Pieter Evenepoel

University of Leuven, Louvain, Flanders, Belgium

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Publications (246)1261.64 Total impact

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    ABSTRACT: Background Phosphorus control is generally considered to be better in peritoneal dialysis (PD) patients as compared with haemodialysis (HD) patients. Predialysis phosphorus concentrations are misleading as a measure of phosphorus exposure in HD, as these neglect significant dialysis-related fluctuations. Methods Parameters of mineral metabolism, including parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF-23), were determined in 79 HD and 61 PD patients. In PD, phosphorus levels were determined mid-morning. In HD, time-averaged phosphorus concentrations were modelled from measurements before and after the mid-week dialysis session. Weekly renal, dialytic and total phosphorus clearances as well as total mass removal were calculated from urine and dialysate collections. Results Time-averaged serum phosphorus concentrations in HD (3.5 ± 1.0 mg/dL) were significantly lower than the mid-morning concentrations in PD (5.0 ± 1.4 mg/dL, P < 0.0001). In contrast, predialysis phosphorus concentrations (4.6 ± 1.4 mg/dL) were not different from PD. PTH and FGF-23 levels were significantly higher in PD. Despite higher residual renal function, total phosphorus clearance was significantly lower in PD (P < 0.0001). Total phosphorus mass removal, conversely, was significantly higher in PD (P < 0.05). Conclusions Our data suggest that the time-averaged phosphorus concentrations in patients treated with PD are higher as compared with patients treated with HD. Despite a better preserved renal function, total phosphorus clearance is lower in patients treated with PD. Additional studies are needed to confirm these findings in a population with a different demographic profile and dietary background and to define clinical implications.
    No preview · Article · Jan 2016 · Nephrology Dialysis Transplantation
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    Pieter Evenepoel · Marc G. Vervloet
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    ABSTRACT: Correspondence: Pieter Evenepoel, Dienst nefrologie, Universitair Ziekenhuis Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium.
    Full-text · Article · Jan 2016
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    ABSTRACT: In a multi-ethnic population study, we assessed the association of renal glomerular filtration, a microvascular trait, with circulating matrix Gla protein (MGP). In white Flemish and in South African blacks, glomerular filtration decreased and the risk of chronic kidney disease increased with higher levels of inactive desphospho-uncarboxylated MGP. Our findings support the notion that following vitamin-K dependent carboxylation active MGP not only inhibits calcification of large arteries, as was known before, but also protects the renal microcirculation. Future studies might test whether vitamin K supplementation promotes renal health in the general population.
    Preview · Article · Jan 2016 · EBioMedicine
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    Full-text · Dataset · Dec 2015

  • No preview · Article · Dec 2015 · Artery Research
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    ABSTRACT: In 2011, Nephrology Dialysis and Transplantation (NDT) established a more restrictive selection process for manuscripts submitted to the journal, reducing the acceptance rate from 25% (2008–2009) to currently about 12–15%. To achieve this goal, we decided to score the priority of manuscripts submitted to NDT and to reject more papers at triage than in the past. This new scoring system allows a rapid decision for the authors without external review. However, the risk of such a restrictive policy may be that the journal might fail to capture important studies that are eventually published in higher-ranked journals. To look into this problem, we analysed random samples of papers (∼10%) rejected by NDT in 2012. Of the papers rejected at triage and those rejected after regular peer review, 59 and 61%, respectively, were accepted in other journals. A detailed analysis of these papers showed that only 4 out of 104 and 7 out of 93 of the triaged and rejected papers, respectively, were published in journals with an impact factor higher than that of NDT. Furthermore, for all these papers, independent assessors confirmed the evaluation made by the original reviewers. The number of citations of these papers was similar to that typically obtained by publications in the corresponding journals. Even though the analyses seem reassuring, previous observations made by leading journals warn that the risk of ‘big misses’, resulting from selective editorial policies, remains a real possibility. We will therefore continue to maintain a high degree of alertness and will periodically track the history of manuscripts rejected by NDT, particularly papers that are rejected at triage by our journal.
    Full-text · Article · Dec 2015 · Nephrology Dialysis Transplantation
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    ABSTRACT: Whether warm ischemia during the time to complete the vascular anastomoses determines renal allograft function has not been investigated systematically. We investigated the effect of anastomosis time on allograft outcome in 669 first, single kidney transplantations from brain-dead donors. Anastomosis time independently increased the risk of delayed graft function (odds ratio per minute [OR] 1.05, 95% confidence interval [CI] 1.02-1.07, p-<-0.001) and independently impaired allograft function after transplantation (p-=-0.009, mixed-models repeated-measures analysis). In a subgroup of transplant recipients, protocol-specified biopsies at 3 months (n-=-186), 1 year (n-=-189), and 2 years (n-=-153) were blindly reviewed. Prolonged anastomosis time independently increased the risk of interstitial fibrosis and tubular atrophy on these protocol-specified biopsies posttransplant (p-<-0.001, generalized linear models). In conclusion, prolonged anastomosis time is not only detrimental for renal allograft outcome immediately after transplantation, also longer-term allograft function and histology are affected by the duration of this warm ischemia. The authors associate anastomosis time during kidney transplantation with delayed graft function, reduced allograft function, and interstitial fibrosis in kidney transplants from brain-dead donors. See also the editorial from Knechtle and Sudan on page 2791 and the brief communication from Ausania et al on page 2955. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.
    No preview · Article · Nov 2015 · American Journal of Transplantation
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    ABSTRACT: Also known as the "second human genome," the gut microbiome plays important roles in both the maintenance of health and the pathogenesis of disease. The symbiotic relationship between host and microbiome is disturbed due to the proliferation of dysbiotic bacteria in patients with chronic kidney disease (CKD). Fermentation of protein and amino acids by gut bacteria generates excess amounts of potentially toxic compounds such as ammonia, amines, thiols, phenols, and indoles, but the generation of short-chain fatty acids is reduced. Impaired intestinal barrier function in patients with CKD permits translocation of gut-derived uremic toxins into the systemic circulation, contributing to the progression of CKD, cardiovascular disease, insulin resistance, and protein-energy wasting. The field of microbiome research is still nascent, but is evolving rapidly. Establishing symbiosis to treat uremic syndrome is a novel concept, but if proved effective, it will have a significant impact on the management of patients with CKD.
    No preview · Article · Nov 2015 · American Journal of Kidney Diseases
  • P Evenepoel · E Goffin · B Meijers · N Kanaan · B Bammens · E Coche · K Claes · M Jadoul
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    ABSTRACT: Context: Vascular calcification (VC) is prevalent and progressive in renal transplant recipients. Recent cross-sectional data suggest that activated Wnt signaling contributes to VC. Objective: to investigate whether circulating levels of the Wnt antagonist sclerostin associate with progression of VC. Design: post hoc analysis of the longitudinal observational Brussels Renal Transplant Cohort (BRTC) study. Setting: Tertiary care academic hospital. Patients: Coronary artery (CAC) and aortic calcification (AoC) were measured by multislice spiral CT in 268 prevalent renal transplant recipients (age 53 ± 13 years, 61% male) at baseline and re-measured in 189 patients after a median follow-up of 4.4 years. Baseline serum sclerostin levels were assessed on stored blood samples. Regression analysis was performed to identify determinants of baseline VC and progression. Main outcome measure: progression of VC Results: VC was present in up to 84% of participants at baseline. Almost half of the patients showed progression of VC, according to Hokanson criteria. The cross-sectional analysis at baseline demonstrated a direct association between sclerostin levels and VC score in univariate analysis, which became inverse after adjustment for age, gender and PTH level. Remarkably, a lower sclerostin level was identified as an independent determinant of a higher baseline AoC score in the final regression model. Moreover, baseline sclerostin levels showed an inverse association with VC progression, at least after adjustment for traditional risk factors. Conclusions: serum sclerostin levels inversely associated with vascular calcification burden and progression in prevalent renal transplant recipients after adjustment for traditional risk factors. Our data corroborate previous findings in non-transplanted CKD patients and support the notion that sclerostin may be up-regulated in the vascular wall during the vascular calcification process as part of a local counter regulatory mechanism directed to suppress vascular calcification. Additional clinical and experimental data are required for confirmation.
    No preview · Article · Oct 2015 · The Journal of Clinical Endocrinology and Metabolism
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    ABSTRACT: Although there has been increasing interest in the use of high protein diets, little is known about dietary protein related changes in the mammalian metabolome. We investigated the influence of protein intake on selected tryptophan and phenolic compounds, derived from both endogenous and colonic microbial metabolism. Furthermore, potential inter-species metabolic differences were studied. For this purpose, 29 healthy subjects were allocated to a high (n = 14) or low protein diet (n = 15) for 2 weeks. In addition, 20 wild-type FVB mice were randomized to a high protein or control diet for 21 days. Plasma and urine samples were analyzed with liquid chromatography-mass spectrometry for measurement of tryptophan and phenolic metabolites. In human subjects, we observed significant changes in plasma level and urinary excretion of indoxyl sulfate (P 0.004 and P 0.001), and in urinary excretion of indoxyl glucuronide (P 0.01), kynurenic acid (P 0.006) and quinolinic acid (P 0.02). In mice, significant differences were noted in plasma tryptophan (P 0.03), indole-3-acetic acid (P 0.02), p-cresyl glucuronide (P 0.03), phenyl sulfate (P 0.004) and phenylacetic acid (P 0.01). Thus, dietary protein intake affects plasma levels and generation of various mammalian metabolites, suggesting an influence on both endogenous and colonic microbial metabolism. Metabolite changes are dissimilar between human subjects and mice, pointing to inter-species metabolic differences with respect to protein intake.
    Preview · Article · Oct 2015 · PLoS ONE
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    ABSTRACT: There is increasing interest in the colonic microbiota as a relevant source of uremic retention solutes accumulating in CKD. Renal disease can also profoundly affect the colonic microenvironment and has been associated with a distinct colonic microbial composition. However, the influence of CKD on the colonic microbial metabolism is largely unknown. Therefore, we studied fecal metabolite profiles of hemodialysis patients and healthy controls using a gas chromatography-mass spectrometry method. We observed a clear discrimination between both groups, with 81 fecal volatile organic compounds detected at significantly different levels in hemodialysis patients and healthy controls. To further explore the differential impact of renal function loss per se versus the effect of dietary and other CKD-related factors, we also compared fecal metabolite profiles between patients on hemodialysis and household contacts on the same diet, which revealed a close resemblance. In contrast, significant differences were noted between the fecal samples of rats 6 weeks after 5/6th nephrectomy and those of sham-operated rats, still suggesting an independent influence of renal function loss. Thus, CKD associates with a distinct colonic microbial metabolism, although the effect of renal function loss per se in humans may be inferior to the effects of dietary and other CKD-related factors. The potential beneficial effect of therapeutics targeting colonic microbiota in patients with CKD remains to be examined.
    No preview · Article · Sep 2015 · Journal of the American Society of Nephrology
  • L Viaene · G J Behets · S Heye · K Claes · D Monbaliu · J Pirenne · P C D'Haese · P Evenepoel
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    ABSTRACT: Bone loss and vascular calcification coincide in patients with end-stage renal disease, similar as to what is observed in the general population. In the present bone biopsy study, we provide further evidence that (micro-)inflammation may represent a common soil for both diseases. Vascular calcification is a common complication of end-stage renal disease (ESRD) and is predictive of subsequent cardiovascular disease and mortality. Mounting evidence linking bone disorders with vascular calcification has contributed to the development of the concept of the bone-vascular axis. Inflammation is involved in the pathogenesis of both disorders. The aim of the present study was to evaluate the relationship between aortic calcification, inflammation, and bone histomorphometry in patients with ESRD. Parameters of inflammation and mineral metabolism were assessed in 81 ESRD patients (55 ± 13 year, 68 % male) referred for renal transplantation. Static bone histomorphometry parameters were determined on transiliac bone biopsies performed during the transplant procedure. Aortic calcification was quantified on lateral lumbar X-rays using the Kauppila method. Aortic calcification, low bone turnover, and low bone area were observed in 53, 37, and 21 % of patients respectively. Inflammatory markers were found to be independently associated with aortic calcification (hsIL-6) and low bone area (TNF-α). Low bone area associated with aortic calcification, independent of age, diabetes, and inflammation. Low bone area and inflammation associates with aortic calcification, independent of each other and traditional risk factors. Our data emphasize the role of (micro-)inflammation in the bone-vascular axis in CKD.
    No preview · Article · Aug 2015 · Osteoporosis International
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    ABSTRACT: CD14 plays a key role in the innate immunity as pattern-recognition receptor of endotoxin. Higher levels of soluble CD14 (sCD14) are associated with overall mortality in hemodialysis patients. The influence of kidney function on plasma sCD14 levels and its relationship with adverse outcomes in patients with CKD not yet on dialysis is unknown. This study examines the associations between plasma levels of sCD14 and endotoxin with adverse outcomes in patients with CKD. We measured plasma levels of sCD14 and endotoxin in 495 Leuven Mild-to-Moderate CKD Study participants. Mild-to-moderate CKD was defined as presence of kidney damage or eGFR<60 ml/min per 1.73 m(2) for ≥3 months, with exclusion of patients on RRT. Study participants were enrolled between November 2005 and September 2006. Plasma sCD14 was negatively associated with eGFR (ρ=-0.34, P<0.001). During a median follow-up of 54 (interquartile range, 23-58) months, 53 patients died. Plasma sCD14 was predictive of mortality, even after adjustment for renal function, Framingham risk factors, markers of mineral bone metabolism, and nutritional and inflammatory parameters (hazard ratio [HR] per SD higher of 1.90; 95% confidence interval [95% CI],1.32 to 2.74; P<0.001). After adjustment for the same risk factors, plasma sCD14 was also a predictor of cardiovascular disease (HR, 1.30; 95% CI, 1.00 to 1.69; P=0.05). Although plasma sCD14 was associated with progression of CKD, defined as reaching ESRD or doubling of serum creatinine in models adjusted for CKD-specific risk factors (HR, 1.24; 95% CI, 1.01 to 1.52; P=0.04), significance was lost when adjusted for proteinuria (HR, 1.19; 95% CI, 0.96 to 1.48; P=0.11). There was neither correlation between plasma endotoxin and sCD14 (ρ=-0.06, P=0.20) nor was endotoxin independently associated with adverse outcome during follow-up. Plasma sCD14 is elevated in patients with decreased kidney function and associated with mortality and cardiovascular disease in patients with CKD not yet on dialysis. Copyright © 2015 by the American Society of Nephrology.
    No preview · Article · Jul 2015 · Clinical Journal of the American Society of Nephrology
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    ABSTRACT: Proteinuria is routinely measured to assess renal allograft status, but the diagnostic and prognostic values of this measurement for renal transplant pathology and outcome remain unclear. We included 1518 renal allograft recipients in this prospective, observational cohort study. All renal allograft biopsy samples with concomitant data on 24-hour proteinuria were included in the analyses (n=2274). Patients were followed for ≥7 years post-transplantation. Compared with proteinuria <0.3 g/24 h, the hazard ratios for graft failure were 1.14 (95% confidence interval [95% CI], 0.81 to 1.60; P=0.50), for proteinuria 0.3-1.0 g/24 h, 2.17 (95% CI, 1.49 to 3.18; P<0.001), for proteinuria 1.0-3.0 g/24 h, and 3.01 (95% CI, 1.75 to 5.18; P<0.001), for proteinuria >3.0 g/24 h, independent of GFR and allograft histology. The predictive performance of proteinuria for graft failure was lower at 3 months after transplant (area under the receiver-operating characteristic curve [AUC] 0.64, P<0.001) than at 1, 2, and 5 years after transplant (AUC 0.73, 0.71, and 0.77, respectively, all P<0.001). Independent determinants of proteinuria were repeat transplantation, mean arterial pressure, transplant glomerulopathy, microcirculation inflammation, and de novo/recurrent glomerular disease. The discriminatory power of proteinuria for these intragraft injury processes was better in biopsy samples obtained >3 months after transplant (AUC 0.73, P<0.001) than in those obtained earlier (AUC 0.56, P<0.01), with 85% specificity but lower sensitivity (47.8%) for proteinuria >1.0 g/24 h. These data support current clinical guidelines to routinely measure proteinuria after transplant, but illustrate the need for more sensitive biomarkers of allograft injury and prognosis. Copyright © 2015 by the American Society of Nephrology.
    No preview · Article · Jul 2015 · Journal of the American Society of Nephrology
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    ABSTRACT: Calcific uraemic arteriolopathy (CUA) is a rare disease and continues to be a clinical challenge. The typical course of CUA is characterized by painful skin discolouration and induration evolving to necrotic ulcerations. Medial calcification of cutaneous arterioles and extensive extracellular matrix remodelling are the hallmarks of CUA. The epidemiology and risk factors associated with this disease are still not fully understood. Moreover, CUA treatment strategies vary significantly among centres and expert recommendations are heterogeneous. Registries may provide important insights and information to increase our knowledge about epidemiology and clinical aspects of CUA and may help to optimize its therapeutic management. In 2006, we established an internet-based registry in Germany (www.calciphylaxie.de) to allow online notification of patients with established or suspected CUA. The registry includes a comprehensive database with questions covering >70 parameters and items regarding patient-related and laboratory data, clinical background and presentation as well as therapeutic strategies. The next phase will be to allow international patient registration via www.calciphylaxis.net as part of the multinational EuCalNet (European Calciphylaxis Network) initiative, which is supported by the ERA-EDTA scientific working group ‘CKD-MBD’. Based on the valuable experience with the previous German CUA registry, EuCalNet will be a useful tool to collect data on the rare disease CUA and may become a basis for prospective controlled trials in the near future.
    Full-text · Article · Jul 2015 · CKJ: Clinical Kidney Journal
  • Pieter Evenepoel · Patrick D'Haese · Vincent Brandenburg
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    ABSTRACT: For more than a decade, the Wnt-β-catenin pathway has been the focus of intense basic and clinical research in the bone field because of its importance in skeletal development and maintenance of bone mass. Wnt activation increases bone formation and decreases bone resorption. The Wnt-β-catenin signaling pathway is tightly regulated by several inhibitors, among which Dickkopf-related protein 1 (DKK1) and sclerostin have been most comprehensively studied. Mounting evidence indicates that a disturbed Wnt-β-catenin signaling is also implicated in the pathogenesis of the chronic kidney disease-associated bone and mineral disorder (CKD-MBD) and affects its various components. DKK1 and sclerostin, more specifically, may be involved in the intense cross-talk between the kidneys, vasculature, and bone. Studies exploring clinical correlates of circulating sclerostin and DKK1 levels so far yielded conflicting results. Biological variability and analytical issues account at least partly for this inconsistency. Antibodies neutralizing Wnt inhibitors may be an appealing strategy to prevent or treat CKD-MBD. Caution is however warranted as sclerostin not only opposes mineralization in the bone but possibly also in the vasculature. Additional studies are required to define determinants of Wnt inhibitors in CKD and to evaluate the efficacy and safety of recently introduced pharmaceuticals targeting these inhibitors.Kidney International advance online publication, 17 June 2015; doi:10.1038/ki.2015.156.
    No preview · Article · Jun 2015 · Kidney International

  • No preview · Article · Jun 2015

  • No preview · Conference Paper · May 2015

  • No preview · Article · May 2015
  • Ruben Poesen · Pieter Evenepoel · Björn Meijers
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    ABSTRACT: Kidney International aims to inform the renal researcher and practicing nephrologists on all aspects of renal research. Clinical and basic renal research, commentaries, The Renal Consult, Nephrology sans Frontieres, minireviews, reviews, Nephrology Images, Journal Club. Published weekly online and twice a month in print.
    No preview · Article · Apr 2015 · Kidney International

Publication Stats

6k Citations
1,261.64 Total Impact Points

Institutions

  • 1997-2016
    • University of Leuven
      • Department of Microbiology and Immunology
      Louvain, Flanders, Belgium
  • 1998-2015
    • Université catholique de Louvain
      Лувен-ла-Нев, Wallonia, Belgium
  • 1997-2015
    • Universitair Ziekenhuis Leuven
      • • Department of Nephrology
      • • Department of Gastroenterology
      Louvain, Flemish, Belgium
  • 2013
    • University of Antwerp
      • Laboratory of Pathophysiology
      Antwerpen, Flemish, Belgium
  • 2001-2012
    • Universitair Ziekenhuis Ghent
      • Department of Surgery
      Gand, Flanders, Belgium
  • 2010
    • University of Geneva
      • Division of Thoracic Surgery
      Genève, Geneva, Switzerland