular Heart Failure

The deleterious consequences of chronically elevated venous pressure in patients with profound right ventricular or biventricular dysfunction are well known, including renal and hepatic dysfunction, and volume overload. The only option for these patients, if they fail optimal medical treatment, is a heart transplant, as they are not candidates for left ventricular assist device therapy. Mean perfusion pressure (MPP) is important in the outcomes of critically ill patients with high venous pressure. The question arises whether MPP is important for the outcomes of heart transplants in patients with elevated pre-transplant venous pressure. Medical management of heart failure patients with reduced ejection fraction involves lowering the systemic afterload with vasodilators while awaiting a transplant. We hypothesised that when venous pressure is elevated prior to transplant, a substantial reduction in systemic arterial elastance (Ea) through vasodilation may significantly decrease MPP, resulting in compromised end-organ function and consequent unfavourable outcomes after heart transplantation. This study aims to investigate whether a low MPP serves as a risk factor for adverse outcomes in heart transplant recipients with high venous pressure. A retrospective analysis was conducted on 250 heart transplant recipients undergoing isolated heart transplantation at a single institution from October 2012 to March 2020. Right atrial pressure (RAP) of more than 15 mmHg was considered high. Additionally, Ea calculated as the ratio of end-systolic pressure to stroke volume, and MPP calculated as the difference between mean arterial pressure and RAP were considered in our analysis. The outcomes of transplantation were measured in terms of 90-day mortality and survival up to 7 years. High RAP was a significant risk factor for short-term and medium-term survival if Ea was low (<2.7 mmHg/mL, the median value). This group had 39.39% in-hospital mortality compared to 14.49% for RAP<15 mmHg (p∼0.005). When Ea was high, this difference in survival was not evident: 8% for RAP<15 mmHg vs 4.8% for RAP>15 mmHg (p∼0.550). This effect was mediated through a lower MPP, and the mortality due to lower MPP increased strikingly with higher body surface area (BSA). A negative correlation was observed between MPP indexed to BSA (MPPI) and the Model for End-Stage Liver Disease score (r∼-0.3580, p<0.0001) as well as creatinine (r∼-0.3551, p<0.0001). MPPI less than 40 mmHg/m2 was associated with poorer short-term (23.2% for MPPI<40 mmHg/m2 vs 7.1% for MPPI>40 mmHg/m2, p∼0.001) and medium-term survival. The impact of high RAP and low Ea on survival was evident even on medium-term follow-up; only 30% survival at 7 years follow-up for high RAP and low Ea vs 75% for RAP<15 mmHg (p∼0.0033). The acceptable blood pressure during vasodilator therapy in patients with high RAP needs to be higher, especially in those with higher BSA. MPPI less than 40 mmHg/m2 is a risk factor for survival, in the short and medium-term, after heart transplantation.

Maternal and neonatal outcomes for kidney transplant recipients

ObjectiveTo report pregnancy outcomes for women with kidney transplantation and investigate whether different intervals after transplantation have different effects on pregnancy outcomes. MethodsA single-center retrospective study was performed. Based on intervals after transplantation, pregnant women with kidney transplantation are divided into two groups: intervals <5 years and ≧5 years. The maternal and neonatal outcomes were compared between the two groups. ResultsNo maternal and neonatal deaths occurred. The average age of mothers during pregnancy was 32.3 ± 4.1 years and they had a functioning transplant for 4 (interquartile ranges, 3, 6) years. Preeclampsia occurs in sixteen (16.5 %) pregnancies and gestational diabetes (GDM) occurs in twenty (20.6 %). Eighty-eight newborns (90.7 %) had a gestational age of <37 weeks. The average gestational age for live births was 33.8 ± 2.2 weeks and the average birth weight was 2285.6 ± 581.8 g. Neonatal respiratory distress syndrome (NRDS) occurs in fifty-one babies (52.6 %), intraventricular hemorrhage (ICH) occurs in twenty-nine (29.8 %), atrial septal defects (ASD) occurs in thirty-two (32.9 %) and bronchopulmonary dysplasia (BPD) occurs in seven (7.2 %). Further analysis, pregnancy results, including pre-eclampsia, hypertension or GDM, did not differentiate between the two groups (intervals <5 years vs. ≧5 years). Neonatal outcomes, including premature delivery, low birth weight, mode of birth, small for gestational age (SGA), RDS, ICH, ASD, BPD were not distinguishable between the two groups (intervals <5 years vs. ≧5 years). The level of neonatal blood creatinine after birth was linearly related to high maternal creatinine, and can drop to normal levels within a week. ConclusionsThe incidence of maternal and neonatal complications in pregnancies following kidney transplantation is still high, despite the success of most pregnancies. Various posttransplant intervals had no significant impact on pregnancy outcomes.

Effect of Body Composition on Graft Function and Cardiovascular Outcomes in Normotensive Renal Transplant Recipients.

We evaluated the effects of body composition on graft function and cardiovascular outcomes in normotensive renal transplant recipients. In this cross-sectional study, we analyzed ambulatory blood pressure monitoring data from 136 renal transplant recipients with stable allograft function after living related donor transplant. We enrolled 87 normotensive recipients. We analyzed left ventricular mass index, renal resistive index, and body composition of recipients. We divided recipients into 2 groups according to mean lean body mass, defined by bioimpedance analysis, with 38 in group 1 (lean body mass <47 kg) and 49 in group 2 (lean body mass ≥47 kg). Mean time posttransplant was 35.0 ± 23.3 months. Mean renal resistive index, left ventricular mass index, lean body mass, body mass index, and fat mass were 0.67 ± 0.1, 195.0 ± 118.5 g/m2, 47.3 ± 9.1 kg, 25.9 ± 5.0 kg, and 44.6±10.5 kg,respectively. Lean body mass was positively correlated to sex (r = 0.36, P = .03), body mass index (r = 0.04, P = .416),renalresistive index (r = 0.495, P = .01), and left ventricular mass index (r = 0.713, P = .02) but negatively correlated to serum albumin levels (r=-0.343, P=0.04). Lean body mass was significantly higher in males than in females (P = .03). Patients in group 2 had significantly higher left ventricular mass index (P = .01) and renal resistive index (P = .03). In multiple regression analysis, lean body mass (P = .01) and left ventricular mass index (P = .01) were predictors of renal resistive index. Lean body mass significantly influences left ventricular mass index and renal resistive index. Hence, body composition analysis could be an early predictor of graft function and cardiovascular outcomes in normotensive renal transplant recipients.

Assessment of the Relation between Infused Cell Dose and Clinical Outcomes of Autologous and Allogeneic Stem Cell Transplant Recipients By Patient Ethnicity before and during the COVID19 Pandemic.

Assessment of the Relation between Infused Cell Dose and Clinical Outcomes of Autologous and Allogeneic Stem Cell Transplant Recipients By Patient Ethnicity before and during the COVID19 Pandemic.

Renal Transplant in Elderly End-Stage Renal Disease Patients: Impact of Comorbidities and Posttransplant Adverse Events on Outcomes.

Elderly renal transplant continues to be debated because of age-related factors affecting transplant success and long-term prognosis. We investigated the effects ofrecipient age and predictors of renal transplant outcomes in elderly renal transplant recipients. We retrospectively analyzed 506 patients who had a first renal transplant between January 2010 and December 2020; there were 165 recipients aged ≥60 years (elderly) and 341 recipients aged <60 years (young).We collected recipient, donor, and transplant characteristics and assessed 1-, 3-, and 5-year overall patient and death-censored graft survival and risk factors influencing outcomes ofrenal transplant in elderly recipients. Elderly recipients showed significantly lower 1-, 3-, and 5-year patient survival rates (96.3%, 89.8%, 80.9%) than young recipients (98.8%, 98.5%, 97.8%; P < .001). However, death-censored graft survival rates were not significantly different (P = .459) between elderly (96.3%, 94.3%, 93.2%) and young recipients (97.7%, 97.0%, 93.9%). Advanced recipient age was identified as an independent risk factor for patient survival, irrespective of donor age. In elderly recipients, male gender (hazard ratio 2.013; 95% CI, 1.110-3.649), pretransplant cardiovascular disease (hazard ratio 1.774; 95% CI, 1.030-3.553), and posttransplant chestinfection (hazard ratio 2.421; 95% CI, 1.439-4.076) were significant predictors of inferior patient survival. Proteinuria at 1 month (hazard ratio 1.006; 95% CI, 1.000-1.011) and low estimated glomerular filtration rate at 3 months (hazard ratio 0.943; 95% CI, 0.899-0.988) posttransplant were early predictors of worse death-censored graft survival. Elderly renaltransplantrecipients showed promising 5-year patient and death-censored graft survival, exceeding 80%, despite higher mortality risk compared with young recipients. Optimizing outcomes of elderly renal transplant necessitates a multifaceted approach encompassing meticulous pretransplant cardiovascular disease assessment, rigorous posttransplant chest infection prevention and management, and proactive monitoring for early posttransplant kidney dysfunction, to permit timely intervention.

Outcomes in Heart Transplant Recipients by Bridge to Transplant Strategy When Using the SherpaPak Cardiac Transport System.

The last several years have seen a rise in use of mechanical circulatory support (MCS) to bridge heart transplant recipients. A controlled hypothermic organ preservation system, the SherpaPak Cardiac Transport System (SCTS), was introduced in 2018 and has grown in utilization with reports of improved posttransplant outcomes. The Global Utilization And Registry Database for Improved heArt preservatioN (GUARDIAN)-Heart registry is an international, multicenter registry assessing outcomes after transplant using the SCTS. This analysis examines outcomes in recipients bridged with various MCS devices in the GUARDIAN-Heart Registry. A total of 422 recipients with donor hearts transported using SCTS were included and identified. Durable ventricular assist devices (VADs) were used exclusively in 179 recipients, temporary VADs or intra-aortic balloon pump (IABP) in 197, and extracorporeal membrane oxygenation (ECMO) in 14 recipients. Average ischemic times were over 3.5 hours in all cohorts. Severe primary graft dysfunction (PGD) posttransplant increased across groups (4.5% VAD, 5.1% temporary support, 21.4% ECMO), whereas intensive care unit (ICU) length of stay (18.2 days) and total hospital stay (39.4 days) was longer in the ECMO cohort than the VAD and IABP groups. A comparison of outcomes of MCS bridging in SCTS versus traditional ice revealed significantly lower rates of both moderate/severe right ventricular (RV) dysfunction and severe PGD in the SCTS cohort; however, upon propensity matching only the reductions in moderate/severe RV dysfunction were statistically significant. Use of SCTS in transplant recipients with various bridging strategies results in excellent outcomes.

Obesity is associated with a higher incidence of rejection in patients on belatacept: A pooled analysis from the BENEFIT/BENEFIT-EXT clinical trials

Though belatacept is administered with a weight-based dosing schema, there has been higher clearance reported in obese patients. Therefore, we evaluated the association between body mass index (BMI) and transplant outcomes in kidney transplant recipients who were randomized to cyclosporine- or belatacept-based immunosuppression in the BENEFIT and BENEFIT-EXT randomized clinical trials. A total of 666 and 543 patients underwent randomization and transplantation in BENEFIT and BENEFIT-EXT, respectively, of which 1056 had complete data and were included in this analysis. Patients were grouped categorically according to BMI: <25, 25 to <30, and ≥30 kg/m2. BMI did influence both the incidence and severity of acute rejection. Obese patients with BMI >30 kg/m2 in the low intensity belatacept group experienced significantly more rejection at 12 months than did patients with BMI <25 kg/m2 or BMI 25 to <30 kg/m2. In both the moderate intensity belatacept and low intensity belatacept groups, obese patients with BMI >30 kg/m2 experienced significantly more severe acute rejection than did patients with BMI < 25 kg/m2 or BMI 25 to <30 kg/m2. These results suggest that obese kidney transplant recipients are at an increased risk for acute rejection when under belatacept-based immunosuppression when compared to nonobese patients.

Outcomes of Haploidentical Stem Cell Transplant Recipients with HHV-6 Reactivation Receiving Antiviral Therapy

Outcomes of Haploidentical Stem Cell Transplant Recipients with HHV-6 Reactivation Receiving Antiviral Therapy

Outcomes in solid organ transplant recipients with a pretransplant diagnosis of melanoma

Melanoma causes significant morbidity in solid organ transplant recipients (SOTRs). Melanomas diagnosed before transplantation can recur with intensive immunosuppression, but outcomes have not been well studied. We evaluated 901 non-Hispanic White SOTRs with a pretransplant melanoma identified using linked transplant and cancer registry data in the United States. Most pretransplant melanomas were invasive (60.7%), and the median time from diagnosis to transplantation was 5.1 years. After transplantation, 41 SOTRs developed a new invasive melanoma, corresponding to 9-fold increased risk compared with the general population (standardized incidence ratio, 9.2; 95% confidence interval [CI], 6.6-12). Twenty-two SOTRs died from melanoma after transplantation, corresponding to 52-fold increased risk (standardized mortality ratio, 52; 95% CI, 33-79). Risk factors for posttransplant melanoma included age at transplantation (adjusted hazard ratio [HR], 2.86; 95% CI, 1.24-6.60; for age 55+ vs <55 years) and maintenance immunosuppression with cyclosporine/azathioprine (adjusted HR, 2.53; 95% CI, 1.08-5.90). Melanoma mortality was strongly elevated after a posttransplant melanoma diagnosis (HR, 35.6; 95% CI, 14.0-90.4; adjusted for cyclosporine/azathioprine maintenance therapy and calendar year of transplantation). In conclusion, SOTRs with a pretransplant melanoma are at risk of adverse melanoma-related outcomes after transplantation. These findings support thorough dermatologic evaluation prior to transplantation and frequent posttransplant surveillance.

Do pre-transplant cultural factors predict health-related quality of life after kidney transplantation?

Post-transplant health-related quality of life (HRQOL) is associated with health outcomes for kidney transplant (KT) recipients. However, pretransplant predictors of improvements in post-transplant HRQOL remain incompletely understood. Namely, important pretransplant cultural factors, such as experience of discrimination, perceived racism in healthcare, or mistrust of the healthcare system, have not been examined as potential HRQOL predictors. Also, few have examined predictors of decline in HRQOL post-transplant. Using data from a prospective cohort study, we examined HRQOL change pre- to post-transplant, and novel cultural predictors of the change. We measured physical, mental, and kidney-specific HRQOL as outcomes, and used cultural factors as predictors, controlling for demographic, clinical, psychosocial, and transplant knowledge covariates. Among 166 KT recipients (57% male; mean age 50.6 years; 61.4%>high school graduates; 80% non-Hispanic White), we found mental and physical, but not kidney-specific, HRQOL significantly improved post-transplant. No culturally related factors outside of medical mistrust significantly predicted change in any HRQOL outcome. Instead, demographic, knowledge, and clinical factors significantly predicted decline in each HRQOL domain: physical HRQOL-older age, more post-KT complications, higher pre-KT physical HRQOL; mental HRQOL-having less information pre-KT, greater pre-KT mental HRQOL; and, kidney-specific HRQOL-poorer kidney functioning post-KT, lower expectations for physical condition to improve, and higher pre-KT kidney-specific HRQOL. Instead of cultural factors, predictors of HRQOL decline included demographic, knowledge, and clinical factors. These findings are useful for identifying patient groups that may be at greater risk of poorer post-transplant outcomes, in order to target individualized support to patients.

Outcomes of older Black renal transplant recipients receiving basiliximab induction and early steroid withdrawal

AbstractThe efficacy and safety of early steroid withdrawal (ESW) in Black renal transplant recipients (RTR) remains uncertain, especially when combined with non‐lymphocyte depleting induction. This study compared patient and graft outcomes of older Black and Non‐Black RTR who received basiliximab induction followed by ESW.Included subjects in this single center, retrospective study were first‐time deceased and living donor RTR aged over 65 years who received basiliximab induction therapy and ESW. Black RTR and Non‐Black deceased donor RTR received an oral prednisone taper starting POD3 which was discontinued by POD21 per protocol.Of 139 patients (55 Black and 84 Non‐Black), the Black patient group included a higher percentage of deceased donors and hepatitis C positive donors, and more frequently underwent renal replacement therapy prior to transplant. One Black and zero Non‐Black RTR experienced graft loss within 3 years (p = 1.0). Patient survival was similar at 1 year (93% vs. 97%, p = .16) and 3 years (91% vs. 96%, p = .17). Rejection‐free survival and biopsy‐proven rejection did not differ at 1 or 3 years. Median eGFR and change in eGFR also did not differ between groups. Black patients were maintained on significantly higher median mycophenolate doses from 6 months post‐transplant to the end of the study period (p = .03 and .048).In older Black RTR, basiliximab induction followed by ESW produced comparable patient, graft, and rejection‐free survival compared to Non‐Black RTR over 3 years post‐transplant.

Heart transplantation from COVID-positive donors with 6-month follow-up: A case series.

Data on long term outcomes in heart transplant recipients from Coronavirus disease 2019 (COVID-19) positive donors are limited. We present a series of nine patients who underwent heart transplants from COVID-19 PCR-positive donors between November 2021 to August 2022 with mean follow-up of 12.12±3 months. All the recipients received two doses of COVID-19 vaccine and had at least 6 months follow-up. Eight recipients had acceptable long-term outcomes; one patient died during index admission from primary graft dysfunction. Details regarding donor and recipient characteristics, management and outcomes are provided. Two patients developed deep vein thrombosis, and one patient underwent pacemaker implantation for sinus node dysfunction. Among the surviving eight patients, none developed COVID-19 infection during follow-up period. There was no significant difference in outcome parameters when compared to patients who received hearts from donors who tested negative for COVID-19 during the same time period at our center. Keeping in mind the significant waitlist mortality in patients awaiting heart transplantation, COVID-19-positive donors should be considered for heart transplantation to help expand the donor pool and potentially reduce waitlist mortality.

COVID-19 Outcomes in Lung Transplant Recipients Following Pre-Exposure Prophylaxis With Tixagevimab-Cilgavimab During the Omicron BA.5 Surge: A Single Center Analysis.

Lung transplant (LTx) recipients are at high risk for COVID-19 related morbidity and mortality. Data regarding pre-exposure prophylaxis (PrEP) with tixagevimab-cilgavimab in this population are scarce. We therefore evaluated COVID-19 breakthrough infections and COVID-19 related complications after PrEP in a retrospective single-center study, including 264 LTx recipients who received PrEP between June 2022 and December 2022, when Omicron BA.5 was the dominant circulating SARS-CoV-2 variant. PrEP was indicated for fully vaccinated patients with poor seroconversion (anti-S <260BAU/mL). COVID-19 breakthrough infection after PrEP occurred in 11.0% within the first 3months, increasing to 17.4% within 6months. Hospitalization rate rose from 27.6% to 52.9% (p = 0.046), while ICU admissions and COVID-19 mortality remained low, respectively occurring in 6.5% and 4.3% of patients with breakthrough infection within 6months. COVID-19 breakthrough infection and associated hospitalization remained an important problem during the Omicron BA.5 surge in fully vaccinated LTx recipients with deficient seroconversion, despite PrEP with tixagevimab-cilgavimab. However, ICU admissions and COVID-19 mortality were low. Waning of neutralizing effects of PrEP and changing circulating SARS-CoV-2 variants may explain increases in COVID-19 infections and hospitalizations over time after PrEP, highlighting the need for novel, long-term effective PrEP strategies in these high-risk patients.

Outcomes of Liver Transplant Recipients Hospitalized With COVID-19: A Nationwide Analysis From the United States

IntroductionCurrently available data regarding the impact of liver transplantation on the outcomes of patients hospitalized with COVID-19 is conflicting. This study aims to compare the outcomes and resource utilization between patients with and without a history of liver transplant hospitalized with COVID-19. Methods and materialsThis is a retrospective study using the National Inpatient Sample. All adults hospitalized with COVID-19 in the year 2020 were included. Mortality was the primary outcome, while endotracheal intubation, length of hospital stay, and total hospital charges were the secondary outcomes. ResultsOut of 1,050,720 adults admitted with COVID-19 as the primary diagnosis, 1,455 had a secondary diagnosis of liver transplant. Mortality was not significantly increased in transplant recipients (OR adjusted = 0.69, 95% CI: 0.46–1.03, P = 0.07). Intubation rates and total hospital charges did not differ significantly between liver transplant recipients and patients without a history of liver transplant receipt. LOS was shorter by a coefficient of almost two days in patients with a history of LT (P < 0.001). ConclusionLiver transplant recipients do not appear to be at increased risk of severe COVID-19 and COVID-19 mortality.

Usage of older donors is associated with higher mortality after heart transplantation: A UNOS observational study

IntroductionUtilization of heart from older donors is variable across centers with uncertain outcomes of recipients. We sought to utilize a national registry to examine usage and outcomes of heart transplant recipients from older donors. We also explored the impact of current donor heart allocation scheme on outcomes of hearts from older donors. MethodsThis observational study utilized the United Network for Organ Sharing database between 2015 and 2023 with donors categorized into age < 45 years or ≥ 45 years and evaluated organ disposition and geographical variation. 30-day, 1- and 3- year mortality, and graft failure rates were compared amongst recipients as per donor age group. We also evaluated annual trends in HT for each group over the follow-up period. Results24,966 adult donors were recovered: 3,742 (15.0%) were ≥ 45 years; 3,349 (15.6%) adults received heart from such donors with significant geographical variation, and a declining utilization in the transplantation rate in current donor allocation system. Donors with age ≥ 45 years had higher comorbidities and were allotted with a significantly shorter ischemic time to recipients who were significantly less likely to receive temporary mechanical circulatory support and more likely female. Unadjusted and adjusted, 30-day mortality were similar but 1- and 3-year mortality and graft failure rates were significantly higher in recipients of such donors. spline analysis suggested a higher 1-year mortality risk at older donor age with risk increasing after age 40 years. ConclusionsOlder donor age was associated with worsened 1- and 3-year mortality and graft failure for heart transplant recipients.

COVID-19 in transplant recipients: Multicentric report of Mexican experience

Solid Organ Transplant recipients (SOTR) appear to be at particular high risk for critical COVID-19 due to immunosuppressive drugs and comorbidities. We report the first description of clinical course and short-term outcomes of kidney and liver transplant recipients with confirmed COVID-19 in Mexico. The objective of this paper was evaluate the clinical course of transplant patients with COVID-19 infection. We retrospectively evaluated SOTR (kidney and liver) over 18 years of age with confirmed diagnosis of COVID-19 from tertiary care centers in Mexico. Data from 45 kidney transplant recipients were recorded. Median (IQR) age was 43 (IQR 25-70) years. Admission to hospital was required in 37 (75.5 %) patients, of which 8 (16.3%) were hospitalized at Intensive Care Unit (ICU). Acute kidney injury (AKI) stage was documented in 33 (67%) patients. The time of hospitalization was 8 (IQR 6-12) days. Six patients died (12.2%). Additionally, data from 10 liver transplant recipients were included. During their evolution, 5 / 10 required hospital admission and there were no deaths in this group. Transplant recipients show a higher fatality rate and complications from SARS-CoV-2 infection; more studies are needed to identify prognostic factors and effective anti-SARS-CoV-2 therapies.

Association of metformin with cardiovascular and graft outcomes in kidney transplant recipients with posttransplantation diabetes mellitus.

Posttransplantation diabetes mellitus (PTDM) is a crucial problem after kidney transplantation. We aimed to determine whether metformin affects cardiovascular and graft outcomes in patients with PTDM. This retrospective cohort study included 1,663 kidney transplant recipients without preexisting diabetes mellitus. The patients were divided into metformin and non-metformin groups, with matched propensity scores. We also estimated metformin's effect on percutaneous coronary intervention (PCI), major adverse cardiovascular events (MACEs), acute rejection, and graft failure. Of 634 recipients with PTDM, 406 recipients were treated with metformin. The incidence of PCI was 2.4% and 7.1% in the metformin and non-metformin groups, respectively (p = 0.04). The metformin group exhibited a lower risk of PCI in Cox regression analyses (hazard ratio [HR], 0.27; 95% confidence interval [CI], 0.10-0.77; p = 0.014), especially in subgroups with male sex, age over 49 years (median), long-term metformin use (mean of ≥1,729 days), and simultaneous tacrolimus administration. Long-term metformin use was also associated with lower incidence of MACEs (HR, 0.09; 95% CI, 0.01-0.67; p = 0.02). Incidence of graft failure was 9.9% and 17.0% in the metformin and non-metformin groups, respectively (p = 0.046). Both long-term use and higher dose of metformin, as well as tacrolimus administration with metformin, were associated with a lower risk of graft failure (HR, 0.29; 95% CI, 0.11-0.75; p = 0.01; HR, 0.39; 95% CI, 0.18-0.85; p = 0.02; and HR, 0.39; 95% CI, 0.19-0.79; p = 0.009, respectively). Metformin use is associated with a decreased risk of developing coronary artery disease and better graft outcomes in PTDM.

Post-transplant lymphoproliferative disorder risk and outcomes in renal transplant patients treated with belatacept immunosuppression.

Post-transplant lymphoproliferative disorder (PTLD) is a rare but life-threatening malignancy that arises in the setting of immunosuppression (IS) after solid organ transplant. IS regimens containing belatacept have been associated with an increased risk of PTLD in Epstein-Barr virus (EBV)-seronegative renal transplant recipients, and the use of belatacept is contraindicated in this population. However, the impact of belatacept-based regimens on PTLD risk and outcomes in EBV-seropositive renal transplant recipients is less well characterized. A case-control study was conducted to investigate how combinatorial IS regimens impact the risk of PTLD and survival outcomes in renal transplant recipients at a large transplant center between 2010 and 2019. In total, 17 cases of PTLD were identified and matched 1:2 to controls without PTLD by age, sex, and transplanted organ(s). We compared baseline clinical characteristics, examined changes in IS regimen, viral loads, and renal function over time, and evaluated time-to-event analyses, including graft rejection and survival. Cases of PTLD largely resembled matched controls in terms of baseline characteristics, although expected differences in EBV serostatus trended toward significance (42.9% of PTLD cases were donor-positive/recipient-negative vs. 8.3% controls, p = 0.063). PTLD cases were not more likely to have received belatacept than controls. Belatacept was not associated with graft rejection or failure, re-transplant, hospitalization, or decreased survival. Belatacept was not associated with an increased risk of PTLD, and was not associated with decreased survival in either PTLD cases or in the entire cohort. Our case-control study supports the concept that belatacept remains a safe and effective option for IS in EBV-seropositive renal transplant patients.

Airway pepsinogen A4 identifies lung transplant recipients with microaspiration and predicts chronic lung allograft dysfunction

BackgroundAspiration is a known risk-factor for adverse outcomes post-lung transplantation. Airway bile acids are the gold-standard biomarker of aspiration – however they are released into the duodenum and likely reflect concurrent gastrointestinal dysmotility. Previous studies investigating total airway pepsin have found conflicting results on its relationship with adverse outcomes post-lung transplantation. These studies measured total pepsin and pepsinogen in the airways. Certain pepsinogens are constitutively expressed in the lungs while others, like pepsinogen A4 (PGA4), are not. We sought to evaluate the utility of measuring airway PGA4 as a biomarker of aspiration and predictor of adverse outcomes in lung transplant recipients (LTRs) early post-transplant. MethodsExpression of PGA4 was compared to other pepsinogens in lung tissue. Total pepsin and PGA4 were measured in large airway bronchial washings and compared to pre-existing markers of aspiration. Two independent cohorts of LTRs were used to assess the relationship between airway PGA4 and chronic lung allograft dysfunction (CLAD). Changes to airway PGA4 after anti-reflux surgery was assessed in a third cohort of LTRs. ResultsPGA4 was expressed in healthy human stomach but not lung. Airway PGA4, but not total pepsin, was associated with aspiration. Airway PGA4 was associated with an increased risk of CLAD in two independent cohorts of LTRs. Anti-reflux surgery was associated with reduced airway PGA4. ConclusionsAirway PGA4 is a marker of aspiration that predicts CLAD in LTRs. Measuring PGA4 at surveillance bronchoscopies can help triage high-risk LTRs for anti-reflux surgery.

Pregnancy outcomes post-kidney transplantation across 23 years.

Pregnancy in kidney transplant recipients has become increasingly common. However, pregnancy carries higher risks to these patients compared to the general population. To describe pregnancy outcomes in kidney transplant recipients. We conducted a single-centre retrospective cohort study of kidney transplant recipients who delivered after 20 weeks gestation at a quaternary hospital in Victoria, Australia, between 2000 and 2022 inclusive. The study included 37 pregnancies from 27 patients, accounting for 38 infants. Over half of recorded pregnancies occurred in the past five years (56.8%, n = 21). There were high rates of pre-existing hypertension (75.7%, n = 28). Pregnancy-induced hypertension and pre-eclampsia were common antenatal complications (21.6%, n = 8 and 48.6%, n = 18 respectively). Soluble fms-like tyrosine kinase-1 / placental growth factor ratios were elevated in all patients who developed severe pre-eclampsia (16.2%, n = 6). The median gestational age at birth was 36.4 weeks (range 20-40.4, Q1 32.9, Q3 37.6) and 59.5% (n = 22) of births were preterm. Unplanned caesarean without labour was the most common mode of birth (35.1%, n = 13). The overall caesarean rate was 62.1% (n = 23). Post-partum haemorrhage complicated over half of pregnancies (56.8%, n = 21). Fifty percent (n = 19) of infants were admitted for neonatal care, in particular neonatal intensive care, and had low birthweights under 2500 g. While there was a transient deterioration in kidney function, there was no graft rejection within one year of birth. Clinicians should consider the high rates of pre-existing hypertension, preterm birth, and caesarean birth when counselling and managing pregnant kidney transplant recipients.