Preservation Of Allograft Function Research Articles

A retrospective cohort analysis comparing the effectiveness and safety of perioperative angiotensin II to adrenergic vasopressors as a first-line vasopressor in kidney transplant recipients

BackgroundPerioperative adrenergic vasopressors in kidney transplantation have been linked to negative outcomes and arrhythmias. Synthetic angiotensin II (AT2S) could improve renal hemodynamics, preserve allograft function, and reduce arrhythmias.ObjectiveWe aimed to compare the effectiveness and safety of AT2S to adrenergic vasopressors when used for perioperative hypotension in kidney transplant.MethodsThis single-center, retrospective cohort study included adults with perioperative shock requiring AT2S or adrenergic agents as first-line vasopressors during kidney transplant. The primary outcome was the need for a second continuous infusion vasopressor agents beyond the first-line agent. Secondary outcomes assessed adverse events and early allograft outcomes.ResultsTwenty patients receiving AT2S and 60 patients receiving adrenergic vasopressor agents were included. Intraoperatively, 1 of 20 patients (5%) in the AT2S group needed a second continuous vasopressor compared to 7 of 60 patients (11.7%) who needed a second continuous vasopressor in the adrenergic vasopressor group (P = 0.672). Postoperatively, 1 of 20 patients (5%) in the AT2S group compared to 12 of 60 patients (20%) in the adrenergic vasopressor group required a second vasopressor (P = 0.168). There were significantly fewer arrhythmias (1/20 [5%] vs. 17/60 [28.3%]), P = 0.03) and ischemic complications (0/20 [0%] vs. 11/20 [18.3%], P = 0.031) in patients who received AT2S. There were no differences in immediate, slow, or delayed graft function or in discharge, 1-month, and 3-month glomerular filtration rates (p > 0.05).Conclusion and RelevanceBoth AT2S and adrenergic vasopressors are effective for perioperative hypotension in kidney transplant, with AT2S showing a lower incidence of arrhythmias and ischemic complications.

Does Early Belatacept Conversion in Delayed Graft Function Preserve Allograft Function?

Does Early Belatacept Conversion in Delayed Graft Function Preserve Allograft Function?

Perfusion Techniques in Kidney Allograft Preservation to Reduce Ischemic Reperfusion Injury: A Systematic Review and Meta-Analysis.

The limited supply and rising demand for kidney transplantation has led to the use of allografts more susceptible to ischemic reperfusion injury (IRI) and oxidative stress to expand the donor pool. Organ preservation and procurement techniques, such as machine perfusion (MP) and normothermic regional perfusion (NRP), have been developed to preserve allograft function, though their long-term outcomes have been more challenging to investigate. We performed a systematic review and meta-analysis to examine the benefits of MP and NRP compared to traditional preservation techniques. PubMed (MEDLINE), Embase, Cochrane, and Scopus databases were queried, and of 13,794 articles identified, 54 manuscripts were included (n = 41 MP; n = 13 NRP). MP decreased the rates of 12-month graft failure (OR 0.67; 95%CI 0.55, 0.80) and other perioperative outcomes such as delayed graft function (OR 0.65; 95%CI 0.54, 0.79), primary nonfunction (OR 0.63; 95%CI 0.44, 0.90), and hospital length of stay (15.5 days vs. 18.4 days) compared to static cold storage. NRP reduced the rates of acute rejection (OR 0.48; 95%CI 0.35, 0.67) compared to in situ perfusion. Overall, MP and NRP are effective techniques to mitigate IRI and play an important role in safely expanding the donor pool to satisfy the increasing demands of kidney transplantation.

Helical TomoTherapy Total Lymphoid Irradiation and Hematopoietic Cell Transplantation for Kidney Transplant Tolerance in Rhesus Macaques.

Development of a post-transplant kidney transplant tolerance induction protocol involving a novel total lymphoid irradiation (TLI) conditioning method in a rhesus macaque model is described. We examined the feasibility of acheiving tolerance to MHC 1-haplotype matched kidney transplants by establishing a mixed chimeric state with infusion of donor hematopoietic cells (HC) using TomoTherapy TLI. The chimeric state was hypothesized to permit the elimination of all immunosuppressive (IS) medications while preserving allograft function long-term without development of graft-versus-host-disease (GVHD) or rejection. An experimental group of 11 renal transplant recipients received the tolerance induction protocol and outcomes were compared to a control group (n = 7) that received the same conditioning but without donor HC infusion. Development of mixed chimerism and operational tolerance was accomplished in two recipients in the experimental group. Both recipients were withdrawn from all IS and continued to maintain normal renal allograft function for 4 years without rejection or GVHD. None of the animals in the control group achieved tolerance when IS was eliminated. This novel experimental model demonstrated the feasibility for inducing of long-term operational tolerance when mixed chimerism is achieved using a TLI post-transplant conditioning protocol in 1-haplotype matched non-human primate recipients of combined kidney and HC transplantation.

Evaluation and management of abnormal liver enzymes in the liver transplant recipient: When, why, and what now?

Evaluation and management of abnormal liver enzymes in the liver transplant recipient: When, why, and what now?

The Prognostic Role of CYP Enzyme in Kidney Transplantation: A Single Centre Experience

The main goal of immunosuppressive agents is to reach a balance of preserving allograft function while minimizing adverse effects. The purpose of our research is to corroborate the role of CYP3A enzyme in developing individual medication therapy via measuring medicine levels in patients' blood samples. This retrospective analysis studies 15 kidney transplant recipients. We carried out genotyping (CYP3A5, CYP3A4) after isolating DNA and RNA in patient and donor blood samples; we also determined CYP3A4 messenger RNA expression in case of recipients. Tacrolimus blood levels, dosage, and tacrolimus concentration normalized by dose and the body weight (C0/D ratio) were evaluated. In this research, recipients were divided into 2 groups based on their CYP3A5 genotype. Those who carry CYP3A5*1 allele (*1/*1 or *1/*3) are CYP3A5 expressors, whereas those who are homozygous for the nonfunctional CYP3A5*3 allele are CYP3A5 nonexpressors. There were 3 patients with functioning CYP3A5 enzyme (patients with CYP3A5*1/*3 genotype) where increased tacrolimus metabolism was expected. Our data show that C0/D ratio of CYP3A5 nonexpressors was around 3 times higher than of CYP3A5 expressors. Looking at CYP3A4 enzyme, we found 1 patient carried CYP3A4*22/*22 genotype where we expected decreased CYP3A4 expression. It is clear that this patient had adequate therapy medication levels (9.50 μg/L) despite having received very low dosage of tacrolimus (0.03 mg/weight/d). Our results confirmed the importance of determining CYP status of recipients after a transplant because individual differences were observed in tacrolimus treatment that were partly influenced by CYP status of recipients.

MPN-166 Myeloproliferative Neoplasm (MPN) Post-Renal Transplant (RT)-A Single-Center Review.

MPN post-RT is a rare disease. There is little data on the clinicopathological features and outcomes of patients with post-RT MPN. The main objective of this study was to analyze the clinical outcome of MPN post-RT. This was a single-center retrospective study Settings: Patients who had post-RT MPN at Memorial Herman Hospital, Texas Medical Center. We reviewed 1998 patients who underwent RT between January 1, 1999, and December 31, 2019. Three cases of post-RT MPN were identified. None Main Outcome Measures: We analyzed the incidence, the interval between RT and MPN diagnosis, MPN treatment, and clinical outcome of patients with post-RT MPN. Among 1998 RT recipients, 3 cases (0.1%) of MPN were identified. All occurred in women with a mean age of 53 years. Races were African American (n=2) and white (n=1). Causes of end-stage renal disease were diabetes, hypertensive, and IgA nephropathy. Two patients received RT, and one patient simultaneous kidney and pancreas transplant. All three patients were on tacrolimus, mycophenolate, and prednisone for post-transplant immunosuppression. Two patients developed chronic myeloid leukemia (CML), and one had polycythemia vera (PV). The mean interval between RT and diagnosis of MPN was 9 years. Cytogenetics demonstrated JAK-2 mutation in the patient with PV and BCR-ABL translocation in the two CML patients. The CML patients received BCR-ABL tyrosine kinase inhibitors (TKIs; imatinib/dasatinib) and continue to have a major molecular response. The patient with PV remains on hydroxyurea (HU) and aspirin with excellent hematocrit control. Mycophenolate was discontinued in all three patients after the diagnosis of MPN. TKI and HU were well tolerated. No thrombotic events or leukemic transformation were reported. One CML patient developed cytomegalovirus colitis. No other infectious complications were noted. She also developed immune-related hemolytic anemia and thrombocytopenia that were successfully treated with glucocorticoids. All three patients still have preserved allograft function and are alive at a median follow-up of 42 months. MPN post-RT is rare. Standard-of-care therapies for MPN are well tolerated. Further studies are required to explore the pathophysiology and outcomes of MPN in RT recipients.

An Assessment of the Value of Donor-derived Cell-free DNA Surveillance in Patients With Preserved Kidney Allograft Function.

Donor-derived cell-free DNA (dd-cfDNA) is a biomarker validated to detect rejection when measured to assess kidney allograft dysfunction. However, it remains unclear whether routine surveillance with dd-cfDNA provides additional information over standard monitoring of kidney allografts with creatinine and donor-specific antibodies (DSAs), particularly among those with little suspicion of rejection or injury. We investigated the value of measuring dd-cfDNA in patients with preserved allograft function and describe its association with future events. Three-hundred seventeen kidney transplant recipients with a creatinine ≤1.5 mg/dL, no current DSA, and no prior rejection were assessed with dd-cfDNA and categorized into low (dd-cfDNA <0.5%; n = 239), moderate (dd-cfDNA 0.5% to <1.0%; n = 43), and high (dd-cfDNA ≥1.0%; n = 35) groups. The occurrence of rejection, DSA, graft loss, and change in estimated glomerular filtration rate over time after dd-cfDNA assessment was compared. Over follow-up, rejections were more commonly found among patients with high vs low dd-cfDNA (17% versus 5%; P = 0.01); a similar nonsignificant trend was observed among patients with moderate compared to low dd-cfDNA (12% versus 5%; P = 0.13). DSA development was uncommon and not different between groups (low: 4%; moderate: 3%; high: 0%; P = 0.52). There was only 1 graft loss in a patient with low dd-cfDNA, and dd-cfDNA was not associated with graft dysfunction over time. Most patients with elevated dd-cfDNA in conjunction with preserved allograft function remained stable over follow-up without deterioration in function or graft loss. Studies are needed to differentiate patients with elevated dd-cfDNA who will develop adverse outcomes from those who will remain clinically stable.

Donor-derived Cell-free DNA Measurement in Kidney Transplant Patients Without Allograft Dysfunction: More Evidence and More Questions.

Donor-derived Cell-free DNA Measurement in Kidney Transplant Patients Without Allograft Dysfunction: More Evidence and More Questions.

International Survey of Clinical Monitoring Practices in Pancreas and Islet Transplantation.

The long-term outcomes of both pancreas and islet allotransplantation have been compromised by difficulties in the detection of early graft dysfunction at a time when a clinical intervention can prevent further deterioration and preserve allograft function. The lack of standardized strategies for monitoring pancreas and islet allograft function prompted an international survey established by an International Pancreas and Islet Transplant Association/European Pancreas and Islet Transplant Association working group. A global survey was administered to 24 pancreas and 18 islet programs using Redcap. The survey addressed protocolized and for-cause immunologic and metabolic monitoring strategies following pancreas and islet allotransplantation. All invited programs completed the survey. The survey identified that in both pancreas and islet allograft programs, protocolized clinical monitoring practices included assessing body weight, fasting glucose/C-peptide, hemoglobin A1c, and donor-specific antibody. Protocolized monitoring in islet transplant programs relied on the addition of mixed meal tolerance test, continuous glucose monitoring, and autoantibody titers. In the setting of either suspicion for rejection or serially increasing hemoglobin A1c/fasting glucose levels postpancreas transplant, Doppler ultrasound, computed tomography, autoantibody titers, and pancreas graft biopsy were identified as adjunctive strategies to protocolized monitoring studies. No additional assays were identified in the setting of serially increasing hemoglobin A1c levels postislet transplantation. This international survey identifies common immunologic and metabolic monitoring strategies utilized for protocol and for cause following pancreas and islet transplantation. In the absence of any formal studies to assess the efficacy of immunologic and metabolic testing to detect early allograft dysfunction, it can serve as a guidance document for developing monitoring algorithms following beta-cell replacement.

Nivolumab (NIVO) + tacrolimus (TACRO) + prednisone (PRED) +/- ipilimumab (IPI) for kidney transplant recipients (KTR) with advanced cutaneous cancers.

9507 Background: Cancer is a leading cause of death among KTR, but these patients (pts) have been excluded from trials of immune checkpoint inhibitors due to immunosuppression and risk of allograft loss. We report findings from the first prospective clinical trial of NIVO + TACRO + PRED +/- IPI in KTR with selected advanced cutaneous cancers. Methods: The primary composite endpoint was lack of tumor progression per RECIST v1.1 without allograft loss at 16 weeks (W) on NIVO. Adult KTR with advanced melanoma, basal, cutaneous squamous, or Merkel cell carcinoma (MEL, BCC, CSCC, MCC), for whom non-immune therapies were insufficient were eligible. Immunosuppression was standardized to low-dose TACRO (goal trough 2-5 ng/mL) + PRED 5mg daily; pts then received NIVO 480mg IV q4W. Pts with progressive disease (PD) could receive NIVO 3mg/kg + IPI 1mg/kg IV q3W x 4 followed by NIVO 480mg IV q4W. Donor-derived cell-free DNA (dd-cfDNA) levels were measured q2W as a potential predictor of allograft rejection. Results: From 11/2019 - 4/2021, of 12 pts enrolled, 8 pts with CSCC, MCC or MEL were evaluable for response (Table). All pts experienced PD on NIVO; treatment-related allograft loss (TRAL) occurred in 1 pt. 6 pts then received IPI + NIVO. Responses: 2 (33%) with marked tumor regression at 6W and eventual complete response (CR; 1 with TRAL), and 4 (67%) with PD (1 with TRAL). 7/8 pre-NIVO tumor biopsies contained a paucity of infiltrating immune cells. Only 2/5 on-NIVO biopsies demonstrated moderate immune infiltrates; both of these pts later developed a CR to IPI + NIVO. Rejecting allografts contained dense immune responses (plasma cells, CD4+ &amp; CD8+ lymphocytes, PD-1+ lymphocytes, macrophages, PD-L1+ glomerular endothelium, and focal PD-1 &amp; PD-L1 positivity in renal tubules). In 2/3 pts with TRAL, elevations in dd-cfDNA levels occurred 10 and 15 days earlier than increases in weekly serum creatinine levels. TRAL #3 occurred after discontinuation of study therapy (including TACRO) and dd-cfDNA monitoring. Conclusions: In KTR receiving low-dose TACRO + PRED, NIVO augments tumor immune cell infiltration in some pts but is insufficient to mediate tumor regression. Adding IPI can enhance anti-tumor immunity and mediate tumor regression. TACRO + PRED was insufficient to prevent allograft rejection after PD-1 +/- CTLA-4 blockade in 2/8 pts. In pts with TRAL, increased dd-cfDNA levels preceded increased serum creatinine. Based on these findings, we are modifying the trial therapy regimen to augment anti-tumor immunity and preserve allograft function. Clinical trial information: NCT03816332. [Table: see text]

Perioperative outcomes and readmissions following cardiac operations in kidney transplant recipients

ObjectiveAlthough kidney transplant (KTx) recipients are at significant risk for cardiovascular disease, outcomes following cardiac operations have been examined in limited series. The present study thus aimed to assess the...

Left Ventricular Apical Hypertrophic Cardiomyopathy After Heart Transplant: Case Report.

<h3>Background</h3> Apical hypertrophic cardiomyopathy (ApHCM) is a rare variant of HCM which predominantly involves the left ventricular apex, and therefore does not typically result in obstructive physiology. It has been infrequently reported in general, with a rarity in heart transplant patients, mostly due to a modest or delayed presentation with symptoms. We present a case of a heart transplant patient with a stable postoperative course who was incidentally found to have ApHCM during follow up non-invasive testing. <h3>Case presentation</h3> Patient is a 45-year-old gentleman with a history of cardiac transplantation in March 2013 for heart failure in the setting of arrhythmogenic right ventricular cardiomyopathy, on chronic dual immunosuppression therapy. He has maintained preserved allograft function with no treatable rejection. Mild donor-derived atherosclerotic disease was found on the first surveillance coronary angiogram with no progression over subsequent years. He has remained asymptomatic and extremely active. In September 2020, he underwent surveillance myocardial perfusion imaging, which showed a large area of moderately severe ischemia laterally extending from the mid ventricle to the apex, prompting coronary angiography which did not show significant epicardial coronary disease. A subsequent echocardiogram with contrast demonstrated normal biventricular function, with evidence of hypertrophy with classic spading of the apical myocardium, along with a corresponding reduction in longitudinal straining, consistent with ApHCM. Upon retrospective evaluation of prior echocardiograms, the finding was likely also present though less evident. Holter monitor detected no arrhythmia and treadmill exercise testing confirmed normal functional capacity, normal blood pressure response to exercise, and no arrhythmias.. Review of the details of the donor's death did not suggest cardiac etiology or arrhythmia. <h3>Conclusion</h3> In our literature search, we found only one similar presentation in a cardiac transplant patient with apical HCM. In general, familial ApHCM is known to follow an autosomal dominant inheritance, whereas sporadic forms are caused by acquired mutations of various sarcomeric and nonsarcomeric protein genes. Other associated factors include long-standing high-pressure states, as well as medications, with one case report suggesting a possible relation with tacrolimus. One literature review suggested a possible increase in mortality in ApHCM patients. Therefore, although it is usually a rare condition, pre and post transplant monitoring must take into account that this condition may clinically manifest post transplantation.

Physical Inactivity: A Modifiable Risk Factor for Morbidity and Mortality in Kidney Transplantation.

In patients with chronic kidney disease, sedentary behavior is widely recognized as a significant risk factor for cardiovascular disease, diabetes, obesity, osteoporosis, cancer, and depression. Nevertheless, the real impact of physical inactivity on the health of kidney transplant (KT) recipients remains uncertain. Over the last decade, there has been a renewed interest in exploring the effects of regular physical exercise on transplant-related outcomes. There is now mounting evidence that physical activity may reduce the burden of cardiovascular risk factors, preserve allograft function, minimize immunosuppression requirement, and ameliorate the quality of life of KT recipients. Many positive feedbacks can be detected in the early stages of the interventions and with a minimal exercise load. Despite these encouraging results, the perceived role of physical activity in the management of KT candidates and recipients is often underrated. The majority of trials on exercise training are small, relatively short, and focused on surrogate outcomes. While waiting for larger studies with longer follow-up, these statistical limitations should not discourage patients and doctors from initiating exercise and progressively increasing intensity and duration. This narrative review summarizes current knowledge about the deleterious effects of physical inactivity after KT. The benefits of regular physical exercise are also outlined.

Six-Month Outcomes of Heart Transplant Recipients Infected by COVID-19

PurposeCOVID-19 infection might be associated with higher mortality risk for transplanted patients, as a result of their multiple co-morbidities and their immunosuppressed status. We sought to describe the six-month outcomes of heart transplant (HT) recipients infected by COVID-19.MethodsWe retrospectively analyzed clinical and echocardiographic data from all HT recipients infected with COVID-19 between March and April 2020. All patients were followed for a minimum of 6 months or until death.ResultsTwenty-eight HT patients were studied, median age was 64 (range 59-69) and 22 were male. Co-morbidities included obesity (25%), diabetes (61%), HTN (71%), CKD (68 %) and chronic lung disease (36%). Eight patients died (29%) (non-survivors) and 20 survived (survivors) COVID-19 infection. All patients who survived the initial hospitalization period remained alive at 6 months (figure 1). There was no difference in the prevalence of co-morbidities between survivors and non-survivors. Survivors had lower peak ferritin (2185 ± 793 vs 18023 ± 16724, p= 0.04) and procalcitonin (0.8 ± 0.3 vs 104 ± 31, p<0.005). Baseline allograft function was similar between survivors and non-survivors and it remained unchanged at 6 months for the survivors’ group (LVEF baseline: 58 ± 1% vs LVEF 6 m 61 ± 3%). Renal function returned to baseline in 85% of survivors at 6 months after hospitalization. Mycophenolate mofetil was held during the acute infection and was resumed after discharge. At 6 months follow-up, all patients returned to their baseline immunosuppression regimen, have no further symptoms of COVID-19 and there have been no subsequent rejection events.ConclusionCOVID-19 infection is associated with a high fatality rate (29%) among HT recipients, however, HT recipients that survive the acute COVID-19 infection have preserved allograft function and end-organ function has returned to baseline at 6 months follow-up.

Strategies for Liver Transplantation Tolerance.

Liver transplant (LT) recipients require life-long immunosuppression (IS) therapy to preserve allograft function. The risks of chronic IS include an increased frequency of malignancy, infection, renal impairment, and other systemic toxicities. Despite advances in IS, long-term LT outcomes have not been improved over the past three decades. Standard-of-care (SoC) therapy can, in rare cases, lead to development of operational tolerance that permits safe withdrawal of maintenance IS. However, successful IS withdrawal cannot be reliably predicted and, in current prospective studies, is attempted several years after the transplant procedure, after considerable exposure to the cumulative burden of maintenance therapy. A recent pilot clinical trial in liver tolerance induction demonstrated that peri-transplant immunomodulation, using a regulatory T-cell (Treg) approach, can reduce donor-specific alloreactivity and allow early IS withdrawal. Herein we review protocols for active tolerance induction in liver transplantation, with a focus on identifying tolerogenic cell populations, as well as barriers to tolerance. In addition, we propose the use of novel IS agents to promote immunomodulatory mechanisms favoring tolerance. With numerous IS withdrawal trials underway, improved monitoring and use of novel immunomodulatory strategies will help provide the necessary knowledge to establish an active liver tolerance induction protocol for widespread use.

A Pilot Study of Checkpoint Inhibitors in Solid Organ Transplant Recipients with Metastatic Cutaneous Squamous Cell Carcinoma.

Immune checkpoint inhibitors (ICIs) are increasingly used in various solid organ malignancies. However, there are limited data regarding their safety and efficacy in solid organ transplant (SOT) recipients. The aim of this study was to review our experience with ICIs in SOT recipients with advanced head and neck cutaneous squamous cell carcinoma (cSCC). A retrospective review of ICIs used in SOT recipients from April 2011 to September 2019 was undertaken. Patient clinical and demographic features, ICI regimen, immunosuppression, treatment efficacy, and adverse events were reviewed. The seven SOT recipients (four kidney, two liver, one lung) were diagnosed with metastatic head and neck cSCC. All had undergone prior locoregional surgery and adjuvant radiation therapy. At a median of 10.8 years (range, 6.6-18.1) post-transplant, six were treated with cemiplimab and one with pembrolizumab after minimizing calcineurin inhibitors (CNIs) or conversion of CNI to mammalian target of rapamycin (mTOR) inhibitors. During a median follow-up of 7.1 months, overall tumor response rate was 57.1% with one complete responder and three partial responders. Four patients died at a median of 135 days after starting ICI with two dying from tumor progression and two dying from other causes. Regarding adverse events, one lung transplant recipient developed severe pneumonitis that resolved with high-dose steroids, and one renal transplant patient developed progressive renal injury and died of unrelated causes. The three patients who received prophylactic prednisone all responded to cemiplimab with preserved allograft function and no adverse events. Our data suggest that minimization of CNI and conversion of CNI to mTOR inhibitors along with judicious use of prophylactic steroids may allow for the safe use of ICIs in SOT recipients with advanced cSCC. Short-term efficacy appears promising, but prospective studies with further follow-up and a standardized protocol for prophylactic steroids are needed. Solid organ transplant (SOT) recipients are at increased risk of developing malignancy because of long-term post-transplant immunosuppression. Although immune checkpoint inhibitors (ICIs) are increasingly shown to be successful in treating multiple types of cancer, SOT recipients have been excluded from clinical trials because of concerns regarding potential allograft rejection. This pilot study provides evidence that ICIs along with prophylactic steroids may be a safe and efficacious treatment option for selected SOT recipients with advanced cutaneous squamous cell carcinoma. However, further prospective studies using ICIs in this high-risk patient population are needed.

Proteomic analysis of differentially expressed proteins in the serum of patients with acute renal allograft rejection using iTRAQ labelling technology.

Transplantation is currently the best treatment for patients with end-stage renal disease. However, acute rejection (AR) is the major source of failure in renal transplantation. The current best practice for the diagnosis of AR involves renal biopsy, but it is invasive, time-consuming, costly and inconvenient. Sensitive and less invasive detection of AR episodes in renal transplant patients is essential to preserve allograft function. The present study applied isobaric tags for relative and absolute quantitation (iTRAQ) mass spectrometry to analyze serum protein expression in patients with AR and healthy controls. Overall, 1,399 proteins were identified. Using a cut-off of Q<0.05 and a fold change of >1.2 for the variation in expression, 109 proteins were identified to be differentially expressed between the AR and control groups, 72 of which were upregulated and 37 were downregulated. Several proteins, including properdin, keratin 1, lipoprotein(a) and vitamin D-binding protein, may have roles in the pathogenesis of AR. The present study focused on iTRAQ-based proteomic profiling of serum samples in AR. Insight from the present study may help advance the understanding of the molecular mechanisms of AR and identify potential novel biomarkers of AR for further characterization.

P1261DIAGNOSTIC VALUE OF TEMPORARY OCCLUSION OF ARTERIO-VENOUS HIGH FLOW FISTULA DURING RIGHT HEART CATHETERISATION IN PATIENTS WITH PULMONARY HYPERTENSION

Abstract Background and Aims Pulmonary hypertension (PH) is prevalent in patients with functioning high-flow arterio-venous fistula (HFAVF) and associated with congestive heart failure (CHF). The real incidence and possible causes of this phenomenon is a matter of debate. Hemodynamic effects of HFAVF is considering as one of the reasons for PH formation. The subject of study was the impact of HFAVF on selected parameters of central hemodynamics. In particular, the diagnostic relevance of test of temporary HFAVF occlusion (TTO) was evaluated during right heart catheterization (RHC). Method A total of 13 patients were enrolled: 8 - after kidney transplantation (KT) with preserved allograft function and 5 - on maintenance hemodialysis (HD). All of them demonstrated clinical presentation of CHF III-IV class (NYHA). Severe PH and diastolic disfunction (DD) were observed at a baseline: echocardiographic systolic pulmonary arterial pressure sPAP (mmHg): M=59 (SD 13), ratio of mitral early diastolic inflow velocity (E) (pulsed wave Doppler) to average of septal and lateral mitral annular early-diastolic peak velocity (e′) (tissue Doppler imaging) E/e′ M=18 (SD 5). The ones who have comorbid conditions that cause PH were excluded. All patients bore an upper arm HFAVF, flow of the AVF (Qa) measured by Doppler ultrasonography was markedly high (Qa): M = 3,8 l/min (SD 1,2), the cardio-pulmonary recirculation (Qa/CO): M = 51% (SD 13). All patients underwent RHC and TTO AVF. Echocardiography (Echo) was performed initially and on the follow up (8 weeks after AVF closure/flow reduction). Statistical analysis was performed using the STATISTICA 13 software (Wilcoxon, T-test). Results The results of RHC and Echo data are presented in tables 1, 2. As can be seen from the table data, all cases demonstrated instrumental features of high output CHF (HO CHF) in accordance with patient’s clinical status. TTO of HFAVF resulted in statistically significant decrease in CO and CI values, but no changes in PAP parameters were observed. Taking into account clinical and instrumental features of advanced CHF, HF AVF was closed in 8 patients after KT and in 2 patients on HD. 3 patients on HD underwent AVF flow reduction up to Qa not exceeding 1,1 l/min. Follow-up demonstrated complete resolution of CHF and dramatic improvement of DD, reduction in CO, CI, sPAP, volume parameters. CO, cardiac output; CI, cardiac index; sPAP, systolic pulmonary arterial pressure; meanPAP, mean pulmonary arterial pressure; RAP, mean right atrial pressure; PCWP, pulmonary capillary wedge pressure; LV EDVi, left ventricular end-diastolic volume index; LAVi, left atrial volume index; RAVi, right atrial volume index; Conclusion PH is a component of AVF-induced HO CHF and could be classified as postcapillary one. TTO confirms significant HFAVF contribution to specific changes of parameters of central hemodynamics due to HO CHF. TTO does not impact on PAP values and therefore is not valid to clarify PH genesis per se.

P1605THE EARLY RISE OF URINARY EXOSOMAL BK VIRUS MICRORNA AS A PREDICTIVE MARKER FOR BK VIRUS NEPHROPATHY IN A PROSPECTIVE KIDNEY TRANSPLANTATION COHORT

Abstract Background and Aims BK virus nephropathy (BKVN) is one of the significant contributors to allograft dysfunction in kidney transplantation. Because of the lack of effective anti-viral medication, early detection of BKV replication and preemptive management is vital to preserving allograft function. Herein, we investigated the predictive value of urinary exosomal BKV-microRNA for BKVN in the kidney transplantation cohort. Method ARTKT (assessment of immunologic risk and tolerance in kidney transplantation) is a prospective observational cohort in which a total of 420 kidney transplant recipients were enrolled from 7 teaching hospitals in South Korea since 2015. Urine samples were collected at 0.5, 3, 6, 12, and 24 months after kidney transplantation in this cohort. All enrolled patients were reviewed to identify the patients diagnosed with BKVN histologically (biopsy-proven BKVN) and those experienced BK viremia defined as plasma BKV DNA load &amp;gt; 4 log10 copies per mL (presumptive BKVN). Urinary exosomal miR was quantified using real-time reverse transcription PCR. Results 10 patients and 14 patients developed biopsy-proven BKVN and presumptive BKVN, respectively. Because of unavailable urine samples, urinary exosomal BKV-microRNA was investigated in 8 patients with biopsy-proven BKVN and 13 patients with presumptive BKVN. 61 patients with no evidence of BKVN were selected as a negative control. Most of BKVN was developed in a median time of 3.4 months after transplantation. In line with this pattern, urinary exosomal BKV-microRNA peaked at 3 months after transplantation and decreased thereafter in biopsy-proven BKVN and presumptive BKVN, keeping higher value in biopsy-proven BKVN compared to presumptive BKVN after 3 months. At 2 weeks after transplantation, half of the patients with biopsy-proven BKVN showed an early rise of urinary exosomal BKV-microRNA, whereas patients with presumptive BKVN and no evidence of BKVN did not. However, plasma BK virus DNA was not detected in all groups at 2 weeks after transplantation. In multivariate cox proportional hazards model, urinary exosomal BKV-microRNA was significantly associated with biopsy-proven BKVN. Conclusion A urinary exosomal BKV-microRNA increase as early as 2 weeks after kidney transplantation predicts future BKVN development, enabling early intervention.