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Background Apixaban, a direct oral anticoagulant inhibiting factor Xa, has been proven to reduce the risk of atrial fibrillation-related stroke and thromboembolism in patients with mild to moderate renal insufficiency. Patients on renal replacement therapy, however, were excluded from randomized controlled trials. Therefore, uncertainty remains concerning benefits, dosing and timing of intake in haemodialysis population. Methods We conducted a Phase II pharmacokinetics study in which 24 patients on maintenance haemodialysis were given a single dose (2.5 mg or 5 mg) of apixaban, either 30 min before or immediately after dialysis on the mid-week dialysis day. Results Apixaban 5 mg resulted in higher area under the curve (AUC0–48) in comparison with 2.5 mg, although significance could only be reached for dosing pre-dialysis (2.5 mg versus 5 mg, P = 0.008). In line, peak concentrations (Cmax) after dosing pre-dialysis were significantly higher in the 5 mg than in the 2.5 mg groups (P = 0.02). In addition, dialysis resulted in significant reduction of drug exposure. AUC0–48 pre-dialysis were on average 48% (2.5 mg) and 26% (5 mg) lower than the AUC0–48 post-dialysis, in line with Cmax. As a result, a dose of 2.5 mg post-dialysis and a dose of 5 mg pre-dialysis resulted in similar AUC0–48. In contrast, significant differences were found between the 5 mg group post-dialysis and the 2.5 mg group pre-dialysis (P = 0.02). Conclusions Our data suggest that exposure to apixaban in patients on maintenance haemodialysis is dependent not only on drug dose but also on timing of intake relative to the haemodialysis procedure.
Ines Van Den Bosch; Thomas Bouillon; Peter Verhamme; Thomas Vanassche; Marc Jacquemin; Maarten Coemans; Dirk Kuypers; Björn Meijers. Apixaban in patients on haemodialysis: a single-dose pharmacokinetics study. Nephrology Dialysis Transplantation 2020, 36, 884 -889.
AMA StyleInes Van Den Bosch, Thomas Bouillon, Peter Verhamme, Thomas Vanassche, Marc Jacquemin, Maarten Coemans, Dirk Kuypers, Björn Meijers. Apixaban in patients on haemodialysis: a single-dose pharmacokinetics study. Nephrology Dialysis Transplantation. 2020; 36 (5):884-889.
Chicago/Turabian StyleInes Van Den Bosch; Thomas Bouillon; Peter Verhamme; Thomas Vanassche; Marc Jacquemin; Maarten Coemans; Dirk Kuypers; Björn Meijers. 2020. "Apixaban in patients on haemodialysis: a single-dose pharmacokinetics study." Nephrology Dialysis Transplantation 36, no. 5: 884-889.
Background In haemodialysis, maintaining patency of the extracorporeal circuit requires the use of anticoagulants. Although (low molecular weight) heparins are the mainstay, these are not well tolerated in all patients. Alternative approaches include saline infusion, citrate-containing dialysate, regional citrate anticoagulation or the use of heparin-coated membranes. Asymmetric cellulose triacetate (ATA) dialysers have a low degree of platelet contact activation and might be an alternative to heparin-coated dialysers. The aim of this study was to test the clotting propensity of ATA when used without systemic anticoagulation. Methods We performed a Phase II pilot study in maintenance dialysis patients. The ‘Strategies for Asymmetrical Triacetate dialyzer heparin-Free Effective hemodialysis’ (SAFE) study was a two-arm open-label crossover study. In Arm A, patients were dialysed using 1.9 m2 ATA membranes in combination with a citrate-containing dialysate (1 mM). In Arm B, the ATA membrane was combined with high-volume predilution haemodiafiltration (HDF) without any other anticoagulation. The primary endpoint was the success rate to complete 4 h of haemodialysis without preterm clotting. Secondary endpoints included time to clotting and measures of dialysis adequacy. Results We scheduled 240 dialysis sessions (120/arm) in 20 patients. Patients were randomized 1:1 to start with Arm A or B. All patients crossed to the other arm halfway through the study. A total of 232 (96.7%) study treatments were delivered. Overall, 23 clotting events occurred, 7 in Arm A and 16 in Arm B. The success rate in Arm A (ATA + citrate-containing dialysate) was 90.8/94.0% [intention to treat (ITT)/as treated]. The success rate in Arm B (ATA + predilution HDF) was 83.3/86.2% (ITT/as treated). Time to clotting was borderline significantly better in Arm A (Mantel-Cox log rank P = 0.05). Conclusion ATA dialysers have a low clotting propensity and both predilution HDF and a citrate-containing dialysate resulted in high rates of completed dialysis sessions.
Ines Vandenbosch; Sander Dejongh; Kathleen Claes; Bert Bammens; Katrien De Vusser; Amaryllis Van Craenenbroeck; Dirk Kuypers; Pieter Evenepoel; Björn Meijers. Strategies for asymmetrical triacetate dialyser heparin-free effective haemodialysis: the SAFE study. Clinical Kidney Journal 2020, 14, 1901 -1907.
AMA StyleInes Vandenbosch, Sander Dejongh, Kathleen Claes, Bert Bammens, Katrien De Vusser, Amaryllis Van Craenenbroeck, Dirk Kuypers, Pieter Evenepoel, Björn Meijers. Strategies for asymmetrical triacetate dialyser heparin-free effective haemodialysis: the SAFE study. Clinical Kidney Journal. 2020; 14 (8):1901-1907.
Chicago/Turabian StyleInes Vandenbosch; Sander Dejongh; Kathleen Claes; Bert Bammens; Katrien De Vusser; Amaryllis Van Craenenbroeck; Dirk Kuypers; Pieter Evenepoel; Björn Meijers. 2020. "Strategies for asymmetrical triacetate dialyser heparin-free effective haemodialysis: the SAFE study." Clinical Kidney Journal 14, no. 8: 1901-1907.
Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection disproportionally affects frail, elderly patients and those with multiple chronic comorbidities. Whether patients on RRT have an additional risk because of their specific exposure and complex immune dysregulation is controversial. Methods To describe the incidence, characteristics, and outcomes of SARS-CoV-2 infection, we conducted a prospective, multicenter, region-wide registry study in adult patients on RRT versus the general population from March 2 to May 25, 2020. This study comprised all patients undergoing RRT in the Flanders region of Belgium, a country that has been severely affected by coronavirus disease 2019 (COVID-19). Results At the end of the epidemic wave, crude and age-standardized cumulative incidence rates of SARS-CoV-2 infection were 5.3% versus 2.5%, respectively, among 4297 patients on hemodialysis, and 1.4% versus 1.6%, respectively, among 3293 patients with kidney transplants (compared with 0.6% in the general population). Crude and age-standardized cumulative mortality rates were 29.6% versus 19.9%, respectively, among patients on hemodialysis, and 14.0% versus 23.0%, respectively, among patients with transplants (compared with 15.3% in the general population). We found no excess mortality in the hemodialysis population when compared with mean mortality rates during the same 12-week period in 2015–2019 because COVID-19 mortality was balanced by lower than expected mortality among uninfected patients. Only 0.18% of the kidney transplant population died of SARS-CoV-2 infection. Conclusions Mortality associated with SARS-CoV-2 infection is high in patients on RRT. Nevertheless, the epidemic’s overall effect on the RRT population remained remarkably limited in Flanders. Calculation of excess mortality and age standardization provide a more reliable picture of the mortality burden of COVID-19 among patients on RRT.
Johan De Meester; Dirk De Bacquer; Maarten Naesens; Bjorn Meijers; Marie M. Couttenye; An S. De Vriese; for the NBVN Kidney Registry Group. Incidence, Characteristics, and Outcome of COVID-19 in Adults on Kidney Replacement Therapy: A Regionwide Registry Study. Journal of the American Society of Nephrology 2020, 32, 385 -396.
AMA StyleJohan De Meester, Dirk De Bacquer, Maarten Naesens, Bjorn Meijers, Marie M. Couttenye, An S. De Vriese, for the NBVN Kidney Registry Group. Incidence, Characteristics, and Outcome of COVID-19 in Adults on Kidney Replacement Therapy: A Regionwide Registry Study. Journal of the American Society of Nephrology. 2020; 32 (2):385-396.
Chicago/Turabian StyleJohan De Meester; Dirk De Bacquer; Maarten Naesens; Bjorn Meijers; Marie M. Couttenye; An S. De Vriese; for the NBVN Kidney Registry Group. 2020. "Incidence, Characteristics, and Outcome of COVID-19 in Adults on Kidney Replacement Therapy: A Regionwide Registry Study." Journal of the American Society of Nephrology 32, no. 2: 385-396.
We are facing a full-blown pandemic, caused by a recently identified beta-coronavirus [1] now known as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical disease, coined coronavirus disease 2019 (COVID-19), is quite heterogeneous. While most patients are asymptomatic or have minor symptoms, a minority of patients develop more serious and potentially life-threatening respiratory disease [2]. In this issue of Nephrology Dialysis Transplantation, Portolés and coworkers report on a large European cohort of patients with COVID-19. They explore kidney involvement as part of the clinical spectrum of SARS-CoV-2 infection [3].
Björn Meijers; Luuk B Hilbrands. The clinical characteristics of coronavirus-associated nephropathy. Nephrology Dialysis Transplantation 2020, 35, 1279 -1281.
AMA StyleBjörn Meijers, Luuk B Hilbrands. The clinical characteristics of coronavirus-associated nephropathy. Nephrology Dialysis Transplantation. 2020; 35 (8):1279-1281.
Chicago/Turabian StyleBjörn Meijers; Luuk B Hilbrands. 2020. "The clinical characteristics of coronavirus-associated nephropathy." Nephrology Dialysis Transplantation 35, no. 8: 1279-1281.
Chronic use of proton-pump inhibitors (PPIs) is common in kidney transplant recipients (KTRs). However, concerns are emerging about the potential long-term complications of PPI therapy. We aimed to investigate whether PPI use is associated with excess mortality risk in KTRs. We investigated the association of PPI use with mortality risk using multivariable Cox proportional hazard regression analyses in a single-center prospective cohort of 703 stable outpatient KTRs, who visited the outpatient clinic of the University Medical Center Groningen (UMCG) between November 2008 and March 2011 (ClinicalTrials.gov Identifier NCT02811835). Independent replication of the results was performed in a prospective cohort of 656 KTRs from the University Hospitals Leuven (NCT01331668). Mean age was 53 ± 13 years, 57% were male, and 56.6% used PPIs. During median follow-up of 8.2 (4.7-9.0) years, 194 KTRs died. In univariable Cox regression analyses, PPI use was associated with an almost 2 times higher mortality risk (hazard ratio [HR] 1.86, 95% CI 1.38-2.52, P < 0.001) compared with no use. After adjustment for potential confounders, PPI use remained independently associated with mortality (HR 1.68, 95% CI 1.21-2.33, P = 0.002). Moreover, the HR for mortality risk in KTRs taking a high PPI dose (>20 mg omeprazole equivalents/day) compared with patients taking no PPIs (HR 2.14, 95% CI 1.48-3.09, P < 0.001) was higher than in KTRs taking a low PPI dose (HR 1.72, 95% CI 1.23-2.39, P = 0.001). These findings were replicated in the Leuven Renal Transplant Cohort. The main limitation of this study is its observational design, which precludes conclusions about causation. We demonstrated that PPI use is associated with an increased mortality risk in KTRs, independent of potential confounders. Moreover, our data suggest that this risk is highest among KTRs taking high PPI dosages. Because of the observational nature of our data, our results require further corroboration before it can be recommended to avoid the long-term use of PPIs in KTRs. ClinicalTrials.gov Identifier: NCT02811835, NCT01331668.
Rianne M. Douwes; António W. Gomes-Neto; Michele F. Eisenga; Elisabet Van Loon; Joëlle C. Schutten; Reinold Gans; Maarten Naesens; Else Van Den Berg; Ben Sprangers; Stefan P. Berger; Gerjan Navis; Hans Blokzijl; Björn Meijers; Stephan J. L. Bakker; Dirk Kuypers. The association between use of proton-pump inhibitors and excess mortality after kidney transplantation: A cohort study. PLOS Medicine 2020, 17, e1003140 .
AMA StyleRianne M. Douwes, António W. Gomes-Neto, Michele F. Eisenga, Elisabet Van Loon, Joëlle C. Schutten, Reinold Gans, Maarten Naesens, Else Van Den Berg, Ben Sprangers, Stefan P. Berger, Gerjan Navis, Hans Blokzijl, Björn Meijers, Stephan J. L. Bakker, Dirk Kuypers. The association between use of proton-pump inhibitors and excess mortality after kidney transplantation: A cohort study. PLOS Medicine. 2020; 17 (6):e1003140.
Chicago/Turabian StyleRianne M. Douwes; António W. Gomes-Neto; Michele F. Eisenga; Elisabet Van Loon; Joëlle C. Schutten; Reinold Gans; Maarten Naesens; Else Van Den Berg; Ben Sprangers; Stefan P. Berger; Gerjan Navis; Hans Blokzijl; Björn Meijers; Stephan J. L. Bakker; Dirk Kuypers. 2020. "The association between use of proton-pump inhibitors and excess mortality after kidney transplantation: A cohort study." PLOS Medicine 17, no. 6: e1003140.
Gut microbial metabolism is not only an important source of uremic toxins but may also help to maintain the vitamin K stores of the host. We hypothesized that sevelamer therapy, a commonly used phosphate binder in patients with end-stage kidney disease (ESKD), associates with a disturbed gut microbial metabolism. Important representatives of gut-derived uremic toxins, including indoxyl sulfate (IndS), p-Cresyl sulfate (pCS), trimethylamine N-oxide (TMAO), phenylacetylglutamine (PAG) and non-phosphorylated, uncarboxylated matrix-Gla protein (dp-ucMGP; a marker of vitamin K status), were analyzed in blood samples from 423 patients (65% males, median age 54 years) with ESKD. Demographics and laboratory data were extracted from electronic files. Sevelamer users (n = 172, 41%) were characterized by higher phosphate, IndS, TMAO, PAG and dp-ucMGP levels compared to non-users. Sevelamer was significantly associated with increased IndS, PAG and dp-ucMGP levels, independent of age, sex, calcium-containing phosphate binder, cohort, phosphate, creatinine and dialysis vintage. High dp-ucMGP levels, reflecting vitamin K deficiency, were independently and positively associated with PAG and TMAO levels. Sevelamer therapy associates with an unfavorable gut microbial metabolism pattern. Although the observational design precludes causal inference, present findings implicate a disturbed microbial metabolism and vitamin K deficiency as potential trade-offs of sevelamer therapy.
Lu Dai; Björn K. Meijers; Bert Bammens; Henriette De De Loor; Leon J. Schurgers; Abdul Rashid Qureshi; Peter Stenvinkel; Pieter Evenepoel. Sevelamer Use in End-Stage Kidney Disease (ESKD) Patients Associates with Poor Vitamin K Status and High Levels of Gut-Derived Uremic Toxins: A Drug–Bug Interaction? Toxins 2020, 12, 351 .
AMA StyleLu Dai, Björn K. Meijers, Bert Bammens, Henriette De De Loor, Leon J. Schurgers, Abdul Rashid Qureshi, Peter Stenvinkel, Pieter Evenepoel. Sevelamer Use in End-Stage Kidney Disease (ESKD) Patients Associates with Poor Vitamin K Status and High Levels of Gut-Derived Uremic Toxins: A Drug–Bug Interaction? Toxins. 2020; 12 (6):351.
Chicago/Turabian StyleLu Dai; Björn K. Meijers; Bert Bammens; Henriette De De Loor; Leon J. Schurgers; Abdul Rashid Qureshi; Peter Stenvinkel; Pieter Evenepoel. 2020. "Sevelamer Use in End-Stage Kidney Disease (ESKD) Patients Associates with Poor Vitamin K Status and High Levels of Gut-Derived Uremic Toxins: A Drug–Bug Interaction?" Toxins 12, no. 6: 351.
Patients with chronic kidney disease (CKD) are at increased risk of bone mineral density loss and vascular calcification. Bone demineralization and vascular mineralization often concur in CKD, similar to what observed in the general population. This contradictory association is commonly referred to as the ‘calcification paradox’ or the bone–vascular axis. Mounting evidence indicates that CKD-associated gut dysbiosis may be involved in the pathogenesis of the bone–vascular axis. A disrupted intestinal barrier function, a metabolic shift from a predominant saccharolytic to a proteolytic fermentation pattern, and a decreased generation of vitamin K may, alone or in concert, drive a vascular and skeletal pathobiology in CKD patients. A better understanding of the role of gut dysbiosis in the bone–vascular axis may open avenues for novel therapeutics, including nutriceuticals.
Pieter Evenepoel; Sander DeJongh; Kristin Verbeke; Bjorn Meijers. The Role of Gut Dysbiosis in the Bone–Vascular Axis in Chronic Kidney Disease. Toxins 2020, 12, 285 .
AMA StylePieter Evenepoel, Sander DeJongh, Kristin Verbeke, Bjorn Meijers. The Role of Gut Dysbiosis in the Bone–Vascular Axis in Chronic Kidney Disease. Toxins. 2020; 12 (5):285.
Chicago/Turabian StylePieter Evenepoel; Sander DeJongh; Kristin Verbeke; Bjorn Meijers. 2020. "The Role of Gut Dysbiosis in the Bone–Vascular Axis in Chronic Kidney Disease." Toxins 12, no. 5: 285.
Introduction Quantification of serum-free light chains (FLCs) is important in the diagnosis and monitoring of paraprotein-related diseases. There are currently 2 FLC assays available: the Freelite assay (Binding Site) and the N Latex assay (Siemens). There is emerging evidence that these assays give different results, but it is not established how kidney dysfunction affects these assays differently. Methods In this study, we measured and compared serum FLCs in patients with mild-to-moderate chronic kidney disease (CKD) using both assays. Results Although κ FLCs are higher by Freelite, λ FLCs are higher by N Latex. Both κ and λ FLCs correlate inversely with estimated glomerular filtration rate (eGFR) in the 2 assays, but this effect is more pronounced in λ-free light-chain measurement by N Latex. Consequently, although the κ/λ ratio by Freelite is inversely correlated by eGFR, the κ/λ ratio by N Latex is positively correlated with eGFR. Conclusion Our results clearly demonstrate that the 2 available FLC assays cannot be used interchangeably in patients with CKD.
Ben Sprangers; Kathleen Claes; Pieter Evenepoel; Dirk Kuypers; Koen Poesen; Michel Delforge; Xavier Bossuyt V; Björn Meijers. Comparison of 2 Serum-Free Light-Chain Assays in CKD Patients. Kidney International Reports 2020, 5, 627 -631.
AMA StyleBen Sprangers, Kathleen Claes, Pieter Evenepoel, Dirk Kuypers, Koen Poesen, Michel Delforge, Xavier Bossuyt V, Björn Meijers. Comparison of 2 Serum-Free Light-Chain Assays in CKD Patients. Kidney International Reports. 2020; 5 (5):627-631.
Chicago/Turabian StyleBen Sprangers; Kathleen Claes; Pieter Evenepoel; Dirk Kuypers; Koen Poesen; Michel Delforge; Xavier Bossuyt V; Björn Meijers. 2020. "Comparison of 2 Serum-Free Light-Chain Assays in CKD Patients." Kidney International Reports 5, no. 5: 627-631.
Mounting evidence indicates that sclerostin, a well-known inhibitor of bone formation, may qualify as a clinically relevant biomarker of chronic kidney disease-related mineral and bone disorder (CKD-MBD), including abnormal mineral and bone metabolism and extraskeletal calcification. For this purpose, in this study we investigate the extent to which circulating sclerostin, skeletal sclerostin expression, bone histomorphometric parameters, and serum markers of bone metabolism associate with each other. Bone biopsies and serum samples were collected in a cohort of 68 end-stage kidney disease (ESKD) patients. Serum sclerostin levels were measured using 4 different commercially available assays. Skeletal sclerostin expression was evaluated on immunohistochemically stained bone sections. Quantitative bone histomorphometry was performed on Goldner stained tissue sections. Different serum markers of bone metabolism were analyzed using in-house techniques or commercially available assays. Despite large inter-assay differences for circulating sclerostin, results obtained with the 4 assays under study closely correlated with each other, whilst moderate significant correlations with skeletal sclerostin expression were also found. Both skeletal and circulating sclerostin negatively correlated with histomorphometric bone and serum parameters reflecting bone formation and turnover. In this study, the unique combined evaluation of bone sclerostin expression, bone histomorphometry, bone biomarkers, and serum sclerostin levels, as assessed by 4 different assays, demonstrated that sclerostin may qualify as a clinically relevant marker of disturbed bone metabolism in ESKD patients.
Annelies De Maré; Anja Verhulst; Etienne Cavalier; Pierre Delanaye; Geert J. Behets; Bjorn Meijers; Dirk Kuypers; Patrick C. D’Haese; Pieter Evenepoel; Maré; D’ Haese. Clinical Inference of Serum and Bone Sclerostin Levels in Patients with End-Stage Kidney Disease. Journal of Clinical Medicine 2019, 8, 2027 .
AMA StyleAnnelies De Maré, Anja Verhulst, Etienne Cavalier, Pierre Delanaye, Geert J. Behets, Bjorn Meijers, Dirk Kuypers, Patrick C. D’Haese, Pieter Evenepoel, Maré, D’ Haese. Clinical Inference of Serum and Bone Sclerostin Levels in Patients with End-Stage Kidney Disease. Journal of Clinical Medicine. 2019; 8 (12):2027.
Chicago/Turabian StyleAnnelies De Maré; Anja Verhulst; Etienne Cavalier; Pierre Delanaye; Geert J. Behets; Bjorn Meijers; Dirk Kuypers; Patrick C. D’Haese; Pieter Evenepoel; Maré; D’ Haese. 2019. "Clinical Inference of Serum and Bone Sclerostin Levels in Patients with End-Stage Kidney Disease." Journal of Clinical Medicine 8, no. 12: 2027.
Optimal fluid management is a challenge in patients with end-stage kidney disease (ESKD). Most physicians still rely on physical examination, and technical aides are used in a minority of patients. Yet, subclinical abnormalities cannot be detected. As a result, acute and chronic hypovolaemia or hypervolaemia will occur in patients with ESKD. Hypervolaemia is associated with hypertension and patients experiencing chronic hypervolaemia are at increased risk of left ventricular hypertrophy, coronary artery disease and mortality [1, 2].
Sander DeJongh; Ricard Farre; Bert Bammens; Kathleen Claes; Dirk Kuypers; Pieter Evenepoel; Björn Meijers. Discrepancies between bioimpedance spectroscopy devices in haemodialysis patients. Clinical Kidney Journal 2019, 13, 906 -908.
AMA StyleSander DeJongh, Ricard Farre, Bert Bammens, Kathleen Claes, Dirk Kuypers, Pieter Evenepoel, Björn Meijers. Discrepancies between bioimpedance spectroscopy devices in haemodialysis patients. Clinical Kidney Journal. 2019; 13 (5):906-908.
Chicago/Turabian StyleSander DeJongh; Ricard Farre; Bert Bammens; Kathleen Claes; Dirk Kuypers; Pieter Evenepoel; Björn Meijers. 2019. "Discrepancies between bioimpedance spectroscopy devices in haemodialysis patients." Clinical Kidney Journal 13, no. 5: 906-908.
Autosomal dominant polycystic kidney disease (ADPKD) is among the most common hereditary nephropathies. Low bone turnover osteopenia has been reported in mice with conditional deletion of the PKD1 and PKD2 genes in osteoblasts, and preliminary clinical data also suggest suppressed bone turnover in patients with ADPKD. The present study compared the bone phenotype between patients with end stage renal disease (ESRD) due to ADPKD and controls with ESRD due to other causes. Laboratory parameters of bone mineral metabolism (fibroblast growth factor 23 and sclerostin), bone turnover markers (bone alkaline phosphatase, tartrate-resistant acid phosphatase 5b) and bone mineral density (BMD, by dual energy x-ray absorptiometry, DXA) were assessed in 518 patients with ESRD, including 99 with ADPKD. Bone histomorphometry data were available in 71 patients, including 10 with ADPKD. Circulating levels of bone alkaline phosphatase were significantly lower in patients with ADPKD (17.4 vs 22.6 ng/mL), as were histomorphometric parameters of bone formation. Associations between ADPKD and parameters of bone formation persisted after adjustment for classical determinants including parathyroid hormone, age, and sex. BMD was higher in skeletal sites rich in cortical bone in patients with ADPKD compared to non-ADPKD patients (Z-score midshaft radius -0.04 vs -0.14; femoral neck -0.72 vs -1.02). Circulating sclerostin levels were significantly higher in ADPKD patients (2.20 vs 1.84 ng/L). In conclusion, patients with ESRD due to ADPKD present a distinct bone and mineral phenotype, characterized by suppressed bone turnover, better preserved cortical BMD, and high sclerostin levels.
Pieter Evenepoel; Kathleen Claes; Etienne Cavalier; Bjorn Meijers; Peter Stenvinkel; Geert Behets; Magdalena Jankowska; Patrick D’Haese; Bert Bammens. A distinct bone phenotype in ADPKD patients with end-stage renal disease. Kidney International 2019, 95, 412 -419.
AMA StylePieter Evenepoel, Kathleen Claes, Etienne Cavalier, Bjorn Meijers, Peter Stenvinkel, Geert Behets, Magdalena Jankowska, Patrick D’Haese, Bert Bammens. A distinct bone phenotype in ADPKD patients with end-stage renal disease. Kidney International. 2019; 95 (2):412-419.
Chicago/Turabian StylePieter Evenepoel; Kathleen Claes; Etienne Cavalier; Bjorn Meijers; Peter Stenvinkel; Geert Behets; Magdalena Jankowska; Patrick D’Haese; Bert Bammens. 2019. "A distinct bone phenotype in ADPKD patients with end-stage renal disease." Kidney International 95, no. 2: 412-419.
In recent decades, considerable research attention has been devoted to new synthetic procedures for thiacyclophanes. Thiacyclophanes are widely used as host molecules for the molecular recognition of organic compounds as well as metals. Herein, we report the selective and high-yielding synthesis of novel alternate-linked-meta-para-thiacyclophanes. These novel thiacyclophanes are selectively synthesized in high-yielding procedures. Furthermore, post-functionalization of the phenolic moieties was successfully performed. The 3D structure of the alternate-linked-meta-para-[22.12]thiacyclophane was further elucidated via X-ray crystallographic analysis.
Wout De Leger; Koen Adriaensen; Koen Robeyns; Luc Van Meervelt; Joice Thomas; Björn Meijers; Mario Smet; Wim Dehaen. Synthesis and post-functionalization of alternate-linked-meta-para-[2n.1n]thiacyclophanes. Beilstein Journal of Organic Chemistry 2018, 14, 2190 -2197.
AMA StyleWout De Leger, Koen Adriaensen, Koen Robeyns, Luc Van Meervelt, Joice Thomas, Björn Meijers, Mario Smet, Wim Dehaen. Synthesis and post-functionalization of alternate-linked-meta-para-[2n.1n]thiacyclophanes. Beilstein Journal of Organic Chemistry. 2018; 14 (1):2190-2197.
Chicago/Turabian StyleWout De Leger; Koen Adriaensen; Koen Robeyns; Luc Van Meervelt; Joice Thomas; Björn Meijers; Mario Smet; Wim Dehaen. 2018. "Synthesis and post-functionalization of alternate-linked-meta-para-[2n.1n]thiacyclophanes." Beilstein Journal of Organic Chemistry 14, no. 1: 2190-2197.
The kidneys are key contributors to body homeostasis, by virtue of controlled excretion of excessive fluid, electrolytes, and toxic waste products. The syndrome of uremia equals the altered physiology due to irreversible loss of kidney function that is left uncorrected for, despite therapeutic intervention(s). The intestines and its microbial content are prime contributors to this syndrome. The intestinal barrier separates the self (or the so-called “milieu intérior”) from the environment. In the large intestine, the intestinal barrier keeps apart human physiology and the microbiota. The enterocytes and the extracellular mucin layer functions form a complex multilayered structure, facilitating complex bidirectional metabolic and immunological crosstalk. The current review focuses on the intestinal barrier in chronic kidney disease (CKD). Loss of kidney function results in structural and functional alterations of the intestinal barrier, contribution to the syndrome of uremia.
Björn Meijers; Ricard Farré; Sander DeJongh; Maria Vicario; Pieter Evenepoel. Intestinal Barrier Function in Chronic Kidney Disease. Toxins 2018, 10, 298 .
AMA StyleBjörn Meijers, Ricard Farré, Sander DeJongh, Maria Vicario, Pieter Evenepoel. Intestinal Barrier Function in Chronic Kidney Disease. Toxins. 2018; 10 (7):298.
Chicago/Turabian StyleBjörn Meijers; Ricard Farré; Sander DeJongh; Maria Vicario; Pieter Evenepoel. 2018. "Intestinal Barrier Function in Chronic Kidney Disease." Toxins 10, no. 7: 298.
Bidirectional interactions exist between the kidneys and the gut. These interactions are commonly referred to as the gut-kidney axis. Chronic kidney disease leads to disturbances of the gut ecosystem. Key features include the increase of protein fermentation at the expense of carbohydrate fermentation and a disrupted epithelial barrier. A disturbed gut ecosystem may contribute to the high burden of cardiovascular disease in patients with CKD. The present review discusses the impact of CKD on the gut microenvironment and provides an update as to how gut dysbiosis and a leaky gut may be linked to accelerated cardiovascular disease and hypertension.
B. Meijers; F. Jouret; P. Evenepoel. Linking gut microbiota to cardiovascular disease and hypertension: Lessons from chronic kidney disease. Pharmacological Research 2018, 133, 101 -107.
AMA StyleB. Meijers, F. Jouret, P. Evenepoel. Linking gut microbiota to cardiovascular disease and hypertension: Lessons from chronic kidney disease. Pharmacological Research. 2018; 133 ():101-107.
Chicago/Turabian StyleB. Meijers; F. Jouret; P. Evenepoel. 2018. "Linking gut microbiota to cardiovascular disease and hypertension: Lessons from chronic kidney disease." Pharmacological Research 133, no. : 101-107.
Jae Il Shin; Andreas Kronbichler; Jun Oh; Björn Meijers. Nephrotic Syndrome: Genetics, Mechanism, and Therapies. BioMed Research International 2018, 2018, 1 -2.
AMA StyleJae Il Shin, Andreas Kronbichler, Jun Oh, Björn Meijers. Nephrotic Syndrome: Genetics, Mechanism, and Therapies. BioMed Research International. 2018; 2018 ():1-2.
Chicago/Turabian StyleJae Il Shin; Andreas Kronbichler; Jun Oh; Björn Meijers. 2018. "Nephrotic Syndrome: Genetics, Mechanism, and Therapies." BioMed Research International 2018, no. : 1-2.
An increasing body of experimental and clinical evidence suggests that p-cresol sulfate and indoxyl sulfate contribute to the high cardiovascular burden in patients with chronic kidney disease. In a post hoc analysis on the HEMO trial, Shafi et al. failed to confirm an association between total p-cresol sulfate and indoxyl sulfate and cardiovascular outcomes in dialysis patients. Analytical issues and case-mix may explain the discrepant findings.
Pieter Evenepoel; Griet Glorieux; Björn Meijers. p -cresol sulfate and indoxyl sulfate: some clouds are gathering in the uremic toxin sky. Kidney International 2017, 92, 1323 -1324.
AMA StylePieter Evenepoel, Griet Glorieux, Björn Meijers. p -cresol sulfate and indoxyl sulfate: some clouds are gathering in the uremic toxin sky. Kidney International. 2017; 92 (6):1323-1324.
Chicago/Turabian StylePieter Evenepoel; Griet Glorieux; Björn Meijers. 2017. "p -cresol sulfate and indoxyl sulfate: some clouds are gathering in the uremic toxin sky." Kidney International 92, no. 6: 1323-1324.
Primary membranous nephropathy (MN) is the leading cause of nephrotic syndrome in adults. Discovery of several antibodies has contributed to an increased understanding of MN. Antibodies against the M-type phospholipase A2 receptor (PLA2R) are present in 50–100% with primary MN and are associated with a lower frequency of spontaneous remission. High levels are linked with a higher probability of treatment resistance, higher proteinuria, and impaired renal function, as well as a more rapid decline of kidney function during follow-up. Immunologic remission precedes reduction of proteinuria by months. Pretransplant evaluation of PLA2R antibodies is warranted to predict recurrence of disease following renal transplantation. Several risk alleles related to the PLA2R1 gene and within the HLA loci have been identified, whereas epitope spreading of PLA2R may predict treatment response. More recently, thrombospondin type 1 domain-containing 7A (THSD7A) antibodies have been discovered in primary MN. Several other rare antigens have been described, including antibodies against neutral endopeptidase as a cause of antenatal MN and circulating cationic bovine serum albumin as an antigen with implications in childhood MN. This review focuses on the progress with a special focus on diagnostic accuracy, predictive value, and treatment implications of the established and proposed antigens.
Andreas Kronbichler; Jun Oh; Björn Meijers; Gert Mayer; Jae Il Shin. Recent Progress in Deciphering the Etiopathogenesis of Primary Membranous Nephropathy. BioMed Research International 2017, 2017, 1 -14.
AMA StyleAndreas Kronbichler, Jun Oh, Björn Meijers, Gert Mayer, Jae Il Shin. Recent Progress in Deciphering the Etiopathogenesis of Primary Membranous Nephropathy. BioMed Research International. 2017; 2017 ():1-14.
Chicago/Turabian StyleAndreas Kronbichler; Jun Oh; Björn Meijers; Gert Mayer; Jae Il Shin. 2017. "Recent Progress in Deciphering the Etiopathogenesis of Primary Membranous Nephropathy." BioMed Research International 2017, no. : 1-14.
Little is known about potential differences in binding characteristics of protein-bound uremic toxins (PBUTs) in patients with chronic kidney disease (CKD) versus healthy controls. The question arises whether eventual differences are attributed to (i) the elevated levels of competing uremic toxins, and/or (ii) post-translational modifications of albumin. We evaluated the binding characteristics of hippuric acid (HA), indole-3-acetic acid (IAA), indoxyl sulfate (IS), and p-cresylsulfate (pCS) by deriving a binding curve in three distinct conditions: (i) serum from healthy controls (healthy serum), (ii) blank serum from hemodialysis patients (blank HD serum; i.e. cleared from uremic toxins), and (iii) non-treated serum from HD patients (HD serum). Additionally, the mutual binding competition of these uremic toxins was studied in blank HD in pairs. In both experiments, equilibrium dialysis (37 °C, 5 h) was used to separate the free and bound fractions of each PBUT. Free and total PBUT concentrations were quantified by an ultra-high performance liquid chromatography method with tandem mass spectrometer detection and the percentage protein binding (%PB) of each PBUT was calculated. For all four compounds, the binding capacity of healthy serum was higher than blank HD serum, which was comparable to non-treated HD serum, except for HA. The competition experiments revealed that at high uremic concentrations, mutual competition was observed for the strongly bound PBUTs IS and pCS. The %PB of the weakly bound HA and IAA was lower (trend) only for the addition to blank HD serum containing the strongly bound IS or pCS. There is an intrinsic impact on protein binding in uremia, revealing a lower binding capacity, as compared to healthy controls. Competitive binding is only relevant for the strongly bound PBUTs at high uremic concentrations. In addition, at least part of the effect on binding capacity can be attributed to post-translational modifications of albumin.
Olivier Deltombe; Henriette De Loor; Griet Glorieux; Annemieke Dhondt; Wim Van Biesen; Björn Meijers; Sunny Eloot. Exploring binding characteristics and the related competition of different protein-bound uremic toxins. Biochimie 2017, 139, 20 -26.
AMA StyleOlivier Deltombe, Henriette De Loor, Griet Glorieux, Annemieke Dhondt, Wim Van Biesen, Björn Meijers, Sunny Eloot. Exploring binding characteristics and the related competition of different protein-bound uremic toxins. Biochimie. 2017; 139 ():20-26.
Chicago/Turabian StyleOlivier Deltombe; Henriette De Loor; Griet Glorieux; Annemieke Dhondt; Wim Van Biesen; Björn Meijers; Sunny Eloot. 2017. "Exploring binding characteristics and the related competition of different protein-bound uremic toxins." Biochimie 139, no. : 20-26.
Mounting evidence indicates that a disturbed Wnt–β-catenin signaling may be involved in the pathogenesis of chronic kidney disease-mineral and bone and mineral disorder (CKD-MBD). Data on the impact of CKD on circulating levels of the Wnt antagonists sclerostin and Dickkopf related protein 1 (DKK1) and the relationship with laboratory parameters of CKD-MBD are incomplete. We analyzed serum sclerostin and DKK1 in 308 patients across the stages of chronic kidney disease (kDOQI stage 1–2 n = 41; CKD stage 3 n = 54; CKD stage 4–5 n = 54; hemodialysis n = 100; peritoneal dialysis n = 59) as well as in 49 healthy controls. We investigated associations with demographics, renal function, parameters of mineral metabolism including 25(OH) vitamin D, 1,25(OH)2 vitamin D, biointact fibroblast growth factor 23 (FGF23), and parathyroid hormone (PTH), and bone turnover markers. Serum sclerostin, but not DKK1, increases in more advanced stages of CKD and associates with PTH, phosphate, and 1,25(OH)2 vitamin D concentrations. Bone turnover markers are highest in hemodialysis patients presenting the combination of high PTH with low sclerostin level. Serum DKK1 levels are lower in CKD patients than in controls and are not associated with laboratory parameters of mineral metabolism. Interestingly, a direct association between DKK1 and platelet count was observed. In CKD, serum levels of the Wnt inhibitors DKK1 and sclerostin are unrelated, indicating different sites of origin and/ or different regulatory mechanisms. Sclerostin, as opposed to DKK1, may qualify as a biomarker of CKD-MBD, particularly in dialysis patients. DKK1 serum levels, remarkably, correlate almost uniquely with blood platelet counts.
Geert J. Behets; Liesbeth Viaene; Björn Meijers; Frank Blocki; Vincent M. Brandenburg; Anja Verhulst; Patrick C. D’Haese; Pieter Evenepoel. Circulating levels of sclerostin but not DKK1 associate with laboratory parameters of CKD-MBD. PLOS ONE 2017, 12, e0176411 .
AMA StyleGeert J. Behets, Liesbeth Viaene, Björn Meijers, Frank Blocki, Vincent M. Brandenburg, Anja Verhulst, Patrick C. D’Haese, Pieter Evenepoel. Circulating levels of sclerostin but not DKK1 associate with laboratory parameters of CKD-MBD. PLOS ONE. 2017; 12 (5):e0176411.
Chicago/Turabian StyleGeert J. Behets; Liesbeth Viaene; Björn Meijers; Frank Blocki; Vincent M. Brandenburg; Anja Verhulst; Patrick C. D’Haese; Pieter Evenepoel. 2017. "Circulating levels of sclerostin but not DKK1 associate with laboratory parameters of CKD-MBD." PLOS ONE 12, no. 5: e0176411.
Björn Meijers; Christoph Metalidis; Thomas Vanhove; Ruben Poesen; Dirk Kuypers; Pieter Evenepoel. A noninferiority trial comparing a heparin-grafted membrane plus citrate-containing dialysate versus regional citrate anticoagulation: results of the CiTED study. Nephrology Dialysis Transplantation 2017, 32, 707 -714.
AMA StyleBjörn Meijers, Christoph Metalidis, Thomas Vanhove, Ruben Poesen, Dirk Kuypers, Pieter Evenepoel. A noninferiority trial comparing a heparin-grafted membrane plus citrate-containing dialysate versus regional citrate anticoagulation: results of the CiTED study. Nephrology Dialysis Transplantation. 2017; 32 (4):707-714.
Chicago/Turabian StyleBjörn Meijers; Christoph Metalidis; Thomas Vanhove; Ruben Poesen; Dirk Kuypers; Pieter Evenepoel. 2017. "A noninferiority trial comparing a heparin-grafted membrane plus citrate-containing dialysate versus regional citrate anticoagulation: results of the CiTED study." Nephrology Dialysis Transplantation 32, no. 4: 707-714.