Publications by authors named "Amaryllis H Van Craenenbroeck"

52 Publications

Renal Infarction Imaged With [18F]Prostate-Specific Membrane Antigen-1007 PET/CT.

Clin Nucl Med 2021 Oct 12. Epub 2021 Oct 12.

From the Departments of Nuclear Medicine Nephrology and Renal Transplantation, University Hospitals Leuven Department of Microbiology and Immunology, KU Leuven Department of Radiology, University Hospitals Leuven Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.

Abstract: A 61-year-old post-renal transplant man developed pain in the region of the allograft 4 days after transplantation. Contrast-enhanced CT scan revealed multiple small perfusion defects in the renal graft cortex. Multifocal renal cortical infarction was suspected. A [99mTc]Tc-DMSA SPECT/CT showed several small regions with decreased uptake. In addition, an [18F]PSMA-1007 PET/CT confirmed these uptake defects and revealed additional defects. The renal cortical infarctions presumably originated from intraoperative emboli emerging from the arterial anastomosis. Treatment with acetylsalicylic acid 100 mg led to favorable evolution of the renal function biochemically. Follow-up DMSA scintigraphy 3 months later showed resolution of the renal cortical defects.
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http://dx.doi.org/10.1097/RLU.0000000000003924DOI Listing
October 2021

Plasma-Derived microRNAs Are Influenced by Acute and Chronic Exercise in Patients With Heart Failure With Reduced Ejection Fraction.

Front Physiol 2021 27;12:736494. Epub 2021 Sep 27.

Research Group Cardiovascular Diseases, GENCOR, University of Antwerp, Antwerp, Belgium.

Exercise training improves VOpeak in heart failure with reduced ejection fraction (HFrEF), but the effect is highly variable as it is dependent on peripheral adaptations. We evaluated changes in plasma-derived miRNAs by acute and chronic exercise to investigate whether these can mechanistically be involved in the variability of exercise-induced adaptations. Twenty-five male HFrEF patients (left ventricular ejection fraction < 40%, New York Heart Association class ≥ II) participated in a 15-week combined strength and aerobic training program. The effect of training on plasma miRNA levels was compared to 21 male age-matched sedentary HFrEF controls. Additionally, the effect of a single acute exercise bout on plasma miRNA levels was assessed. Levels of 5 miRNAs involved in pathways relevant for exercise adaptation (miR-23a, miR-140, miR-146a, miR-191, and miR-210) were quantified using RT-qPCR and correlated with cardiopulmonary exercise test (CPET), echocardiographic, vascular function, and muscle strength variables. Expression levels of miR-146a decreased with training compared to controls. Acute exercise resulted in a decrease in miR-191 before, but not after training. Baseline miR-23a predicted change in VOpeak independent of age and left ventricular ejection fraction (LVEF). Baseline miR-140 was independently correlated with change in load at the respiratory compensation point and change in body mass index, and baseline miR-146a with change in left ventricular mass index. Plasma-derived miRNAs may reflect the underlying mechanisms of exercise-induced adaptation. In HFrEF patients, baseline miR-23a predicted VOpeak response to training. Several miRNAs were influenced by acute or repeated exercise. These findings warrant exploration in larger patient populations and further mechanistic studies on their molecular involvement.
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http://dx.doi.org/10.3389/fphys.2021.736494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8502864PMC
September 2021

miR-181c level predicts response to exercise training in patients with heart failure and preserved ejection fraction: an analysis of the OptimEx-Clin trial.

Eur J Prev Cardiol 2021 Sep 11. Epub 2021 Sep 11.

Research Group Cardiovascular Diseases, GENCOR Department, University of Antwerp, Campus Drie Eiken D.T.228, Universiteitsplein 1, 2610 Antwerp, Belgium.

Aims: In patients with heart failure with preserved ejection fraction (HFpEF), exercise training improves the quality of life and aerobic capacity (peakV·O2). Up to 55% of HF patients, however, show no increase in peakV·O2 despite adequate training. We hypothesized that circulating microRNAs (miRNAs) can distinguish exercise low responders (LR) from exercise high responders (HR) among HFpEF patients.

Methods And Results: We selected HFpEF patients from the Optimizing Exercise Training in Prevention and Treatment of Diastolic HF (OptimEx) study which attended ≥70% of training sessions during 3 months (n = 51). Patients were defined as HR with a change in peakV·O2 above median (6.4%), and LR as below median (n = 30 and n = 21, respectively). Clinical, ergospirometric, and echocardiographic characteristics were similar between LR and HR. We performed an miRNA array (n = 377 miRNAs) in 14 age- and sex-matched patients. A total of 10 miRNAs were upregulated in LR, of which 4 correlated with peakV·O2. Validation in the remaining 37 patients indicated that high miR-181c predicted reduced peakV·O2 response (multiple linear regression, β = -2.60, P = 0.011), and LR status (multiple logistic regression, odds ratio = 0.48, P = 0.010), independent of age, sex, body mass index, and resting heart rate. Furthermore, miR-181c decreased in LR after exercise training (P-group = 0.030, P-time = 0.048, P-interaction = 0.037). An in silico pathway analysis identified several downstream targets involved in exercise adaptation.

Conclusions: Circulating miR-181c is a marker of the response to exercise training in HFpEF patients. High miR-181c levels can aid in identifying LR prior to training, providing the possibility for individualized management.
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http://dx.doi.org/10.1093/eurjpc/zwab151DOI Listing
September 2021

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

J Ren Nutr 2021 Aug 12. Epub 2021 Aug 12.

Alberta Kidney Care - South, Calgary, Alberta, Canada.

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.
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http://dx.doi.org/10.1053/j.jrn.2021.06.007DOI Listing
August 2021

MicroRNAs targeting VEGF are related to vascular dysfunction in preeclampsia.

Biosci Rep 2021 08;41(8)

Research Group Cardiovascular Diseases, GENCOR, University of Antwerp, Antwerp, Belgium.

In preeclampsia (PE), pre-existent maternal endothelial dysfunction leads to impaired placentation and vascular maladaptation. The vascular endothelial growth factor (VEGF) pathway is essential in the placentation process and VEGF expression is regulated through post-transcriptional modification by microRNAs (miRNAs). We investigated the expression of VEGF-related circulating miR-16, miR-29b, miR-126, miR-155 and miR-200c in PE vs healthy pregnancies (HPs), and their relation with vascular function, oxidative stress (OS) and systemic inflammation. In this case-control study, 24 women with early PE (<34 weeks) were compared with 30 women with HP. Circulating microRNA levels (RT-qPCR), OS and systemic inflammation were assessed in plasma samples (PE 29.5 vs HP 25.8 weeks) and related to extensive in vivo vascular function (flow-mediated dilatation (FMD), modified FMD (mFMD), carotid-femoral pulse wave velocity (CF-PWV), heart rate corrected augmentation index (AIx75) and reactive hyperemia index (RHI)). FMD, CF-PWV, AIx75 and RHI were all significantly impaired in PE (P<0.05). PE patients had reduced levels of miR-16 (5.53 ± 0.36 vs 5.84 ± 0.61) and increased levels of miR-200c (1.34 ± 0.57 vs 0.97 ± 0.68) (P<0.05). Independent of age and parity, miR-16 was related to impaired FMD (β 2.771, 95% C.I.: 0.023-5.519, P=0.048) and mFMD (β 3.401, 95% C.I.: 0.201-6.602, P=0.038). Likewise, miR-200c was independently associated with CF-PWV (β 0.513, 95% C.I.: 0.034-0.992, P=0.036). In conclusion, circulating levels of miR-16 were lower in PE, which correlated with impaired endothelial function. Circulating miR-200c was increased in PE and correlated with higher arterial stiffness. These findings suggest a post-transcriptional dysregulation of the VEGF pathway in PE and identify miR-16 and miR-200c as possible diagnostic biomarkers for PE.
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http://dx.doi.org/10.1042/BSR20210874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360826PMC
August 2021

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

J Am Soc Nephrol 2021 08 17;32(8):1838-1852. Epub 2021 Jun 17.

Department of Microbiology, Immunology and Transplantation, Laboratory of Molecular Immunology, Rega Institute, KU Leuven, Leuven, Belgium

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.
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http://dx.doi.org/10.1681/ASN.2021020157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455274PMC
August 2021

Prevention of tunneled cuffed catheter dysfunction with prophylactic use of a taurolidine urokinase lock: A randomized double-blind trial.

PLoS One 2021 20;16(5):e0251793. Epub 2021 May 20.

Department of Nephrology, Universitair Ziekenhuis Brussel, Vrije Universteit Brussel, Brussels, Belgium.

Background: The efficacy and cost-effectiveness of prophylactic thrombolytic locks in hemodialysis patients at high-risk of thrombotic dialysis catheter dysfunction is uncertain. We investigated this question in a double-blinded randomized controlled study.

Methods: Prevalent hemodialysis patients from 8 Belgian hemodialysis units, with ≥2 separate episodes of thrombotic dysfunction of their tunneled cuffed catheter during the 6 months before inclusion, were randomized to either: taurolidine heparin locks thrice weekly (control arm) or the same locks twice a week combined with taurolidine urokinase locks once a week before the longest interval without HD (TaurolockU arm). The primary efficacy outcome was the incidence rate of catheter thrombotic dysfunction requiring thrombolytic locks to restore function.

Results: 68 hemodialysis patients (32 controls, 36 urokinase) were followed during 9875 catheter days between May 2015 and June 2017. Incidence rate of thrombotic catheter dysfunction was 4.8 in TaurolockU vs 12.1/1000 catheter days in control group (rate ratio 0.39; 95%CI 0.23-0.64). 15/36 (42%) catheters in the treatment group required at least one therapeutic urokinase lock vs 23/32 (72%) in the control group (P = 0.012). The two groups did not differ significantly in catheter-related bloodstream infection and combined cost of prophylactic and therapeutic catheter locks. The TaurolockU group had a numerically higher number of episodes of refractory thrombosis.

Conclusions: Prophylactic use of urokinase locks is highly effective in reducing the number of thrombotic catheter dysfunctions in catheters with a history of recurring dysfunction. Prophylactic use of urokinase locks did not reduce the overall costs associated with catheter locks and was associated with a numerically higher number of episodes of refractory thrombosis.

Trial Registration: ClinicalTrials.gov Identifier: NCT02036255.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251793PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136626PMC
October 2021

Exercise training in patients after kidney transplantation.

Clin Kidney J 2021 Apr 2;14(Suppl 2):ii15-ii24. Epub 2021 Feb 2.

Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.

Kidney transplantation is the treatment of choice for patients with end-stage renal disease. Next to the risk of allograft failure, major obstacles for disease-free survival after kidney transplantation include a higher incidence of cancer, infection and cardiovascular events. Risk factors for adverse clinical outcomes include pre-existent comorbidities, the introduction of an immunodeficient status and (lack of) lifestyle changes after transplantation. Indeed, physical inactivity and poor physical fitness are important targets to address in order to improve clinical outcomes after kidney transplantation. This review summarizes the current evidence on exercise training after kidney transplantation, derived from randomized controlled trials. As much as possible, results are discussed in the perspective of the Standardized Outcomes in Nephrology-Transplantation core outcomes, which were recently described as critically important outcome domains for trials in kidney transplant recipients.
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http://dx.doi.org/10.1093/ckj/sfab022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101622PMC
April 2021

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

Kidney Blood Press Res 2021 30;46(2):185-195. Epub 2021 Mar 30.

Department of Nephrology and Renal Transplantation, University Hospital Leuven, Leuven, Belgium.

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.
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http://dx.doi.org/10.1159/000514173DOI Listing
June 2021

Circulating microRNA as predictors for exercise response in heart failure with reduced ejection fraction.

Eur J Prev Cardiol 2021 Mar 20. Epub 2021 Mar 20.

Research Group Cardiovascular Diseases, GENCOR, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.

Aims: Exercise training is a powerful adjunctive therapy in patients with heart failure with reduced ejection fraction (HFrEF), but ca. 55% of patients fail to improve VO2peak. We hypothesize that circulating microRNAs (miRNAs), as epigenetic determinants of VO2peak, can distinguish exercise responders (ER) from exercise non-responders (ENR).

Methods And Results: We analysed 377 miRNAs in 18 male HFrEF patients (9 ER and 9 ENR) prior to 15 weeks of exercise training using a miRNA array. ER and ENR were defined as change in VO2peak of >20% or <6%, respectively. First, unsupervised clustering analysis of the miRNA pattern was performed. Second, differential expression of miRNA in ER and ENR was analysed and related to percent change in VO2peak. Third, a gene set enrichment analysis was conducted to detect targeted genes and pathways. Baseline characteristics and training volume were similar between ER and ENR. Unsupervised clustering analysis of miRNAs distinguished ER from ENR with 83% accuracy. A total of 57 miRNAs were differentially expressed in ENR vs. ER. A panel of seven miRNAs up-regulated in ENR (Let-7b, miR-23a, miR-140, miR-146a, miR-191, miR-210, and miR-339-5p) correlated with %changeVO2peak (all P < 0.05) and predicted ENR with area under the receiver operating characteristic curves ≥0.77. Multiple pathways involved in exercise adaptation processes were identified.

Conclusion: A fingerprint of seven miRNAs involved in exercise adaptation processes is highly correlated with VO2peak trainability in HFrEF, which holds promise for the prediction of training response and patient-targeted exercise prescription.
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http://dx.doi.org/10.1093/eurjpc/zwaa142DOI Listing
March 2021

The Histological Picture of Indication Biopsies in the First 2 Weeks after Kidney Transplantation.

Clin J Am Soc Nephrol 2020 10 10;15(10):1484-1493. Epub 2020 Aug 10.

Department of Microbiology, Immunology and Transplantation, Katholieke Universiteit Leuven, Leuven, Belgium

Background And Objectives: In preclinical studies, ischemia-reperfusion injury and older donor age are associated with graft inflammation in the early phase after transplantation. In human kidney transplantation, impaired allograft function in the first days after transplantation is often adjudicated to donor- and procedure-related characteristics, such as donor age, donor type, and ischemia times.

Design: In a cohort of 984 kidney recipients, 329 indication biopsies were performed within the first 14 days after transplantation. The histologic picture of these biopsies and its relationship with alloimmune risk factors and donor- and procedure-related characteristics were studied, as well as the association with graft failure. Multivariable Cox models were applied to quantify the cause-specific hazard ratios for early rejection and early inflammatory scores, adjusted for potential confounders. For quantification of hazard ratios of early events for death-censored graft failure, landmark analyses starting from day 15 were used.

Results: Early indication biopsy specimens displayed microvascular inflammation score ≥2 in 30% and tubulointerstitial inflammation score ≥2 in 49%. Rejection was diagnosed in 186 of 329 (57%) biopsies and associated with the presence of pretransplant donor-specific HLA antibodies and the number of HLA mismatches, but not nonimmune risk factors in multivariable Cox proportional hazards analysis. In multivariable Cox proportional hazards analysis, delayed graft function, the graft dysfunction that prompted an early indication biopsy, HLA mismatches, and pretransplant donor-specific HLA antibodies were significantly associated with a higher risk for death-censored graft failure, whereas early acute rejection was not.

Conclusions: Indication biopsies performed early after kidney transplantation display inflammatory changes related to alloimmune risk factors. Nonimmune risk factors for ischemia-reperfusion injury, such as cold and warm ischemia time, older donor age, and donor type, were not identified as strong risk factors for early inflammation after human kidney transplantation.
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http://dx.doi.org/10.2215/CJN.04230320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536761PMC
October 2020

Markers of protein-energy wasting and physical performance in haemodialysis patients: A cross-sectional study.

PLoS One 2020 30;15(7):e0236816. Epub 2020 Jul 30.

Laboratory of Experimental Medicine and Paediatrics, University of Antwerp, Antwerp, Belgium.

Background: Physical impairments are common in uraemia, as reflected by the high risk of falls of haemodialysis (HD) patients. Furthermore, these patients often suffer from malnutrition.

Objective: Up to now, it is unknown which aspects of physical performance are predominantly driven by malnutrition in HD patients. As this answer could steer different interventions, the aim of this study was to evaluate the cross-sectional relationship between nutritional status, muscle strength, exercise capacity and the risk of falls.

Methods: This study recruited HD patients between December 2016 and March 2018 from two hospital-based and five satellite dialysis units (registration number on clinicaltrial.gov: NCT03910426). The mini-nutritional assessment scale as well as objective measures of protein-energy wasting were obtained (total iron-binding capacity, total protein levels, and CRP). Physical assessment included muscle strength (quadriceps, handgrip force, and sit-to-stand test), exercise capacity (six-minute walking test) and the risk of falls (Tinetti, FICSIT, and dialysis fall index). Their interrelationship was analysed by ridge regression models.

Results: Out of 113 HD patients (mean age 67 years ± 16.1, 57.5% male) 36.3% were malnourished according to the mini-nutritional assessment scale and a majority had impaired quadriceps force (86.7%), six-minute walking test (92%), and an increased risk of falls (73.5%). Total protein and CRP levels were identified as relevant nutritional factors in the association with physical performance. Nutritional parameters explained 9.2% of the variance in the risk of falls and 7.6% of the variance in exercise capacity. No conclusive association was found between nutritional status and muscle strength.

Conclusion: Protein-energy wasting is a determinant of the risk of falls and exercise capacity in patients on HD. The association between malnutrition and muscle weakness remains inconclusive.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236816PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392314PMC
September 2020

The screening score of Mini Nutritional Assessment (MNA) is a useful routine screening tool for malnutrition risk in patients on maintenance dialysis.

PLoS One 2020 4;15(3):e0229722. Epub 2020 Mar 4.

Renal Division, Department of Internal Medicine, Ghent University Hospital, Ghent, Belgium.

Purpose: Malnutrition is prevalent in patients on dialysis and is associated with morbidity and mortality. Nutritional status can be assessed by a variety of biochemical and physical parameters or nutritional assessment scores. Most of these methods are expensive or cumbersome to use and are not suitable for routine repetitive follow-up in dialysis patients. The Mini Nutritional Assessment (MNA) has a short form screening set (MNA-SF), which would be suitable as a screening tool, but has not been validated yet in dialysis patients. We aimed to assess whether the MNA is an appropriate tool for identifying nutritional problems in dialysis patients.

Method: MNA, routine biochemistry, physical parameters, comorbidities were assessed in cross-sectional multicentric cohorts of hemodialysis and peritoneal dialysis patients with a longitudinal follow up of 2 years for mortality.

Results: In this cohort of 216 patients, mortality was 27.3% at a follow up of 750±350 days. The mean MNA-SF score was 9.9±1.8, with 30.1%, 59.3% and 10.6% of patients categorized as having normal nutritional status, at risk for malnutrition and malnourished, respectively. The screening score was associated with mortality (HR 0.86, 95% CI 0.75-0.98 per point). With normal nutrition as reference, adjusted mortality was 2.50 (95% CI 1.16-5.37) and 3.89 (95% CI 1.48-10.13) for patients at risk for malnutrition and with malnutrition, respectively. After recalibrating the MNA full score for the specificity of some of its domains for dialysis patients, the MNA-SF had a good sensitivity and specificity for not being well nourished (0.95 and 0.63 respectively) in the full score, and a high negative predictive value (0.91).

Conclusion: The MNA-SF is independently associated with 2 year mortality in dialysis patients. It has a high negative predictive value for excluding being at risk or having malnutrition in the full score. Therefore, it can be advocated as a screening tool for nutritional status in dialysis patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0229722PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055863PMC
June 2020

Composite Uremic Load and Physical Performance in Hemodialysis Patients: A Cross-Sectional Study.

Toxins (Basel) 2020 02 22;12(2). Epub 2020 Feb 22.

Department of Internal Medicine, Renal Division, Ghent University Hospital, B-9000 Ghent, Belgium.

Impaired physical performance is common in patients on hemodialysis (HD) and is associated with poor prognosis. A patient relevant marker of adequacy of dialysis is lacking. Previous studies evaluated uremic toxicity by assessing the impact of different uremic toxins separately. However, such an approach is most likely not reflective of true uremic toxicity. Therefore, this cross-sectional study aimed to examine if the uremic syndrome, estimated as one composite of different uremic toxins (facilitated by ridge regression method) to reflect the kinetic behavior during dialysis, is associated with physical performance in patients on HD. Levels of p-cresyl glucuronide and sulfate, indole-acetic acid, indoxyl sulfate, uric acid, hippuric acid, and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid were assessed and associated by ridge regression to muscle strength, functional exercise capacity, and measures of balance and coordination. 75 HD patients were included (mean age 68 years, 57% male). The composite of different uremic toxins (i.e., uremic load) explained 22% of the variance in handgrip strength. Although there was an association between full body muscle strength and the composite uremic load independent of nutritional status, age and gender, the predictive power of composite uremic load for muscle weakness is limited. Single uremic toxins as well as composite uremic load were not associated with exercise capacity, coordination, and balance, indicating that the degree of uremia does not predict physical performance in patients on HD.
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http://dx.doi.org/10.3390/toxins12020135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076769PMC
February 2020

The Causes of Kidney Allograft Failure: More Than Alloimmunity. A Viewpoint Article.

Transplantation 2020 02;104(2):e46-e56

Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.

Kidney allograft failure is a serious condition, as it implies the need for reinitiation of dialysis with associated morbidity and mortality, reduced quality of life, and higher economic cost. Despite improvements in short-term survival of kidney allografts, this progress was not matched in long-term graft survival. In this viewpoint article, we summarize the available literature on the causes of kidney allograft failure, both early and late, both nonimmune and alloimmune, to gain better insight into the causes of graft failure. Such insight is necessary to better target therapies or take preventative measures that improve long-term outcome after kidney transplantation.
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http://dx.doi.org/10.1097/TP.0000000000003012DOI Listing
February 2020

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

BMC Nephrol 2020 01 6;21(1). Epub 2020 Jan 6.

Department of Internal Medicine, Renal Division, Ghent University Hospital, Ghent, Belgium.

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 (R = 0.32) and the risk of falls, the risk of falls itself was related to psycho-social domains (R = 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.
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http://dx.doi.org/10.1186/s12882-019-1671-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945514PMC
January 2020

154 compared to 54 mmol per liter of sodium in intravenous maintenance fluid therapy for adult patients undergoing major thoracic surgery (TOPMAST): a single-center randomized controlled double-blind trial.

Intensive Care Med 2019 10 1;45(10):1422-1432. Epub 2019 Oct 1.

Department of Intensive Care Medicine, Antwerp University Hospital, Wilrijkstraat 10, Edegem, 2650, Antwerp, Belgium.

Purpose: To determine the effects of the sodium content of maintenance fluid therapy on cumulative fluid balance and electrolyte disorders.

Methods: We performed a randomized controlled trial of adults undergoing major thoracic surgery, randomly assigned (1:1) to receive maintenance fluids containing 154 mmol/L (Na154) or 54 mmol/L (Na54) of sodium from the start of surgery until their discharge from the ICU, the occurrence of a serious adverse event or the third postoperative day at the latest. Investigators, caregivers and patients were blinded to the treatment. Primary outcome was cumulative fluid balance. Electrolyte disturbances were assessed as secondary endpoints, different adverse events and physiological markers as safety and exploratory endpoints.

Findings: We randomly assigned 70 patients; primary outcome data were available for 33 and 34 patients in the Na54 and Na154 treatment arms, respectively. Estimated cumulative fluid balance at 72 h was 1369 mL (95% CI 601-2137) more positive in the Na154 arm (p < 0.001), despite comparable non-study fluid sources. Hyponatremia < 135 mmol/L was encountered in four patients (11.8%) under Na54 compared to none under Na154 (p = 0.04), but there was no significantly more hyponatremia < 130 mmol/L (1 versus 0; p = 0.31). There was more hyperchloremia > 109 mmol/L under Na154 (24/35 patients, 68.6%) than under Na54 (4/34 patients, 11.8%) (p < 0.001). The treating clinicians discontinued the study due to clinical or radiographic fluid overload in six patients receiving Na154 compared to one patient under Na54 (excess risk 14.2%; 95% CI - 0.2-30.4%, p = 0.05).

Conclusions: In adult surgical patients, sodium-rich maintenance solutions were associated with a more positive cumulative fluid balance and hyperchloremia; hypotonic fluids were associated with mild and asymptomatic hyponatremia.
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http://dx.doi.org/10.1007/s00134-019-05772-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6773673PMC
October 2019

Next-generation protein analysis in the pathology department.

J Clin Pathol 2020 Jan 15;73(1):1-6. Epub 2019 Jul 15.

Department of Pathology, University Hospital of Antwerp, Antwerp, Belgium

Traditionally, immunohistochemistry (IHC) is used by pathologists to localise specific proteins or peptides in tissue slides. In the era of personalised medicine, however, molecular tissue analysis becomes indispensable for correct diagnosis, prognosis and therapeutic decision, not only on the DNA or mRNA level but also on the protein level. Combining molecular information with imaging presents many advantages. Therefore, matrix-assisted laser desorption/ionisation imaging mass spectrometry (MALDI IMS) is a promising technique to be added to the armamentarium of the pathologist. Here, we focus on the workflow, advantages and drawbacks of both MALDI IMS and IHC. We also briefly discuss a few other protein imaging modalities and give examples of applications.
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http://dx.doi.org/10.1136/jclinpath-2019-205864DOI Listing
January 2020

Analytical and clinical performance of three hand-held point-of-care creatinine analyzers for renal function measurements prior to contrast-enhanced imaging.

Clin Chim Acta 2019 Oct 2;497:13-19. Epub 2019 Jul 2.

Antwerp University Hospital, Laboratory Medicine, Wilrijkstraat 10, 2650 Edegem, Belgium. Electronic address:

Background: As iodine-based contrast can cause deterioration of renal function in patients with impaired kidney function, guidelines advise to measure creatinine and calculate estimated glomerular filtration (eGFR) prior to administration. Point-of-care (POC) devices seem an attractive alternative to central laboratory testing but uncertainty regarding analytical and clinical comparability remains.

Methods: This study compared three POC devices, i-STAT (Abbott), StatSensor (Nova) and epoc (Siemens) with a central laboratory method (enzymatic creatinine, Siemens Vista 1500 platform). 120 patients were included and underwent simultaneous finger prick capillary blood analysis on the StatSensor and heparine whole blood analysis on StatSensor, i-STAT and epoc.

Results: All POC devices generated results which showed considerable variability around the creatinine value of the reference standard, with StatSensor having the widest (-1,12-1,11 mg/dL) and epoc the tightest (-0,49-0,49 mg/dL) 95% limits of agreement. I-STAT showed the highest clinical concordance with the reference standard (Kappa: 0,94) and had the smallest average analytical error (6%) for creatinine and eGFR compared to the reference standard, meeting the predefined criteria of 8,87% and 10%, respectively. Epoc only met criteria for eGFR. StatSensor did not meet any of the criteria.

Conclusions: I-STAT and epoc were, analytically and clinically, the most performant POC devices included in this study but showed to be less user-friendly. StatSensor did not meet any of the error criteria, neither for creatinine nor for eGFR measurements, and gave more clinical major classification errors. However, it proved to be more user-friendly compared to the other POC devices.
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http://dx.doi.org/10.1016/j.cca.2019.06.025DOI Listing
October 2019

A rare case of hemodialysis-related portosystemic encephalopathy and review of the literature.

Acta Clin Belg 2020 Aug 28;75(4):296-300. Epub 2019 Mar 28.

Department of Gastro-enterology and Hepatology, University Hospital of Antwerp , Edegem, Belgium.

Hemodialysis-related portosystemic encephalopathy (HRPSE) is a clinical phenomenon where portosystemic encephalopathy (PSE) develops without liver dysfunction, usually caused by changes in the portosystemic blood flow related to hemodialysis. We describe the case of a 22-year old patient with a transjugular intrahepatic portosystemic shunt (TIPS) who developed HRPSE several months after initiation of hemodialysis. Despite initial therapy with laxatives and neomycin symptoms recurred. It was only after relocation of the hemodialysis catheter from the superior caval vein to the femoral vein that symptoms completely resolved.
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http://dx.doi.org/10.1080/17843286.2019.1595836DOI Listing
August 2020

Predictors of response to exercise training in patients with coronary artery disease - a subanalysis of the SAINTEX-CAD study.

Eur J Prev Cardiol 2019 07 12;26(11):1158-1163. Epub 2019 Feb 12.

1 Laboratory of Cellular and Molecular Cardiology, Research group Cardiovascular Diseases, GENCOR, University of Antwerp, Belgium.

Exercise training improves peak oxygen uptake, an important predictor of mortality in coronary artery disease patients. The influence of clinical and disease characteristics on training response is not well established in coronary artery disease. Therefore, we aimed to evaluate whether baseline cardiovascular disease variables and training intensity can predict the maximal aerobic response to exercise training. The Study on Aerobic INTerval EXercise training in coronary artery disease patients (SAINTEX-CAD) previously showed that 12 weeks of aerobic interval training and continuous training equally improved peak oxygen uptake in coronary artery disease patients. We identified 24 exercise non-responders (change peak oxygen uptake <1 ml/kg/min) among 167 participants in SAINTEX-CAD. In a between-group comparison, exercise non-responders were older, their baseline peak oxygen uptake and oxygen uptake efficiency slope were higher, and exercise non-responders were more frequently included after elective percutaneous coronary intervention (all  < 0.05). In multiple logistic regression analysis, age (odds ratio = 1.11 (1.04-1.18),  = 0.001), history of elective percutaneous coronary intervention (odds ratio = 3.31 (1.12-9.76),  = 0.030) and higher baseline peak oxygen uptake (odds ratio = 1.16 (1.06-1.27),  = 0.001) were independent predictors of exercise non-response. In multiple linear regression analysis, age (ß = -0.605,  = 0.001), history of elective percutaneous coronary intervention (ß = -15.401,  = 0.010), training intensity (ß=0.447,  = 0.008), baseline physical activity (ß=0.014,  = 0.003) and oxygen uptake efficiency slope (ß = -0.014,  < 0.001) predicted percentage change in peak oxygen uptake and explained 41% of the variability in percentage change in peak oxygen uptake. To summarize, 14% of coronary artery disease patients were exercise non-responders. Higher baseline peak oxygen uptake and oxygen uptake efficiency slope, history of elective percutaneous coronary intervention, older age, lower training intensity and lower baseline physical activity were predictors of training non-response. Identification of patients with a large likelihood of non-response is a first step towards patient tailored exercise programmes.
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http://dx.doi.org/10.1177/2047487319828478DOI Listing
July 2019

MicroRNAs in AKI and Kidney Transplantation.

Clin J Am Soc Nephrol 2019 03 2;14(3):454-468. Epub 2019 Jan 2.

Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, Wilrijk, Belgium;

MicroRNAs are epigenetic regulators of gene expression at the posttranscriptional level. They are involved in intercellular communication and crosstalk between different organs. As key regulators of homeostasis, their dysregulation underlies several morbidities including kidney disease. Moreover, their remarkable stability in plasma and urine makes them attractive biomarkers. Beyond biomarker studies, clinical microRNA research in nephrology in recent decades has focused on the discovery of specific microRNA signatures and the identification of novel targets for therapy and/or disease prevention. However, much of this research has produced equivocal results and there is a need for standardization and confirmation in prospective trials. This review aims to provide an overview of general concepts and available clinical evidence in both the pathophysiology and biomarker fields for the role of microRNA in AKI and kidney transplantation.
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http://dx.doi.org/10.2215/CJN.08020718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419285PMC
March 2019

Endothelial dysfunction and cellular repair in heart failure with preserved ejection fraction: response to a single maximal exercise bout.

Eur J Heart Fail 2019 01 23;21(1):125-127. Epub 2018 Nov 23.

Laboratory for Cellular and Molecular Cardiology, Research Group Cardiovascular Diseases, Department of Translational Pathophysiological Research, University of Antwerp, Antwerp, Belgium.

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http://dx.doi.org/10.1002/ejhf.1339DOI Listing
January 2019

MicroRNA Isolation from Plasma for Real-Time qPCR Array.

Curr Protoc Hum Genet 2018 10 14;99(1):e69. Epub 2018 Sep 14.

Laboratory of Cellular and Molecular Cardiology, Research Group Cardiovascular Diseases, Department of Translational Pathophysiological Research, University of Antwerp, Antwerp, Belgium.

MicroRNAs are short non-coding RNAs that regulate gene expression at the post-transcriptional level by mRNA degradation or suppression of translation. Their stability in plasma makes them attractive biomarkers. Since many plasma microRNA isolation procedures exist and the yield can be highly variable, we recently optimized the microRNA isolation and preamplification procedure using the mirVana PARIS kit (Thermo Fisher Scientific) for miRNA quantification with TaqMan Low Density Arrays in plasma samples. The method here is slightly modified from the original procedure supplied by Thermo Fisher. Based on our findings, recommendations are the following: (1) use Arabidopsis thaliana (Ath) miR-159a as spike-in control, (2) use a 100-µl elution volume during RNA isolation, and (3) add a preamplification step without dilution of the preamplification product. In this article we provide a step-by-step microRNA isolation and quantification procedure using human plasma samples for TaqMan Low Density Arrays. © 2018 by John Wiley & Sons, Inc.
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http://dx.doi.org/10.1002/cphg.69DOI Listing
October 2018

The effects of aerobic exercise on eGFR, blood pressure and VO2peak in patients with chronic kidney disease stages 3-4: A systematic review and meta-analysis.

PLoS One 2018 11;13(9):e0203662. Epub 2018 Sep 11.

Department of Rehabilitation Sciences and Physiotherapy, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.

Background: CKD is associated with several comorbidities, cardiovascular disease being the most significant. Aerobic training has a beneficial effect on cardiovascular health in healthy and some well-defined non-healthy populations. However, the effect of aerobic training on glomerular filtration rate in patients with CKD stages 3-4 is unclear.

Objective: To review the effects of aerobic exercise training on kidney and cardiovascular function in patients with chronic kidney disease (CKD) stages 3-4.

Methods: A random-effects meta-analysis was performed to analyse published randomized controlled trials through February 2018 on the effect of aerobic training on estimated glomerular filtration rate, blood pressure and exercise tolerance in patients with CKD stages 3-4. Web of Science, PubMed and Embase databases were searched for eligible studies.

Results: 11 randomized controlled trials were selected including 362 participants in total. Favourable effects were observed on estimated glomerular filtration rate (+2.16 ml/min per 1.73m2; [0.18; 4.13]) and exercise tolerance (+2.39 ml/kg/min; [0.99; 3.79]) following an on average 35-week aerobic training program when compared to standard care. No difference in change in blood pressure was found.

Conclusions: There is a small beneficial effect of aerobic training on estimated glomerular filtration rate and exercise tolerance, but not on blood pressure, in patients with CKD stages 3-4. However, data are limited and pooled findings were rated as of low to moderate quality.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203662PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6133282PMC
February 2019

[Hereditary kidney disease in adolescents and adults].

Ned Tijdschr Geneeskd 2018 May 25;162. Epub 2018 May 25.

UZ Antwerpen, afd. Nefrologie, Antwerpen, België.

In recent years, there has been a great deal of interest in the literature on genetic kidney disease. It has become clear that chronic kidney disease (CKD) may be caused by single gene mutations, not only in paediatric patients but also in adult patients. Studies indicate that pathogenic mutations can be found in approximately 10% of patients with CKD, and figures are still rising. Syndrome characteristics do not have to be present. In this article, we would like to draw attention on this aspect of a common health problem. We present three cases of genetic kidney disease from our daily practice, showing the value of a multidisciplinary approach for reaching a correct diagnosis. Additionally, we would like to emphasise the value of taking a familial history in every patient with renal disease.
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May 2018

MicroRNA profiling in plasma samples using qPCR arrays: Recommendations for correct analysis and interpretation.

PLoS One 2018 23;13(2):e0193173. Epub 2018 Feb 23.

Laboratory of Cellular and Molecular Cardiology, Research Group Cardiovascular Diseases, Department of Translational Pathophysiological Research, University of Antwerp, Antwerp, Belgium.

MicroRNA (miRNA) regulate gene expression through posttranscriptional mRNA degradation or suppression of translation. Many (pre)analytical issues remain to be resolved for miRNA screening with TaqMan Low Density Arrays (TLDA) in plasma samples, such as optimal RNA isolation, preamplification and data normalization. We optimized the TLDA protocol using three RNA isolation protocols and preamplification dilutions. By using 100μL elution volume during RNA isolation and adding a preamplification step without dilution, 49% of wells were amplified. Informative target miRNA were defined as having quantification cycle values ≤35 in at least 20% of samples and low technical variability (CV across 2 duplicates of 1 sample <4%). A total of 218 miRNA was considered informative (= 59% of all target miRNA). Different normalization strategies were compared: exogenous Ath-miR-159a, endogenous RNA U6, and three mathematical normalization techniques: geNorm (Qbase, QB) and NormFinder (NF) normalization algorithms, and global mean calculation. To select the best normalization method, technical variability, biological variability, stability, and the extent to which the normalization method reduces data dispersion were calculated. The geNorm normalization algorithm reduced data dispersion to the greatest extent, while endogenous RNA U6 performed worst. In conclusion, for miRNA profiling in plasma samples using TLDA cards we recommend: 1. Implementing a preamplification step in the TLDA protocol without diluting the final preamplification product 2. A stepwise approach to exclude non-informative miRNA based on quality control parameters 3. Against using snoRNA U6 as normalization method for relative quantification 4. Using the geNorm algorithm as normalization method for relative quantification.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0193173PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5825041PMC
May 2018

Introducing TOPMAST, the first double-blind randomized clinical trial specifically dedicated to perioperative maintenance fluid therapy in adults.

Anaesthesiol Intensive Ther 2017;49(5):366-372. Epub 2017 Nov 24.

Department of Intensive Care Medicine, Ziekenhuis Netwerk Antwerpen, Campus Stuivenberg, Antwerp, Belgium.

Background: Although prescribed to every patient undergoing surgery, maintenance fluid therapy is a poorly researched part of perioperative fluid therapy. The tonicity of the chosen solutions, could be an important cause of morbidity, with hyponatremia being a potential side effect of hypotonic solutions, where isotonic solution could lead to fluid overload.

Methods: The TOPMAST-trial is an ongoing prospective single-center double-blind randomized trial comparing an isotonic and a hypotonic maintenance fluid strategy during and after surgery in patients undergoing different types of major thoracic surgery. Patients receive NaCl 0.9% in glucose 5% with an added 40 mmol L-1 of potassium chloride or a premixed solution containing 54 mmol L-1 sodium, 55 mmol L-1 chloride and 26 mmol of potassium at a rate of 27 mL per kg of body weight per day. The primary hypothesis is that isotonic maintenance solutions cause a more positive perioperative fluid balance than hypotonic fluids. Different secondary safety endpoints will be explored, especially the effect of the study treatments on the occurrence electrolyte disturbances (e.g. hyponatremia, hyperchloremia) and a set of clinical endpoints. Efficacy endpoints include the need for resuscitation fluids and assessment of renal and hormonal adaptive mechanisms. An anticipated 68 patients will be included between March 2017 and January 2018.

Discussion: The study will provide the most comprehensive evaluation of clinically important outcomes associated with the choice of perioperative maintenance fluid therapy.
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http://dx.doi.org/10.5603/AIT.a2017.0070DOI Listing
November 2018

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

Kidney Blood Press Res 2017 22;42(5):877-885. Epub 2017 Nov 22.

Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.

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.
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http://dx.doi.org/10.1159/000484537DOI Listing
August 2018
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