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A bone biopsy with prior tetracycline labeling is the gold standard to diagnose renal osteodystrophy. In cases of missing tetracycline labels, it is still paramount to gain clinically relevant information from the extracted bone sample, by evaluating the static histomorphometry. This study investigates the diagnostic performance of static histomorphometry for the evaluation of high and low bone turnover. Transiliac bone biopsies taken pre- or post- kidney transplantation, of sufficient quality for a full histomorphometric analysis were included (n = 205). The cohort was randomly split to provide separate exploration and validation subsets. Diagnostic performance was evaluated by area under the receiver operator characteristics curve (AUC). All histomorphometric parameters were significantly different across categories of low (24%), normal (60%), and high (16%) bone turnover, and all were significant predictors of both high and low bone turnover (AUC 0.71–0.84). Diagnostic performance was very good for high turnover, as a combination of static parameters resulted in negative and positive predictive values (NPV and PPV) of 80% and 96%, respectively. For low turnover, the combined model resulted in PPV of 71% and NPV of 82%. We conclude that in the absence of tetracycline labels, static histomorphometry provide an acceptable alternative for a diagnosis of bone turnover in renal osteodystrophy.
Hanne Skou Jørgensen; Geert Behets; Liesbeth Viaene; Bert Bammens; Kathleen Claes; Bjorn Meijers; Maarten Naesens; Ben Sprangers; Dirk Kuypers; Patrick C. D'Haese; Pieter Evenepoel. Static HISTOMORPHOMETRY allows for a diagnosis of bone turnover in renal OSTEODYSTROPHY in the absence of tetracycline labels. Bone 2021, 152, 116066 .
AMA StyleHanne Skou Jørgensen, Geert Behets, Liesbeth Viaene, Bert Bammens, Kathleen Claes, Bjorn Meijers, Maarten Naesens, Ben Sprangers, Dirk Kuypers, Patrick C. D'Haese, Pieter Evenepoel. Static HISTOMORPHOMETRY allows for a diagnosis of bone turnover in renal OSTEODYSTROPHY in the absence of tetracycline labels. Bone. 2021; 152 ():116066.
Chicago/Turabian StyleHanne Skou Jørgensen; Geert Behets; Liesbeth Viaene; Bert Bammens; Kathleen Claes; Bjorn Meijers; Maarten Naesens; Ben Sprangers; Dirk Kuypers; Patrick C. D'Haese; Pieter Evenepoel. 2021. "Static HISTOMORPHOMETRY allows for a diagnosis of bone turnover in renal OSTEODYSTROPHY in the absence of tetracycline labels." Bone 152, no. : 116066.
The European Renal Association–European Dialysis and Transplant Association (ERA-EDTA) CKD-MBD working group, in collaboration with the Committee of Scientific Advisors of the International Osteoporosis Foundation, published a position paper for the diagnosis and management of osteoporosis in patients with CKD stages 4–5D (eGFR < 30 ml/min 1.73 m2). The present article reports and summarizes the main recommendations included in this 2021 document. The following areas are reviewed: diagnosis of osteoporosis; risk factors for fragility fractures; fracture risk assessment; intervention thresholds for pharmacological intervention; general and pharmacological management of osteoporosis; monitoring of treatment, and systems of care, all in patients with CKD stages 4–5D. Guidance is provided for clinicians caring for CKD stages 4–5D patients with osteoporosis, allowing for a pragmatic individualized diagnostic and therapeutic approach as an alternative to current variations in care and treatment nihilism.
P. Evenepoel; J. Cunningham; S. Ferrari; M. Haarhaus; M.K. Javaid; M.-H. Lafage-Proust; D. Prieto-Alhambra; P.U. Torres; J. Cannata-Andia; On Behalf Of The European Renal Osteodystrophy (Eurod) Workgroup; an initiative of the CKD-MBD working group of the ERA-EDTA; and the committee of Scientific Advisors and National Societies of the IOF. Diagnosis and management of osteoporosis in chronic kidney disease stages 4 to 5D: a call for a shift from nihilism to pragmatism. Osteoporosis International 2021, 1 -9.
AMA StyleP. Evenepoel, J. Cunningham, S. Ferrari, M. Haarhaus, M.K. Javaid, M.-H. Lafage-Proust, D. Prieto-Alhambra, P.U. Torres, J. Cannata-Andia, On Behalf Of The European Renal Osteodystrophy (Eurod) Workgroup, an initiative of the CKD-MBD working group of the ERA-EDTA, and the committee of Scientific Advisors and National Societies of the IOF. Diagnosis and management of osteoporosis in chronic kidney disease stages 4 to 5D: a call for a shift from nihilism to pragmatism. Osteoporosis International. 2021; ():1-9.
Chicago/Turabian StyleP. Evenepoel; J. Cunningham; S. Ferrari; M. Haarhaus; M.K. Javaid; M.-H. Lafage-Proust; D. Prieto-Alhambra; P.U. Torres; J. Cannata-Andia; On Behalf Of The European Renal Osteodystrophy (Eurod) Workgroup; an initiative of the CKD-MBD working group of the ERA-EDTA; and the committee of Scientific Advisors and National Societies of the IOF. 2021. "Diagnosis and management of osteoporosis in chronic kidney disease stages 4 to 5D: a call for a shift from nihilism to pragmatism." Osteoporosis International , no. : 1-9.
Patients with chronic kidney disease (CKD) experience an increased fracture risk due to impaired bone quality and quantity. Low bone mineral density (BMD) predicts fracture risk in all CKD stages, including advanced CKD (CKD G4-5D). Pharmacological therapy improves BMD and reduces fracture risk in moderate CKD. Its efficacy in advanced CKD remains to be determined, although pilot studies suggest a positive effect on BMD. Currently, antiresorptive agents are the most commonly prescribed drugs for prevention and therapy of osteoporosis. Their use in advanced CKD has been limited by lack of large clinical trials and fear of causing kidney dysfunction and adynamic bone disease (ABD). In recent decades, ABD has evolved as the most predominant form of renal osteodystrophy, commonly associated with poor outcomes, including premature mortality and progression of vascular calcification. Evolving evidence indicates that reduction of bone turnover by parathyroidectomy or pharmacological therapies, such as calcimimetics and antiresorptive agents, are not associated with premature mortality or accelerated vascular calcification in CKD. In contrast, chronic inflammation, oxidative stress, malnutrition, and diabetes can induce low bone turnover and associate with poor prognosis. Thus, the conditions causing suppression of bone turnover rather than the low bone turnover per se may account for the perceived association with outcomes. Anabolic treatment, in contrast, has been suggested to improve turnover and bone mass in patients with advanced CKD and low bone turnover, however, uncertainty about safety even exceeds that of antiresorptive agents. Here, we critically review the pathophysiologic concept of ABD and discuss the impact of low bone turnover on safety and efficacy of anti-osteoporosis pharmacotherapy in advanced CKD.
Mathias Haarhaus; Pieter Evenepoel. Differentiating the causes of adynamic bone in advanced chronic kidney disease informs osteoporosis treatment. Kidney International 2021, 100, 546 -558.
AMA StyleMathias Haarhaus, Pieter Evenepoel. Differentiating the causes of adynamic bone in advanced chronic kidney disease informs osteoporosis treatment. Kidney International. 2021; 100 (3):546-558.
Chicago/Turabian StyleMathias Haarhaus; Pieter Evenepoel. 2021. "Differentiating the causes of adynamic bone in advanced chronic kidney disease informs osteoporosis treatment." Kidney International 100, no. 3: 546-558.
The General Data Protection Regulation (GDPR) became binding law in the European Union Member States in 2018, as a step toward harmonizing personal data protection legislation in the European Union. The Regulation governs almost all types of personal data processing, hence, also, those pertaining to biomedical research. The purpose of this article is to highlight the main practical issues related to data and biological sample sharing that biomedical researchers face regularly, and to specify how these are addressed in the context of GDPR, after consulting with ethics/legal experts. We identify areas in which clarifications of the GDPR are needed, particularly those related to consent requirements by study participants. Amendments should target the following: (1) restricting exceptions based on national laws and increasing harmonization, (2) confirming the concept of broad consent, and (3) defining a roadmap for secondary use of data. These changes will be achieved by acknowledged learned societies in the field taking the lead in preparing a document giving guidance for the optimal interpretation of the GDPR, which will be finalized following a period of commenting by a broad multistakeholder audience. In parallel, promoting engagement and education of the public in the relevant issues (such as different consent types or residual risk for re-identification), on both local/national and international levels, is considered critical for advancement. We hope that this article will open this broad discussion involving all major stakeholders, toward optimizing the GDPR and allowing a harmonized transnational research approach.
Antonia Vlahou; Dara Hallinan; Rolf Apweiler; Angel Argiles; Joachim Beige; Ariela Benigni; Rainer Bischoff; Peter C. Black; Franziska Boehm; Jocelyn Céraline; George P. Chrousos; Christian Delles; Pieter Evenepoel; Ivo Fridolin; Griet Glorieux; Alain J. van Gool; Isabel Heidegger; John P.A. Ioannidis; Joachim Jankowski; Vera Jankowski; Carmen Jeronimo; Ashish M. Kamat; Rosalinde Masereeuw; Gert Mayer; Harald Mischak; Alberto Ortiz; Giuseppe Remuzzi; Peter Rossing; Joost P. Schanstra; Bernd J. Schmitz-Dräger; Goce Spasovski; Jan A. Staessen; Dimitrios Stamatialis; Peter Stenvinkel; Christoph Wanner; Stephen B. Williams; Faiez Zannad; Carmine Zoccali; Raymond Vanholder. Data Sharing Under the General Data Protection Regulation. Hypertension 2021, 77, 1029 -1035.
AMA StyleAntonia Vlahou, Dara Hallinan, Rolf Apweiler, Angel Argiles, Joachim Beige, Ariela Benigni, Rainer Bischoff, Peter C. Black, Franziska Boehm, Jocelyn Céraline, George P. Chrousos, Christian Delles, Pieter Evenepoel, Ivo Fridolin, Griet Glorieux, Alain J. van Gool, Isabel Heidegger, John P.A. Ioannidis, Joachim Jankowski, Vera Jankowski, Carmen Jeronimo, Ashish M. Kamat, Rosalinde Masereeuw, Gert Mayer, Harald Mischak, Alberto Ortiz, Giuseppe Remuzzi, Peter Rossing, Joost P. Schanstra, Bernd J. Schmitz-Dräger, Goce Spasovski, Jan A. Staessen, Dimitrios Stamatialis, Peter Stenvinkel, Christoph Wanner, Stephen B. Williams, Faiez Zannad, Carmine Zoccali, Raymond Vanholder. Data Sharing Under the General Data Protection Regulation. Hypertension. 2021; 77 (4):1029-1035.
Chicago/Turabian StyleAntonia Vlahou; Dara Hallinan; Rolf Apweiler; Angel Argiles; Joachim Beige; Ariela Benigni; Rainer Bischoff; Peter C. Black; Franziska Boehm; Jocelyn Céraline; George P. Chrousos; Christian Delles; Pieter Evenepoel; Ivo Fridolin; Griet Glorieux; Alain J. van Gool; Isabel Heidegger; John P.A. Ioannidis; Joachim Jankowski; Vera Jankowski; Carmen Jeronimo; Ashish M. Kamat; Rosalinde Masereeuw; Gert Mayer; Harald Mischak; Alberto Ortiz; Giuseppe Remuzzi; Peter Rossing; Joost P. Schanstra; Bernd J. Schmitz-Dräger; Goce Spasovski; Jan A. Staessen; Dimitrios Stamatialis; Peter Stenvinkel; Christoph Wanner; Stephen B. Williams; Faiez Zannad; Carmine Zoccali; Raymond Vanholder. 2021. "Data Sharing Under the General Data Protection Regulation." Hypertension 77, no. 4: 1029-1035.
Osteoporosis is a state of bone fragility with reduced skeletal resistance to trauma, and consequently increased risk of fracture. A wide range of conditions, including traditional risk factors, lifestyle choices, diseases and their treatments may contribute to bone fragility. It is therefore not surprising that the multi-morbid patient with chronic kidney disease (CKD) is at a particularly high risk. CKD is associated with reduced bone quantity, as well as impaired bone quality. Bone fragility in CKD is a composite of primary osteoporosis, accumulation of traditional and uremia-related risk factors, assaults brought on by systemic disease, and detrimental effects of drugs. Some risk factors are modifiable and represent potential targets for intervention. This review provides an overview of the heterogeneity of bone fragility in CKD.
Hanne Skou Jørgensen; Karel David; Syazrah Salam; Pieter Evenepoel. Traditional and Non-traditional Risk Factors for Osteoporosis in CKD. Calcified Tissue International 2021, 108, 496 -511.
AMA StyleHanne Skou Jørgensen, Karel David, Syazrah Salam, Pieter Evenepoel. Traditional and Non-traditional Risk Factors for Osteoporosis in CKD. Calcified Tissue International. 2021; 108 (4):496-511.
Chicago/Turabian StyleHanne Skou Jørgensen; Karel David; Syazrah Salam; Pieter Evenepoel. 2021. "Traditional and Non-traditional Risk Factors for Osteoporosis in CKD." Calcified Tissue International 108, no. 4: 496-511.
Parathyroid hormone (PTH) is a key regulator of bone turnover but can be oxidized in vivo, which impairs biological activity. Variable PTH oxidation may account for the rather poor correlation of PTH with indices of bone turnover in chronic kidney disease. Here, we tested whether non-oxidized PTH is superior to total PTH as a marker of bone turnover in 31 patients with kidney failure included from an ongoing prospective observational bone biopsy study and selected to cover the whole spectrum of bone turnover. Receiver Operating Characteristic (ROC) curves, Spearman correlation and regression analysis of non-oxidized PTH, total PTH and bone turnover markers (bone-specific alkaline phosphatase, procollagen N-terminal pro-peptide and tartrate-resistant acid phosphatase 5b) were used to assess the capability of non-oxidized PTH vs. total PTH to discriminate low from non-low and high from non-high bone turnover, as assessed quantitatively by bone histomorphometry. Serum levels of non-oxidized PTH and total PTH were strongly and significantly correlated. Histomorphometric parameters of bone turnover and the circulating bone turnover markers showed similar correlation coefficients with non-oxidized PTH and total PTH. The area under the ROC (AUROC) values for discriminating between low/non-low turnover for non-oxidized PTH and total PTH were significant and comparable (0.82 and 0.79, respectively). For high/non-high turnover the AUROCs were also significant and of the same magnitude (0.76 and 0.80, respectively). Thus, measuring non-oxidized PTH using the currently available method provides no added value compared to total PTH as an indicator of bone turnover in patients with kidney failure.
Stan R. Ursem; Annemieke C. Heijboer; Patrick C. D’Haese; Geert J. Behets; Etienne Cavalier; Marc G. Vervloet; Pieter Evenepoel. Non-oxidized parathyroid hormone (PTH) measured by current method is not superior to total PTH in assessing bone turnover in chronic kidney disease. Kidney International 2021, 99, 1173 -1178.
AMA StyleStan R. Ursem, Annemieke C. Heijboer, Patrick C. D’Haese, Geert J. Behets, Etienne Cavalier, Marc G. Vervloet, Pieter Evenepoel. Non-oxidized parathyroid hormone (PTH) measured by current method is not superior to total PTH in assessing bone turnover in chronic kidney disease. Kidney International. 2021; 99 (5):1173-1178.
Chicago/Turabian StyleStan R. Ursem; Annemieke C. Heijboer; Patrick C. D’Haese; Geert J. Behets; Etienne Cavalier; Marc G. Vervloet; Pieter Evenepoel. 2021. "Non-oxidized parathyroid hormone (PTH) measured by current method is not superior to total PTH in assessing bone turnover in chronic kidney disease." Kidney International 99, no. 5: 1173-1178.
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.
Mineral and bone disorder (MBD) is widely prevalent in children with chronic kidney disease (CKD) and is associated with significant morbidity. CKD may cause disturbances in bone remodelling/modelling, which are more pronounced in the growing skeleton, manifesting as short stature, bone pain and deformities, fractures, slipped epiphyses and ectopic calcifications. Although assessment of bone health is a key element in the clinical care of children with CKD, it remains a major challenge for physicians. On the one hand, bone biopsy with histomorphometry is the gold standard for assessing bone health, but it is expensive, invasive and requires expertise in the interpretation of bone histology. On the other hand, currently available non-invasive measures, including dual-energy X-ray absorptiometry and biomarkers of bone formation/resorption, are affected by growth and pubertal status and have limited sensitivity and specificity in predicting changes in bone turnover and mineralization. In the absence of high-quality evidence, there are wide variations in clinical practice in the diagnosis and management of CKD-MBD in childhood. We present clinical practice points (CPPs) on the assessment of bone disease in children with CKD Stages 2–5 and on dialysis based on the best available evidence and consensus of experts from the CKD-MBD and Dialysis working groups of the European Society for Paediatric Nephrology and the CKD-MBD working group of the European Renal Association–European Dialysis and Transplant Association. These CPPs should be carefully considered by treating physicians and adapted to individual patients’ needs as appropriate. Further areas for research are suggested.
Sevcan A Bakkaloglu; Justine Bacchetta; Alexander D Lalayiannis; Maren Leifheit-Nestler; Stella Stabouli; Mathias Haarhaus; George Reusz; Jaap Groothoff; Claus Peter Schmitt; Pieter Evenepoel; Rukshana Shroff; Dieter Haffner; the European Society for Paediatric Nephrology (ESPN) Chronic Kidney Disease Mineral and Bone Disorder (CKD-MBD) and Dialysis working groups and CKD-MBD working group of the European Renal Association–European Dialysis and Transplant Association (ERA-EDTA. Bone evaluation in paediatric chronic kidney disease: clinical practice points from the European Society for Paediatric Nephrology CKD-MBD and Dialysis working groups and CKD-MBD working group of the ERA-EDTA. Nephrology Dialysis Transplantation 2020, 36, 413 -425.
AMA StyleSevcan A Bakkaloglu, Justine Bacchetta, Alexander D Lalayiannis, Maren Leifheit-Nestler, Stella Stabouli, Mathias Haarhaus, George Reusz, Jaap Groothoff, Claus Peter Schmitt, Pieter Evenepoel, Rukshana Shroff, Dieter Haffner, the European Society for Paediatric Nephrology (ESPN) Chronic Kidney Disease Mineral and Bone Disorder (CKD-MBD) and Dialysis working groups and CKD-MBD working group of the European Renal Association–European Dialysis and Transplant Association (ERA-EDTA. Bone evaluation in paediatric chronic kidney disease: clinical practice points from the European Society for Paediatric Nephrology CKD-MBD and Dialysis working groups and CKD-MBD working group of the ERA-EDTA. Nephrology Dialysis Transplantation. 2020; 36 (3):413-425.
Chicago/Turabian StyleSevcan A Bakkaloglu; Justine Bacchetta; Alexander D Lalayiannis; Maren Leifheit-Nestler; Stella Stabouli; Mathias Haarhaus; George Reusz; Jaap Groothoff; Claus Peter Schmitt; Pieter Evenepoel; Rukshana Shroff; Dieter Haffner; the European Society for Paediatric Nephrology (ESPN) Chronic Kidney Disease Mineral and Bone Disorder (CKD-MBD) and Dialysis working groups and CKD-MBD working group of the European Renal Association–European Dialysis and Transplant Association (ERA-EDTA. 2020. "Bone evaluation in paediatric chronic kidney disease: clinical practice points from the European Society for Paediatric Nephrology CKD-MBD and Dialysis working groups and CKD-MBD working group of the ERA-EDTA." Nephrology Dialysis Transplantation 36, no. 3: 413-425.
Controlling the excessive fracture burden in patients with chronic kidney disease (CKD) Stages G4–G5D remains an impressive challenge. The reasons are 2-fold. First, the pathophysiology of bone fragility in patients with CKD G4–G5D is complex and multifaceted, comprising a mixture of age-related (primary male/postmenopausal), drug-induced and CKD-related bone abnormalities. Second, our current armamentarium of osteoporosis medications has not been developed for, or adequately studied in patients with CKD G4–G5D, partly related to difficulties in diagnosing osteoporosis in this specific setting and fear of complications. Doubts about the optimal diagnostic and therapeutic approach fuel inertia in daily clinical practice. The scope of the present consensus paper is to review and update the assessment and diagnosis of osteoporosis in patients with CKD G4-G5D and to discuss the therapeutic interventions available and the manner in which these can be used to develop management strategies for the prevention of fragility fracture. As such, it aims to stimulate a cohesive approach to the management of osteoporosis in patients with CKD G4–G5D to replace current variations in care and treatment nihilism.
Pieter Evenepoel; John Cunningham; Serge Ferrari; Mathias Haarhaus; Muhammad Kassim Javaid; Marie-Hélène Lafage-Proust; Daniel Prieto-Alhambra; Pablo Ureña Torres; Jorge Cannata-Andia; Marc Vervloet; Sandro Mazzaferro; Patrick D’Haese; Justine Bacchetta; Annibal Ferreira; Syazrah Salam; Goce Spasovski. European Consensus Statement on the diagnosis and management of osteoporosis in chronic kidney disease stages G4–G5D. Nephrology Dialysis Transplantation 2020, 36, 42 -59.
AMA StylePieter Evenepoel, John Cunningham, Serge Ferrari, Mathias Haarhaus, Muhammad Kassim Javaid, Marie-Hélène Lafage-Proust, Daniel Prieto-Alhambra, Pablo Ureña Torres, Jorge Cannata-Andia, Marc Vervloet, Sandro Mazzaferro, Patrick D’Haese, Justine Bacchetta, Annibal Ferreira, Syazrah Salam, Goce Spasovski. European Consensus Statement on the diagnosis and management of osteoporosis in chronic kidney disease stages G4–G5D. Nephrology Dialysis Transplantation. 2020; 36 (1):42-59.
Chicago/Turabian StylePieter Evenepoel; John Cunningham; Serge Ferrari; Mathias Haarhaus; Muhammad Kassim Javaid; Marie-Hélène Lafage-Proust; Daniel Prieto-Alhambra; Pablo Ureña Torres; Jorge Cannata-Andia; Marc Vervloet; Sandro Mazzaferro; Patrick D’Haese; Justine Bacchetta; Annibal Ferreira; Syazrah Salam; Goce Spasovski. 2020. "European Consensus Statement on the diagnosis and management of osteoporosis in chronic kidney disease stages G4–G5D." Nephrology Dialysis Transplantation 36, no. 1: 42-59.
Background Optimal parathyroid hormone (PTH) control during non-dialysis chronic kidney disease (ND-CKD) might decrease the subsequent risk of parathyroid hyperplasia and uncontrolled secondary hyperparathyroidism (SHPT) on dialysis. However, the evidence for recommending PTH targets and therapeutic strategies is weak for ND-CKD. We evaluated the patient characteristics, treatment patterns and PTH control over the first year of haemodialysis (HD) by PTH prior to HD initiation. Methods We studied 5683 incident HD patients from 21 countries in Dialysis Outcomes and Practice Patterns Study Phases 4–6 (2009–18). We stratified by PTH measured immediately prior to HD initiation and reported the monthly prescription prevalence of active vitamin D and calcimimetics over the first year of HD and risk of PTH >600 pg/mL after 9–12 months on HD. Results The 16% of patients with PTH >600 pg/mL prior to HD initiation were more likely to be prescribed active vitamin D and calcimimetics during the first year of HD. The prevalence of PTH >600 pg/mL 9–12 months after start of HD was greater for patients who initiated HD with PTH >600 (29%) versus 150–300 (7%) pg/mL (adjusted risk difference: 19%; 95% confidence interval : 15%, 23%). The patients with sustained PTH >600 pg/mL after 9–12 months on HD were younger, more likely to be black, and had higher serum phosphorus and estimated glomerular filtration rates at HD initiation. Conclusions Increased PTH before HD start predicted a higher PTH level 9–12 months later, despite greater use of active vitamin D and calcimimetics. More targeted PTH control during ND-CKD may influence outcomes during HD, raising the need for PTH target guidelines in these patients.
Nahid Tabibzadeh; Angelo Karaboyas; Bruce M Robinson; Philipp A Csomor; David M Spiegel; Pieter Evenepoel; Stefan H Jacobson; Pablo-Antonio Ureña-Torres; Masafumi Fukagawa; Issa Al Salmi; Xinling Liang; Ronald L Pisoni; Eric W Young. The risk of medically uncontrolled secondary hyperparathyroidism depends on parathyroid hormone levels at haemodialysis initiation. Nephrology Dialysis Transplantation 2020, 36, 160 -169.
AMA StyleNahid Tabibzadeh, Angelo Karaboyas, Bruce M Robinson, Philipp A Csomor, David M Spiegel, Pieter Evenepoel, Stefan H Jacobson, Pablo-Antonio Ureña-Torres, Masafumi Fukagawa, Issa Al Salmi, Xinling Liang, Ronald L Pisoni, Eric W Young. The risk of medically uncontrolled secondary hyperparathyroidism depends on parathyroid hormone levels at haemodialysis initiation. Nephrology Dialysis Transplantation. 2020; 36 (1):160-169.
Chicago/Turabian StyleNahid Tabibzadeh; Angelo Karaboyas; Bruce M Robinson; Philipp A Csomor; David M Spiegel; Pieter Evenepoel; Stefan H Jacobson; Pablo-Antonio Ureña-Torres; Masafumi Fukagawa; Issa Al Salmi; Xinling Liang; Ronald L Pisoni; Eric W Young. 2020. "The risk of medically uncontrolled secondary hyperparathyroidism depends on parathyroid hormone levels at haemodialysis initiation." Nephrology Dialysis Transplantation 36, no. 1: 160-169.
The cardiorenal syndrome relates to the detrimental interplay between the vascular system and the kidney. The uremic milieu induced by reduced kidney function alters the phenotype of vascular smooth muscle cells (VSMC) and promotes vascular calcification, a condition which is strongly linked to cardiovascular morbidity and mortality. Biological mechanisms involved include generation of reactive oxygen species, inflammation and accelerated senescence. A better understanding of the vasotoxic effects of uremic retention molecules may reveal novel avenues to reduce vascular calcification in CKD. The present review aims to present a state of the art on the role of uremic toxins in pathogenesis of vascular calcification. Evidence, so far, is fragmentary and limited with only a few uremic toxins being investigated, often by a single group of investigators. Experimental heterogeneity furthermore hampers comparison. There is a clear need for a concerted action harmonizing and standardizing experimental protocols and combining efforts of basic and clinical researchers to solve the complex puzzle of uremic vascular calcification
Nikolas Rapp; Pieter Evenepoel; Peter Stenvinkel; Leon Schurgers. Uremic Toxins and Vascular Calcification–Missing the Forest for All the Trees. Toxins 2020, 12, 624 .
AMA StyleNikolas Rapp, Pieter Evenepoel, Peter Stenvinkel, Leon Schurgers. Uremic Toxins and Vascular Calcification–Missing the Forest for All the Trees. Toxins. 2020; 12 (10):624.
Chicago/Turabian StyleNikolas Rapp; Pieter Evenepoel; Peter Stenvinkel; Leon Schurgers. 2020. "Uremic Toxins and Vascular Calcification–Missing the Forest for All the Trees." Toxins 12, no. 10: 624.
The observation that unhealthy diets (those that are low in whole grains, fruits and vegetables, and high in sugar, salt, saturated fat and ultra-processed foods) are a major risk factor for poor health outcomes has boosted interest in the concept of ‘food as medicine’. This concept is especially relevant to metabolic diseases, such as chronic kidney disease (CKD), in which dietary approaches are already used to ameliorate metabolic and nutritional complications. Increased awareness that toxic uraemic metabolites originate not only from intermediary metabolism but also from gut microbial metabolism, which is directly influenced by diet, has fuelled interest in the potential of ‘food as medicine’ approaches in CKD beyond the current strategies of protein, sodium and phosphate restriction. Bioactive nutrients can alter the composition and metabolism of the microbiota, act as modulators of transcription factors involved in inflammation and oxidative stress, mitigate mitochondrial dysfunction, act as senolytics and impact the epigenome by altering one-carbon metabolism. As gut dysbiosis, inflammation, oxidative stress, mitochondrial dysfunction, premature ageing and epigenetic changes are common features of CKD, these findings suggest that tailored, healthy diets that include bioactive nutrients as part of the foodome could potentially be used to prevent and treat CKD and its complications. Here, the authors discuss the mechanisms by which food and specific nutrients could affect the uraemic phenotype in chronic kidney disease (CKD). They suggest that a food-as-medicine approach could potentially be used to prevent and treat CKD and its complications.
Denise Mafra; Natalia A. Borges; Bengt Lindholm; Paul G. Shiels; Pieter Evenepoel; Peter Stenvinkel. Food as medicine: targeting the uraemic phenotype in chronic kidney disease. Nature Reviews Nephrology 2020, 17, 153 -171.
AMA StyleDenise Mafra, Natalia A. Borges, Bengt Lindholm, Paul G. Shiels, Pieter Evenepoel, Peter Stenvinkel. Food as medicine: targeting the uraemic phenotype in chronic kidney disease. Nature Reviews Nephrology. 2020; 17 (3):153-171.
Chicago/Turabian StyleDenise Mafra; Natalia A. Borges; Bengt Lindholm; Paul G. Shiels; Pieter Evenepoel; Peter Stenvinkel. 2020. "Food as medicine: targeting the uraemic phenotype in chronic kidney disease." Nature Reviews Nephrology 17, no. 3: 153-171.
The assessment of the vitamin K status and its effects on clinical outcomes in kidney transplantation (KT) patients has sparked interest, but it is still largely unfulfilled. In part, this is due to difficulties in laboratory measurements of vitamin K, especially K2 vitamers. Vitamin K status is currently best assessed by measuring undercarboxylated vitamin-K-dependent proteins. The relative contribution of vitamin K1 and K2 to the health status of the general population and CKD (chronic kidney disease) patients, including KT patients, is also poorly studied. Through a complete and first review of the existing literature, we summarize the current knowledge of vitamin K pathophysiology and its potential role in preventing KT complications and improving organ survival. A specific focus is placed on cardiovascular complications, bone fractures, and the relationship between vitamin K and cancer. Vitamin K deficiency could determine adverse outcomes, and KT patients should be better studied for vitamin K assessment and modalities of effective therapeutic approaches.
Maria Fusaro; Laura Cosmai; Pieter Evenepoel; Thomas L. Nickolas; Angela M. Cheung; Andrea Aghi; Giovanni Tripepi; Mario Plebani; Giorgio Iervasi; Roberto Vettor; Martina Zaninotto; Maura Ravera; Marina Foramitti; Sandro Giannini; Stefania Sella; Maurizio Gallieni. Vitamin K and Kidney Transplantation. Nutrients 2020, 12, 2717 .
AMA StyleMaria Fusaro, Laura Cosmai, Pieter Evenepoel, Thomas L. Nickolas, Angela M. Cheung, Andrea Aghi, Giovanni Tripepi, Mario Plebani, Giorgio Iervasi, Roberto Vettor, Martina Zaninotto, Maura Ravera, Marina Foramitti, Sandro Giannini, Stefania Sella, Maurizio Gallieni. Vitamin K and Kidney Transplantation. Nutrients. 2020; 12 (9):2717.
Chicago/Turabian StyleMaria Fusaro; Laura Cosmai; Pieter Evenepoel; Thomas L. Nickolas; Angela M. Cheung; Andrea Aghi; Giovanni Tripepi; Mario Plebani; Giorgio Iervasi; Roberto Vettor; Martina Zaninotto; Maura Ravera; Marina Foramitti; Sandro Giannini; Stefania Sella; Maurizio Gallieni. 2020. "Vitamin K and Kidney Transplantation." Nutrients 12, no. 9: 2717.
Uremic toxins originate, to a significant extent, from gut microbial metabolism. Important representatives include p-cresyl sulfate (PCS) and indoxyl sulfate.1Evenepoel P. Meijers B.K.I. Bammens B.R.M. Verbeke K. Uremic toxins originating from colonic microbial metabolism.Kidney Int. 2009; 76: S12-S19Abstract Full Text Full Text PDF PubMed Scopus (234) Google Scholar It remains a matter of controversy whether chronic kidney disease affects gut microbiome composition and metabolism, thereby altering the generation of toxins.2Gryp T. De Paepe K. Vanholder R. et al.Gut microbiota generation of protein-bound uremic toxins and related metabolites is not altered at different stages of chronic kidney disease.Kidney Int. 2020; 97: 1230-1242Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar, 3Poesen R. Viaene L. Verbeke K. et al.Renal clearance and intestinal generation of p-cresyl sulfate and indoxyl sulfate in CKD.Clin J Am Soc Nephrol. 2013; 8: 1508-1514Crossref PubMed Scopus (58) Google Scholar, 4Wang X, Yang S, Li S, et al. Aberrant gut microbiota alters host metabolome and impacts renal failure in humans and rodents [e-pub ahead of print]. Gut. https://doi.org/10.1136/gutjnl-2019-319766. Accessed May 1, 2020.Google Scholar Gryp et al. argued against this, partly based on the analysis of spot urine samples in 141 patients with chronic kidney disease.2Gryp T. De Paepe K. Vanholder R. et al.Gut microbiota generation of protein-bound uremic toxins and related metabolites is not altered at different stages of chronic kidney disease.Kidney Int. 2020; 97: 1230-1242Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar We studied whether spot urine is a reasonable alternative to a 24-hour urine collection, considered to be the gold standard for the assessment of the 24-hour intestinal toxin generation rate. Ten healthy volunteers (31 years [range, 20–46 years], 40% men, estimated glomerular filtration rate 96 ml/min [interquartile range, 69–110 ml/min]) and 10 patients with chronic kidney disease (66 years [interquartile range, 29–84 years], 50% men, estimated glomerular filtration rate 32 ml/min [interquartile range, 11–117 ml/min]) collected 24-hour urine and one voiding sample immediately before or after the 24-hour collection. Volunteers collected urine for 3 consecutive days. On day 1, urine was collected in 4 fractions. PCS/creatinine ratios showed moderate intra- and inter-day variability (coefficients of variation 22% and 29%, respectively). Spot urine PCS/creatinine ratios were numerically higher in patients with chronic kidney disease. The correlation between spot urine PCS/creatinine ratio and 24-hour urine PCS was poor, and the Bland-Altman plot between spot and 24-hour urine PCS/creatinine ratios revealed substantial bias (Figure 1). Results were similar for indoxyl sulfate. Taken together, spot urine toxin/creatinine ratios are only weakly correlated to 24-hour urine excretion, and as a proxy of toxin generation should thus be interpreted with caution, especially with values in the low range. Analyzing spot urine increases the risk of type II statistical error.Figure 1Evaluation of spot and 24-hour urine samples for uremic toxin analysis in chronic kidney disease patients and healthy controls; rho by Spearman’s rank correlation. IndS, indoxyl sulfate; PCS, p-cresyl sulfate.View Large Image Figure ViewerDownload Hi-res image Download (PPT)
Pieter Evenepoel; Henriette De Loor; H.S. Jorgensen; Bjorn Meijers. Spot urine versus 24-hour urine collection for estimation of the generation of uremic toxins originating from gut microbial metabolism. Kidney International 2020, 98, 782 -784.
AMA StylePieter Evenepoel, Henriette De Loor, H.S. Jorgensen, Bjorn Meijers. Spot urine versus 24-hour urine collection for estimation of the generation of uremic toxins originating from gut microbial metabolism. Kidney International. 2020; 98 (3):782-784.
Chicago/Turabian StylePieter Evenepoel; Henriette De Loor; H.S. Jorgensen; Bjorn Meijers. 2020. "Spot urine versus 24-hour urine collection for estimation of the generation of uremic toxins originating from gut microbial metabolism." Kidney International 98, no. 3: 782-784.
We describe a case harboring a homozygous CYP24A1 mutation with mild loss of function, first presenting with recurrent nephrolithiasis from the age of 22 onward, initially associated with hypercalcemia and low PTH concentrations. Over the years, hyperparathyroidism developed, resulting in more severe hypercalcemia. Also, kidney function deteriorated, most probably as a consequence of biopsy-proven nephrocalcinosis. Conventional treatment options for CYP24A1 mutation were not effective and/or tolerated (avoidance of sun exposure, diet, pamidronate, itraconazole). A total parathyroidectomy was performed resulting in a normocalcemic hypoparathyroidism without need for treatment with vitamin D analogs, a positive bone mineral balance and an improved kidney function.
K. David; R. Khalil; H. Hannon; P. Evenepoel; B. Decallonne. Therapy-Resistant Hypercalcemia in a Patient with Inactivating CYP24A1 Mutation and Recurrent Nephrolithiasis: Beware of Concomitant Hyperparathyroidism. Calcified Tissue International 2020, 107, 524 -528.
AMA StyleK. David, R. Khalil, H. Hannon, P. Evenepoel, B. Decallonne. Therapy-Resistant Hypercalcemia in a Patient with Inactivating CYP24A1 Mutation and Recurrent Nephrolithiasis: Beware of Concomitant Hyperparathyroidism. Calcified Tissue International. 2020; 107 (5):524-528.
Chicago/Turabian StyleK. David; R. Khalil; H. Hannon; P. Evenepoel; B. Decallonne. 2020. "Therapy-Resistant Hypercalcemia in a Patient with Inactivating CYP24A1 Mutation and Recurrent Nephrolithiasis: Beware of Concomitant Hyperparathyroidism." Calcified Tissue International 107, no. 5: 524-528.
Hanne Skou Jørgensen; Etienne Cavalier; Pieter Evenepoel. Clinical evidence of direct bone effects of cinacalcet. Kidney International 2020, 98, 514 -515.
AMA StyleHanne Skou Jørgensen, Etienne Cavalier, Pieter Evenepoel. Clinical evidence of direct bone effects of cinacalcet. Kidney International. 2020; 98 (2):514-515.
Chicago/Turabian StyleHanne Skou Jørgensen; Etienne Cavalier; Pieter Evenepoel. 2020. "Clinical evidence of direct bone effects of cinacalcet." Kidney International 98, no. 2: 514-515.
Background Serial assessment of phosphorus is currently recommended by the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, but its additional value versus a single measurement is uncertain. Methods We studied data from 17 414 HD patients in the Dialysis Outcomes and Practice Patterns Study, a prospective cohort study, and calculated the area under the curve (AUC) by multiplying the time spent with serum phosphorus >4.5 mg/dL over a 6-month run-in period by the extent to which this threshold was exceeded. We estimated the association between the monthly average AUC and cardiovascular (CV) mortality using Cox regression. We formally assessed whether AUC was a better predictor of CV mortality than other measures of phosphorus control according to the Akaike information criterion. Results Compared with the reference group of AUC = 0, the adjusted hazard ratio (HR) of CV mortality was 1.12 [95% confidence interval (CI) 0.90–1.40] for AUC > 0–0.5, 1.26 (95% CI 0.99–1.62) for AUC > 0.5–1, 1.44 (95% CI 1.11–1.86) for AUC > 1–2 and 2.03 (95% CI 1.53–2.69) for AUC > 2. The AUC was predictive of CV mortality within strata of the most recent phosphorus level and had a better model fit than other serial measures of phosphorus control (mean phosphorus, months out of target). Conclusions We conclude that worse phosphorus control over a 6-month period was strongly associated with CV mortality. The more phosphorus values do not exceed 4.5 mg/dL the better is survival. Phosphorus AUC is a better predictor of CV death than the single most recent phosphorus level, supporting with real-world data KDIGO’s recommendation of serial assessment of phosphorus to guide clinical decisions.
Marcelo Barreto Lopes; Angelo Karaboyas; Brian Bieber; Ronald L Pisoni; Sebastian Walpen; Masafumi Fukagawa; Anders Christensson; Pieter Evenepoel; Marisa Pegoraro; Bruce M Robinson; Roberto Pecoits-Filho. Impact of longer term phosphorus control on cardiovascular mortality in hemodialysis patients using an area under the curve approach: results from the DOPPS. Nephrology Dialysis Transplantation 2020, 35, 1794 -1801.
AMA StyleMarcelo Barreto Lopes, Angelo Karaboyas, Brian Bieber, Ronald L Pisoni, Sebastian Walpen, Masafumi Fukagawa, Anders Christensson, Pieter Evenepoel, Marisa Pegoraro, Bruce M Robinson, Roberto Pecoits-Filho. Impact of longer term phosphorus control on cardiovascular mortality in hemodialysis patients using an area under the curve approach: results from the DOPPS. Nephrology Dialysis Transplantation. 2020; 35 (10):1794-1801.
Chicago/Turabian StyleMarcelo Barreto Lopes; Angelo Karaboyas; Brian Bieber; Ronald L Pisoni; Sebastian Walpen; Masafumi Fukagawa; Anders Christensson; Pieter Evenepoel; Marisa Pegoraro; Bruce M Robinson; Roberto Pecoits-Filho. 2020. "Impact of longer term phosphorus control on cardiovascular mortality in hemodialysis patients using an area under the curve approach: results from the DOPPS." Nephrology Dialysis Transplantation 35, no. 10: 1794-1801.
Histomorphometric analysis of a transiliac bone biopsy is the gold standard for the diagnosis of renal osteodystrophy (ROD). This procedure is costly, invasive and usually performed with a trephine with an internal diameter of 7.5 mm. Our objective was to evaluate the accuracy of ROD diagnosis on halved histological bone sections to determine if they are comparable to the standard 7.5 mm samples. We included 68 bone biopsies performed in CKD patients for diagnostic purposes with a 7.5 mm diameter trephine. Quantitative histomorphometric analysis of the whole bone samples was performed including assessment of bone mineralization, turnover and volume. Each histological section (representing the whole 7.5 mm diameter biopsy) was then divided lengthwise in two hemisections (representing the 3.5 mm diameter biopsy). Histomorphometric analysis was repeated this time on the two hemibiopsies for each sample, blinded from initial results. Diagnoses were classified as osteitis fibrosa, adynamic bone disease, mixed uremic bone disease, osteomalacia or other. Correlations between the whole sample and the hemibiopsies for each parameter were studied. Concordance between the various bone parameters and final ROD diagnosis obtained from the whole section versus the two hemi sections was evaluated. Highly significant correlations were found between parameters measured on the whole section and the corresponding hemisections, with r coefficient of 0.98 for osteoid surface and thickness and bone formation rate, 0.97 for osteoclast surface, and 0.96 for bone volume (p < 0.001). Final diagnosis was in full accordance between the whole biopsy and the two corresponding hemi-biopsies in 91% of cases. Accurate diagnosis of ROD type was obtained by evaluation of bone surface areas of 3 mm diameter. These data suggest that small invasive bone biopsies might provide accurate ROD diagnostics while decreasing both invasiveness and cost of the procedure.
Etienne Novel-Catin; Solenne Pelletier; Denis Fouque; Jean-Paul Roux; Roland Chapurlat; Patrick D'Haese; Geert Behets; Peter Evenepoel; Thomas L. Nickolas; Marie-Hélène Lafage-Proust. Quantitative histomorphometric analysis of halved iliac crest bone biopsies yield comparable ROD diagnosis as full 7.5mm wide samples. Bone 2020, 138, 115460 .
AMA StyleEtienne Novel-Catin, Solenne Pelletier, Denis Fouque, Jean-Paul Roux, Roland Chapurlat, Patrick D'Haese, Geert Behets, Peter Evenepoel, Thomas L. Nickolas, Marie-Hélène Lafage-Proust. Quantitative histomorphometric analysis of halved iliac crest bone biopsies yield comparable ROD diagnosis as full 7.5mm wide samples. Bone. 2020; 138 ():115460.
Chicago/Turabian StyleEtienne Novel-Catin; Solenne Pelletier; Denis Fouque; Jean-Paul Roux; Roland Chapurlat; Patrick D'Haese; Geert Behets; Peter Evenepoel; Thomas L. Nickolas; Marie-Hélène Lafage-Proust. 2020. "Quantitative histomorphometric analysis of halved iliac crest bone biopsies yield comparable ROD diagnosis as full 7.5mm wide samples." Bone 138, no. : 115460.
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.