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Background/Objectives: Neutropenia is a frequent complication among solid organ transplant (SOT) recipients receiving immunosuppressive therapy and antimicrobial prophylaxis. However, there are limited studies analysing the frequency and impact of neutropenia in lung transplant recipients (LTRs). Our aim was to analyse the frequency of neutropenia, the need for granulocyte colony-stimulating factor (GCSF) treatment within the first 18 months post-transplant and its association with acute rejection, chronic lung allograft dysfunction (CLAD), overall survival and the development of infections. Methods: This observational and retrospective study recruited 305 patients who underwent lung transplantation between 2009 and 2019, with outpatient quarterly follow-up during the first 18 months post-surgery.Results: During this period, 51.8% of patients experienced at least one episode of neutropenia. Neutropenia was classified as mild in 50.57% of cases, moderate in 36.88% and severe in 12.54%. GCSF treatment was indicated in 23.28% of patients, with a mean dose of 3.53 units. No statistically significant association was observed between neutropenia or its severity and the development of acute rejection, CLAD or overall survival. However, the patients who received GCSF treatment had a higher mortality rate compared to those who did not. Sixteen patients (5.25%) developed infections during neutropenia, with bacterial infections being the most common. Conclusions: Neutropenia is common in the first 18 months after lung transplantation and most episodes are mild. We did not find an association between neutropenia and acute rejection, CLAD, or mortality. However, the use of GCSF were associated with worse post-transplant survival. [ABSTRACT FROM AUTHOR]

Purpose: Hepatocellular carcinoma (HCC) is one of the malignant tumors responsible for high mortality and recurrence rates. Although liver transplantation (LT) is an effective treatment option for HCC, ischemia-reperfusion injury (IRI) is a contributor to HCC recurrence after LT. Moreover, prolonged cold ischemia time (CIT) is a risk factor for IRI during LT, and there is insufficient clinical evidence regarding the impact of CIT on HCC recurrence after LT. Patients and Methods: This retrospective study analyzed 420 patients who underwent LT for HCC between February 2015 and November 2020 at The First Affiliated Hospital, Sun Yat-sen University. The duration of CIT was defined as the time from clamping of the donor aorta until portal reperfusion. Results: A total of 133 patients (31.7%) experienced tumor recurrence after LT, and CIT > 568 min was the independent risk factor for HCC recurrence (OR, 2.406; 95% CI [1.371–4.220]; p = 0.002). Multivariate Cox's regression analysis revealed that the recipients' gender, exceeding Milan criteria, poor differentiation, and alpha-fetoprotein (AFP) ≥400 ng/ml in CIT > 568 min group were independent risk factors for disease-free survival. The peak 7-day postoperative alanine aminotransferase (ALT) level (p < 0.001), the peak 7-day postoperative aspartate aminotransferase (AST) level (p < 0.001), the peak 7-day postoperative peak total bilirubin (TBIL) level (p = 0.012), and the incidence of early allograft dysfunction (EAD) (p = 0.006) were significantly higher in the CIT > 568 min group compared to the CIT ≤ 568 min group. Moreover, the amount of fresh frozen plasma (FFP) infusion during the operation increased (p = 0.02), and the time of mechanical ventilation postoperative was longer (p = 0.045). Conclusion: An effective strategy to improve the prognosis is to reduce CIT; this strategy lowers the recurrence of HCC in patients undergoing LT, especially those within the Milan criteria. [ABSTRACT FROM AUTHOR]

Rationale & Objective: Nearly half of kidney transplant recipients develop allograft failure within 10 years of transplantation and experience high mortality, significant symptom burden, and complex communication challenges. These patients may benefit from palliative care, but palliative care is infrequently provided in this population. This study explores palliative care perceptions and needs among patients with poorly functioning and declining kidney allografts. Study Design: A qualitative study using semistructured interviews. Setting & Participants: Adult kidney transplant recipients with a glomerular filtration rate of

Background: Observational studies have suggested that herpes virus infections increase the risk of allograft dysfunction after tissue and organ transplantation, but it is still unclear whether this association is causal. The aim of this study was to assess the causal relationship between four herpes virus infections and allograft dysfunction. Methods: We used two-sample bidirectional Mendelian randomization (MR) to investigate the causality between four herpes virus infections -- cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus (HSV) and varicella zoster virus (VZV) -- and allograft dysfunction after tissue and organ transplantation. Based on summary data extracted from genome-wide association studies (GWAS), we chose eligible single nucleotide polymorphisms (SNPs) as instrumental variables. The Inverse variance weighted (IVW) method was used as the main analysis method, supplemented by Weighted median and MR-Egger analyses. The MR-PRESSO test, MR-Egger intercept test, heterogeneity test, leave-one-out analysis and funnel plot were used to analyze the sensitivity of MR results. Results: We found EBV early antigen-D (EA-D) antibody levels and shingles were the only two variables associated with an increased risk of allograft dysfunction. No evidence of allograft dysfunction increasing the risk of the four herpes virus infections was observed. Sensitivity analyses confirmed the robustness of our results. Conclusions: Our results suggest that EBV and VZV are involved in graft rejection or dysfunction. However, the relationship between CMV and HSV infections and allograft dysfunction remains unclear and requires further clarification. [ABSTRACT FROM AUTHOR]

During the last few years, cell-free DNA (cfDNA) has emerged as a possible noninvasive biomarker for prediction of complications after lung transplantation. We previously published a proof-of-concept study using a digital droplet polymerase chain reaction (ddPCR)-based method for detection of cfDNA. In the current study, we aimed to further evaluate the potential clinical usefulness of detecting chronic lung allograft dysfunction (CLAD) using three different ddPCR applications measuring and calculating the donor fraction (DF) of cfDNA as well as one method using the absolute amount of donor-derived cfDNA. We analyzed 246 serum samples collected from 26 lung transplant recipients. Nine of the patients had ongoing CLAD at some point during follow-up. All four methods showed statistically significant elevation of the measured variable in the CLAD samples compared to the non-CLAD samples. The results support the use of ddPCR-detected cfDNA as a potential biomarker for prediction of CLAD. These findings need to be validated in a subsequent prospective study. [ABSTRACT FROM AUTHOR]

Background: Plasma percent donor-derived cell-free DNA (%dd-cfDNA) has been investigated as a biomarker of allograft injury after lung transplantation. We sought to determine the clinical utility of %dd-cfDNA as a screen for acute cellular rejection (ACR) and respiratory infections (RIs) among lung transplant recipients (LTRs). Methods: We retrospectively analyzed %dd-cfDNA results from 95 plasma samples collected from 81 bilateral LTRs >45 days after transplant with a paired transbronchial biopsy performed within 24 hours after sample collection. We calculated sensitivity, specificity, negative predictive value (NPV), and positive predictive value of %dd-cfDNA to detect ACR and RIs and used a generalized estimating equation model to compare %dd-cfDNA between groups. Results: A dd-cfDNA threshold of 0.5% had low sensitivity to detect ACR among LTRs (41.67%), as did a 70% increase in %dd-cfDNA (50.00%). The NPV was high (88.89% and 87.50%, respectively) but driven by the low prevalence of ACR (12/95 [12.6%]). The area under the receiver operating characteristic curve (AUC) was 0.499 (95% confidence interval [CI] [0.326-0.672]) and 0.360 (95%CI [0.132-0.588]) for the detection of ACR and ACR grade ≥A2, respectively. The adjusted mean %dd-cfDNA trended higher in LTRs with a definite or possible RI (1.218, 95%CI [0.671-2.212]) than in LTRs without microbial isolation (0.731, 95%CI [0.525-1.017], p = 0.059), but was not significantly different from those with microbial colonization (0.873, 95%CI [0.538-1.415], p = 0.390). The AUC for the detection of allograft dysfunction due to ACR and/or RI was 0.573 (95%CI [0.431-0.716]). Conclusions: %dd-cfDNA may have limited utility as a screening tool to detect ACR and/or RI among LTRs.

Purpose Hepatocellular carcinoma (HCC) is one of the malignant tumors responsible for high mortality and recurrence rates. Although liver transplantation (LT) is an effective treatment option for HCC, ischemia-reperfusion injury (IRI) is a contributor to HCC recurrence after LT. Moreover, prolonged cold ischemia time (CIT) is a risk factor for IRI during LT, and there is insufficient clinical evidence regarding the impact of CIT on HCC recurrence after LT. Patients and Methods This retrospective study analyzed 420 patients who underwent LT for HCC between February 2015 and November 2020 at The First Affiliated Hospital, Sun Yat-sen University. The duration of CIT was defined as the time from clamping of the donor aorta until portal reperfusion. Results A total of 133 patients (31.7%) experienced tumor recurrence after LT, and CIT > 568 min was the independent risk factor for HCC recurrence (OR, 2.406; 95% CI [1.371–4.220]; p = 0.002). Multivariate Cox’s regression analysis revealed that the recipients’ gender, exceeding Milan criteria, poor differentiation, and alpha-fetoprotein (AFP) ≥400 ng/ml in CIT > 568 min group were independent risk factors for disease-free survival. The peak 7-day postoperative alanine aminotransferase (ALT) level (p 568 min group compared to the CIT ≤ 568 min group. Moreover, the amount of fresh frozen plasma (FFP) infusion during the operation increased (p = 0.02), and the time of mechanical ventilation postoperative was longer (p = 0.045). Conclusion An effective strategy to improve the prognosis is to reduce CIT; this strategy lowers the recurrence of HCC in patients undergoing LT, especially those within the Milan criteria.

Solid organ transplantation (SOT) is a life-saving procedure for people with end-stage organ failure. However, patients experience significant symptom burden, complex decision making, morbidity, and mortality during both pre- and post-transplant periods. Palliative care (PC) is well suited and historically underdelivered for the transplant population. This article, written by a team of transplant specialists (surgeons, cardiologists, nephrologists, hepatologists, and pulmonologists), PC clinicians, and an ethics specialist, shares 10 high-yield tips for PC clinicians to consider when caring for SOT patients.

Background/Objectives: Neutropenia is a frequent complication among solid organ transplant (SOT) recipients receiving immunosuppressive therapy and antimicrobial prophylaxis. However, there are limited studies analysing the frequency and impact of neutropenia in lung transplant recipients (LTRs). Our aim was to analyse the frequency of neutropenia, the need for granulocyte colony-stimulating factor (GCSF) treatment within the first 18 months post-transplant and its association with acute rejection, chronic lung allograft dysfunction (CLAD), overall survival and the development of infections. Methods: This observational and retrospective study recruited 305 patients who underwent lung transplantation between 2009 and 2019, with outpatient quarterly follow-up during the first 18 months post-surgery.Results: During this period, 51.8% of patients experienced at least one episode of neutropenia. Neutropenia was classified as mild in 50.57% of cases, moderate in 36.88% and severe in 12.54%. GCSF treatment was indicated in 23.28% of patients, with a mean dose of 3.53 units. No statistically significant association was observed between neutropenia or its severity and the development of acute rejection, CLAD or overall survival. However, the patients who received GCSF treatment had a higher mortality rate compared to those who did not. Sixteen patients (5.25%) developed infections during neutropenia, with bacterial infections being the most common. Conclusions: Neutropenia is common in the first 18 months after lung transplantation and most episodes are mild. We did not find an association between neutropenia and acute rejection, CLAD, or mortality. However, the use of GCSF were associated with worse post-transplant survival.

Tissue-invasive cytomegalovirus (CMV) disease represents a well-recognized complication after kidney transplantation. However, direct involvement of the urogenital tract and CMV-ureteritis occur less frequently. Nephrogenic adenomas are benign lesions of the urinary tract preferentially reported in kidney transplant recipients. We herein report a second case of a 33-year-old male kidney transplant recipient with acute post-renal allograft dysfunction due to CMV-positive ureteral nephrogenic adenoma. A causal connection might be suspected but remains to be proven.

Anemia is a frequent complication in pediatric kidney transplant recipients (KTR) with a variable reported prevalence estimated between 20 and 80% depending on how defined. Causes of and risk factors for post-transplantation anemia (PTA) are multifactorial with iron deficiency being the primary cause of early PTA (within the first 6 months after transplantation) and impaired glomerular filtration rate (GFR) commonly responsible for late PTA (after 6 months). Medications, viral infections, chronic inflammation, and comorbidities also play a role. PTA has relevant long-term consequences and is a potential risk factor for allograft dysfunction, cardiovascular morbidity, and mortality. Thus, an anemia evaluation, approximately 3 months post-transplantation, is recommended in order to start early treatment and improve prognosis. Iron status, vitamin B12, folate, markers of hemolysis, and viral PCR should be checked, and medications, in particular combinations of medications, should be carefully evaluated. PTA treatment may be challenging and should be directed to the underlying causes. Iron supplementation and erythropoietin therapy, not extensively used in KTR, may be indicated. Every effort should be made to avoid blood transfusions in the pre-transplant period to avoid allosensitization. Anemia should be corrected to prepare candidates for kidney transplantation in order to reduce the need for perioperative blood transfusions as well. [ABSTRACT FROM AUTHOR]

Kidney transplantation is the treatment of choice for patients with end-stage renal disease, as it extends survival and increases quality of life in these patients. However, chronic allograft injury continues to be a major problem, and leads to eventual graft loss. Early detection of allograft injury is essential for guiding appropriate intervention to delay or prevent irreversible damage. Several advanced MRI techniques can offer some important information regarding functional changes such as perfusion, diffusion, structural complexity, as well as oxygenation and fibrosis. This review highlights the potential of multiparametric MRI for noninvasive and comprehensive assessment of renal allograft injury.

• Why carry out this study? • Does sex matter? The importance of sex inequalities in solid organ transplantation. • There is limited evidence assessing the impact of sex on transplant recipient outcomes. • What was learned from the study? • Females account for 1/3 of the solid organ transplant recipient's cohort and have higher survival than males after liver and kidney transplant. • Allograft dysfunction was influenced by combination of donor-recipient sex and age. • Consider sex as a factor to optimize the management of transplant patients. Sex disparities are related to biological differences, which may have significant impact on patient and allograft outcomes. The aim was to investigate the impact of sex on clinical and safety outcomes after solid organ transplantation (SOT). A systematic review and meta-analysis was performed. Observational studies comparing females vs. males after SOT were considered for inclusion after a systematic search of the Pubmed, Cochrane Library, and Web of Science databases conducted from 2016 to 2021. Primary outcome was mortality. PROSPERO register number: CRD42021282615. After retrieving 1103 studies, 22 observational studies (1,045,380 subjects) were finally deemed eligible for inclusion. Females accounted 36.3% of SOT recipients, but presented significantly lower mortality (odds ratio (OR): 0.87, 95% confidence interval (CI): 0.83–0.92, I2=78%). In subgroup analyses, mortality was significantly lower in females undergoing liver (OR: 0.89 95%CI: 0.86–0.92, I2=0%) or kidney transplantation (OR: 0.82 95%CI: 0.76–0.89, I2=72%). Male sex was consistently reported as a protective factor against hospital readmission. Among the outcomes, allograft dysfunction was influenced by a combination of donor-recipient sex and age. Data on overall infections were inconclusive. Several reports suggest a higher risk of malignancy among males. Females represent one-third of SOT recipients but have higher survival rates than males after liver and kidney transplantation. The impact on graft dysfunction was heterogeneous. While further research is warranted, our findings should encourage clinicians and researchers to consider sex as a factor when taking decisions regarding SOT management. [ABSTRACT FROM AUTHOR]

Abstract Background Page kidney (PK) is the occurrence of kidney hypoperfusion and ischemia due to pressure on the kidney by a subcapsular hematoma (SH), a mass, or fluid collection. SH after renal transplantation may result in kidney ischemia and graft loss. Case presentation We present a rare case of early spontaneous SH in an allograft kidney that led to a decrease in renal function. A 56-year-old male patient underwent deceased donor kidney transplantation. After declamping, appropriate renal perfusion and immediate diuresis were observed, with no evidence of SH. However, his urinary output abruptly decreased 6 h postoperatively. Abdominal ultrasonography showed 28 mm deep SH on transplant and the resistive index (RI) increased to 0.98–1 and diastolic flow reversal was observed. Surgical interventions were performed 2 days after transplantation, following a further decrease in urinary output. Serum creatinine decreased to 2.2 mg/dL, urinary output increased to an average of 200 cc per hour and the RI value was decreased to 0.7 on POD 7. Conclusion In patients with abrupt decreased renal function after transplantation, SH should be suspected and the presence of PK should be determined using Doppler USG. In these cases, surgical intervention may avoid allograft dysfunction.

Standard methods for detecting chronic lung allograft dysfunction (CLAD) and rejection have poor sensitivity and specificity and have conventionally required bronchoscopies and biopsies. Plasma cell-free DNA (cfDNA) has been shown to be increased in various types of allograft injury in transplant recipients and CXCL10 has been reported to be increased in the lung tissue of patients undergoing CLAD. This study used a novel cfDNA and CXCL10 assay to evaluate the noninvasive assessment of CLAD phenotype and prediction of survival from bronchoalveolar lavage (BAL) fluid. A total of 60 BAL samples (20 with bronchiolitis obliterans (BOS), 20 with restrictive allograft syndrome (RAS), and 20 with stable allografts (STA)) were collected from 60 unique lung transplant patients; cfDNA and CXCL10 were measured by the ELISA-based KIT assay. Median cfDNA was significantly higher in BOS patients (6739 genomic equivalents (GE)/mL) versus STA (2920 GE/mL) and RAS (4174 GE/mL) (p < 0.01 all comparisons). Likelihood ratio tests revealed a significant association of overall survival with cfDNA (p = 0.0083), CXCL10 (p = 0.0146), and the interaction of cfDNA and CXCL10 (p = 0.023) based on multivariate Cox proportional hazards regression. Dichotomizing patients based on the median cfDNA level controlled for the mean level of CXCL10 revealed an over two-fold longer median overall survival time in patients with low levels of cfDNA. The KIT assay could predict allograft survival with superior performance compared with traditional biomarkers. These data support the pursuit of larger prospective studies to evaluate the predictive performance of cfDNA and CXCL10 prior to lung allograft failure.

Background Urinary extracellular vesicles (UEVs) hold RNA in their cargo and are potential sources of biomarkers for gene expression studies. The most used technique for gene-expression studies is quantitative polymerase chain reaction (qPCR). It is critical to use stable reference genes (RGs) as internal controls for normalising gene expression data, which aren't currently available for UEVs. Methods UEVs were precipitated from urine of graft dysfunction patients and healthy controls by Polyethylene glycol, Mn6000 (PEG6K). Vesicular characterisation confirmed the presence of UEVs. Gene expression levels of five commonly used RGs, i.e., Beta-2-Microglobulin (B2M), ribosomal-protein-L13a (RPL13A), Peptidylprolyl-Isomerase-A (PPIA), hydroxymethylbilane synthase (HMBS), and glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) were quantified, and their stability was established through the RefFinder. The stability of identified RGs was validated by quantification of Perforin and granzyme B, signature molecules of renal graft dysfunction. Results Urine precipitated with 12% 6 K PEG yielded round and double-membraned UEVs of size ranging from 30 to 100 nm, as confirmed through transmission electron microscopy. Nanoparticle tracking analysis (59 ± 22 nm) and Dynamic-light-scattering (78 ± 56.5 nm) confirmed their size profile. Semi-quantitative Exocheck antibody array demonstrated the presence of EV protein markers in UEV. Using the comparative ΔCт method and RefFinder analysis, B2M (1.6) and RPL13A (1.8) genes emerged as the most stable reference genes. Validation of target gene expression in renal graft dysfunction patients confirmed the efficiency of B2M and RPL13A through significant upregulation compared to other RGs. Conclusions Our study identified and validated B2M and RPL13A as optimal RGs for mRNA quantification studies in the UEVs of patients with renal graft dysfunction. [ABSTRACT FROM AUTHOR]

Objective: To evaluate outcome of diagnostic kidney biopsy in patients with renal allograft dysfunction at a tertiary care hospital. Study Design: Retrospective observational study. Place and Duration of Study: Armed Forces Institute of Urology, Rawalpindi, from Jan 2014 to Jan 2020. Methodology: A consolidate registry review was carried to formulate this study. The registry data exists at our center containing information about the graft dysfunction (manifesting as proteinuria, deranged urea and creatinine or urine sediment abnormalities) and other major indications which warrant probing with biopsy. The histopathological diagnosis of these biopsies is confirmed from the nephro-pathology registry before finalization of diagnosis. Results: A total of 94 diagnostic kidney biopsies were performed in patients with graft dysfunction. Out of 94 biopsies, 80 (85.1%) patients were male while 14 (14.9%) were female patients. The most frequent single cause for graft dysfunction was Cell Mediated Rejection (n 12, 24.5%) followed by Interstitial Fibrosis and Tubular Atrophy/Acute Tubular Injury. The most common cause among the glomerulonephritis was Membranoproliferative Glomerulonephritis (n 3, 6.1%) followed by others. The most common cause for mixed pathology remainedcell mediated rejection with Interstitial fibrosis and tubular atrophy (n 8, 17.8%). Conclusion: Cell mediated rejection is thecommonest pathology responsible for renal allograft dysfunction both as a single lesion as well as part of mixed pathology.

Leptospirosis (LTPS) is a bacterial infection that affects humans, often with mild or no symptoms. It is estimated that approximately 10 % of patients with LTPS may experience multi-organ dysfunction, including renal abnormalities. In regions where LTPS is widespread, a considerable number of instances involving acute kidney injury (AKI) and chronic kidney disease (CKD) of unknown etiology (CKDu) have been reported. Additionally, studies have shown a correlation between kidney graft dysfunction in patients with stable kidney transplants after LTPS. These findings indicate that exposure to LTPS may increase the likelihood of kidney transplantation due to the onset of both acute and chronic kidney injuries. Simultaneously, it poses a potential risk to the stability of kidney grafts. Unfortunately, there is limited scientific literature addressing this issue, making it difficult to determine the negative impact that LTPS may have, such as its role as a risk factor for the need of kidney transplantation or as a threat to individuals who have undergone kidney transplants. This study aims to shed light on the immune mechanisms triggered during LTPS infection and their importance in both kidney damage and allograft dysfunction. [ABSTRACT FROM AUTHOR]

Background: Page kidney (PK) is the occurrence of kidney hypoperfusion and ischemia due to pressure on the kidney by a subcapsular hematoma (SH), a mass, or fluid collection. SH after renal transplantation may result in kidney ischemia and graft loss.Case Presentation: We present a rare case of early spontaneous SH in an allograft kidney that led to a decrease in renal function. A 56-year-old male patient underwent deceased donor kidney transplantation. After declamping, appropriate renal perfusion and immediate diuresis were observed, with no evidence of SH. However, his urinary output abruptly decreased 6 h postoperatively. Abdominal ultrasonography showed 28 mm deep SH on transplant and the resistive index (RI) increased to 0.98-1 and diastolic flow reversal was observed. Surgical interventions were performed 2 days after transplantation, following a further decrease in urinary output. Serum creatinine decreased to 2.2 mg/dL, urinary output increased to an average of 200 cc per hour and the RI value was decreased to 0.7 on POD 7.Conclusion: In patients with abrupt decreased renal function after transplantation, SH should be suspected and the presence of PK should be determined using Doppler USG. In these cases, surgical intervention may avoid allograft dysfunction. [ABSTRACT FROM AUTHOR]

Background: In India, a large number of end-stage renal disease patients are undergoing renal replacement therapy. A successful renal transplantation relives the burden of dialysis with improved quality of life and a productive life thereafter. This also reduces the cost of health care to the government and the society. Graft dysfunction is an important cause of graft loss.The objective of this retrospective study is to evaluate the graft dysfunction and its impact on patient and graft survival. Methods: We did a retrospective record-based analysis of 83 cases (including both deceased and live-related renal transplants) from 2014 to 2019 who were on triple immunosuppression (tacrolimus, mycophenolate mofetil, and steroids) as maintenance therapy. Patients who had graft dysfunction, underwent graft biopsy and were analyzed subsequently. Results: The most common causes for graft dysfunction on biopsy were acute rejection, acute tubular injury, and calcineurin inhibitor toxicity. About 39% of the patients had infections, predominantly bacterial and viral infections. The rejections were associated with poor patient survival (statistically significant). The overall patient survival at our center after 1 year and 3 years was 88% and 84%, respectively, while the death-censored graft survival was 86% and 81%, respectively. Conclusion: In our center, following renal transplantation, patients had a fairly successful outcome. However, early detection and prompt management of the graft dysfunction can improve the graft and the patient survival.

Background: This retrospective multicenter long‐term cohort study investigates de novo donor‐specific HLA antibodies (dnDSA) impact on allograft survival in pediatric kidney transplantation (KTx), depending on allograft function at dnDSA detection. Methods: Seventy patients with dnDSA screening in the context of acute allograft dysfunction (AAD) (>50% serum creatinine increase) or routine follow‐up were included during a 20‐year period. Number of dnDSA specificities and HLA total mean fluorescence intensity (MFI‐sum) were collected. Results: Median follow‐up time was 8.6 years. Among the 22 dnDSA+ patients, 8 patients presented AAD. Compared with dnDSA− patients, allograft survival was shorter only in dnDSA+/AAD+ patients, regardless of dnDSA detection during the 5‐year post‐transplant period (9 patients) or later (13 patients) (log rank p <.001 and p <.001, respectively). One dnDSA+/AAD−, 7 dnDSA+/AAD+, and 5 dnDSA− patients lost their allograft. Allograft survival was shorter in dnDSA+/AAD+ patients compared with the 16 dnDSA−/AAD+ patients (log rank p <.001) but did not differ between dnDSA+/AAD− and dnDSA−/AAD− patients (log rank p =.157). dnDSA+/AAD+ and dnDSA−/AAD+ patients presented higher risk of allograft failure compared with the other patient groups after adjustment for recipient age at KTx, donor type, and incidence of delayed graft function (HR 11.322, 95% CI 3.094–41.429, p <.001). Concurrent MFI‐sum >10 000 and multiple dnDSA specificities were more significantly associated with AAD, compared with each factor separately (p <.001). Conclusions: In pediatric KTx, AAD shortens allograft survival in dnDSA+ patients, regardless of dnDSA time detection, and is commonly observed when high MFI‐sum concurs with multiple dnDSA specificities. dnDSA without AAD incidence does not determinately affect allograft survival. [ABSTRACT FROM AUTHOR]

Background: Despite multiple studies evaluating the immunological responsiveness to vaccines, the clinical effectiveness of the two‐dose mRNA vaccine schedule among lung transplant (LT) patients has not been evaluated. Methods: We included LT patients who tested positive for SARS‐CoV‐2 on a nasopharyngeal swab between March 1, 2020, and August 25, 2021 (n = 70). The study group was divided based on their vaccination status. Results: During the study period, 14 fully vaccinated LT patients with one of the mRNA vaccines tested positive for COVID‐19 (median age 54, range 30–62 years, M:F 9:5). The vaccinated cohort was younger with bilateral LT, have suppurative conditions as the transplant indication, and present with milder symptoms. However, pulmonary parenchymal involvement was seen among all 12 patients where computed tomography (CT) of chest was available. The laboratory profile indicated a more subdued inflammatory response among the vaccinated group. A lower proportion of vaccinated patients developed respiratory failure, needed ICU admission or ventilator support, although none of the differences achieved statistical significance. None of the vaccinated patients succumbed to COVID‐19 during the study period, while the 4‐week mortality among unvaccinated patients was nearly 15% (8/56). Conclusions: In this cohort of vaccinated LT patients who developed breakthrough COVID‐19, the clinical course, risk of complications, and outcomes trended better than unvaccinated patients. However, universal involvement of the allograft demonstrates the continued vulnerability of these patients to significant sequelae from COVID‐19. Future studies may evaluate the incremental protection of vaccination after the completion of the third dose of mRNA vaccines among LT patients. [ABSTRACT FROM AUTHOR]

Background: There is limited data on the predictors and outcomes of new or worsening respiratory failure among lung transplant (LT) patients with Coronavirus disease 2019 (COVID‐19). Methods: We included all the LT patients diagnosed with COVID‐19 during a 1‐year period (March 2020 to February 2021; n = 54; median age: 60, 20–73 years; M:F 37:17). Development of new or worsening respiratory failure (ARF) was the primary outcome variable. Results: The overall incidence of ARF was 48.1% (n = 26). More than 20% of patients (n = 11) needed intubation and mechanical ventilation. Body mass index > 25 Kg/m2 (adjusted OR: 5.7,.99–32.93; P =.05) and peak D‐dimer levels >.95 mcg/ml (adjusted OR: 24.99, 1.77–353.8; P =.017) were independently associated with ARF while anticoagulation use prior to COVID‐19 was protective (adjusted OR:.024,.001–.55; P =.02). Majority patients survived the acute illness (85.2%). Pre‐infection chronic lung allograft dysfunction (CLAD) was an independent predictor of mortality (adjusted HR: 5.03, 1.14–22.25; P =.033). Conclusions: COVID‐19 is associated with significant morbidity and mortality among LT patients. Patients on chronic anticoagulation seem to enjoy favorable outcomes, while higher BMI and peak D‐dimer levels are associated with development of ARF. Pre‐infection CLAD is associated with an increased risk of death from COVID‐19. [ABSTRACT FROM AUTHOR]

Sabina Janciauskiene,1,2,* Pierre-Joseph Royer,3,* Jan Fuge,1 Sabine Wrenger,1 Joanna Chorostowska-Wynimko,2 Christine Falk,4,5 Tobias Welte,1 Martine Reynaud-Gaubert,6 Antoine Roux,7– 9 Adrien Tissot,3 Antoine Magnan3 1Department of Pulmonary and Infectious Diseases, BREATH German Center for Lung Research (DZL) Hannover University School, Hannover, Germany; 2Department of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, Warsaw, Poland; 3CHU de Nantes, Centre National De Référence Mucoviscidose Nantes-Roscoff, Nantes, France; 4Institute of Transplant Immunology, Hannover Medical School, Hannover, Germany; 5German Center for Infection Research DZIF Hannover Braunschweig Site, TTU-IICH, Hannover, Germany; 6Department ofPulmonary Diseases and Lung Transplantation, CHU Nord de Marseille; IHU - Méditerranée Infection, Aix Marseille Université, Marseille, France; 7Hôpital Foch, Suresnes, France; 8Université Versailles Saint-Quentin- en-Yvelines, Versailles, France; 9 l’Institut du Thorax, Université de Nantes, Nantes, France*These authors contributed equally to this workCorrespondence: Sabina Janciauskiene Department of Pulmonary and InfectiousDiseases, Hannover Medical School, Feodor-Lynen Str. 23, Hannover 30625, GermanyTel +49-511-532-7297Email Janciauskiene.sabina@mh-hannover.deAbstract: Cumulating reports suggest that acute phase proteins (APPs) have diagnostic and prognostic value in different clinical conditions. Among others, APPs are proposed to serve as markers that help to control the outcome of transplant recipients. Here, we questioned whether plasma concentrations of APPs mirror the development of chronic lung allograft dysfunction (CLAD). We performed blinded analysis of serial plasma samples retrospectively collected from 35 lung transplanted patients, of whom 25 developed CLAD and 10 remained stable during the follow-up period of 3 to 4.5 years. Albumin (ALB), alpha1-antitrypsin (AAT), high sensitivity C-reactive protein (CRPH), antithrombin-3 (AT3), ceruloplasmin (CER), and alpha2-macroglobulin (A2MG) were measured by the nephelometric method. We found that within the first six months post-transplantation, levels of A2MG, CER and AAT were higher in stable patients relative to those who later developed CLAD. Moreover, in stable patient’s plasma CRPH levels decreased during the follow-up period whereas opposite, in those developing CLAD, the CRPH gradually increased. The ALB levels became significantly lower at the end of the follow-up period in CLAD relative to a stable group. A logistic regression model based on A2MG, CER and AT3 at cut-offs levels of ≥ 175.5 mg/dL, ≥ 37.8 mg/dL and ≥ 27.35 mg/dL enabled to discriminate between stable and CLAD patients with a sensitivity of 87.5%, 100% and 62.5%, and specificity of 65.9%, 72.7% and 79.5%, respectively. We identified A2MG (below  175.5 mg/dL) as an independent predictor of CLAD (hazard ratio 11.5, 95% CI (1.5– 91.3), p< 0.021). Our findings suggest that profiles of certain APPs may help to predict the development of lung dysfunction at the very early stages after transplantation.Keywords: acute phase proteins, transplantation, allograft dysfunction

Background and Aim: The role of circulating mitochondrial DNA (cmtDNA) in transplantation remains to be elucidated. cmtDNA may be released into the circulation as a consequence of liver injury; yet recent work also suggests a causative role for cmtDNA leading to hepatocellular injury. We hypothesized that elevated cmtDNA would be associated with adverse events after liver transplantation (LT) and conducted an observational cohort study. Methods: Twenty‐one patients were enrolled prospectively prior to LT. Results: Postoperative complications were observed in 47.6% (n = 10). Seven patients (33.3%) had early allograft dysfunction (EAD), and six patients (28.5%) experienced acute cellular rejection within 6 months of LT. cmtDNA levels were significantly elevated in all recipients after LT compared with healthy controls and preoperative samples (1 361 937 copies/mL [IQR 586 781–3 399 687] after LT; 545 531 copies/mL [IQR 238 562–1 381 015] before LT; and 194 562 copies/mL [IQR 182 359–231 515] in healthy controls) and returned to normal levels by 5 days after transplantation. cmtDNA levels were particularly elevated in those who developed EAD in the early postoperative period (P < 0.001). In all patients, there was initially a strong overall positive correlation between cmtDNA and plasma hepatocellular enzyme levels (P < 0.05). However, the patients with EAD demonstrated a second peak in cmtDNA at postoperative day 7, which did not correlate with liver function tests. Conclusions: The early release of plasma cmtDNA is strongly associated with hepatocellular damage; however, the late surge in cmtDNA in patients with EAD appeared to be independent of hepatocellular injury as measured by conventional tests. [ABSTRACT FROM AUTHOR]

Background: There is limited data on outcomes among lung transplant (LT) patients who survive Coronavirus disease 2019 (COVID‐19). Methods: Any single or bilateral LT patients who tested positive for SARS‐CoV‐2 between March 1, 2020, to February 15, 2021 (n = 54) and survived the acute illness were included (final n = 44). Each patient completed at least 3 months of follow‐up (median: 4.5; range 3–12 months) after their index hospitalization for COVID‐19. The primary endpoint was a significant loss of lung functions (defined as > 10% decline in forced vital capacity (FVC) or forced expiratory volume in 1 s (FEV1) on two spirometries, at least 3 weeks apart compared to the pre‐infection baseline). Results: A majority of the COVID‐19 survivors had persistent parenchymal opacities (n = 29, 65.9%) on post‐infection CT chest. Patients had significantly impaired functional status, with the majority reporting residual disabilities (Karnofsky performance scale score of 70% or worse; n = 32, 72.7%). A significant loss of lung function was observed among 18 patients (40.9%). Three patients met the criteria for new chronic lung allograft dysfunction (CLAD) following COVID‐19 (5.6%), with all three demonstrating restrictive allograft syndrome phenotype. An absolute lymphocyte count < 0.6 × 103/dl and ferritin > 150 ng/ml at the time of hospital discharge was independently associated with significant lung function loss. Conclusions: A significant proportion of COVID‐19 survivors suffer persistent allograft injury. Low absolute lymphocyte counts (ALC) and elevated ferritin levels at the conclusion of the hospital course may provide useful prognostic information and form the basis of a customized strategy for ongoing monitoring and management of allograft dysfunction. Tweet: Twitter handle: @AmitBangaMD Lung transplant patients who survive COVID‐19 suffer significant morbidity with persistent pulmonary opacities, loss of lung functions, and functional deficits. Residual elevation of the inflammatory markers is predictive. [ABSTRACT FROM AUTHOR]

The extant study aimed to explore the influence of two cytokines TNF-α − 308 and IFN-γ + 874 gene polymorphism on development of renal transplant rejection and to investigate the feasibility of Th1 cytotoxic immune reaction (CD3). It includes 152 kidney recipients were divided into two subgroups: 76 stable graft functions (SGF) and 76 allograft dysfunctions (AD) compared with 56 healthy individuals as control group. TNF-α − 308 G > A and IFN-γ + 874 A > T genetic polymorphisms were characterized using ARMS-PCR technique. CD3 protein expression was measured using ELISA Kit. The effect on transplant outcome was analyzed where, statistically significant differences of TNF-a-308 G/A were observed between AD group when compared to SGF group (OR = 0.296, 95% CI = 0.091–0.965, p =.031) in AG genotype (intermediate producer genotype). Also, AD group displayed a statistically significant increase of IFN-γ + 874 TT (high producer genotype) when compared to SGF group (OR = 0.290, 95% CI = 0.127–0.665, p =.003). The expression of CD3+ T lymphocytes in recipients with allograft dysfunction was statistically higher than that with stable allograft function and control groups (732 ± 76, 235 ± 51 and 442 ± 50) respectively and (p ≤ 0.001). In conclusion, IFN-γ + 874 T and TNF-α − 308 A alleles are risk alleles for renal transplant rejection and these two single nucleotide polymorphisms (SNPs) may be implicated in the tendency of rejection after renal transplantation. CD3 may be used as non-invasive biomarker in monitoring of rejection and avoid exposing patients for biopsy risks and sampling error. [ABSTRACT FROM AUTHOR]

There are limited data on management strategies and outcomes among lung transplant (LT) patients with Coronavirus disease 2019 (COVID-19). We implemented management protocols based on the best available evidence and consensus among multidisciplinary teams. The current study reports our experience and outcomes using this protocol-based management strategy. We included single or bilateral LT patients who tested positive for SARS-CoV-2 on nasopharyngeal swab between March 1, 2020, to December 15, 2020 (n = 25; median age: 60, range 20-73 years; M: F 17:8). A group of patients with Respiratory Syncytial Virus (RSV) infection during 2016-18 were included to serve as a comparator group (n = 36). As compared to RSV, patients with COVID-19 were more likely to present with constitutional symptoms, spirometric decline, pulmonary opacities, new or worsening respiratory failure, and need for ventilator support. Patients with SARS-CoV-2 infection were less likely to receive a multimodality treatment strategy, and they experienced worse post-infection lung function loss, functional decline, and three-month survival. A significant proportion of patients with COVID-19 needed readmission for worsening allograft function (36.4%), and chronic kidney disease at initial presentation was associated with this complication. Lower pre-morbid FEV 1 appeared to increase the risk of new or worsening respiratory failure, which was associated with worse outcomes. Overall hospital survival was 88% (n = 22). Follow-up data was available for all discharged patients (median: 43.5 days, range 15-287 days). A majority had persistent radiological opacities (19/22, 86.4%), with nearly half of the patients with available post-COVID-19 spirometry showing > 10% loss in lung function (6/13, median loss: 14.5%, range 10%-31%). Despite similar demographic characteristics and predispositions, LT patients with COVID-19 are sicker and experience worse outcomes as compared to RSV. Despite the availability of newer therapeutic agents, COVID-19 continues to be associated with significant morbidity and mortality. [ABSTRACT FROM AUTHOR]

Aortoiliac occlusive disease (AIOD), especially proximal to the transplant artery, in kidney transplant patient activates the renin-angiotensin-aldosterone system by limiting graft renal perfusion and causes symptoms that can occur with transplant renal artery stenosis (TRAS) such as refractory hypertension, water retention, and graft renal dysfunction. Immediate clinical suspicion is difficult due to the nature of the progressive disease unlike TRAS. Herein, we present an interesting case of bilateral common iliac artery occlusion (AIOD, TASC II, type C) that manifested as uncontrolled blood pressure and decreased allograft function in a patient who had kidney transplant 17 years ago. The patient was successfully diagnosed with duplex scan, ankle-brachial index (ABI) and computed tomography angiography and treated with percutaneous luminal angioplasty and stent graft insertion.

Introduction: The literature on dengue infection in renal transplant recipients has shown wide diversity in clinical presentation and outcome. The objective of this study was to report the clinical profile, short‐term and long‐term outcomes of dengue among renal transplant recipients. Methods: A total of 59 post‐transplant dengue suspected cases were admitted from July 2019 to April 2020 of which 31 had confirmed dengue infection. The clinical and laboratory profile of the confirmed dengue cases (n = 31) were compared with non‐dengue cases (n = 28). Results: Among the clinical and laboratory features retro‐orbital pain, conjunctival redness, thrombocytopenia on admission, and absence of arthralgia were significantly associated with dengue compared to non‐dengue cases. No mortality was observed in the dengue cases. Allograft dysfunction, acute rejection and graft losses were identified in 64.5% (n = 20), 6.4% (n = 2) and 6.4% (n = 2) dengue cases respectively. No rejection or graft losses were observed in 1‐year follow‐up. Conclusions: We report a differential clinical profile for dengue in transplant settings which will aid in the diagnosis. We also report successful management of dengue infection in renal transplant recipients with the majority having allograft dysfunction. A long‐term follow‐up of the cohort was uneventful. [ABSTRACT FROM AUTHOR]

Background: In India, a large number of end-stage renal disease patients are undergoing renal replacement therapy. A successful renal transplantation relives the burden of dialysis with improved quality of life and a productive life thereafter. This also reduces the cost of health care to the government and the society. Graft dysfunction is an important cause of graft loss.The objective of this retrospective study is to evaluate the graft dysfunction and its impact on patient and graft survival. Methods: We did a retrospective record-based analysis of 83 cases (including both deceased and live-related renal transplants) from 2014 to 2019 who were on triple immunosuppression (tacrolimus, mycophenolate mofetil, and steroids) as maintenance therapy. Patients who had graft dysfunction, underwent graft biopsy and were analyzed subsequently. Results: The most common causes for graft dysfunction on biopsy were acute rejection, acute tubular injury, and calcineurin inhibitor toxicity. About 39% of the patients had infections, predominantly bacterial and viral infections. The rejections were associated with poor patient survival (statistically significant). The overall patient survival at our center after 1 year and 3 years was 88% and 84%, respectively, while the death-censored graft survival was 86% and 81%, respectively. Conclusion: In our center, following renal transplantation, patients had a fairly successful outcome. However, early detection and prompt management of the graft dysfunction can improve the graft and the patient survival. [ABSTRACT FROM AUTHOR]

Objective: To evaluate outcome of diagnostic kidney biopsy in patients with renal allograft dysfunction at a tertiary care hospital. Study Design: Retrospective observational study. Place and Duration of Study: Armed Forces Institute of Urology, Rawalpindi, from Jan 2014 to Jan 2020. Methodology: A consolidate registry review was carried to formulate this study. The registry data exists at our center containing information about the graft dysfunction (manifesting as proteinuria, deranged urea and creatinine or urine sediment abnormalities) and other major indications which warrant probing with biopsy. The histopathological diagnosis of these biopsies is confirmed from the nephro-pathology registry before finalization of diagnosis. Results: A total of 94 diagnostic kidney biopsies were performed in patients with graft dysfunction. Out of 94 biopsies, 80 (85.1%) patients were male while 14 (14.9%) were female patients. The most frequent single cause for graft dysfunction was Cell Mediated Rejection (n 12, 24.5%) followed by Interstitial Fibrosis and Tubular Atrophy/Acute Tubular Injury. The most common cause among the glomerulonephritis was Membranoproliferative Glomerulonephritis (n 3, 6.1%) followed by others. The most common cause for mixed pathology remainedcell mediated rejection with Interstitial fibrosis and tubular atrophy (n 8, 17.8%). Conclusion: Cell mediated rejection is thecommonest pathology responsible for renal allograft dysfunction both as a single lesion as well as part of mixed pathology. [ABSTRACT FROM AUTHOR]

Long term outcomes in lung transplant are limited by the development of chronic lung allograft dysfunction (CLAD). Within the past several decades, antibody-mediated rejection (AMR) has been recognized as a risk factor for CLAD. The presence of HLA antibodies in lung transplant candidates, “sensitized patients” may predispose patients to AMR, CLAD, and higher mortality after transplant. This review will discuss issues surrounding the sensitized patient, including mechanisms of sensitization, implications within lung transplant, and management strategies.

Long term outcomes in lung transplant are limited by the development of chronic lung allograft dysfunction (CLAD). Within the past several decades, antibody-mediated rejection (AMR) has been recognized as a risk factor for CLAD. The presence of HLA antibodies in lung transplant candidates, "sensitized patients" may predispose patients to AMR, CLAD, and higher mortality after transplant. This review will discuss issues surrounding the sensitized patient, including mechanisms of sensitization, implications within lung transplant, and management strategies. [ABSTRACT FROM AUTHOR]

Exosomes isolated from plasma of lung transplant recipients with allograft injury contain donor‐derived lung self‐antigens (collagen V and Kα1 tubulin) and human leukocyte antigen (HLA) molecules. We present a case of a 76‐year‐old, female lung transplant recipient treated for acute cellular rejection with methylprednisolone and anti‐thymocyte globulin, who subsequently contracted SARS‐CoV‐2 and developed a sharp increase in the mean fluorescent intensity of anti‐HLA antibodies. Analysis of circulating exosomes during rejection, but before SARS‐CoV‐2 infection, revealed the presence of lung self‐antigens and HLA class II molecules. After the patient contracted SARS‐CoV‐2, exosomes with the SARS‐CoV‐2 spike protein were also found. After resolution of infectious symptoms, exosomes with SARS‐CoV‐2 spike protein were no longer detected; however, exosomes with lung self‐antigens and HLA class II molecules persisted, which coincided with a progressive decline in spirometric flows, suggesting chronic lung allograft dysfunction. We propose that the analysis of circulating exosomes may be used to detect allograft injury mediated by both rejection and infection. Furthermore, the detection of exosomes containing viral proteins may be helpful in identifying allograft injury driven by viral pathogens. [ABSTRACT FROM AUTHOR]

In the last years, several scoring systems based on pre- and post-transplant parameters have been developed to predict early post-LT graft function. However, some of them showed poor diagnostic abilities. This study aims to evaluate the role of the comprehensive complication index (CCI) as a useful scoring system for accurately predicting 90-day and 1-year graft loss after liver transplantation. A training set (n = 1262) and a validation set (n = 520) were obtained. The study was registered at https://www.ClinicalTrials.gov (ID: NCT03723317). CCI exhibited the best diagnostic performance for 90 days in the training (AUC = 0.94; p < 0.001) and Validation Sets (AUC = 0.77; p < 0.001) when compared to the BAR, D-MELD, MELD, and EAD scores. The cut-off value of 47.3 (third quartile) showed a diagnostic odds ratio of 48.3 and 7.0 in the two sets, respectively. As for 1-year graft loss, CCI showed good performances in the training (AUC = 0.88; p < 0.001) and validation sets (AUC = 0.75; p < 0.001). The threshold of 47.3 showed a diagnostic odds ratio of 21.0 and 5.4 in the two sets, respectively. All the other tested scores always showed AUCs < 0.70 in both the sets. CCI showed a good stratification ability in terms of graft loss rates in both the sets (log-rank p < 0.001). In the patients exceeding the CCI ninth decile, 1-year graft survival rates were only 0.7% and 23.1% in training and validation sets, respectively. CCI shows a very good diagnostic power for 90-day and 1-year graft loss in different sets of patients, indicating better accuracy with respect to other pre- and post-LT scores. Clinical Trial Notification: NCT03723317. [ABSTRACT FROM AUTHOR]

Liver transplant (LT) recipients require close follow-up with regular monitoring of the liver function tests (LFTs). Evaluation of deranged LFT should be individualized depending upon the time since LT, peri-operative events, clinical course, and any complications. These derangements can range from mild and asymptomatic to severe and symptomatic elevations requiring expedited personalized assessment and management. Pattern of LFT derangement (hepatocellular, cholestatic, or mixed), donor–recipient risk factors, timing after LT (post-operative, 1–12 months, and >12 months since LT) along with clinical context and symptomatology are important considerations before proceeding with the initial evaluation. Compliance to immunosuppression and drug interactions should be ascertained along with local epidemiology of infections. Essential initial evaluation must include an ultrasound abdomen with Doppler to rule out any structural causes such as biliary or vascular complications apart from focussed laboratory evaluation. Early allograft dysfunction, ischemia reperfusion injury, small-for-size syndrome, biliary leaks, hepatic artery, and portal vein thrombosis are usual culprits in the early post-operative period whereas viral hepatitis (acute or reactivation), opportunistic infections, and recurrence of the primary disease are more frequent in the later period. Graft rejection, biliary strictures, sepsis, and drug induced liver injury remain possible etiologies at all times points after LT. Initial evaluation algorithm must be customized based on history, clinical examination, risk factors, and pattern and severity of deranged LFT. Allograft rejection is a diagnosis of exclusion and requires liver biopsy to confirm and assess severity. Empirical treatment of rejection sans liver biopsy is discouraged. [ABSTRACT FROM AUTHOR]

Introduction: In solid organ transplant (SOT) recipients, influenza is associated with significant morbidity, including high hospital admission and mortality rates. Influenza may also impair allograft outcomes, in particular in lung transplant recipients. Early treatment with antivirals and seasonal vaccination contribute to reduce influenza-associated morbidity in this population.Areas covered: We selected a number of publications by searching into Pubmed to review the epidemiology, clinical presentation, outcomes, and management of influenza in SOT recipients. We discuss current treatment options and recent advances in the development of new vaccination strategies.Expert opinion: Our review showed that despite recent studies addressing the current epidemiology of influenza in SOT recipients, data in this population remain sparse. Large international multi-season cohort studies should better describe the actual burden of influenza. Although oseltamivir is an effective drug and should be given to all SOT recipients, the use of novel antivirals and combination therapies need to be tested prospectively in this population. Finally, recent studies aiming to improve the immunogenicity of influenza vaccine in SOT recipients showed promising results, in particular with the use of high-dose vaccines and booster-dose. Clinical trials using clinical endpoints would be important to foster the introduction of these vaccines in the routine clinical practice. [ABSTRACT FROM AUTHOR]

Objective: Transplant renal artery stenosis (TRAS) and post-transplant arterial hypertension is a treatable cause of allograft dysfunction and graft loss. The risk factors for the development of TRAS include: donor age, prolonged and delayed graft function, cold ischemia time,concomitant CMV infection and surgical technique. Percutaneous transluminal angioplasty (PTA) has proven successful in treating TRAS in 60-90% of cases by providing renal reperfusion. In this study,we evaluated six TRAS cases in our clinic. Material and Method: We evaluated patients retrospectively from medical records who underwent transplantation in 2017. We recorded the age, gender, creatinine, other findings during transplantation, and the demographic features of transplant patients with TRAS. Results: TRAS was reported in 6 of 26 cases. The presence of iliac artery stenosis associated with renal artery stenosis was seen in two patients with CMV PCR (+). Patients underwent PTA and stent implantation. The need for antihypertensive treatment of the patients lessened during follow-up. Conclusion: TRAS is one of the reasons for allograft dysfunction after kidney transplantation. For this reason it should be kept in mind when determining the cause of the allograft disfunction. In addition to other risk factors, surgical technique plays an important role in the development of TRAS. Graft function can be preserved with early intervention. [ABSTRACT FROM AUTHOR]

BACKGROUND In chronic kidney disease, intensive systolic blood pressure (SBP) control reduces mortality at a cost of greater acute kidney injury risk. Kidney transplantation involves implantation of denervated kidneys and immunosuppressive medications that increase acute kidney injury risk. The optimal blood pressure (BP) target in kidney transplant recipients (KTRs) is uncertain. Prior observational studies from the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial demonstrate associations of lower SBP levels and reduced mortality risk, but the relationship of BP with kidney allograft function remains unknown. Thus, in FAVORIT, we investigated the relationship of SBP and diastolic blood pressure (DBP) with risk of kidney allograft failure and estimated glomerular filtration rate (eGFR) slope among stable KTRs. METHODS Cox proportional hazards and multivariable linear regression models adjusted for demographics, transplant characteristics, comorbidities, baseline eGFR, and urine albumin-to-creatinine ratio were used to determine associations of SBP and DBP with time to a composite kidney outcome of ≥50% eGFR decline or dialysis dependence, and with annualized eGFR change, respectively. Multivariable restricted cubic spline plots were developed to evaluate the functional form of the relationships. RESULTS Among 3,598 KTRs, mean age was 52 ± 9 years, SBP was 136 ± 20 mm Hg, DBP was 79 ± 12 mm Hg, and eGFR was 49 ± 18 ml/minute/1.73 m2. There were 369 events of ≥50% eGFR decline or dialysis dependence during a mean follow-up of 4.0 ± 1.5 years. There was no association of either SBP (compared with SBP 120 to <130 mm Hg, hazard ratio (HR) for the SBP < 110 was 1.01 (95% confidence interval (CI) 0.60 to 1.70) and 130 to <140 was 0.89 (0.64 to 1.24)) or DBP (compared with DBP 70 to <80 mm Hg, HR for the DBP 60 to <70 was 1.00 (95% CI 0.74 to 1.34) and 80 to <90 was 0.90 (0.68 to 1.18)) with the kidney failure outcome or annualized eGFR slope, and, when examined using restricted cubic splines, there was no evidence of "J"- or "U"-shaped relationships. CONCLUSIONS In a large sample of stable KTRs, we found no evidence of thresholds at which lower BPs were related to higher risk of allograft failure or eGFR decline. In light of prior findings of mortality benefit at low SBP, these observational findings suggest lower BP may be beneficial in KTRs. This important question requires confirmation in future randomized trials in KTRs. [ABSTRACT FROM AUTHOR]

Antibodies against two G-protein coupled receptors (GPCRs), angiotensin II type 1 receptor (AT1R) and endothelin A receptor (ETAR) are among a growing number of autoantibodies that are found to be associated with allograft dysfunction. AT1R antibodies (AT1Rabs) and ETAR antibodies (ETARabs) have been shown to activate their target receptors and affect signaling pathways. Multiple single center reports have shown an association between presence of these antibodies and acute or chronic rejection and graft loss in kidney, heart, liver, lung and composite tissue transplantations. However, the characteristics of patients that are most likely to develop adverse outcomes, the phenotypes associated with graft damage solely due to these antibodies, and the antibody titer required to cause dysfunction are areas that remain controversial. This review compiles existing knowledge on the effect of antibodies against GPCRs in other diseases in order to bridge the gap in knowledge within transplantation biology. Future areas for research are highlighted and include the need for functional assays and treatment protocols for transplant patients who present with AT1Rabs and ETARabs. Understanding how antibodies that activate GPCRs influence transplantation outcome will have direct clinical implications for preemptive evaluation of transplant candidates as well as the post-transplant care of organ recipients. [ABSTRACT FROM AUTHOR]