Automated Urinary Chemokine Assays for Noninvasive Detection of Kidney Transplant Rejection: A Prospective Cohort Study.

RATIONALE & OBJECTIVE: Prior studies have demonstrated the diagnostic potential of urinary chemokines C-X-C motif ligand 9 (CXCL9) and CXCL10 for kidney transplant rejection. However, their benefit in addition to clinical information has not been demonstrated. We evaluated the diagnostic performance for detecting acute rejection of urinary CXCL9 and CXCL10 when integrated with clinical information. STUDY DESIGN: Single-center prospective cohort study. SETTING & PARTICIPANTS: We analyzed 1,559 biopsy-paired urinary samples from 622 kidney transplants performed between April 2013 and July 2019 at a single transplant center in Belgium. External validation was performed in 986 biopsy-paired urinary samples. TESTS COMPARED: We quantified urinary CXCL9 (uCXCL9) and CXCL10 (uCXCL10) using an automated immunoassay platform and normalized the values to urinary creatinine. Urinary chemokines were incorporated into a multivariable model with routine clinical markers (estimated glomerular filtration rate, donor-specific antibodies, and polyoma viremia) (integrated model). This model was then compared with the tissue diagnosis according to the Banff classification for acute rejection. OUTCOME: Acute rejection detected on kidney biopsy using the Banff classification. RESULTS: Chemokines integrated with routine clinical markers had high diagnostic value for detection of acute rejection (n=150) (receiver operating characteristic area under the curve 81.3% [95% CI, 77.6-85.0]). The integrated model would help avoid 59 protocol biopsies per 100 patients when the risk for rejection is predicted to be below 10%. The performance of the integrated model was similar in the external validation cohort. LIMITATIONS: The cross-sectional nature obviates investigating the evolution over time and prediction of future rejection. CONCLUSIONS: The use of an integrated model of urinary chemokines and clinical markers for noninvasive monitoring of rejection could enable a reduction in the number of biopsies. Urinary chemokines may be useful noninvasive biomarkers whose use should be further studied in prospective randomized trials to clarify their role in guiding clinical care and the use of biopsies to detect rejection after kidney transplantation. PLAIN-LANGUAGE SUMMARY: Urinary chemokines CXCL9 and CXCL10 have been suggested to be good noninvasive biomarkers of kidney transplant rejection. However, defining a context of use and integration with clinical information is necessary before clinical implementation can begin. In this study, we demonstrated that urinary chemokines CXCL9 and CXCL10, together with clinical information, have substantial diagnostic accuracy for the detection of acute kidney transplant rejection. Application of urinary chemokines together with clinical information may guide biopsy practices following kidney transplantation and potentially reduce the need for kidney transplant biopsies.

Physical Exercise After Solid Organ Transplantation: A Cautionary Tale.

An increasing body of randomized controlled trials suggests the safety of engaging in moderate to vigorous intensity exercise training following solid organ transplantation. Fueled by emerging sport events designed for transplant recipients and the ever-growing body of research highlighting the diverse health benefits of physical activity, transplant recipients are now increasingly participating in strenuous and occasionally competitive physical endeavors that largely surpass those evaluated in controlled research settings. This viewpoint article adopts a cautionary stance to counterbalance the prevalent one-sided optimistic perspective regarding posttransplant physical activity. While discussing methodological limitations, we explore plausible adverse impacts on the cardiovascular, immunological, and musculoskeletal systems. We also examine the physiological consequences of exercising in the heat, at high altitude, and in areas with high air pollution. Risks associated with employing performance-enhancing strategies and the conceivable psychological implications regarding physical activity as a tribute to the 'gift of life' are discussed. With a deliberate focus on the potential adverse outcomes of strenuous posttransplant physical activity, this viewpoint aims to restore a balanced dialogue on our comprehension of both beneficial and potentially detrimental outcomes of physical activity that ultimately underscores the imperative of well-informed decision-making and tailored exercise regimens in the realm of posttransplant care.

Needs, barriers and facilitators for a healthier lifestyle in haemodialysis patients: The GoodRENal project.

BACKGROUND: Malnutrition, sedentary lifestyle, cognitive dysfunction and poor psychological well-being are often reported in patients on haemodialysis (HD). AIMS: We aimed to explore needs, barriers and facilitators-as perceived by patients, their carers, and healthcare professionals (HCPs) for increasing the adherence to the diet, to physical activity and cognition and psychological well-being. METHODS: This is an observational cross-sectional study following the STROBE statement. This study is part of an ERASMUS+ project, GoodRENal-aiming to develop digital tools as an educational approach to patients on HD. For that, the GoodRENal comprises HD centers located in four Belgium, Greece, Spain and Sweden. Exploratory questionnaires were developed regarding the perceived needs, barriers and facilitators regarding the diet, physical activity, cognition and psychological well-being from the perspective of patients, their carers and HCPs. RESULTS: In total, 38 patients, 34 carers and 38 HCPs were included. Nutrition: For patients and carers, the main needs to adhere to the diet included learning more about nutrients and minerals. For patients, the main barrier was not being able to eat what they like. Physical activity: As needs it was reported information about type of appropriate physical activity, while fatigue was listed as the main barrier. For Cognitive and emotional state, it was perceived as positive for patients and carers perception but not for HCPs. The HCPs identified as needs working as a team, having access to specialised HCP and being able to talk to patients in private. CONCLUSIONS: Patients and their carers listed as needs guidance regarding nutrition and physical activity but were positive with their cognitive and emotional state. The HCPs corroborated these needs and emphasised the importance of teamwork and expert support.

An observational cohort study of histological screening for BK polyomavirus nephropathy following viral replication in plasma.

Systematic screening for BKPyV-DNAemia has been advocated to aid prevention and treatment of polyomavirus associated nephropathy (PyVAN), an important cause of kidney graft failure. The added value of performing a biopsy at time of BKPyV-DNAemia, to distinguish presumptive PyVAN (negative SV40 immunohistochemistry) and proven PyVAN (positive SV40) has not been established. Therefore, we studied an unselected cohort of 950 transplantations, performed between 2008-2017. BKPyV-DNAemia was detected in 250 (26.3%) transplant recipients, and positive SV40 in 91 cases (9.6%). Among 209 patients with a concurrent biopsy at time of first BKPyV-DNAemia, 60 (28.7%) biopsies were SV40 positive. Plasma viral load showed high diagnostic value for concurrent SV40 positivity (ROC-AUC 0.950, 95% confidence interval 0.916-0.978) and the semiquantitatively scored percentage of tubules with evidence of polyomavirus replication (pvl score) (0.979, 0.968-0.988). SV40 positivity was highly unlikely when plasma viral load is below 4 log10 copies/ml (negative predictive value 0.989, 0.979-0.994). In SV40 positive patients, higher plasma BKPyV-DNA load and higher pvl scores were associated with slower viral clearance from the blood (hazard ratio 0.712, 95% confidence interval 0.604-0.839, and 0.327, 0.161-0.668, respectively), whereas the dichotomy positivity/negativity of SV40 immunohistochemistry did not predict viral clearance. Although the pvl score offers some prognostic value for viral clearance on top of plasma viral load, the latter provided good guidance for when a biopsy was unnecessary to exclude PyVAN. Thus, the distinction between presumptive and proven PyVAN, based on SV40 immunohistochemistry, has limited clinical value. Hence, management of BKPyV-DNAemia and immunosuppression reduction should be weighed against the risk of occurrence of rejection, or exacerbation of rejection observed concomitantly.

Data-Driven Chronic Allograft Phenotypes: A Novel and Validated Complement for Histologic Assessment of Kidney Transplant Biopsies.

BACKGROUND: No validated system currently exists to realistically characterize the chronic pathology of kidney transplants that represents the dynamic disease process and spectrum of disease severity. We sought to develop and validate a tool to describe chronicity and severity of renal allograft disease and integrate it with the evaluation of disease activity. METHODS: The training cohort included 3549 kidney transplant biopsies from an observational cohort of 937 recipients. We reweighted the chronic histologic lesions according to their time-dependent association with graft failure, and performed consensus k-means clustering analysis. Total chronicity was calculated as the sum of the weighted chronic lesion scores, scaled to the unit interval. RESULTS: We identified four chronic clusters associated with graft outcome, based on the proportion of ambiguous clustering. The two clusters with the worst survival outcome were determined by interstitial fibrosis and tubular atrophy (IFTA) and by transplant glomerulopathy. The chronic clusters partially overlapped with the existing Banff IFTA classification (adjusted Rand index, 0.35) and were distributed independently of the acute lesions. Total chronicity strongly associated with graft failure (hazard ratio [HR], 8.33; 95% confidence interval [CI], 5.94 to 10.88; P<0.001), independent of the total activity scores (HR, 5.01; 95% CI, 2.83 to 7.00; P<0.001). These results were validated on an external cohort of 4031 biopsies from 2054 kidney transplant recipients. CONCLUSIONS: The evaluation of total chronicity provides information on kidney transplant pathology that complements the estimation of disease activity from acute lesion scores. Use of the data-driven algorithm used in this study, called RejectClass, may provide a holistic and quantitative assessment of kidney transplant injury phenotypes and severity.

Biological pathways and comparison with biopsy signals and cellular origin of peripheral blood transcriptomic profiles during kidney allograft pathology.

Kidney transplant injury processes are associated with molecular changes in kidney tissue, primarily related to immune cell activation and infiltration. How these processes are reflected in the circulating immune cells, whose activation is targeted by strong immunosuppressants, is poorly understood. To study this, we analyzed the molecular alterations in 384 peripheral blood samples from four European transplant centers, taken at the time of a kidney allograft biopsy, selected for their phenotype, using RNA-sequencing. In peripheral blood, differentially expressed genes in 136 rejection and 248 no rejection samples demonstrated upregulation of glucocorticoid receptor and nucleotide oligomerization domain-like receptor signaling pathways. Pathways enriched in antibody-mediated rejection (ABMR) were strongly immune-specific, whereas pathways enriched in T cell-mediated rejection were less immune related. In polyomavirus infection, upregulation of mitochondrial dysfunction and interferon signaling pathways was seen. Next, we integrated the blood results with transcriptomics of 224 kidney allograft biopsies which showed consistently upregulated genes per phenotype in both blood and biopsy. In single-cell RNASeq (scRNASeq) analysis of seven kidney allograft biopsies, the consistently overexpressed genes in ABMR were mostly expressed by infiltrating leukocytes in the allograft. Similarly, in peripheral blood scRNASeq analysis, these genes were overexpressed in ABMR in immune cell subtypes. Furthermore, overexpression of these genes in ABMR was confirmed in independent cohorts in blood and biopsy. Thus, our results highlight the immune activation pathways in peripheral blood leukocytes at the time of kidney allograft pathology, despite the use of current strong immunosuppressants, and provide a framework for future therapeutic interventions.

Association of Predicted HLA T-Cell Epitope Targets and T-Cell-Mediated Rejection After Kidney Transplantation.

RATIONALE & OBJECTIVE: The relationship between human leukocyte antigen (HLA) molecular mismatches and T-cell-mediated rejection (TCMR) is unknown. We investigated the associations between the different donor HLA-derived T-cell targets and the occurrence of TCMR and borderline histologic changes suggestive of TCMR after kidney transplantation. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: All kidney transplant recipients at a single center between 2004 and 2013 with available biopsy data and a DNA sample for high-resolution HLA donor/recipient typing (N = 893). EXPOSURE: Scores calculated by the HLA matching algorithm PIRCHE-II and HLA eplet mismatches. OUTCOME: TCMR, borderline changes suggestive of TCMR, and allograft failure. ANALYTICAL APPROACH: Multivariable cause-specific hazards models were fit to characterize the association between HLA epitopes targets and study outcomes. RESULTS: We found 277 patients developed TCMR, and 134 developed only borderline changes suggestive of TCMR on at least 1 biopsy. In multivariable analyses, only the PIRCHE-II scores for HLA-DRB1 and HLA-DQB1 were independently associated with the occurrence of TCMR and with allograft failure; this was not the case for HLA class I molecules. If restricted to rejection episodes within the first 3 months after transplantation, only the T-cell epitope targets originating from the donor's HLA-DRB1 and HLA-DQB1, but not class I molecules, were associated with the early acute TCMR. Also, the median PIRCHE-II score for HLA class II was statistically different between the patients with TCMR compared to the patients without TCMR (129 [IQR, 60-240] vs 201 [IQR, 96-298], respectively; P < 0.0001). These differences were not observed for class I PIRCHE-II scores. LIMITATIONS: Observational clinical data and residual confounding. CONCLUSIONS: In the absence of HLA-DSA, HLA class II but not class I mismatches are associated with early episodes of acute TCMR and allograft failure. This suggests that current immunosuppressive therapies are largely able to abort the most deleterious HLA class I-directed alloimmune processes; however, alloresponses against HLA-DRB1 and HLA-DQB1 molecular mismatches remain insufficiently suppressed. PLAIN-LANGUAGE SUMMARY: Genetic differences in the human leukocyte antigen (HLA) complex between kidney transplant donors and recipients play a central role in T-cell-mediated rejection (TCMR), which can lead to failure of the transplanted kidney. Evaluating this genetic disparity (mismatch) in the HLA complex at the molecular (epitope) level could contribute to better prediction of the immune response to the donor organ posttransplantation. We investigated the associations of the different donor HLA-derived T-cell epitope targets and scores obtained from virtual crossmatch algorithms with the occurrence of TCMR, borderline TCMR, and graft failure after kidney transplantation after taking into account the influence of donor-specific anti-HLA antibodies. This study illustrates the greater importance of the molecular mismatches in class II molecules compared to class I HLA molecules.

Global Policy Barriers and Enablers to Exercise and Physical Activity in Kidney Care.

OBJECTIVE: Impairment in physical function and physical performance leads to decreased independence and health-related quality of life in people living with chronic kidney disease and end-stage kidney disease. Physical activity and exercise in kidney care are not priorities in policy development. We aimed to identify global policy-related enablers, barriers, and strategies to increase exercise participation and physical activity behavior for people living with kidney disease. DESIGN AND METHODS: Guided by the Behavior Change Wheel theoretical framework, 50 global renal exercise experts developed policy barriers and enablers to exercise program implementation and physical activity promotion in kidney care. The consensus process consisted of developing themes from renal experts from North America, South America, Continental Europe, United Kingdom, Asia, and Oceania. Strategies to address enablers and barriers were identified by the group, and consensus was achieved. RESULTS: We found that policies addressing funding, service provision, legislation, regulations, guidelines, the environment, communication, and marketing are required to support people with kidney disease to be physically active, participate in exercise, and improve health-related quality of life. We provide a global perspective and highlight Japanese, Canadian, and other regional examples where policies have been developed to increase renal physical activity and rehabilitation. We present recommendations targeting multiple stakeholders including nephrologists, nurses, allied health clinicians, organizations providing renal care and education, and renal program funders. CONCLUSIONS: We strongly recommend the nephrology community and people living with kidney disease take action to change policy now, rather than idly waiting for indisputable clinical trial evidence that increasing physical activity, strength, fitness, and function improves the lives of people living with kidney disease.

Current Methodological Challenges of Single-Cell and Single-Nucleus RNA-Sequencing in Glomerular Diseases.

Single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA-seq (snRNA-seq) allow transcriptomic profiling of thousands of cells from a renal biopsy specimen at a single-cell resolution. Both methods are promising tools to unravel the underlying pathophysiology of glomerular diseases. This review provides an overview of the technical challenges that should be addressed when designing single-cell transcriptomics experiments that focus on glomerulopathies. The isolation of glomerular cells from core needle biopsy specimens for single-cell transcriptomics remains difficult and depends upon five major factors. First, core needle biopsies generate little tissue material, and several samples are required to identify glomerular cells. Second, both fresh and frozen tissue samples may yield glomerular cells, although every experimental pipeline has different (dis)advantages. Third, enrichment for glomerular cells in human tissue before single-cell analysis is challenging because no effective standardized pipelines are available. Fourth, the current warm cell-dissociation protocols may damage glomerular cells and induce transcriptional artifacts, which can be minimized by using cold dissociation techniques at the cost of less efficient cell dissociation. Finally, snRNA-seq methods may be superior to scRNA-seq in isolating glomerular cells; however, the efficacy of snRNA-seq on core needle biopsy specimens remains to be proven. The field of single-cell omics is rapidly evolving, and the integration of these techniques in multiomics assays will undoubtedly create new insights in the complex pathophysiology of glomerular diseases.

Data-driven Derivation and Validation of Novel Phenotypes for Acute Kidney Transplant Rejection using Semi-supervised Clustering.

BACKGROUND: Over the past decades, an international group of experts iteratively developed a consensus classification of kidney transplant rejection phenotypes, known as the Banff classification. Data-driven clustering of kidney transplant histologic data could simplify the complex and discretionary rules of the Banff classification, while improving the association with graft failure. METHODS: The data consisted of a training set of 3510 kidney-transplant biopsies from an observational cohort of 936 recipients. Independent validation of the results was performed on an external set of 3835 biopsies from 1989 patients. On the basis of acute histologic lesion scores and the presence of donor-specific HLA antibodies, stable clustering was achieved on the basis of a consensus of 400 different clustering partitions. Additional information on kidney-transplant failure was introduced with a weighted Euclidean distance. RESULTS: Based on the proportion of ambiguous clustering, six clinically meaningful cluster phenotypes were identified. There was significant overlap with the existing Banff classification (adjusted rand index, 0.48). However, the data-driven approach eliminated intermediate and mixed phenotypes and created acute rejection clusters that are each significantly associated with graft failure. Finally, a novel visualization tool presents disease phenotypes and severity in a continuous manner, as a complement to the discrete clusters. CONCLUSIONS: A semisupervised clustering approach for the identification of clinically meaningful novel phenotypes of kidney transplant rejection has been developed and validated. The approach has the potential to offer a more quantitative evaluation of rejection subtypes and severity, especially in situations in which the current histologic categorization is ambiguous.

Beta-Trace Protein as a Potential Marker of Acute Kidney Injury: A Pilot Study.

INTRODUCTION: Acute kidney injury (AKI) is a frequent complication among patients in the intensive care unit (ICU). The limitations of serum Cr (sCr) in timely detecting AKI are well known. Beta-trace protein (BTP) is emerging as a novel endogenous glomerular filtration rate marker. The aim of this study was to explore the role of BTP as a marker of AKI. METHODS: Patients admitted to the ICU undergoing surgery were included. BTP, sCr, Cystatin C (CysC), and neutrophil gelatinase-associated lipocalin (NGAL) were measured preoperatively, postoperatively (post-op), and at the first (D1) and second (D2) post-op day. AKI was defined as an increase of sCr to ≥1.5-fold from baseline within 2 days after surgery. RESULTS: Of the 52 patients studied, 10 patients (19%) developed AKI. Patients with AKI were older (69.6 ± 10.7 vs. 58.1 ± 16.7 years, p = 0.043) and had a longer length of ICU stay (13 [IQR 6-49] vs. 6 [IQR 5-8] days, p = 0.032). Between the 2 groups, the evolution of BTP, sCr, CysC, and NGAL over time differed significantly, with overall higher values in the AKI group. ROC analysis for the detection of AKI within 2 days after surgery showed a great accuracy for BTP. The area under the curve (AUC) for BTP post-op; D1; and D2 was, respectively, 0.869 ± 0.049; 0.938 ± 0.035; and 0.943 ± 0.032. The discriminative power of a BTP measurement on D1 was superior in detecting AKI compared to NGAL (adjusted p value = 0.027). We could not detect a significant difference between the AUCs of other biomarkers (NGAL, sCr, and CysC). CONCLUSION: Serum BTP is a promising marker for diagnosing AKI in ICU patients undergoing surgery.

Associations between the measures of physical function, risk of falls and the quality of life in haemodialysis patients: a cross-sectional study.

BACKGROUND: Impaired physical function due to muscle weakness and exercise intolerance reduces the ability to perform activities of daily living in patients with end-stage kidney disease, and by consequence, Health-Related Quality of Life (HRQoL). Furthermore, the risk of falls is an aggregate of physical function and, therefore, could be associated with HRQoL as well. The present study examined the associations between objective and subjective measures of physical function, risk of falls and HRQoL in haemodialysis patients. METHODS: This cross-sectional multicentre study included patients on maintenance haemodialysis. Physical function (quadriceps force, handgrip force, Sit-to-Stand, and six-minute walking test), the risk of falls (Tinetti, FICSIT-4, and dialysis fall index) and HRQoL (PROMIS-29 and EQ-5D-3 L) were measured and analysed descriptively, by general linear models and logistic regression. RESULTS: Of the 113 haemodialysis patients (mean age 67.5 ± 16.1, 57.5% male) enrolled, a majority had impaired quadriceps force (86.7%) and six-minute walking test (92%), and an increased risk of falls (73.5%). Whereas muscle strength and exercise capacity were associated with global HRQoL (R2 = 0.32) and the risk of falls, the risk of falls itself was related to psycho-social domains (R2 = 0.11) such as depression and social participation, rather than to the physical domains of HRQoL. Objective measures of physical function were not associated with subjective fatigue, nor with subjective appreciation of health status. CONCLUSIONS: More than muscle strength, lack of coordination and balance as witnessed by the risk of falls contribute to social isolation and HRQoL of haemodialysis patients. Mental fatigue was less common than expected, whereas, subjective and objective physical function were decreased.

Current epigenetic aspects the clinical kidney researcher should embrace.

Chronic kidney disease (CKD), affecting 10-12% of the world's adult population, is associated with a considerably elevated risk of serious comorbidities, in particular, premature vascular disease and death. Although a wide spectrum of causative factors has been identified and/or suggested, there is still a large gap of knowledge regarding the underlying mechanisms and the complexity of the CKD phenotype. Epigenetic factors, which calibrate the genetic code, are emerging as important players in the CKD-associated pathophysiology. In this article, we review some of the current knowledge on epigenetic modifications and aspects on their role in the perturbed uraemic milieu, as well as the prospect of applying epigenotype-based diagnostics and preventive and therapeutic tools of clinical relevance to CKD patients. The practical realization of such a paradigm will require that researchers apply a holistic approach, including the full spectrum of the epigenetic landscape as well as the variability between and within tissues in the uraemic milieu.

Does Kidney Donor Risk Index implementation lead to the transplantation of more and higher-quality donor kidneys?

BACKGROUND: The Kidney Donor Risk Index (KDRI) is a quantitative evaluation of the quality of donor organs and is implemented in the US allocation system. This single-centre study investigates whether the implementation of the KDRI in our decision-making process to accept or decline an offered deceased donor kidney, increases our acceptance rate. METHODS: From April 2015 until December 2016, we prospectively calculated the KDRI for all deceased donor kidney offers allocated by Eurotransplant to our centre. The number of the transplanted versus declined kidney offers during the study period were compared to a historical set of donor kidney offers. RESULTS: After implementation of the KDRI, 26.1% (75/288) of all offered donor kidneys were transplanted, compared with 20.7% (136/657) in the previous period (P < 0.001). The median KDRI of all transplanted donor kidneys during the second period was 0.97 [Kidney Donor Profile Index (KDPI) 47%], a value significantly higher than the median KDRI of 0.85 (KDPI 34%) during the first period (P = 0.047). A total of 68% of patients for whom a first-offered donor kidney was declined during this period were transplanted after a median waiting time of 386 days, mostly with a lower KDRI donor kidney. CONCLUSIONS: Implementing the KDRI in our decision-making process increased the transplantation rate by 26%. The KDRI can be a supportive tool when considering whether to accept or decline a deceased donor kidney offer. More data are needed to validate this score in other European centres.

Endothelial maintenance in health and disease: Importance of sex differences.

The vascular endothelium has emerged as more than just an inert monolayer of cells lining the vascular bed. It represents the interface between the blood stream and vessel wall, and has a strategic role in regulating vascular homeostasis by the release of vasoactive substances. Endothelial dysfunction contributes to the development and progression of cardiovascular disease. Recognition of sex-specific factors implicated in endothelial cell biology is important for the identification of clinically relevant preventive and/or therapeutic strategies. This review aims to give an overview of the recent advances in understanding the importance of sex specific observations in endothelial maintenance, both in healthy and diseased conditions. The female endothelium is highlighted in the context of polycystic ovary syndrome and pre-eclampsia. Furthermore, sex differences are explored in chronic kidney disease, which is currently appreciated as one of public health priorities. Overall, this review endorses integration of sex analysis in experimental and patient-oriented research in the exciting field of vascular biology.

Failed Downregulation of Circulating MicroRNA-155 in the Early Phase after ST Elevation Myocardial Infarction Is Associated with Adverse Left Ventricular Remodeling.

BACKGROUND: MicroRNA are noncoding RNA that have a significant role in both inflammatory and cardiovascular diseases. AIMS: We aimed to assess whether the inflammation-related microRNA-155 is associated with the development of adverse left ventricular (LV) remodeling following ST elevation myocardial infarction (STEMI). METHODS: Peripheral blood samples were collected in the inflammatory (day 2), proliferative (day 5), and maturation phases (6 months) after STEMI (n = 20). Granulocytes, monocytes, and lymphocytes were enumerated with flow cytometry. The changes in LV volumes were assessed with 3-D echocardiography on day 1 and after 6 months. Adverse remodeling was defined as a >20% increase in end-diastolic volume. Healthy subjects were recruited as controls. RESULTS: MicroRNA-155 measured on day 5 correlated positively with the relative change in end-diastolic volume (ρ = 0.490, p = 0.028). MicroRNA-155 (day 5) was significantly higher in patients with compared to patients without adverse LV remodeling. The expression level was similar in healthy subjects (n = 8) and in patients with LV remodeling. There was a positive correlation between microRNA-155 and the amount of monocytes (day 5, ρ = 0.463, p = 0.046). CONCLUSION: Impaired downregulation of microRNA-155 during the second phase of the post- STEMI inflammatory response is a determinant of the development of adverse LV remodeling.

Plasma Beta-Trace Protein as a Marker of Residual Renal Function: The Effect of Different Hemodialysis Modalities and Intra-Individual Variability over Time.

BACKGROUND/AIMS: Beta-trace protein (BTP) is a low-molecular-weight molecule, which may be used to assess residual renal function (RRF) in dialysis patients. Here we evaluated the influence of hemodialysis (HD) and hemodiafiltration (HDF) on plasma BTP, and analyzed the inter- and intra-individual variability of plasma BTP over time in HD and peritoneal dialysis (PD) patients. METHODS: In 12 prevalent HD patients, the effect of a single session of low-flux HD, high-flux HD and HDF on plasma BTP was studied. Blood samples were taken at baseline, after 120 and 240 minutes, and at the start of the next dialysis session. In 13 HD patients and 10 PD patients, inter- and intra-individual variability over three months was studied (monthly and weekly, respectively). Plasma BTP was measured using a nephelometric method. RESULTS: No significant decrease in plasma BTP was seen following a session of low-flux HD. Both high-flux HD and HDF resulted in a significant decrease immediately after dialysis (22% and 61% median decrease, respectively). A significant reduction of the molecule persisted only in HDF and a significant decrease (-15%) was still found immediately before the start of the next dialysis session. In both HD and PD patients, the reproducibility over time was excellent with intra-class correlation coefficient of 0.96 (0.93-0.99) and 0.92 (0.86-0.99) respectively. In a small cohort of PD patients, fair agreement existed between mGFR (average of renal urea and creatinine clearance from a 24 hours urine collection) and the BTP-based GFR estimation. CONCLUSION: BTP is a stable marker and a promising tool for RRF estimations in PD and HD patients. In patients receiving HDF, plasma levels of BTP should be interpreted with caution.