Pieter Evenepoel

Universitair Ziekenhuis Leuven, Louvain, Flanders, Belgium

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Publications (198)1010.78 Total impact

  • Björn K I Meijers, Ruben Poesen, Pieter Evenepoel
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    ABSTRACT: Evidence on the optimal anticoagulation regimen for hemodialysis in patients at high bleeding risk is scarce. The HepZero study is the first large multinational study comparing two different anticoagulation strategies to avoid systemic heparinization. The use of a heparin-coated dialysis membrane proved to be non-inferior to saline infusion. Superiority of either treatment, however, could not be demonstrated. These findings challenge current guidelines but equally raise questions on the choice of either strategy as compared with regional citrate anticoagulation.
    Kidney international. 12/2014; 86(6):1084-6.
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    ABSTRACT: Sclerostin is a Wnt pathway antagonist regulating osteoblast activity and bone turnover, and it plays a role in cardiovascular calcification processes. Previous findings indicate that sclerostin regulation is disturbed in chronic kidney disease (CKD). The aim of this study was to assess the association of circulating sclerostin levels with mortality in dialysis patients.
    09/2014;
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    ABSTRACT: Persistent hyperparathyroidism (HPT) after kidney transplantation (KTx) is associated with hypercalcemia, hypophosphatemia and abnormally high levels of parathyroid hormone (PTH). In this randomized trial, cinacalcet was compared to placebo for the treatment of hypercalcemia in adult patients with persistent HPT after KTx. Subjects were randomized 1:1 to cinacalcet or placebo with randomization stratified by baseline corrected total serum calcium levels (≤11.2 mg/dL [2.80 mmol/L] or >11.2 mg/dL [2.80 mmol/L]). The primary end point was achievement of a mean corrected total serum calcium value <10.2 mg/dL (2.55 mmol/L) during the efficacy period. The two key secondary end points were percent change in bone mineral density (BMD) at the femoral neck and absolute change in phosphorus; 78.9% cinacalcet- versus 3.5% placebo-treated subjects achieved the primary end point with a difference of 75.4% (95% confidence interval [CI]: 63.8, 87.1), p < 0.001. There was no statistical difference in the percent change in BMD at the femoral neck between cinacalcet and placebo groups, p = 0.266. The difference in the change in phosphorus between the two arms was 0.45 mg/dL (95% CI: 0.26, 0.64), p < 0.001 (nominal). No new safety signals were detected. In conclusion, hypercalcemia and hypophosphatemia were effectively corrected after treatment with cinacalcet in patients with persistent HPT after KTx.
    American Journal of Transplantation 09/2014; · 6.19 Impact Factor
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    ABSTRACT: The relative impact on renal allograft outcome of specific histological diagnoses versus nonspecific chronic histological damage remains unclear.
    Transplantation 08/2014; 98(4):427-435. · 3.78 Impact Factor
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    ABSTRACT: Although renal transplantation (Tx) improves the outcome of patients with renal disease, cardiovascular (CV) risk remains high. Recently, it was demonstrated that asymmetric dimethylarginine (ADMA) levels predict CV events and graft survival in renal transplant recipients (RTRs). Little is known about the impact of renal Tx on the plasma levels of ADMA and symmetric dimethylarginine (SDMA). The present study aimed to define the time course of ADMA and SDMA after Tx.
    Nephrology Dialysis Transplantation 06/2014; 29(10). · 3.37 Impact Factor
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    ABSTRACT: Functional catheter problems are a major challenge for peritoneal dialysis (PD) programs. Here we performed a retrospective single-center study of 110 consecutive patients receiving a first PD catheter (swan neck double-cuff Missouri curled catheters, open surgical technique). Using postimplantation X-ray, the following categories were defined: swan neck angle (posterioanterio view (PA): under 45°, 45-90°, over 90°), inclination (angle between intramural part of catheter and horizontal line; lateral view: greater than/equal to 30°, under 30°), and the position of silicone bead relative to spine (PA view: L1-2, L3-4, lower) and catheter tip (PA view: hypogastric, umbilical, subcostal). Covariates included demographics, body size, previous abdominal surgery, and abdominal wall hernias. During a mean follow-up of 36 months, the time to first functional catheter problem was significantly associated with both the swan neck angle and inclination. The need for surgical intervention was significantly associated with inclination only. Technique failure was not associated with any parameter. In multivariate analysis, inclination was the sole variable significantly associated with functional catheter problems (hazard ratio 3.65 [1.98-6.72]) and the need for surgical intervention (hazard ratio 2.86 [1.19-6.88]). Thus, our study defines a set of X-ray variables that predict functional PD catheter problems and can be used for troubleshooting in individual cases as well as for education and internal audit purposes.Kidney International advance online publication, 18 June 2014; doi:10.1038/ki.2014.203.
    Kidney international. 06/2014;
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    ABSTRACT: Serum p-cresyl sulfate (PCS) associates with cardiovascular disease in patients with chronic kidney disease. PCS concentrations are determined by intestinal uptake of p-cresol, human metabolism to PCS and renal clearance. Whether intestinal uptake of p-cresol itself is directly associated with cardiovascular disease in patients with renal dysfunction has not been studied to date.
    BMC Nephrology 06/2014; 15(1):87. · 1.64 Impact Factor
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    ABSTRACT: Soluble urokinase-type plasminogen activator receptor (suPAR) accumulates in patients with chronic kidney disease (CKD). In various non-CKD populations, suPAR has been proposed as a prognostic marker for mortality and cardiovascular disease. However, it is not known whether suPAR holds prognostic information in patients with mild-to-moderate CKD. In a prospective observational study of 476 patients with mild-to-moderate kidney disease, we examined multivariate associations between suPAR, overall mortality, and cardiovascular events. After a mean follow-up of 57 months, 52 patients died and 76 patients had at least one fatal or nonfatal cardiovascular event. Higher suPAR was directly and significantly associated with both overall mortality (univariate hazard ratio 5.35) and cardiovascular events (univariate hazard ratio 5.06). In multivariate analysis, suPAR remained significantly associated with cardiovascular events (full model, hazard ratio 3.05). Thus, in patients with mild-to-moderate CKD, suPAR concentrations show a clear, direct, and graded association with a higher risk for new-onset cardiovascular disease.Kidney International advance online publication, 4 June 2014; doi:10.1038/ki.2014.197.
    Kidney international. 06/2014;
  • Nutrition Clinique et Métabolisme 05/2014; 28(2):120. · 0.33 Impact Factor
  • New England Journal of Medicine 04/2014; 370(17):1664. · 54.42 Impact Factor
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    ABSTRACT: The soluble urokinase receptor (suPAR) promotes proteinuria and induces focal segmental glomerulosclerosis (FSGS)-like lesions in mice. A serum suPAR concentration cutoff of 3000 pg/ml has been proposed as a clinical biomarker for patients with FSGS. Interestingly, several studies in patients with glomerulopathy found an inverse correlation between the estimated glomerular filtration rate (eGFR) and suPAR. As patients with FSGS present at different eGFRs, we studied the relationship between eGFR and suPAR in a cohort of 476 non-FSGS patients and 54 patients with biopsy-proven idiopathic FSGS. In the non-FSGS patients, eGFR was the strongest significant determinant of suPAR. The proposed cutoff for suPAR in FSGS patients was exceeded in 17%, 39%, and 88% in patients with eGFRs of more than 60, 45-60, and 30-45 ml/min per 1.73 m(2), respectively. In patients with eGFR of <30 ml/min per 1.73 m(2), suPAR exceeded the cutoff in 95% of patients. Levels of suPAR in patients with idiopathic FSGS overlapped with non-FSGS controls and for any given eGFR did not discriminate FSGS cases from non-FSGS controls. In the overall cohort, there was a negative association between idiopathic FSGS and suPAR, and idiopathic FSGS was not an independent predictor of FSGS concentration over 3000 pg/ml. Thus, this study does not support an absolute, eGFR-independent, suPAR concentration cutoff as a biomarker for underlying FSGS pathology and questions the validity of relative, eGFR-dependent suPAR cutoff values.Kidney International advance online publication, 8 January 2014; doi:10.1038/ki.2013.505.
    Kidney International 01/2014; · 8.52 Impact Factor
  • Pieter Evenepoel, Mariano Rodriguez, Markus Ketteler
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    ABSTRACT: Chronic kidney disease – mineral and bone disorder (CKD-MBD) is characterized by bone abnormalities, vascular calcification and an array of laboratory abnormalities. The latter classically include disturbances in the parathyroid hormone (PTH)/vitamin D axis. More recently, also fibroblast growth factor 23 (FGF23) and klotho have been identified as important regulators of mineral metabolism. Klotho deficiency and high circulating FGF23 levels precede secondary hyperparathyroidism in CKD patients. Levels of FGF23 and PTH increase along the progression of CKD to maintain mineral homeostasis and to overcome end-organ resistance. It is hard to define when the increase of both hormones becomes maladaptive. CKD-MBD is associated with adverse outcomes including cardiovascular disease and mortality. This review aims to summarize the complex pathophysiology of CKD-MBD and to outline which laboratory abnormalities represent biomarkers of disease severity, which ones are predictors of cardiovascular disease and which ones should be considered (direct) uremic toxins exerting organ damage. This information may help to streamline current and future therapeutic efforts.
    Seminars in Nephrology 01/2014; · 2.83 Impact Factor
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    ABSTRACT: Indoxyl sulfate and p-cresyl sulfate are unique microbial co-metabolites. Both co-metabolites have been involved in the pathogenesis of accelerated cardiovascular disease and renal disease progression. Available evidence suggests that indoxyl sulfate and p-cresyl sulfate may be considered candidate biomarkers of the human enterotype and may help to explain the link between diet and cardiovascular disease burden.
    PLoS ONE 01/2014; 9(5):e79682. · 3.53 Impact Factor
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    ABSTRACT: The intrarenal resistive index is routinely measured in many renal-transplantation centers for assessment of renal-allograft status, although the value of the resistive index remains unclear. In a single-center, prospective study involving 321 renal-allograft recipients, we measured the resistive index at baseline, at the time of protocol-specified renal-allograft biopsies (3, 12, and 24 months after transplantation), and at the time of biopsies performed because of graft dysfunction. A total of 1124 renal-allograft resistive-index measurements were included in the analysis. All patients were followed for at least 4.5 years after transplantation. Allograft recipients with a resistive index of at least 0.80 had higher mortality than those with a resistive index of less than 0.80 at 3, 12, and 24 months after transplantation (hazard ratio, 5.20 [95% confidence interval {CI}, 2.14 to 12.64; P<0.001]; 3.46 [95% CI, 1.39 to 8.56; P=0.007]; and 4.12 [95% CI, 1.26 to 13.45; P=0.02], respectively). The need for dialysis did not differ significantly between patients with a resistive index of at least 0.80 and those with a resistive index of less than 0.80 at 3, 12, and 24 months after transplantation (hazard ratio, 1.95 [95% CI, 0.39 to 9.82; P=0.42]; 0.44 [95% CI, 0.05 to 3.72; P=0.45]; and 1.34 [95% CI, 0.20 to 8.82; P=0.76], respectively). At protocol-specified biopsy time points, the resistive index was not associated with renal-allograft histologic features. Older recipient age was the strongest determinant of a higher resistive index (P<0.001). At the time of biopsies performed because of graft dysfunction, antibody-mediated rejection or acute tubular necrosis, as compared with normal biopsy results, was associated with a higher resistive index (0.87 ± 0.12 vs. 0.78 ± 0.14 [P=0.05], and 0.86 ± 0.09 vs. 0.78 ± 0.14 [P=0.007], respectively). The resistive index, routinely measured at predefined time points after transplantation, reflects characteristics of the recipient but not those of the graft. (ClinicalTrials.gov number, NCT01879124 .).
    New England Journal of Medicine 11/2013; 369(19):1797-806. · 54.42 Impact Factor
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    ABSTRACT: High serum concentrations of the protein-bound uremic retention solutes p-cresyl sulfate (PCS) and indoxyl sulfate (IndS) and inflammation are associated with increased cardiovascular morbidity and mortality in chronic kidney disease. Renal clearance contributes to up to 80% of the total clearance of PCS and IndS in peritoneal dialysis (PD) patients. Cross-sectional studies evaluating the impact of residual renal function (RRF) on serum concentrations of PCS, IndS, and circulating inflammatory markers have yielded conflicting results. To clarify this issue, we carried out a prospective observational cohort study in incident PD patients (n = 35; 19 men; mean age: 55 ± 17 years). Midday blood samples were collected and analyzed for total serum PCS, IndS, C-reactive protein, and high-sensitivity interleukin 6. Peritoneal and renal clearances were calculated from urine and dialysate collections, and RRF was calculated as the mean of renal urea nitrogen and creatinine clearances. Patients were assessed 1, 6, 12, and 24 months after PD start. Differences between time points were analyzed using linear mixed models (LMMs). Residual renal function declined significantly over time (LMM p < 0.0001). Peritoneal clearances of both toxins tended to increase, but did not compensate for the declining renal clearances. Serum concentrations of PCS and IndS increased significantly over time (LMM p = 0.01; p = 0.0009). In contrast, total mass removal of both toxins remained stable. Circulating inflammatory markers did not change over time. Our data indicate that serum concentrations of PCS and IndS, but not inflammatory markers, increase in incident PD patients in parallel with loss of RRF.
    Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. 10/2013;
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    ABSTRACT: Bisphosphonates are widely used for the treatment of osteoporosis and are generally well tolerated. However, the United States Food and Drug Administration safety reports have highlighted the issue of renal safety in bisphosphonate-treated patients. All bisphosphonates carry labeled "warnings" or a contraindication for use in patients with severe renal impairment (creatinine clearance <30 or <35 mL/min). Data from pivotal trials and their extension studies of bisphosphonates approved for the management of osteoporosis were obtained via PubMed, and were reviewed with support from published articles available on PubMed. Renal safety analyses of pivotal trials of oral alendronate, risedronate and ibandronate for postmenopausal osteoporosis showed no short- or long-term effects on renal function. Transient post-infusion increases in serum creatinine have been reported in patients receiving intravenous ibandronate and zoledronic acid, however studies showed that treatment with these agents did not result in long-term renal function deterioration in clinical trial patients with osteoporosis. All bisphosphonate therapies have "warnings" for use in patients with severe renal impairment. Clinical trial results have shown that even in elderly, frail osteoporotic patients with renal impairment, intravenous bisphosphonate therapy administration in accordance with the prescribing information did not result in long-term renal function decline. Physicians should follow guidelines for bisphosphonate therapies administration at all times.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 08/2013; · 6.04 Impact Factor
  • Björn Meijers, Pieter Evenepoel
    Artificial Organs 07/2013; · 1.96 Impact Factor
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    ABSTRACT: Renal transplant recipients have an increased risk of cardiovascular (CV) disease. Arterial stiffness (AS) and aortic calcifications (ACs) are well-known CV risk factors in patients with chronic kidney disease. We aimed to determine the prognostic value of AS and AC in incident renal transplant recipients (RTRs). We conducted a prospective study in 253 single RTR. AC were scored by means of lumbar X-ray. Carotid-femoral pulse wave velocity (PWV) was assessed in a subgroup of 115 patients. AC were present in 61% of patients. After a mean follow-up of 36 months, 32 CV events occurred in the overall group and 13 events in the PWV subgroup. When we accounted for age, gender, and CV history, AC score (HR, hazard ratio 1.09 per 1 unit increase; 95% CI 1.02-1.17) and PWV (HR 1.45 per 1 m/s; 95% CI 1.16-1.8) remained an independent predictor of CV events in Cox-regression analyses. Using receiver operating characteristics, the area under the curve for predicting CV events amounted to 0.80 and 0.72 for sum AC and PWV, respectively. Both AS and AC are strong predictors of future CV events in an incident RTR population. These vascular assessments are readily available and easy to perform, making them ideal tools for further risk stratification. (ClinicalTrials.gov number: NCT00547040).
    Transplant International 06/2013; · 3.16 Impact Factor
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    ABSTRACT: p-Cresyl sulfate and indoxyl sulfate contribute to cardiovascular disease and progression of renal disease. Renal clearance of both solutes mainly depends on tubular secretion, and serum concentrations are widely dispersed for any given stage of CKD. From this information, it is inferred that estimated GFR is not a suitable proxy of the clearance of these solutes. Formal clearance studies have, however, not been performed to date. This study analyzed renal clearances of p-cresyl sulfate and indoxyl sulfate in the Leuven CKD cohort (NCT00441623; inclusion between November of 2005 and September of 2006) and explored their relationship with estimated GFR. Multivariate linear regression models were built to evaluate contributions of estimated GFR, demographics, and generation rates to p-cresyl sulfate and indoxyl sulfate serum concentrations. Renal clearances were analyzed in 203 patients with CKD stages 1-5. Indoxyl sulfate clearances (median=17.7, interquartile range=9.4-33.2 ml/min) exceeded p-cresyl sulfate clearances (median=6.8, interquartile range=3.4-12.0 ml/min) by about threefold. A linear relationship was observed between estimated GFR and clearances of p-cresyl sulfate (R(2)=0.50, P<0.001) and indoxyl sulfate (R(2)=0.55, P<0.001). In multivariate regression, p-cresyl sulfate concentrations were associated (R(2)=0.75) with estimated GFR and generation rate (both P<0.001). Indoxyl sulfate concentrations were associated (R(2)=0.74) with estimated GFR, generation rate (both P<0.001), age (P<0.05), and sex (P<0.05). Estimated GFR provides an acceptable estimate of renal clearance of p-cresyl sulfate and indoxyl sulfate. Remarkably, clearances of indoxyl sulfate exceed clearances of p-cresyl sulfate by approximately threefold, suggesting substantial differences between tubular transporter affinities and/or involvement of separate transporter systems for p-cresyl sulfate and indoxyl sulfate.
    Clinical Journal of the American Society of Nephrology 06/2013; · 5.07 Impact Factor
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    ABSTRACT: Context:Sclerostin, a Wnt antagonist, produced by osteocytes regulates osteoblast activity and is a well-established key player in bone turnover. Recent data indicate that the Wnt pathway may also be involved in vascular calcification.Objective:The present study tests the hypothesis that serum sclerostin levels are associated with vascular calcification in patients with chronic kidney disease (CKD) not yet on dialysis.Design, setting, participants and measurements:We performed a cross-sectional analysis in 154 CKD patients. Aortic calcification (AC) was assessed by lumbar X-ray and scored with a maximum score of 24. In addition to traditional and non-traditional cardiovascular risk factors, serum sclerostin levels were assessed (ELISA). Regression analysis was performed to identify determinants of serum sclerostin and AC.Results:AC was present in 59% of patients. Higher age (p <0.0001), male gender (p= 0.006), lower eGFR (p=0.0008), lower bone specific alkaline phosphatase (p= 0.03) and the absence of AC (p=0.006) were identified as independent determinants of higher serum sclerostin levels. In univariate logistic regression, higher age, diabetes, cardiovascular history, higher BMI, higher serum CRP and sclerostin levels and lower eGFR were all associated with the presence of AC. In multivariate analysis, lower, not higher, sclerostin levels (p=0.04; OR per ng/ml 0.24), higher age (p<0.0001, OR per year 1.17) and cardiovascular history (p=0.02, OR for a positive cardiovascular history 3.83) were identified as independent determinants of AC.Conclusions:In this cohort of CKD patients we found that patients with aortic calcifications had higher sclerostin levels. However, in multivariate analysis the association became inverse. Additional clinical and experimental studies are urgently required to clarify whether or not sclerostin protects against progression of vascular calcification.
    The Journal of Clinical Endocrinology and Metabolism 06/2013; · 6.31 Impact Factor

Publication Stats

4k Citations
1,010.78 Total Impact Points

Institutions

  • 1997–2014
    • Universitair Ziekenhuis Leuven
      • • Department of Nephrology
      • • Department of Gastroenterology
      Louvain, Flanders, Belgium
  • 2011
    • Ghent University
      • Department of Internal Medicine
      Gent, VLG, Belgium
  • 2010
    • Cliniques Universitaires Saint-Luc
      • Division of Nephrology
      Brussels, BRU, Belgium
  • 2008–2010
    • University of Geneva
      • Division of Thoracic Surgery
      Genève, GE, Switzerland
  • 2003–2009
    • KU Leuven
      • Department of Microbiology and Immunology
      Leuven, VLG, Belgium