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Background The iron-based phosphate binder (PB), sucroferric oxyhydroxide (SFOH), is indicated to control serum phosphorus levels in patients with chronic kidney disease on dialysis. Methods This non-interventional, prospective, multicentre, cohort study conducted in seven European countries evaluated the safety and effectiveness of SFOH in dialysis patients with hyperphosphataemia in routine practice. Safety outcomes included adverse drug reactions (ADRs) and changes in iron-related parameters. SFOH effectiveness was evaluated by changes-from-baseline (BL) in serum phosphorus and percentage of patients achieving in-target phosphorus levels. Results The safety analysis set included 1365 patients (mean observation: 420.3 ± 239.3 days). Overall, 682 (50.0%) patients discontinued the study. Mean SFOH dose during the observation period was 1172.7 ± 539.9 mg (2.3 pills/day). Overall, 617 (45.2%) patients received concomitant PB(s) during SFOH treatment. ADRs and serious ADRs were observed for 531 (38.9%) and 26 (1.9%) patients. Most frequent ADRs were diarrhoea (194 patients, 14.2%) and discoloured faeces (128 patients, 9.4%). Diarrhoea generally occurred early during SFOH treatment and was mostly mild and transient. Small increases from BL in serum ferritin were observed (ranging from +12 to +75 µg/L). SFOH treatment was associated with serum phosphorus reductions (6.3 ± 1.6 mg/dL at BL versus 5.3 ± 1.8 mg/dL at Month 30; ΔBL: −1.0 mg/dL, P < 0.01). Percentage of patients achieving serum phosphorus ≤4.5 mg/dL increased from 12.0% at BL to 34.8% at Month 30, while the percentage achieving serum phosphorus ≤5.5 mg/dL increased from 29.9% to 63.0%. Conclusions SFOH has a favourable safety and tolerability profile in a real-world setting, consistent with results of the Phase 3 study. Moreover, SFOH improved serum phosphorus control with a low daily pill burden.
Marc G Vervloet; Ioannis N Boletis; Angel L M de Francisco; Philip A Kalra; Markus Ketteler; Piergiorgio Messa; Manuela Stauss-Grabo; Anja Derlet; Sebastian Walpen; Amandine Perrin; Linda H Ficociello; Jacques Rottembourg; Christoph Wanner; Jorge B Cannata-Andía; Denis Fouque. Real-world safety and effectiveness of sucroferric oxyhydroxide for treatment of hyperphosphataemia in dialysis patients: a prospective observational study. Clinical Kidney Journal 2021, 14, 1770 -1779.
AMA StyleMarc G Vervloet, Ioannis N Boletis, Angel L M de Francisco, Philip A Kalra, Markus Ketteler, Piergiorgio Messa, Manuela Stauss-Grabo, Anja Derlet, Sebastian Walpen, Amandine Perrin, Linda H Ficociello, Jacques Rottembourg, Christoph Wanner, Jorge B Cannata-Andía, Denis Fouque. Real-world safety and effectiveness of sucroferric oxyhydroxide for treatment of hyperphosphataemia in dialysis patients: a prospective observational study. Clinical Kidney Journal. 2021; 14 (7):1770-1779.
Chicago/Turabian StyleMarc G Vervloet; Ioannis N Boletis; Angel L M de Francisco; Philip A Kalra; Markus Ketteler; Piergiorgio Messa; Manuela Stauss-Grabo; Anja Derlet; Sebastian Walpen; Amandine Perrin; Linda H Ficociello; Jacques Rottembourg; Christoph Wanner; Jorge B Cannata-Andía; Denis Fouque. 2021. "Real-world safety and effectiveness of sucroferric oxyhydroxide for treatment of hyperphosphataemia in dialysis patients: a prospective observational study." Clinical Kidney Journal 14, no. 7: 1770-1779.
Vascular calcification is a prognostic marker for cardiovascular mortality in chronic kidney disease (CKD) patients. In these patients, magnesium balance is disturbed, mainly due to limited ultrafiltration of this mineral, changes in dietary intake and the use of diuretics. Observational studies in dialysis patients report that a higher blood magnesium concentration is associated with reduced risk to develop vascular calcification. Magnesium prevents osteogenic vascular smooth muscle cell transdifferentiation in in vitro and in vivo models. In addition, recent studies show that magnesium prevents calciprotein particle maturation, which may be the mechanism underlying the anti-calcification properties of magnesium. Magnesium is an essential protective factor in the calcification milieu, which helps to restore the mineral-buffering system that is overwhelmed by phosphate in CKD patients. The recognition that magnesium is a modifier of calciprotein particle maturation and mineralization of the extracellular matrix renders it a promising novel clinical tool to treat vascular calcification in CKD. Consequently, the optimal serum magnesium concentration for patients with CKD may be higher than in the general population.
Anique D Ter Braake; Marc G Vervloet; Jeroen H F De Baaij; Joost G J Hoenderop. Magnesium to prevent kidney disease–associated vascular calcification: crystal clear? Nephrology Dialysis Transplantation 2020, 1 .
AMA StyleAnique D Ter Braake, Marc G Vervloet, Jeroen H F De Baaij, Joost G J Hoenderop. Magnesium to prevent kidney disease–associated vascular calcification: crystal clear? Nephrology Dialysis Transplantation. 2020; ():1.
Chicago/Turabian StyleAnique D Ter Braake; Marc G Vervloet; Jeroen H F De Baaij; Joost G J Hoenderop. 2020. "Magnesium to prevent kidney disease–associated vascular calcification: crystal clear?" Nephrology Dialysis Transplantation , no. : 1.
Summary Background & aims Despite modern treatment, risk for cardiovascular disease and mortality in patients with chronic kidney disease (CKD) is unacceptably high. Observational studies have shown associations of magnesium with risk for several clinical outcomes in CKD of variable magnitude. The aim of this review is to provide a systematic overview and meta-analysis of longitudinal studies assessing the association of plasma magnesium concentration with clinically relevant outcomes in adult patients with chronic kidney disease, with a minimal follow-up of 6 months. Primary outcomes of interest were all-cause mortality, cardiovascular mortality, cardiovascular events, sudden death and hospitalisation. Methods The electronic databases PubMed, Embase and The Cochrane Library were searched using terms relating to plasma magnesium and CKD patients, and two authors independently selected eligible studies. Study quality was assessed according to the Newcastle–Ottawa Scale. Results of studies with a comparable magnesium exposure and outcome measure, were pooled using a random-effects meta-regression analysis. Results The search yielded 6156 records of which 33 studies, involving 348,059 patients, met the eligibility criteria. Finally, 22 studies could be included in the meta-analysis. Higher magnesium was associated with a lower risk for all-cause mortality (HR 0.90 [0.87–0.94] per 0.1 mmol/L increase of magnesium) and cardiovascular mortality and events (HR 0.85 [0.77–0.94] per 0.1 mmol/L). Conclusions Magnesium concentration is inversely associated with all-cause mortality and cardiovascular mortality and events. Therefore, increasing magnesium may improve risk in patients with chronic kidney disease. This meta-analysis forms a firm base for future prospective trials to test whether increasing plasma magnesium, indeed has beneficial effects on clinical outcomes.
Nicoline H.J. Leenders; Emma A. Vermeulen; Adriana J. van Ballegooijen; Tiny Hoekstra; Ralph de Vries; Joline W. Beulens; Marc G. Vervloet. The association between circulating magnesium and clinically relevant outcomes in patients with chronic kidney disease: A systematic review and meta-analysis. Clinical Nutrition 2020, 40, 3133 -3147.
AMA StyleNicoline H.J. Leenders, Emma A. Vermeulen, Adriana J. van Ballegooijen, Tiny Hoekstra, Ralph de Vries, Joline W. Beulens, Marc G. Vervloet. The association between circulating magnesium and clinically relevant outcomes in patients with chronic kidney disease: A systematic review and meta-analysis. Clinical Nutrition. 2020; 40 (5):3133-3147.
Chicago/Turabian StyleNicoline H.J. Leenders; Emma A. Vermeulen; Adriana J. van Ballegooijen; Tiny Hoekstra; Ralph de Vries; Joline W. Beulens; Marc G. Vervloet. 2020. "The association between circulating magnesium and clinically relevant outcomes in patients with chronic kidney disease: A systematic review and meta-analysis." Clinical Nutrition 40, no. 5: 3133-3147.
BACKGROUND: Hyperphosphatemia is associated with increased fibroblast growth factor 23 (FGF23), arterial calcification, and cardiovascular mortality. Effects of phosphate-lowering medication on vascular calcification and arterial stiffness in CKD remain uncertain.METHODS: To assess the effects of non-calcium-based phosphate binders on intermediate cardiovascular markers, we conducted a multicenter, double-blind trial, randomizing 278 participants with stage 3b or 4 CKD and serum phosphate >1.00 mmol/L (3.10 mg/dl) to 500 mg lanthanum carbonate or matched placebo thrice daily for 96 weeks. We analyzed the primary outcome, carotid-femoral pulse wave velocity, using a linear mixed effects model for repeated measures. Secondary outcomes included abdominal aortic calcification and serum and urine markers of mineral metabolism.RESULTS: A total of 138 participants received lanthanum and 140 received placebo (mean age 63.1 years; 69% male, 64% White). Mean eGFR was 26.6 ml/min per 1.73 m2; 45% of participants had diabetes and 32% had cardiovascular disease. Mean serum phosphate was 1.25 mmol/L (3.87 mg/dl), mean pulse wave velocity was 10.8 m/s, and 81.3% had abdominal aortic calcification at baseline. At 96 weeks, pulse wave velocity did not differ significantly between groups, nor did abdominal aortic calcification, serum phosphate, parathyroid hormone, FGF23, and 24-hour urinary phosphate. Serious adverse events occurred in 63 (46%) participants prescribed lanthanum and 66 (47%) prescribed placebo. Although recruitment to target was not achieved, additional analysis suggested this was unlikely to have significantly affected the principle findings.CONCLUSIONS: In patients with stage 3b/4 CKD, treatment with lanthanum over 96 weeks did not affect arterial stiffness or aortic calcification compared with placebo. These findings do not support the role of intestinal phosphate binders to reduce cardiovascular risk in patients with CKD who have normophosphatemia.CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Australian Clinical Trials Registry, ACTRN12610000650099.Copyright © 2020 by the American Society of Nephrology.
Marc Vervloet; Toussaint Nd; Pedagogos E; Lioufas Nm; Elder Gj; Pascoe Em; Badve Sv; Valks A; Block Ga; Boudville N; Cameron Jd; Campbell Kl; Chen Ssm; Faull Rj; Holt Sg; Jackson D; Jardine Mj; Johnson Dw; Kerr Pg; Lau Kk; Hooi Ls; Narayan O; Perkovic V; Polkinghorne Kr; Pollock Ca; Reidlinger D; Robison L; Walker Rj; Wang Aym; Hawley Cm; IMPROVE-CKD Trial Investigators. Faculty Opinions recommendation of A Randomized Trial on the Effect of Phosphate Reduction on Vascular End Points in CKD (IMPROVE-CKD). Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature 2020, 31, 1 .
AMA StyleMarc Vervloet, Toussaint Nd, Pedagogos E, Lioufas Nm, Elder Gj, Pascoe Em, Badve Sv, Valks A, Block Ga, Boudville N, Cameron Jd, Campbell Kl, Chen Ssm, Faull Rj, Holt Sg, Jackson D, Jardine Mj, Johnson Dw, Kerr Pg, Lau Kk, Hooi Ls, Narayan O, Perkovic V, Polkinghorne Kr, Pollock Ca, Reidlinger D, Robison L, Walker Rj, Wang Aym, Hawley Cm, IMPROVE-CKD Trial Investigators. Faculty Opinions recommendation of A Randomized Trial on the Effect of Phosphate Reduction on Vascular End Points in CKD (IMPROVE-CKD). Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature. 2020; 31 (11):1.
Chicago/Turabian StyleMarc Vervloet; Toussaint Nd; Pedagogos E; Lioufas Nm; Elder Gj; Pascoe Em; Badve Sv; Valks A; Block Ga; Boudville N; Cameron Jd; Campbell Kl; Chen Ssm; Faull Rj; Holt Sg; Jackson D; Jardine Mj; Johnson Dw; Kerr Pg; Lau Kk; Hooi Ls; Narayan O; Perkovic V; Polkinghorne Kr; Pollock Ca; Reidlinger D; Robison L; Walker Rj; Wang Aym; Hawley Cm; IMPROVE-CKD Trial Investigators. 2020. "Faculty Opinions recommendation of A Randomized Trial on the Effect of Phosphate Reduction on Vascular End Points in CKD (IMPROVE-CKD)." Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature 31, no. 11: 1.
Background Previous studies in patients on haemodialysis (HD) have shown an association of fibroblast growth factor 23 (FGF23) with all-cause mortality. As of yet, the result of FGF23 lowering on mortality is unknown in this population. Methods FGF23 was measured in a subset of 404 patients from the Dutch CONvective TRansport STudy (CONTRAST study) [a randomized trial in prevalent dialysis patients comparing HD and haemodiafiltration (HDF) with clinical outcome] at baseline and Months 6 and 12. A substantial decline of FGF23 change over time was anticipated in patients randomized to HDF since HDF induces higher dialytic clearance of FGF23. The associations of both baseline FGF23 and 6-months change in FGF23 with all-cause mortality were analysed. In addition, the difference in FGF23 change between HD and HDF was explored. Furthermore, the role of dialysis modality in the association between FGF23 change and outcome was analysed. Results No association was observed between quartiles of baseline FGF23 and all-cause mortality. Over 6 months, FGF23 declined in patients on HDF, whereas FGF23 remained stable in patients on HD. A decrease in FGF23 was not associated with improved survival compared with a stable FGF23 concentration. However, increasing FGF23 was associated with a significantly higher mortality risk, both in crude and fully adjusted models [hazard ratio 2.01 (95% confidence interval 1.30–3.09)]. Conclusion Whereas no association between a single value of FGF23 and all-cause mortality was found, increasing FGF23 concentrations did identify patients at risk for mortality. Since lowering FGF23 did not improve outcome, this study found no argument for therapeutically lowering FGF23.
Annet Bouma-De Krijger; Camiel L M De Roij Van Zuijdewijn; Menso J Nubé; Muriel P C Grooteman; Marc G Vervloet; P J Blankestijn; P M ter Wee; M L Bots; M A Van Den Dorpel; the CONTRAST Study Group. Change in FGF23 concentration over time and its association with all-cause mortality in patients treated with haemodialysis or haemodiafiltration. Clinical Kidney Journal 2020, 14, 891 -897.
AMA StyleAnnet Bouma-De Krijger, Camiel L M De Roij Van Zuijdewijn, Menso J Nubé, Muriel P C Grooteman, Marc G Vervloet, P J Blankestijn, P M ter Wee, M L Bots, M A Van Den Dorpel, the CONTRAST Study Group. Change in FGF23 concentration over time and its association with all-cause mortality in patients treated with haemodialysis or haemodiafiltration. Clinical Kidney Journal. 2020; 14 (3):891-897.
Chicago/Turabian StyleAnnet Bouma-De Krijger; Camiel L M De Roij Van Zuijdewijn; Menso J Nubé; Muriel P C Grooteman; Marc G Vervloet; P J Blankestijn; P M ter Wee; M L Bots; M A Van Den Dorpel; the CONTRAST Study Group. 2020. "Change in FGF23 concentration over time and its association with all-cause mortality in patients treated with haemodialysis or haemodiafiltration." Clinical Kidney Journal 14, no. 3: 891-897.
Fibroblast growth factor can be measured in clinical practice using ELISA, with acceptable validity. Different from many metabolites and minerals, its value can differ by a thousand-fold between individuals, largely because of differences in kidney function and dietary habits. This wide range complicates the proper interpretation of the concentration of FGF23, both in terms of the appropriateness of a given value for a given estimated GFR, and in terms of estimating the magnitude of risk for clinical events, with which FGF23 is clearly associated. In this narrative review, the impact of kidney function, exposure to phosphate from diet, and novel emerging factors that influence FGF23 concentrations are discussed. These and yet to define determinants of FGF23 question the causality of the association of FGF23 with hard (cardiovascular) endpoints, as observed in several epidemiological studies.
Marc G Vervloet. FGF23 measurement in chronic kidney disease: What is it really reflecting? Clinica Chimica Acta 2020, 505, 160 -166.
AMA StyleMarc G Vervloet. FGF23 measurement in chronic kidney disease: What is it really reflecting? Clinica Chimica Acta. 2020; 505 ():160-166.
Chicago/Turabian StyleMarc G Vervloet. 2020. "FGF23 measurement in chronic kidney disease: What is it really reflecting?" Clinica Chimica Acta 505, no. : 160-166.
Patients with chronic kidney disease (CKD) have a greatly enhanced risk of cardiovascular morbidity and mortality. Over the past decade it has come clear that a disturbed calcium-phosphate metabolism, with Fibroblast Growth Factor-23 as a key hormone, is partly accountable for this enhanced risk. Numerous studies have been performed unravelling FGF23s actions and its association with clinical conditions. As FGF23 is strongly associated with adverse outcome it may be a promising biomarker for risk prediction or, even more important, targeting FGF23 may be a strategy to improve patient outcome. This review elaborates on the clinical usefulness of FGF23 measurement. Firstly it discusses the reliability of the FGF23 measurement. Secondly, it evaluates whether FGF23 measurement may lead to improved patient risk classification. Finally, and possibly most importantly, this review evaluates if lowering of FGF23 should be a target for therapy. For this, the review discusses the current evidence indicating that FGF23 may be in the causal pathway to cardiovascular pathology, provides an overview of strategies to lower FGF23 levels and discusses the current evidence concerning the benefit of lowering FGF23.
Annet Bouma-De Krijger; Marc G. Vervloet. Fibroblast growth factor 23: are we ready to use it in clinical practice? Journal of Nephrology 2020, 33, 509 -527.
AMA StyleAnnet Bouma-De Krijger, Marc G. Vervloet. Fibroblast growth factor 23: are we ready to use it in clinical practice? Journal of Nephrology. 2020; 33 (3):509-527.
Chicago/Turabian StyleAnnet Bouma-De Krijger; Marc G. Vervloet. 2020. "Fibroblast growth factor 23: are we ready to use it in clinical practice?" Journal of Nephrology 33, no. 3: 509-527.
Background Fibroblast growth factor 23 (FGF23), a phosphate-regulating hormone that increases early in the course of chronic kidney disease (CKD), is associated with disease progression in patients with established CKD. Here we aimed to investigate the association between plasma FGF23 and new-onset CKD in the general population. Methods We included 5253 individuals without CKD who participated in the Prevention of Renal and Vascular Endstage Disease study, a prospective, population-based cohort. Multi-variable Cox regression was used to study the association of plasma C-terminal FGF23 with new-onset CKD, defined as a combined endpoint of estimated glomerular filtration rate (eGFR) <60 mL/min/ 1.73 m2, urinary 24-h albumin excretion (UAE) >30 mg/24 h or both, or with all-cause mortality. Results The median baseline FGF23 was 68 [interquartile range (IQR) 56–85] RU/mL, eGFR was 95 ± 13 mL/min/1.73 m2 and UAE was 7.8 (IQR 5.8–11.5) mg/24 h. After follow-up of 7.5 (IQR 7.2–8.0) years, 586 participants developed CKD and 214 participants died. A higher FGF23 level was associated with new-onset CKD, independent of risk factors for kidney disease and parameters of bone and mineral homoeostasis {fully adjusted hazard ratio (HR) 1.25 [95% confidence interval (CI) 1.10–1.44] per doubling of FGF23; P = 0.001}. In secondary analyses, FGF23 was independently associated with new-onset eGFR <60 mL/min/1.73 m2 [adjusted HR 1.28 (95% CI 1.00–1.62); P = 0.048] or with UAE >30 mg/24 h [adjusted HR 1.24 (95% CI 1.06–1.45); P = 0.01] individually. A higher FGF23 level was also associated with an increased risk of all-cause mortality [fully adjusted HR 1.30 (95% CI 1.03–1.63); P = 0.03]. Conclusions High FGF23 levels are associated with an increased risk of new-onset CKD and all-cause mortality in this prospective population-based cohort, independent of established CKD risk factors.
Maarten A De Jong; Michele F Eisenga; Adriana J Van Ballegooijen; Joline W J Beulens; Marc G Vervloet; Gerjan Navis; Ron T Gansevoort; Stephan J L Bakker; Martin H De Borst. Fibroblast growth factor 23 and new-onset chronic kidney disease in the general population: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study. Nephrology Dialysis Transplantation 2020, 36, 121 -128.
AMA StyleMaarten A De Jong, Michele F Eisenga, Adriana J Van Ballegooijen, Joline W J Beulens, Marc G Vervloet, Gerjan Navis, Ron T Gansevoort, Stephan J L Bakker, Martin H De Borst. Fibroblast growth factor 23 and new-onset chronic kidney disease in the general population: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study. Nephrology Dialysis Transplantation. 2020; 36 (1):121-128.
Chicago/Turabian StyleMaarten A De Jong; Michele F Eisenga; Adriana J Van Ballegooijen; Joline W J Beulens; Marc G Vervloet; Gerjan Navis; Ron T Gansevoort; Stephan J L Bakker; Martin H De Borst. 2020. "Fibroblast growth factor 23 and new-onset chronic kidney disease in the general population: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study." Nephrology Dialysis Transplantation 36, no. 1: 121-128.
BACKGROUND: Vitamin K antagonists (VKAs), although commonly used to reduce thromboembolic risk in atrial fibrillation, have been incriminated as probable cause of accelerated vascular calcification (VC) in patients on hemodialysis. Functional vitamin K deficiency may further contribute to their susceptibility for VC. We investigated the effect of vitamin K status on VC progression in 132 patients on hemodialysis with atrial fibrillation treated with VKAs or qualifying for anticoagulation.METHODS: Patients were randomized to VKAs with target INR 2-3, rivaroxaban 10 mg daily, or rivaroxaban 10 mg daily plus vitamin K2 2000 µg thrice weekly during 18 months. Systemic dp-ucMGP levels were quantified to assess vascular vitamin K status. Cardiac and thoracic aorta calcium scores and pulse wave velocity were measured to evaluate VC progression.RESULTS: Baseline dp-ucMGP was severely elevated in all groups. Initiation or continuation of VKAs further increased dp-ucMGP, whereas levels decreased in the rivaroxaban group and to a larger extent in the rivaroxaban+vitamin K2 group, but remained nevertheless elevated. Changes in coronary artery, thoracic aorta, and cardiac valve calcium scores and pulse wave velocity were not significantly different among the treatment arms. All cause death, stroke, and cardiovascular event rates were similar between the groups. Bleeding outcomes were not significantly different, except for a lower number of life-threatening and major bleeding episodes in the rivaroxaban arms versus the VKA arm.CONCLUSIONS: Withdrawal of VKAs and high-dose vitamin K2 improve vitamin K status in patients on hemodialysis, but have no significant favorable effect on VC progression. Severe bleeding complications may be lower with rivaroxaban than with VKAs.Copyright © 2020 by the American Society of Nephrology.
Marc Vervloet; De Vriese As; Caluwé R; Pyfferoen L; De Bacquer D; De Boeck K; Delanote J; Van Hoenacker P; Van Vlem B; Verbeke F. Faculty Opinions recommendation of Multicenter Randomized Controlled Trial of Vitamin K Antagonist Replacement by Rivaroxaban with or without Vitamin K2 in Hemodialysis Patients with Atrial Fibrillation: the Valkyrie Study. Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature 2020, 31, 1 .
AMA StyleMarc Vervloet, De Vriese As, Caluwé R, Pyfferoen L, De Bacquer D, De Boeck K, Delanote J, Van Hoenacker P, Van Vlem B, Verbeke F. Faculty Opinions recommendation of Multicenter Randomized Controlled Trial of Vitamin K Antagonist Replacement by Rivaroxaban with or without Vitamin K2 in Hemodialysis Patients with Atrial Fibrillation: the Valkyrie Study. Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature. 2020; 31 (1):1.
Chicago/Turabian StyleMarc Vervloet; De Vriese As; Caluwé R; Pyfferoen L; De Bacquer D; De Boeck K; Delanote J; Van Hoenacker P; Van Vlem B; Verbeke F. 2020. "Faculty Opinions recommendation of Multicenter Randomized Controlled Trial of Vitamin K Antagonist Replacement by Rivaroxaban with or without Vitamin K2 in Hemodialysis Patients with Atrial Fibrillation: the Valkyrie Study." Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature 31, no. 1: 1.
Secondary hyperparathyroidism (SHPT) is an important complication of advanced chronic kidney disease (CKD) in children, which is often difficult to treat with conventional therapy. The calcimimetic cinacalcet is an allosteric modulator of the calcium-sensing receptor. It has proven to be effective and safe in adults to suppress parathyroid hormone (PTH), but data on its use in children are limited. To date, studies in children only consist of two randomized controlled trials, nine uncontrolled interventional or observational studies, and case reports that report the efficacy of cinacalcet as a PTH-lowering compound. In 2017, the European Medical Agency approved the use of cinacalcet for the treatment of SHPT in children on dialysis in whom SHPT is not adequately controlled with standard therapy. Since evidence-based guidelines are so far lacking, we present a position statement on the use of cinacalcet in paediatric dialysis patients based on the available evidence and opinion of experts from the European Society for Paediatric Nephrology, Chronic Kidney Disease-Mineral and Bone Disorder and Dialysis Working Groups, and the ERA-EDTA. Given the limited available evidence the strength of these statements are weak to moderate, and must be carefully considered by the treating physician and adapted to individual patient needs as appropriate. Audit and research recommendations to study key outcome measures in paediatric dialysis patients receiving cinacalcet are suggested.
Justine Bacchetta; Claus Peter Schmitt; Gema Ariceta; Sevcan A Bakkaloglu; Jaap Groothoff; Mandy Wan; Marc Vervloet; Rukshana Shroff; Dieter Haffner; European Society for Paediatric Nephrology and the Chronic Kidney Disease-Mineral and Bone Disorders and Dialysis Working Group of the ERA-EDTA. Cinacalcet use in paediatric dialysis: a position statement from the European Society for Paediatric Nephrology and the Chronic Kidney Disease-Mineral and Bone Disorders Working Group of the ERA-EDTA. Nephrology Dialysis Transplantation 2019, 1 .
AMA StyleJustine Bacchetta, Claus Peter Schmitt, Gema Ariceta, Sevcan A Bakkaloglu, Jaap Groothoff, Mandy Wan, Marc Vervloet, Rukshana Shroff, Dieter Haffner, European Society for Paediatric Nephrology and the Chronic Kidney Disease-Mineral and Bone Disorders and Dialysis Working Group of the ERA-EDTA. Cinacalcet use in paediatric dialysis: a position statement from the European Society for Paediatric Nephrology and the Chronic Kidney Disease-Mineral and Bone Disorders Working Group of the ERA-EDTA. Nephrology Dialysis Transplantation. 2019; ():1.
Chicago/Turabian StyleJustine Bacchetta; Claus Peter Schmitt; Gema Ariceta; Sevcan A Bakkaloglu; Jaap Groothoff; Mandy Wan; Marc Vervloet; Rukshana Shroff; Dieter Haffner; European Society for Paediatric Nephrology and the Chronic Kidney Disease-Mineral and Bone Disorders and Dialysis Working Group of the ERA-EDTA. 2019. "Cinacalcet use in paediatric dialysis: a position statement from the European Society for Paediatric Nephrology and the Chronic Kidney Disease-Mineral and Bone Disorders Working Group of the ERA-EDTA." Nephrology Dialysis Transplantation , no. : 1.
Phosphate toxicity is a well-established phenomenon, especially in chronic kidney disease (CKD), where hyperphosphatemia is a frequent occurrence when CKD is advanced. Many therapeutic efforts are targeted at phosphate, and comprise dietary intervention, modifying dialysis schemes, treating uncontrolled hyperparathyroidism and importantly, phosphate binder therapy. Despite all these interventions, hyperphosphatemia persists in many, and its pathological influence is ongoing. In nephrological care, a somewhat neglected aspect of treatment-when attempts fail to lower exposure to a toxin like phosphate-is to explore the possibility of "anti-dotes". Indeed, quite a long list of factors modify, or are mediators of phosphate toxicity. Addressing these, especially when phosphate itself cannot be sufficiently controlled, may provide additional protection. In this narrative overview, several factors are discussed that may qualify as either such a modifier or mediator, that can be influenced by other means than simply lowering phosphate exposure. A wider scope when targeting phosphate-induced comorbidity in CKD, in particular cardiovascular disease, may alleviate the burden of disease that is the consequence of this potentially toxic mineral in CKD.
Marc Vervloet. Modifying Phosphate Toxicity in Chronic Kidney Disease. Toxins 2019, 11, 522 .
AMA StyleMarc Vervloet. Modifying Phosphate Toxicity in Chronic Kidney Disease. Toxins. 2019; 11 (9):522.
Chicago/Turabian StyleMarc Vervloet. 2019. "Modifying Phosphate Toxicity in Chronic Kidney Disease." Toxins 11, no. 9: 522.
Importance: Systematic differences between patients included in randomized clinical trials (RCTs) and the general patient population may influence the generalizability of RCT findings. Comprehensive national registries of patients with end-stage kidney disease who are undergoing dialysis provide a unique opportunity to compare trial and real-world patient cohorts.Objective: To determine if participants in large, multicenter dialysis trials were similar to the general population undergoing dialysis in terms of age, comorbidities, and mortality rate.Data Sources: MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials were systematically searched on January 6, 2017, for studies published from January 1, 2007, to December 31, 2016. Data sources were published manuscripts, supplementary material, and trial registration information. Data on the general population undergoing dialysis were derived from the US Renal Data System (USRDS). Data were analyzed from March 17 to July 22, 2018.Study Selection: Randomized clinical trials enrolling only participants undergoing dialysis for end-stage kidney disease with 100 or more adult participants from 2 or more sites.Data Extraction and Synthesis: Abstract screening and data extraction were performed independently by 2 researchers. Data were pooled using a random-effects model.Main Outcomes and Measures: The primary outcome was difference in mean age between the RCT and USRDS populations. Secondary outcomes included differences in mortality rate and comorbidities.Results: The search identified 189 RCTs, enrolling 80 104 participants. Compared with the 2011 USRDS population, RCT participants were younger (mean age, 58.9 years; 95% CI, 58.3-59.5 years vs 61.2 years; P Conclusions and Relevance: Participants in large, multicenter RCTs of patients with end-stage kidney disease undergoing dialysis are younger, have a different pattern of comorbidities, and have a lower mortality rate than the general population of patients undergoing dialysis. This finding has implications for the generalization of trial results to the broader patient population and for future trial design.
Marc Vervloet; Smyth B; Haber A; Trongtrakul K; Hawley C; Perkovic V; Woodward M; Jardine M. Faculty Opinions recommendation of Representativeness of Randomized Clinical Trial Cohorts in End-stage Kidney Disease: A Meta-analysis. Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature 2019, 1 .
AMA StyleMarc Vervloet, Smyth B, Haber A, Trongtrakul K, Hawley C, Perkovic V, Woodward M, Jardine M. Faculty Opinions recommendation of Representativeness of Randomized Clinical Trial Cohorts in End-stage Kidney Disease: A Meta-analysis. Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature. 2019; ():1.
Chicago/Turabian StyleMarc Vervloet; Smyth B; Haber A; Trongtrakul K; Hawley C; Perkovic V; Woodward M; Jardine M. 2019. "Faculty Opinions recommendation of Representativeness of Randomized Clinical Trial Cohorts in End-stage Kidney Disease: A Meta-analysis." Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature , no. : 1.
Marc G Vervloet. Chronic kidney disease-mineral and bone disorder: changing insights form changing parameters? Nephrology Dialysis Transplantation 2019, 35, 385 -389.
AMA StyleMarc G Vervloet. Chronic kidney disease-mineral and bone disorder: changing insights form changing parameters? Nephrology Dialysis Transplantation. 2019; 35 (3):385-389.
Chicago/Turabian StyleMarc G Vervloet. 2019. "Chronic kidney disease-mineral and bone disorder: changing insights form changing parameters?" Nephrology Dialysis Transplantation 35, no. 3: 385-389.
Background Etelcalcetide is an intravenous calcimimetic approved for treatment of secondary hyperparathyroidism (sHPT) in patients receiving hemodialysis. Besides lowering parathyroid hormone (PTH), etelcalcetide also significantly reduces fibroblast growth factor 23 (FGF23), but the mechanisms are unknown. Methods To investigate potential mediators of etelcalcetide-induced FGF23 reduction, we performed secondary analyses of the 26-week randomized trials that compared the effects on PTH of etelcalcetide (n = 509) versus placebo (n = 514) and etelcalcetide (n = 340) versus cinacalcet (n = 343) in adults with sHPT receiving hemodialysis. We analyzed changes in FGF23 in relation to changes in PTH, calcium, phosphate and bone turnover markers. We also investigated how concomitant treatments aimed at mitigating hypocalcemia altered the FGF23-lowering effects of etelcalcetide. Results Etelcalcetide reduced FGF23 [median % change (quartile 1–quartile 3)] from baseline to the end of the trial significantly more than placebo [–56% (–85 to –7) versus +2% (–40 to +65); P < 0.001] and cinacalcet [–68% (–87 to –26) versus –41% (–76 to +25); P < 0.001]. Reductions in FGF23 correlated strongly with reductions in calcium and phosphate, but not with PTH; correlations with bone turnover markers were inconsistent and of borderline significance. Increases in concomitant vitamin D administration partially attenuated the FGF23-lowering effect of etelcalcetide, but increased dialysate calcium concentration versus no increase and increased dose of calcium supplementation versus no increase did not attenuate the FGF23-lowering effects of etelcalcetide. Conclusion These data suggest that etelcalcetide potently lowers FGF23 in patients with sHPT receiving hemodialysis and that the effect remains detectable among patients who receive concomitant treatments aimed at mitigating treatment-associated decreases in serum calcium.
Myles Wolf; Geoffrey A Block; Glenn M Chertow; Kerry Cooper; Bruno Fouqueray; Sharon M Moe; Yan Sun; Holly Tomlin; Marc Vervloet; Rainer Oberbauer. Effects of etelcalcetide on fibroblast growth factor 23 in patients with secondary hyperparathyroidism receiving hemodialysis. Clinical Kidney Journal 2019, 13, 75 -84.
AMA StyleMyles Wolf, Geoffrey A Block, Glenn M Chertow, Kerry Cooper, Bruno Fouqueray, Sharon M Moe, Yan Sun, Holly Tomlin, Marc Vervloet, Rainer Oberbauer. Effects of etelcalcetide on fibroblast growth factor 23 in patients with secondary hyperparathyroidism receiving hemodialysis. Clinical Kidney Journal. 2019; 13 (1):75-84.
Chicago/Turabian StyleMyles Wolf; Geoffrey A Block; Glenn M Chertow; Kerry Cooper; Bruno Fouqueray; Sharon M Moe; Yan Sun; Holly Tomlin; Marc Vervloet; Rainer Oberbauer. 2019. "Effects of etelcalcetide on fibroblast growth factor 23 in patients with secondary hyperparathyroidism receiving hemodialysis." Clinical Kidney Journal 13, no. 1: 75-84.
Accumulating evidence indicates that the pathological changes of the endothelium may contribute to the development of cardiovascular complications in chronic kidney disease (CKD). Non-traditional risk factors related to CKD are associated with the incidence of cardiovascular disease, but their role in uraemic endothelial dysfunction has often been disregarded. In this context, soluble α-Klotho and vitamin D are of importance to maintain endothelial integrity, but their concentrations decline in CKD, thereby contributing to the dysfunction of the endothelial lining. These hormonal disturbances are accompanied by an increment of circulating fibroblast growth factor-23 and phosphate, both exacerbating endothelial toxicities. Furthermore, impaired renal function leads to an increment of inflammatory mediators, reactive oxygen species and uraemic toxins that further aggravate the endothelial abnormalities and in turn also inhibit the regeneration of disrupted endothelial lining. Here, we highlight the distinct endothelial alterations mediated by the abovementioned non-traditional risk factors as demonstrated in experimental studies and connect these to pathological changes in CKD patients, which are driven by endothelial disturbances, other than atherosclerosis. In addition, we describe therapeutic strategies that may promote restoration of endothelial abnormalities by modulating imbalanced mineral homoeostasis and attenuate the impact of uraemic retention molecules, inflammatory mediators and reactive oxygen species. A clinical perspective on endothelial dysfunction in CKD may translate into reduced structural and functional abnormalities of the vessel wall in CKD, and ultimately improved cardiovascular disease.
Marc Vila Cuenca; Peter L Hordijk; Marc G Vervloet. Most exposed: the endothelium in chronic kidney disease. Nephrology Dialysis Transplantation 2019, 35, 1478 -1487.
AMA StyleMarc Vila Cuenca, Peter L Hordijk, Marc G Vervloet. Most exposed: the endothelium in chronic kidney disease. Nephrology Dialysis Transplantation. 2019; 35 (9):1478-1487.
Chicago/Turabian StyleMarc Vila Cuenca; Peter L Hordijk; Marc G Vervloet. 2019. "Most exposed: the endothelium in chronic kidney disease." Nephrology Dialysis Transplantation 35, no. 9: 1478-1487.
Background High concentrations of both phosphate and fibroblast growth factor 23 (FGF23) observed in chronic kidney disease (CKD) are associated with an increased risk of cardiovascular morbidity and mortality. Pulse wave velocity (PWV) is a surrogate marker for cardiovascular events and all-cause mortality. It is not known whether a reduction of FGF23 or phosphate alters cardiovascular risk. Sevelamer has shown to have the ability to reduce both phosphate and FGF23 concentrations. Furthermore, reduction of PWV is reported with sevelamer use as well, but it is unclear if this is mediated by decline of phosphate or FGF23. We investigated if sevelamer induced a decline in PWV and if this was associated with a reduction in FGF23. Methods In all, 24 normophosphataemic CKD Stage 3 patients started treatment with a fixed dose of sevelamer-carbonate (Renvela®) 2.4 g twice daily, with their usual diet for 8 weeks in a single-arm study. PWV was measured and blood samples were obtained before, during and after washout of treatment with sevelamer. Vascular calcification was quantified using the Kauppila Index (KI). The primary outcome was the change of PWV from baseline to 8 weeks of treatment and the secondary endpoint was the difference of FGF23 following treatment with sevelamer. One of the linear mixed models was used to analyse the association between treatment and outcome. Mediation analysis was performed as a sensitivity analysis. The study was registered in the Dutch trial register (http://www.trialregister.nl: NTR2383). Results A total of 18 patients completed 8 weeks of treatment with sevelamer and were analysed. Overall, treatment with sevelamer did not induce a significant reduction of PWV (β = −0.36, P = 0.12). However, in patients with less vascular calcification (lower KI score), there was a statistically significant reduction of PWV, adjusted for mean arterial pressure, after treatment (β = 0.63, P = 0.02). Addition of FGF23 to the model did not alter this association. Mediation analysis yielded similar results. FGF23 did not decrease during treatment with sevelamer. Conclusion In this short-term pilot study in normophosphataemic CKD patients, treatment with sevelamer did not improve PWV. In subgroup analysis, however, PWV improved in patients with no or limited abdominal aorta calcifications. This was not associated with a decline of FGF23.
Annet Bouma-De Krijger; Frans J Van Ittersum; Tiny Hoekstra; Pieter M Ter Wee; Marc G Vervloet. Short-term effects of sevelamer-carbonate on fibroblast growth factor 23 and pulse wave velocity in patients with normophosphataemic chronic kidney disease Stage 3. Clinical Kidney Journal 2019, 12, 678 -685.
AMA StyleAnnet Bouma-De Krijger, Frans J Van Ittersum, Tiny Hoekstra, Pieter M Ter Wee, Marc G Vervloet. Short-term effects of sevelamer-carbonate on fibroblast growth factor 23 and pulse wave velocity in patients with normophosphataemic chronic kidney disease Stage 3. Clinical Kidney Journal. 2019; 12 (5):678-685.
Chicago/Turabian StyleAnnet Bouma-De Krijger; Frans J Van Ittersum; Tiny Hoekstra; Pieter M Ter Wee; Marc G Vervloet. 2019. "Short-term effects of sevelamer-carbonate on fibroblast growth factor 23 and pulse wave velocity in patients with normophosphataemic chronic kidney disease Stage 3." Clinical Kidney Journal 12, no. 5: 678-685.
Importance: Patients with chronic kidney disease have impaired vitamin D activation and elevated cardiovascular risk. Observational studies in patients treated with hemodialysis showed that the use of active vitamin D sterols was associated with lower risk of all-cause mortality, regardless of parathyroid hormone levels.Objective: To determine whether vitamin D receptor activators reduce cardiovascular events and mortality in patients without secondary hyperparathyroidism undergoing hemodialysis.Design, Setting, and Participants: Randomized, open-label, blinded end point multicenter study of 1289 patients in 207 dialysis centers in Japan. The study included 976 patients receiving maintenance hemodialysis with serum intact parathyroid hormone levels less than or equal to 180 pg/mL. The first and last participants were enrolled on August 18, 2008, and January 26, 2011, respectively. The final date of follow-up was April 4, 2015.Interventions: Treatment with 0.5 μg of oral alfacalcidol per day (intervention group; n = 495) vs treatment without vitamin D receptor activators (control group; n = 481).Main Outcomes and Measures: The primary outcome was a composite measure of fatal and nonfatal cardiovascular events, including myocardial infarctions, hospitalizations for congestive heart failure, stroke, aortic dissection/rupture, amputation of lower limb due to ischemia, and cardiac sudden death; coronary revascularization; and leg artery revascularization during 48 months of follow-up. The secondary outcome was all-cause death.Results: Among 976 patients who were randomized from 108 dialysis centers, 964 patients were included in the intention-to-treat analysis (median age, 65 years; 386 women [40.0%]), and 944 (97.9%) completed the trial. During follow-up (median, 4.0 years), the primary composite outcome of cardiovascular events occurred in 103 of 488 patients (21.1%) in the intervention group and 85 of 476 patients (17.9%) in the control group (absolute difference, 3.25% [95% CI, -1.75% to 8.24%]; hazard ratio, 1.25 [95% CI, 0.94-1.67]; P = .13). There was no significant difference in the secondary outcome of all-cause mortality between the groups (18.2% vs 16.8%, respectively; hazard ratio, 1.12 [95% CI, 0.83-1.52]; P = .46). Of the 488 participants in the intervention group, 199 (40.8%) experienced serious adverse events that were classified as cardiovascular, 64 (13.1%) experienced adverse events classified as infection, and 22 (4.5%) experienced malignancy-related serious adverse events. Of 476 participants in the control group, 191 (40.1%) experienced cardiovascular-related serious adverse events, 63 (13.2%) experienced infection-related serious adverse events, and 21 (4.4%) experienced malignancy-related adverse events.Conclusions and Relevance: Among patients without secondary hyperparathyroidism undergoing maintenance hemodialysis, oral alfacalcidol compared with usual care did not reduce the risk of a composite measure of select...
Marc Vervloet; J-DAVID Investigators; Shoji T; Inaba M; Fukagawa M; Ando R; Emoto M; Fujii H; Fujimori A; Fukui M; Hase H; Hashimoto T; Hirakata H; Honda H; Hosoya T; Ikari Y; Inaguma D; Inoue T; Isaka Y; Iseki K; Ishimura E; Itami N; Ito C; Kakuta T; Kawai T; Kawanishi H; Kobayashi S; Kumagai J; Maekawa K; Masakane I; Minakuchi J; Mitsuiki K; Mizuguchi T; Morimoto S; Murohara T; Nakatani T; Negi S; Nishi S; Nishikawa M; Ogawa T; Ohta K; Ohtake T; Okamura M; Okuno S; Shigematsu T; Sugimoto T; Suzuki M; Tahara H; Takemoto Y; Tanaka K; Tominaga Y; Tsubakihara Y; Tsujimoto Y; Tsuruya K; Ueda S; Watanabe Y; Yamagata K; Yamakawa T; Yano S; Yokoyama K; Yorioka N; Yoshiyama M; Nishizawa Y. Faculty Opinions recommendation of Effect of Oral Alfacalcidol on Clinical Outcomes in Patients Without Secondary Hyperparathyroidism Receiving Maintenance Hemodialysis: The J-DAVID Randomized Clinical Trial. Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature 2019, 320, 1 .
AMA StyleMarc Vervloet, J-DAVID Investigators, Shoji T, Inaba M, Fukagawa M, Ando R, Emoto M, Fujii H, Fujimori A, Fukui M, Hase H, Hashimoto T, Hirakata H, Honda H, Hosoya T, Ikari Y, Inaguma D, Inoue T, Isaka Y, Iseki K, Ishimura E, Itami N, Ito C, Kakuta T, Kawai T, Kawanishi H, Kobayashi S, Kumagai J, Maekawa K, Masakane I, Minakuchi J, Mitsuiki K, Mizuguchi T, Morimoto S, Murohara T, Nakatani T, Negi S, Nishi S, Nishikawa M, Ogawa T, Ohta K, Ohtake T, Okamura M, Okuno S, Shigematsu T, Sugimoto T, Suzuki M, Tahara H, Takemoto Y, Tanaka K, Tominaga Y, Tsubakihara Y, Tsujimoto Y, Tsuruya K, Ueda S, Watanabe Y, Yamagata K, Yamakawa T, Yano S, Yokoyama K, Yorioka N, Yoshiyama M, Nishizawa Y. Faculty Opinions recommendation of Effect of Oral Alfacalcidol on Clinical Outcomes in Patients Without Secondary Hyperparathyroidism Receiving Maintenance Hemodialysis: The J-DAVID Randomized Clinical Trial. Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature. 2019; 320 (22):1.
Chicago/Turabian StyleMarc Vervloet; J-DAVID Investigators; Shoji T; Inaba M; Fukagawa M; Ando R; Emoto M; Fujii H; Fujimori A; Fukui M; Hase H; Hashimoto T; Hirakata H; Honda H; Hosoya T; Ikari Y; Inaguma D; Inoue T; Isaka Y; Iseki K; Ishimura E; Itami N; Ito C; Kakuta T; Kawai T; Kawanishi H; Kobayashi S; Kumagai J; Maekawa K; Masakane I; Minakuchi J; Mitsuiki K; Mizuguchi T; Morimoto S; Murohara T; Nakatani T; Negi S; Nishi S; Nishikawa M; Ogawa T; Ohta K; Ohtake T; Okamura M; Okuno S; Shigematsu T; Sugimoto T; Suzuki M; Tahara H; Takemoto Y; Tanaka K; Tominaga Y; Tsubakihara Y; Tsujimoto Y; Tsuruya K; Ueda S; Watanabe Y; Yamagata K; Yamakawa T; Yano S; Yokoyama K; Yorioka N; Yoshiyama M; Nishizawa Y. 2019. "Faculty Opinions recommendation of Effect of Oral Alfacalcidol on Clinical Outcomes in Patients Without Secondary Hyperparathyroidism Receiving Maintenance Hemodialysis: The J-DAVID Randomized Clinical Trial." Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature 320, no. 22: 1.
Background Secondary hyperparathyroidism (sHPT), a common complication of chronic kidney disease, is characterized by elevated serum parathyroid hormone (PTH). Etelcalcetide is an intravenous calcimimetic that increases sensitivity of the calcium-sensing receptor to calcium and decreases PTH secretion. This open-label extension (OLE) trial evaluated the long-term effects of etelcalcetide for sHPT treatment in patients receiving hemodialysis. Methods This 52-week, multicenter, single-arm OLE enrolled patients from three parent trials: two randomized, double-blind, placebo-controlled trials and one open-label, single-arm, ‘switch’ study from cinacalcet to etelcalcetide. The primary endpoint was to investigate the nature, frequency, severity and relation to treatment of all adverse events (AEs) reported throughout the trial. Secondary endpoints included the proportion of patients with >30% reduction from baseline in PTH and the percentage change from baseline in PTH, albumin-corrected calcium (Ca), phosphate (P) and the calcium–phosphate product (Ca × P). ClinicalTrials.gov identifier: NCT01785875; Amgen study: 20120231. Results Overall, 89.8% of the patients experienced one or more treatment-emergent AE. The most common were decreased blood Ca (43.3%), diarrhea (10.8%), vomiting (10.4%) and nausea (9.6%); symptomatic hypocalcemia occurred in 3.7% of the patients. Approximately 68% of patients achieved >30% reduction in PTH, and ∼56% achieved PTH ≤300 pg/mL. Mean percent changes from baseline ranged from −25.4% to −26.1% for PTH, −8.3% to −9.1% for Ca, −3.6% to −4.1% for P and −12.0% to −12.6% for Ca × P. Conclusions Etelcalcetide effectively lowered PTH and its effect was sustained, while no new safety concerns emerged over a 1-year treatment period.
David A Bushinsky; Glenn M Chertow; Sunfa Cheng; Hongjie Deng; Nelson Kopyt; Kevin J Martin; Anjay Rastogi; Pablo Ureña-Torres; Marc Vervloet; Geoffrey A Block. One-year safety and efficacy of intravenous etelcalcetide in patients on hemodialysis with secondary hyperparathyroidism. Nephrology Dialysis Transplantation 2019, 35, 1769 -1778.
AMA StyleDavid A Bushinsky, Glenn M Chertow, Sunfa Cheng, Hongjie Deng, Nelson Kopyt, Kevin J Martin, Anjay Rastogi, Pablo Ureña-Torres, Marc Vervloet, Geoffrey A Block. One-year safety and efficacy of intravenous etelcalcetide in patients on hemodialysis with secondary hyperparathyroidism. Nephrology Dialysis Transplantation. 2019; 35 (10):1769-1778.
Chicago/Turabian StyleDavid A Bushinsky; Glenn M Chertow; Sunfa Cheng; Hongjie Deng; Nelson Kopyt; Kevin J Martin; Anjay Rastogi; Pablo Ureña-Torres; Marc Vervloet; Geoffrey A Block. 2019. "One-year safety and efficacy of intravenous etelcalcetide in patients on hemodialysis with secondary hyperparathyroidism." Nephrology Dialysis Transplantation 35, no. 10: 1769-1778.
Magnesium is essential for many physiological functions in the human body. Its homeostasis involves dietary intake, absorption, uptake and release from bone, swifts between the intra- and extracellular compartment, and renal excretion. Renal excretion is mainly responsible for regulation of magnesium balance. In chronic kidney disease (CKD), for a long time the general policy has been limiting magnesium intake. However, this may not be appropriate for many patients. The reference ranges for magnesium are not necessarily optimal concentrations, and risks for insufficient magnesium intake exist in patients with CKD. In recent years, many observational studies have shown that higher (in the high range of “normal” or slightly above) magnesium concentrations are associated with better survival in CKD cohorts. This review gives an overview of epidemiological associations between magnesium and overall and cardiovascular survival in patients with CKD. In addition, potential mechanisms explaining the protective role of magnesium in clinical cardiovascular outcomes are described by reviewing evidence from in vitro studies, animal studies, and human intervention studies with non-clinical endpoints. This includes the role of magnesium in cardiac arrhythmia, heart failure, arterial calcification, and endothelial dysfunction. Possible future implications will be addressed, which will need prospective clinical trials with relevant clinical endpoints before these can be adopted in clinical practice.
Nicoline H. J. Leenders; Marc G. Vervloet. Magnesium: A Magic Bullet for Cardiovascular Disease in Chronic Kidney Disease? Nutrients 2019, 11, 455 .
AMA StyleNicoline H. J. Leenders, Marc G. Vervloet. Magnesium: A Magic Bullet for Cardiovascular Disease in Chronic Kidney Disease? Nutrients. 2019; 11 (2):455.
Chicago/Turabian StyleNicoline H. J. Leenders; Marc G. Vervloet. 2019. "Magnesium: A Magic Bullet for Cardiovascular Disease in Chronic Kidney Disease?" Nutrients 11, no. 2: 455.
Background Kidney transplant recipients (KTRs) experience substantial survival benefit compared with dialysis patients. However, their mortality and graft failure risk remain high. KTRs are often low in micronutrient status, including vitamins D and K. We investigated the association of both vitamins D and K status, and vitamin D treatment with all-cause mortality and death-censored graft failure. Methods We studied 461 KTRs from a single-centre study at median 6.1 years after transplantation. At baseline, vitamins D and K concentrations were measured by 25-hydroxyvitamin D [25(OH)D] and dephosphorylated uncarboxylated matrix gla protein (dp-ucMGP) and patients were categorized into: 25(OH)D <50/≥50 nmol/L and median dp-ucMGP <1057/≥1057 pmol/L. Results Mean age was 52 ± 12 years, and 122 KTRs (26%) had low vitamins D and K status. During median 9.8 years follow-up, 128 patients (28%) died and 48 (10%) developed death-censored graft failure. Low vitamins D and K status was associated with 2.33 (1.26–4.30) [hazard ratio (95% confidence interval)] increased mortality risk and 3.25 (1.17–9.08) increased graft failure risk compared with KTR with 25(OH)D ≥50 nmol/L and dp-ucMGP <1057 pmol/L. Dp-ucMGP was strongly associated with mortality (per 500 pmol/L increase): 1.41 (1.08–1.41) for vitamin D treatment versus no treatment 1.07 (0.97–1.18), and graft failure 1.71 (1.17–2.49) for vitamin D treatment versus 1.19 (1.05–1.36) no treatment, P-interaction <0.07 for vitamin D treatment (n = 44). Conclusions Combined vitamins D and K deficiency are highly prevalent and are associated with increased mortality and graft failure risk compared with high vitamins D and K status. Low vitamin K status was strongly associated with an increased risk of premature mortality and graft failure for patients treated with vitamin D versus no vitamin D treatment.
Adriana J Van Ballegooijen; Joline W J Beulens; Charlotte A Keyzer; Gerjan J Navis; Stefan P Berger; Martin De Borst; Marc G Vervloet; Stephan J L Bakker. Joint association of vitamins D and K status with long-term outcomes in stable kidney transplant recipients. Nephrology Dialysis Transplantation 2019, 35, 706 -714.
AMA StyleAdriana J Van Ballegooijen, Joline W J Beulens, Charlotte A Keyzer, Gerjan J Navis, Stefan P Berger, Martin De Borst, Marc G Vervloet, Stephan J L Bakker. Joint association of vitamins D and K status with long-term outcomes in stable kidney transplant recipients. Nephrology Dialysis Transplantation. 2019; 35 (4):706-714.
Chicago/Turabian StyleAdriana J Van Ballegooijen; Joline W J Beulens; Charlotte A Keyzer; Gerjan J Navis; Stefan P Berger; Martin De Borst; Marc G Vervloet; Stephan J L Bakker. 2019. "Joint association of vitamins D and K status with long-term outcomes in stable kidney transplant recipients." Nephrology Dialysis Transplantation 35, no. 4: 706-714.