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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.
Imbalanced colonic microbial metabolism plays a pivotal role in generating protein-bound uraemic toxins (PBUTs), which accumulate with deteriorating kidney function and contribute to the uraemic burden of children with chronic kidney disease (CKD). Dietary choices impact the gut microbiome and metabolism. The aim of this study was to investigate the relation between dietary fibre and gut-derived PBUTs in paediatric CKD. Sixty-one (44 male) CKD children (9 ± 5 years) were prospectively followed for two years. Dietary fibre intake was evaluated by either 24-h recalls (73%) or 3-day food records (27%) at the same time of blood sampling for assessment of total and free serum levels of different PBUTs using liquid chromatography. We used linear mixed models to assess associations between fibre intake and PBUT levels. We found an inverse association between increase in fibre consumption (g/day) and serum concentrations of free indoxyl sulfate (−3.1% (−5.9%; −0.3%) (p = 0.035)), free p-cresyl sulfate (−2.5% (−4.7%; −0.3%) (p = 0.034)), total indole acetic acid (IAA) (−1.6% (−3.0%; −0.3%) (p = 0.020)), free IAA (−6.6% (−9.3%; −3.7%) (p < 0.001)), total serum p-cresyl glucuronide (pCG) (−3.0% (−5.6%; −0.5%) (p = 0.021)) and free pCG levels (−3.3% (−5.8%; −0.8%) (p = 0.010)). The observed associations between dietary fibre intake and the investigated PBUTs highlight potential benefits of fibre intake for the paediatric CKD population. The present observational findings should inform and guide adaptations of dietary prescriptions in children with CKD.
Amina El Amouri; Evelien Snauwaert; Aurélie Foulon; Charlotte Vande Moortel; Maria Van Dyck; Koen Van Hoeck; Nathalie Godefroid; Griet Glorieux; Wim Van Biesen; Johan Vande Walle; Ann Raes; Sunny Eloot. Dietary Fibre Intake Is Associated with Serum Levels of Uraemic Toxins in Children with Chronic Kidney Disease. Toxins 2021, 13, 225 .
AMA StyleAmina El Amouri, Evelien Snauwaert, Aurélie Foulon, Charlotte Vande Moortel, Maria Van Dyck, Koen Van Hoeck, Nathalie Godefroid, Griet Glorieux, Wim Van Biesen, Johan Vande Walle, Ann Raes, Sunny Eloot. Dietary Fibre Intake Is Associated with Serum Levels of Uraemic Toxins in Children with Chronic Kidney Disease. Toxins. 2021; 13 (3):225.
Chicago/Turabian StyleAmina El Amouri; Evelien Snauwaert; Aurélie Foulon; Charlotte Vande Moortel; Maria Van Dyck; Koen Van Hoeck; Nathalie Godefroid; Griet Glorieux; Wim Van Biesen; Johan Vande Walle; Ann Raes; Sunny Eloot. 2021. "Dietary Fibre Intake Is Associated with Serum Levels of Uraemic Toxins in Children with Chronic Kidney Disease." Toxins 13, no. 3: 225.
Background Several protein-bound uraemic toxins (PBUTs) have been associated with cardiovascular (CV) and all-cause mortality in chronic kidney disease (CKD) but the degree to which this is the case per individual PBUT and the pathophysiological mechanism have only partially been unraveled. Methods We compared the prognostic value of both total and free concentrations of five PBUTs [p-cresyl sulfate (pCS), p-cresyl glucuronide, indoxyl sulfate, indole acetic acid and hippuric acid] in a cohort of 523 patients with non-dialysis CKD Stages G1–G5. Patients were followed prospectively for the occurrence of a fatal or non-fatal CV event as the primary endpoint and a number of other major complications as secondary endpoints. In addition, association with and the prognostic value of nine markers of endothelial activation/damage was compared. Results After a median follow-up of 5.5 years, 149 patients developed the primary endpoint. In multivariate Cox regression models adjusted for age, sex, systolic blood pressure, diabetes mellitus and estimated glomerular filtration rate, and corrected for multiple testing, only free pCS was associated with the primary endpoint {hazard ratio [HR]1.39 [95% confidence interval (CI) 1.14–1.71]; P = 0.0014}. Free pCS also correlated with a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (r = −0.114, P < 0.05), angiopoietin-2 (ANGPT2) (r = 0.194, P < 0.001), matrix metallopeptidase 7 (MMP-7; (r = 0.238, P < 0.001) and syndecan 1 (r = 0.235, P < 0.001). Of these markers of endothelial activation/damage, ANGPT2 [HR 1.46 (95% CI 1.25–1.70); P < 0.0001] and MMP-7 [HR 1.31 (95% CI 1.08–1.59); P = 0.0056] were also predictive of the primary outcome. Conclusions Among PBUTs, free pCS shows the highest association with CV outcome in non-dialysed patients with CKD. Two markers of endothelial activation/damage that were significantly correlated with free pCS, ANGPT2 and MMP-7 were also associated with CV outcome. The hypothesis that free pCS exerts its CV toxic effects by an adverse effect on endothelial function deserves further exploration.
Griet Glorieux; Raymond Vanholder; Wim Van Biesen; Anneleen Pletinck; Eva Schepers; Nathalie Neirynck; Marijn Speeckaert; Dirk De Bacquer; Francis Verbeke. Free p-cresyl sulfate shows the highest association with cardiovascular outcome in chronic kidney disease. Nephrology Dialysis Transplantation 2021, 36, 998 -1005.
AMA StyleGriet Glorieux, Raymond Vanholder, Wim Van Biesen, Anneleen Pletinck, Eva Schepers, Nathalie Neirynck, Marijn Speeckaert, Dirk De Bacquer, Francis Verbeke. Free p-cresyl sulfate shows the highest association with cardiovascular outcome in chronic kidney disease. Nephrology Dialysis Transplantation. 2021; 36 (6):998-1005.
Chicago/Turabian StyleGriet Glorieux; Raymond Vanholder; Wim Van Biesen; Anneleen Pletinck; Eva Schepers; Nathalie Neirynck; Marijn Speeckaert; Dirk De Bacquer; Francis Verbeke. 2021. "Free p-cresyl sulfate shows the highest association with cardiovascular outcome in chronic kidney disease." Nephrology Dialysis Transplantation 36, no. 6: 998-1005.
Amina El Amouri; Evelien Snauwaert; Aurélie Foulon; Charlotte Vande Moortel; Maria Van Dyck; Koen Van Hoeck; Nathalie Godefroid; Griet Glorieux; Wim Van Biesen; Johan Vande Walle; Ann Raes; Sunny Eloot. Dietary fibre intake is low in paediatric chronic kidney disease patients but its impact on levels of gut-derived uraemic toxins remains uncertain. Pediatric Nephrology 2021, 36, 1589 -1595.
AMA StyleAmina El Amouri, Evelien Snauwaert, Aurélie Foulon, Charlotte Vande Moortel, Maria Van Dyck, Koen Van Hoeck, Nathalie Godefroid, Griet Glorieux, Wim Van Biesen, Johan Vande Walle, Ann Raes, Sunny Eloot. Dietary fibre intake is low in paediatric chronic kidney disease patients but its impact on levels of gut-derived uraemic toxins remains uncertain. Pediatric Nephrology. 2021; 36 (6):1589-1595.
Chicago/Turabian StyleAmina El Amouri; Evelien Snauwaert; Aurélie Foulon; Charlotte Vande Moortel; Maria Van Dyck; Koen Van Hoeck; Nathalie Godefroid; Griet Glorieux; Wim Van Biesen; Johan Vande Walle; Ann Raes; Sunny Eloot. 2021. "Dietary fibre intake is low in paediatric chronic kidney disease patients but its impact on levels of gut-derived uraemic toxins remains uncertain." Pediatric Nephrology 36, no. 6: 1589-1595.
Background: Chronic kidney disease (CKD) is a renal disorder characterized by the accumulation of uremic toxins with limited strategies to reduce their concentrations. A large amount of data supports the pivotal role of intestinal microbiota in CKD complications and as a major source of uremic toxins production. Here, we explored whether fecal microbiota transplantation (FMT) could be attenuated in metabolic complication and uremic toxin accumulation in mice with CKD. Methods: Kidney failure was chemically induced by a diet containing 0.25% (w/w) of adenine for four weeks. Mice were randomized into three groups: control, CKD and CKD + FMT groups. After four weeks, CKD mice underwent fecal microbiota transplantation (FMT) from healthy mice or phosphate buffered saline as control. The gut microbiota structure, uremic toxins plasmatic concentrations, and metabolic profiles were explored three weeks after transplantation. Results: Associated with the increase of alpha diversity, we observed a noticeable improvement of gut microbiota disturbance, after FMT treatment. FMT further decreased p-cresyl sulfate accumulation and improved glucose tolerance. There was no change in kidney function. Conclusions: These data indicate that FMT limited the accumulation of uremic toxins issued from intestinal cresol pathway by a beneficial effect on gut microbiota diversity. Further studies are needed to investigate the FMT efficiency, the timing and feces amount for the transplantation before, to become a therapeutic option in CKD patients.
Christophe Barba; Christophe O. Soulage; Gianvito Caggiano; Griet Glorieux; Denis Fouque; Laetitia Koppe. Effects of Fecal Microbiota Transplantation on Composition in Mice with CKD. Toxins 2020, 12, 741 .
AMA StyleChristophe Barba, Christophe O. Soulage, Gianvito Caggiano, Griet Glorieux, Denis Fouque, Laetitia Koppe. Effects of Fecal Microbiota Transplantation on Composition in Mice with CKD. Toxins. 2020; 12 (12):741.
Chicago/Turabian StyleChristophe Barba; Christophe O. Soulage; Gianvito Caggiano; Griet Glorieux; Denis Fouque; Laetitia Koppe. 2020. "Effects of Fecal Microbiota Transplantation on Composition in Mice with CKD." Toxins 12, no. 12: 741.
Referring to Gryp et al.,1Gryp 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 Evenepoel et al. discourage using spot urine uremic toxin/creatinine ratios (Uspot/C) as a proxy of uremic toxin generation,1Gryp 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 because of poor agreement between Uspot/C and 24-hour urine excretion (U24h),2Evenepoel P, de Loor H, Jorgensen HS, Meijers B. Spot urine versus 24-hour urine collection for estimation of the generation of uremic toxins originating from gut microbial metabolism. Kidney Int. 2020;98:782–784.Google Scholar confirming similar observations for 24-hour proteinuria.3Rydzewska-Rosolowska A. Kakareko K. Naumnik B. Hryszko T. Comparison of different methods of urinary protein excretion measurement: is the king really dead?.Kidney Blood Press Res. 2019; 44: 993-1001Crossref Scopus (1) Google Scholar The question is whether the problem raised is specific for Uspot/C.
Tessa Gryp; Raymond Vanholder; Griet Glorieux. The authors reply. Kidney International 2020, 98, 784 .
AMA StyleTessa Gryp, Raymond Vanholder, Griet Glorieux. The authors reply. Kidney International. 2020; 98 (3):784.
Chicago/Turabian StyleTessa Gryp; Raymond Vanholder; Griet Glorieux. 2020. "The authors reply." Kidney International 98, no. 3: 784.
Several of the uremic toxins, which are difficult to remove by dialysis, originate from the gut bacterial metabolism. This opens opportunities for novel targets trying to decrease circulating levels of these toxins and their pathophysiological effects. The current review focuses on immunomodulatory effects of these toxins both at their side of origin and in the circulation. In the gut end products of the bacterial metabolism such as p-cresol, trimethylamine and H2S affect the intestinal barrier structure and function while in the circulation the related uremic toxins stimulate cells of the immune system. Both conditions contribute to the pro-inflammatory status of patients with chronic kidney disease (CKD). Generation and/or absorption of these toxin precursors could be targeted to decrease plasma levels of their respective uremic toxins and to reduce micro-inflammation in CKD.
Griet Glorieux; Tessa Gryp; Alessandra Perna. Gut-Derived Metabolites and Their Role in Immune Dysfunction in Chronic Kidney Disease. Toxins 2020, 12, 245 .
AMA StyleGriet Glorieux, Tessa Gryp, Alessandra Perna. Gut-Derived Metabolites and Their Role in Immune Dysfunction in Chronic Kidney Disease. Toxins. 2020; 12 (4):245.
Chicago/Turabian StyleGriet Glorieux; Tessa Gryp; Alessandra Perna. 2020. "Gut-Derived Metabolites and Their Role in Immune Dysfunction in Chronic Kidney Disease." Toxins 12, no. 4: 245.
Background: Uremic toxins have emerged as potential mediators of morbidity and mortality in patients with chronic kidney disease (CKD). Indole-3-acetic acid (IAA, a tryptophan-derived uremic toxin) might be a useful biomarker in patients with CKD. The objectives of the present study were to (i) describe IAA concentrations in a cohort of non-transplanted patients with CKD and a cohort of transplanted patients with CKD, and (ii) investigate the possible relationship between IAA levels and adverse outcomes in the two cohorts. Methods: Levels of free and total IAA were assayed in the two prospective CKD cohorts (140 non-transplanted patients and 311 transplanted patients). Cox multivariate analyses were used to evaluate the association between IAA levels and outcomes (mortality, cardiovascular events, and graft loss). Results: In the non-transplanted CKD cohort, free and total IAA increased progressively with the CKD stage. In the transplanted CKD cohort, free and total IAA levels were elevated at the time of transplantation but had fallen substantially at one-month post-transplantation. Indole acetic acid concentrations were lower in transplanted patients than non-dialysis non-transplanted patients matched for estimated glomerular filtration rate (eGFR), age, and sex. After adjustment for multiple confounders, the free IAA level predicted overall mortality and cardiovascular events in the non-transplanted CKD cohort (hazard ratio [95% confidence interval]: 2.5 [1.2–5.1] and 2.5 [1.3–4.8], respectively). In the transplanted CKD cohort, however, no associations were found between free or total IAA on one hand, and mortality, CV event, or graft survival on the other. Conclusion: We demonstrated that levels of IAA increase with the CKD stage, and fall substantially, even normalizing, after kidney transplantation. Free IAA appears to be a valuable outcome-associated biomarker in non-transplanted patients, but—at least in our study setting—not in transplanted patients.
Sophie Liabeuf; Solène M. Laville; Griet Glorieux; Lynda Cheddani; François Brazier; Dimitri Titeca Beauport; Raymond Vanholder; Gabriel Choukroun; Ziad A. Massy. Difference in Profiles of the Gut-Derived Tryptophan Metabolite Indole Acetic Acid between Transplanted and Non-Transplanted Patients with Chronic Kidney Disease. International Journal of Molecular Sciences 2020, 21, 2031 .
AMA StyleSophie Liabeuf, Solène M. Laville, Griet Glorieux, Lynda Cheddani, François Brazier, Dimitri Titeca Beauport, Raymond Vanholder, Gabriel Choukroun, Ziad A. Massy. Difference in Profiles of the Gut-Derived Tryptophan Metabolite Indole Acetic Acid between Transplanted and Non-Transplanted Patients with Chronic Kidney Disease. International Journal of Molecular Sciences. 2020; 21 (6):2031.
Chicago/Turabian StyleSophie Liabeuf; Solène M. Laville; Griet Glorieux; Lynda Cheddani; François Brazier; Dimitri Titeca Beauport; Raymond Vanholder; Gabriel Choukroun; Ziad A. Massy. 2020. "Difference in Profiles of the Gut-Derived Tryptophan Metabolite Indole Acetic Acid between Transplanted and Non-Transplanted Patients with Chronic Kidney Disease." International Journal of Molecular Sciences 21, no. 6: 2031.
In chronic kidney disease (CKD), impaired kidney function results in accumulation of uremic toxins, which exert deleterious biological effects and contribute to inflammation and cardiovascular morbidity and mortality. Protein-bound uremic toxins (PBUTs), such as p-cresyl sulfate, indoxyl sulfate and indole-3-acetic acid, originate from phenolic and indolic compounds, which are end products of gut bacterial metabolization of aromatic amino acids (AAA). This study investigates gut microbial composition at different CKD stages by isolating, identifying and quantifying PBUT precursor-generating bacteria. Fecal DNA extracts from 14 controls and 138 CKD patients were used to quantify total bacterial number and 11 bacterial taxa with qPCR. Moreover, isolated bacteria from CKD 1 and CKD 5 fecal samples were cultured in broth medium supplemented with AAA under aerobic and anaerobic conditions, and classified as PBUT precursor-generators based on their generation capacity of phenolic and indolic compounds, measured with U(H)PLC. In total, 148 different fecal bacterial species were isolated, of which 92 were PBUT precursor-generators. These bacterial species can be a potential target for reducing PBUT plasma levels in CKD. qPCR indicated lower abundance of short chain fatty acid-generating bacteria, Bifidobacterium spp. and Streptococcus spp., and higher Enterobacteriaceae and E. coli with impaired kidney function, confirming an altered gut microbial composition in CKD.
Tessa Gryp; Geert R.B. Huys; Marie Joossens; Wim Van Biesen; Griet Glorieux; Mario Vaneechoutte. Isolation and Quantification of Uremic Toxin Precursor-Generating Gut Bacteria in Chronic Kidney Disease Patients. International Journal of Molecular Sciences 2020, 21, 1986 .
AMA StyleTessa Gryp, Geert R.B. Huys, Marie Joossens, Wim Van Biesen, Griet Glorieux, Mario Vaneechoutte. Isolation and Quantification of Uremic Toxin Precursor-Generating Gut Bacteria in Chronic Kidney Disease Patients. International Journal of Molecular Sciences. 2020; 21 (6):1986.
Chicago/Turabian StyleTessa Gryp; Geert R.B. Huys; Marie Joossens; Wim Van Biesen; Griet Glorieux; Mario Vaneechoutte. 2020. "Isolation and Quantification of Uremic Toxin Precursor-Generating Gut Bacteria in Chronic Kidney Disease Patients." International Journal of Molecular Sciences 21, no. 6: 1986.
Tryptophan is an essential dietary amino acid that originates uremic toxins that contribute to end-stage kidney disease (ESKD) patient outcomes. We evaluated serum levels and removal during haemodialysis and haemodiafiltration of tryptophan and tryptophan-derived uremic toxins, indoxyl sulfate (IS) and indole acetic acid (IAA), in ESKD patients in different dialysis treatment settings. This prospective multicentre study in four European dialysis centres enrolled 78 patients with ESKD. Blood and spent dialysate samples obtained during dialysis were analysed with high-performance liquid chromatography to assess uremic solutes, their reduction ratio (RR) and total removed solute (TRS). Mean free serum tryptophan and IS concentrations increased, and concentration of IAA decreased over pre-dialysis levels (67%, 49%, −0.8%, respectively) during the first hour of dialysis. While mean serum total urea, IS and IAA concentrations decreased during dialysis (−72%, −39%, −43%, respectively), serum tryptophan levels increased, resulting in negative RR (−8%) towards the end of the dialysis session (p < 0.001), despite remarkable Trp losses in dialysate. RR and TRS values based on serum (total, free) and dialysate solute concentrations were lower for conventional low-flux dialysis (p < 0.001). High-efficiency haemodiafiltration resulted in 80% higher Trp losses than conventional low-flux dialysis, despite similar neutral Trp RR values. In conclusion, serum Trp concentrations and RR behave differently from uremic solutes IS, IAA and urea and Trp RR did not reflect dialysis Trp losses. Conventional low-flux dialysis may not adequately clear Trp-related uremic toxins while high efficiency haemodiafiltration increased Trp losses.
Joosep Paats; Annika Adoberg; Jürgen Arund; Annemieke Dhondt; Anders Fernström; Ivo Fridolin; Griet Glorieux; Liisi Leis; Merike Luman; Emilio Gonzalez-Parra; Vanessa Maria Perez-Gomez; Kristjan Pilt; Didier Sanchez-Ospina; Mårten Segelmark; Fredrik Uhlin; Alberto Arduan Ortiz. Serum Levels and Removal by Haemodialysis and Haemodiafiltration of Tryptophan-Derived Uremic Toxins in ESKD Patients. International Journal of Molecular Sciences 2020, 21, 1522 .
AMA StyleJoosep Paats, Annika Adoberg, Jürgen Arund, Annemieke Dhondt, Anders Fernström, Ivo Fridolin, Griet Glorieux, Liisi Leis, Merike Luman, Emilio Gonzalez-Parra, Vanessa Maria Perez-Gomez, Kristjan Pilt, Didier Sanchez-Ospina, Mårten Segelmark, Fredrik Uhlin, Alberto Arduan Ortiz. Serum Levels and Removal by Haemodialysis and Haemodiafiltration of Tryptophan-Derived Uremic Toxins in ESKD Patients. International Journal of Molecular Sciences. 2020; 21 (4):1522.
Chicago/Turabian StyleJoosep Paats; Annika Adoberg; Jürgen Arund; Annemieke Dhondt; Anders Fernström; Ivo Fridolin; Griet Glorieux; Liisi Leis; Merike Luman; Emilio Gonzalez-Parra; Vanessa Maria Perez-Gomez; Kristjan Pilt; Didier Sanchez-Ospina; Mårten Segelmark; Fredrik Uhlin; Alberto Arduan Ortiz. 2020. "Serum Levels and Removal by Haemodialysis and Haemodiafiltration of Tryptophan-Derived Uremic Toxins in ESKD Patients." International Journal of Molecular Sciences 21, no. 4: 1522.
Aim To determine the most effective DNA extraction method for bacteria in fecal samples. Materials and Results This study assessed five commercial methods, i.e. NucliSens easyMag, QIAamp DNA Stool Mini kit, PureLink Microbiome DNA purification kit, QIAamp PowerFecal DNA kit, and RNeasy PowerMicrobiome kit, of which the latter has been optimized for DNA extraction. The DNA quantity and quality were determined using Nanodrop, Qubit and qPCR. The PowerMicrobiome kit recovered the highest DNA concentration, whereby this kit also recovered the highest gene copy number of Gram‐positives, Gram‐negatives and total bacteria. Furthermore, the PowerMicrobiome kit in combination with mechanical pre‐treatment (bead beating) and with combined enzymatic and mechanical pre‐treatment (proteinase K+mutanolysin+bead beating) was more effective than without pre‐treatment. Conclusion From the five DNA extraction methods that were compared, the PowerMicrobiome kit, preceded by bead beating, which is standard included, was found to be the most effective DNA extraction method for bacteria in fecal samples. Significance and impact of the study The quantity and quality of DNA extracted from human fecal samples is a first important step to optimize molecular methods. Here we have shown that the PowerMicrobiome kit is an effective DNA extraction method for bacterial cells in fecal samples for downstream qPCR purpose.
Tessa Gryp; Griet Glorieux; Marie Joossens; Mario Vaneechoutte. Comparison of five assays for DNA extraction from bacterial cells in human faecal samples. Journal of Applied Microbiology 2020, 129, 378 -388.
AMA StyleTessa Gryp, Griet Glorieux, Marie Joossens, Mario Vaneechoutte. Comparison of five assays for DNA extraction from bacterial cells in human faecal samples. Journal of Applied Microbiology. 2020; 129 (2):378-388.
Chicago/Turabian StyleTessa Gryp; Griet Glorieux; Marie Joossens; Mario Vaneechoutte. 2020. "Comparison of five assays for DNA extraction from bacterial cells in human faecal samples." Journal of Applied Microbiology 129, no. 2: 378-388.
Carbamoylation is an important risk factor for accelerated atherogenesis and mortality in patients undergoing hemodialysis (HD). We intended to explore whether carbamoylation as assessed by near-infrared (NIR) analysis of nail proteins is associated with (a) plasma concentrations of representative uremic toxins and (b) mortality in HD patients. A total of 53 healthy volunteers and 84 consecutive HD patients were enrolled in this cross-sectional cohort study. Standard laboratory methods were used to measure routine parameters, whereas levels of uremic toxins were determined using reversed-phase high-performance liquid chromatography (RP-HPLC). Spectra of distal fingernail clippings were obtained using an Avantes NIR spectrometer and processed using chemometric data analysis. The second derivative of the peak intensity at 1494 nm attributed to N-H amide bands from NH2 of carbamoyl (-CONH2) groups was higher in HD patients than in control subjects (p < 0.0001). Peak intensity levels were associated with age and plasma levels of representative uremic toxins. Cox-regression analysis revealed a significant association with all-cause mortality, even after adjustment for age. In conclusion, our data revealed that carbamoylation as assessed by NIR analysis of nail proteins is associated with plasma concentrations of uremic toxins and also with mortality in HD patients. Further research to explore whether it is a surrogate marker or a hard indicator of mortality risk is warranted.
Sander De Bruyne; Jonas Himpe; Sigurd E. Delanghe; Griet Glorieux; Wim Van Biesen; Marc L. De Buyzere; Marijn M. Speeckaert; Joris R. Delanghe; Delanghe. Carbamoylated Nail Proteins as Assessed by Near-Infrared Analysis Are Associated with Load of Uremic Toxins and Mortality in Hemodialysis Patients. Toxins 2020, 12, 83 .
AMA StyleSander De Bruyne, Jonas Himpe, Sigurd E. Delanghe, Griet Glorieux, Wim Van Biesen, Marc L. De Buyzere, Marijn M. Speeckaert, Joris R. Delanghe, Delanghe. Carbamoylated Nail Proteins as Assessed by Near-Infrared Analysis Are Associated with Load of Uremic Toxins and Mortality in Hemodialysis Patients. Toxins. 2020; 12 (2):83.
Chicago/Turabian StyleSander De Bruyne; Jonas Himpe; Sigurd E. Delanghe; Griet Glorieux; Wim Van Biesen; Marc L. De Buyzere; Marijn M. Speeckaert; Joris R. Delanghe; Delanghe. 2020. "Carbamoylated Nail Proteins as Assessed by Near-Infrared Analysis Are Associated with Load of Uremic Toxins and Mortality in Hemodialysis Patients." Toxins 12, no. 2: 83.
Advanced glycation end products (AGEs) are a class of proteins or lipids that are non-enzymatically glycated and oxidized after contact with aldose sugars. The accumulation of AGEs results in carbonyl stress, which is characteristic for diabetes mellitus, uremia, atherosclerosis and vascular dysfunction. In recent decades, several innovative methods have been developed to measure the concentration of AGEs in blood or urine. In the present study, we evaluated the use of UV fluorescence as an alternative tool to detect urinary AGEs in four groups of well characterized chronic kidney disease (CKD) patients over a wide range of kidney insufficiency and in a group of healthy subjects. Using an excitation wavelength of 365 nm, the fluorescence spectra of urinary AGEs were recorded in the 400–620 nm emission range. When considering the emission peaks at 440 nm and 490 nm, a significantly higher AGE-specific fluorescence intensity was detected in CKD patients compared to healthy subjects (p < 0.0001 and p = 0.0001, respectively). The urinary creatinine adjusted fluorescence emission spectra in the group of CKD patients with diabetes mellitus were comparable with those of CKD patients without diabetes mellitus. Creatinine-adjusted fluorescence emission spectra were highest in CKD patients with proteinuria, moderate in CKD patients without proteinuria and lowest in healthy controls (p < 0.0001 at both emission wavelengths). In a multiple regression analysis, age, CRP and insulin treatment were predictors of fluorescence intensity at the emission wavelength of 440 nm. Age and insulin treatment were predictors at 490 nm. The presented method is a simple, cheap, alternative method to monitor the AGE-load in the CKD population.
Mieke Steenbeke; Sander De Bruyne; Elisabeth Van Aken; Griet Glorieux; Wim Van Biesen; Jonas Himpe; Gilles De Meester; Marijn Speeckaert; Joris Delanghe. UV Fluorescence-Based Determination of Urinary Advanced Glycation End Products in Patients with Chronic Kidney Disease. Diagnostics 2020, 10, 34 .
AMA StyleMieke Steenbeke, Sander De Bruyne, Elisabeth Van Aken, Griet Glorieux, Wim Van Biesen, Jonas Himpe, Gilles De Meester, Marijn Speeckaert, Joris Delanghe. UV Fluorescence-Based Determination of Urinary Advanced Glycation End Products in Patients with Chronic Kidney Disease. Diagnostics. 2020; 10 (1):34.
Chicago/Turabian StyleMieke Steenbeke; Sander De Bruyne; Elisabeth Van Aken; Griet Glorieux; Wim Van Biesen; Jonas Himpe; Gilles De Meester; Marijn Speeckaert; Joris Delanghe. 2020. "UV Fluorescence-Based Determination of Urinary Advanced Glycation End Products in Patients with Chronic Kidney Disease." Diagnostics 10, no. 1: 34.
Background The urinary proteomic classifier chronic kidney disease 273 (CKD273) is predictive for the development and progression of chronic kidney disease (CKD) and/or albuminuria in type 2 diabetes. This study evaluates its role in the prediction of cardiovascular (CV) events in patients with CKD Stages G1–G5. Methods We applied the CKD273 classifier in a cohort of 451 patients with CKD Stages G1–G5 followed prospectively for a median of 5.5 years. Primary endpoints were all-cause mortality, CV mortality and the composite of non-fatal and fatal CV events (CVEs). Results In multivariate Cox regression models adjusting for age, sex, prevalent diabetes and CV history, the CKD273 classifier at baseline was significantly associated with total mortality and time to fatal or non-fatal CVE, but not CV mortality. Because of a significant interaction between CKD273 and CV history (P = 0.018) and CKD stages (P = 0.002), a stratified analysis was performed. In the fully adjusted models, CKD273 classifier was a strong and independent predictor of fatal or non-fatal CVE only in the subgroup of patients with CKD Stages G1–G3b and without a history of CV disease. In those patients, the highest tertile of CKD273 was associated with a >10-fold increased risk as compared with the lowest tertile. Conclusions The urinary CKD273 classifier provides additional independent information regarding the CV risk in patients with early CKD stage and a blank CV history. Determination of CKD273 scores on a random urine sample may improve the efficacy of intensified surveillance and preventive strategies by selecting patients who potentially will benefit most from early risk management.
Francis Verbeke; Justyna Siwy; Wim Van Biesen; Harald Mischak; Anneleen Pletinck; Eva Schepers; Nathalie Neirynck; Pedro Magalhães; Martin Pejchinovski; Claudia Pontillo; Ralf Lichtinghagen; Korbinian Brand; Antonia Vlahou; Dirk De Bacquer; Griet Glorieux. The urinary proteomics classifier chronic kidney disease 273 predicts cardiovascular outcome in patients with chronic kidney disease. Nephrology Dialysis Transplantation 2019, 36, 811 -818.
AMA StyleFrancis Verbeke, Justyna Siwy, Wim Van Biesen, Harald Mischak, Anneleen Pletinck, Eva Schepers, Nathalie Neirynck, Pedro Magalhães, Martin Pejchinovski, Claudia Pontillo, Ralf Lichtinghagen, Korbinian Brand, Antonia Vlahou, Dirk De Bacquer, Griet Glorieux. The urinary proteomics classifier chronic kidney disease 273 predicts cardiovascular outcome in patients with chronic kidney disease. Nephrology Dialysis Transplantation. 2019; 36 (5):811-818.
Chicago/Turabian StyleFrancis Verbeke; Justyna Siwy; Wim Van Biesen; Harald Mischak; Anneleen Pletinck; Eva Schepers; Nathalie Neirynck; Pedro Magalhães; Martin Pejchinovski; Claudia Pontillo; Ralf Lichtinghagen; Korbinian Brand; Antonia Vlahou; Dirk De Bacquer; Griet Glorieux. 2019. "The urinary proteomics classifier chronic kidney disease 273 predicts cardiovascular outcome in patients with chronic kidney disease." Nephrology Dialysis Transplantation 36, no. 5: 811-818.
Identifying the key toxic players within an in-vivo toxic syndrome is crucial to develop targeted therapies. Here, we established a novel method that characterizes the effect of single substances by means of an ex-vivo incubation set-up. We found that primary human spermatozoa elicit a distinct motile response on a (uremic) toxic milieu. Specifically, this approach describes the influence of a bulk toxic environment (uremia) as well as single substances (uremic toxins) by real-time analyzing motile cellular behavior. We established the human spermatozoa-based toxicity testing (HSTT) for detecting single substance-induced toxicity to be used as a screening tool to identify in-vivo toxins. Further, we propose an application of the HSTT as a method of clinical use to evaluate toxin-removing interventions (hemodialysis).
Tino Vollmer; Börje Ljungberg; Vera Jankowski; Joachim Jankowski; Griet Glorieux; Bernd G. Stegmayr. An in-vitro assay using human spermatozoa to detect toxicity of biologically active substances. Scientific Reports 2019, 9, 1 -11.
AMA StyleTino Vollmer, Börje Ljungberg, Vera Jankowski, Joachim Jankowski, Griet Glorieux, Bernd G. Stegmayr. An in-vitro assay using human spermatozoa to detect toxicity of biologically active substances. Scientific Reports. 2019; 9 (1):1-11.
Chicago/Turabian StyleTino Vollmer; Börje Ljungberg; Vera Jankowski; Joachim Jankowski; Griet Glorieux; Bernd G. Stegmayr. 2019. "An in-vitro assay using human spermatozoa to detect toxicity of biologically active substances." Scientific Reports 9, no. 1: 1-11.
Intermediate (CD14++CD16+) monocytes have important pro-inflammatory and atherogenic features and are increased in patients with chronic kidney disease (CKD). The present study aims to elucidate the role of the uremic milieu and of platelet activation in monocyte differentiation. Monocyte subtypes were analyzed in CKD patients (n = 193) and healthy controls (n = 27). Blood from healthy controls (Ctrl; n = 8) and hemodialysis patients (HD; n = 8) was centrifuged, and plasma (pl) was exchanged between Ctrl and HD (Ctrlcells/HDpl and HDcells/Ctrlpl) or reconstituted as original (Ctrlsham and HDsham) and incubated for 24 h (T24). Monocyte differentiation and platelet aggregation to monocytes (MPA) was assessed by flow cytometry. Especially, a higher proportion of CD14++CD16+ monocytes was found in hemodialysis (HD) patients (p < 0.01). In plasma exchange experiments, Ctrl cells/HD pl T24 showed an increased percentage of CD14++CD16+ monocytes versus Ctrl sham (33.7% ± 15 vs. 15.7% ± 9.6; P < 0.005), comparable to the level of CD14++CD16+ monocytes in the HD sham condition. The percentage of CD14++CD16+ monocytes was lowered by suspending HD cells in Ctrl pl (18.4% ± 7.8 vs. 36.7% ± 15 in HD sham; P < 0.005) reaching the level of the Ctrl sham condition (15.7% ± 9.6). A mixture of uremic sulfates increased CD14++CD16+ monocytes compared to control (19.8 ± 9.6% vs. 15.8 ± 10.9%; P < 0.05), paralleled by a rise MPA. Blocking MPA by abciximab, a potential therapeutic strategy, or anti-CD62P did not inhibit differentiation towards the CD14++CD16+ monocytes. In conclusion, in the present cohort, CD14++CD16+ monocytes are especially increased in HD patients and this can at least in part be attributed to the presence of the uremic milieu, with uremic sulfates inducing a reversible shift towards pro-inflammatory CD14++CD16+ monocytes.
Natalia Borges Bonan; Eva Schepers; Roberto Pecoits-Filho; Annemieke Dhondt; Anneleen Pletinck; Filip De Somer; Raymond Vanholder; Wim Van Biesen; Andréa Moreno-Amaral; Griet Glorieux. Contribution of the uremic milieu to an increased pro-inflammatory monocytic phenotype in chronic kidney disease. Scientific Reports 2019, 9, 1 -11.
AMA StyleNatalia Borges Bonan, Eva Schepers, Roberto Pecoits-Filho, Annemieke Dhondt, Anneleen Pletinck, Filip De Somer, Raymond Vanholder, Wim Van Biesen, Andréa Moreno-Amaral, Griet Glorieux. Contribution of the uremic milieu to an increased pro-inflammatory monocytic phenotype in chronic kidney disease. Scientific Reports. 2019; 9 (1):1-11.
Chicago/Turabian StyleNatalia Borges Bonan; Eva Schepers; Roberto Pecoits-Filho; Annemieke Dhondt; Anneleen Pletinck; Filip De Somer; Raymond Vanholder; Wim Van Biesen; Andréa Moreno-Amaral; Griet Glorieux. 2019. "Contribution of the uremic milieu to an increased pro-inflammatory monocytic phenotype in chronic kidney disease." Scientific Reports 9, no. 1: 1-11.
To better understand the kinetics of protein-bound uremic toxins (PBUTs) during hemodialysis (HD), we investigated the distribution of hippuric acid (HA), indole-3-acetic acid (IAA), indoxyl sulfate (IS), and p-cresyl sulfate (pCS) in erythrocytes of HD patients. Their transport across the erythrocyte membrane was explored in the absence of plasma proteins in vitro in a series of loading and unloading experiments of erythrocytes from healthy subjects and HD patients, respectively. Furthermore, the impact of three inhibitors of active transport proteins in erythrocytes was studied. The four PBUTs accumulated in erythrocytes from HD patients. From loading and unloading experiments, it was found that (i) the rate of transport was dependent on the studied PBUT and increased in the following sequence: HA < IS < pCS < IAA and (ii) the solute partition of intra- to extra-cellular concentrations was uneven at equilibrium. Finally, inhibiting especially Band 3 proteins affected the transport of HA (both in loading and unloading), and of IS and pCS (loading). By exploring erythrocyte transmembrane transport of PBUTs, their kinetics can be better understood, and new strategies to improve their dialytic removal can be developed.
Olivier Deltombe; Griet Glorieux; Sami Marzouki; Rosalinde Masereeuw; Daniel Schneditz; Sunny Eloot. Selective Transport of Protein-Bound Uremic Toxins in Erythrocytes. Toxins 2019, 11, 385 .
AMA StyleOlivier Deltombe, Griet Glorieux, Sami Marzouki, Rosalinde Masereeuw, Daniel Schneditz, Sunny Eloot. Selective Transport of Protein-Bound Uremic Toxins in Erythrocytes. Toxins. 2019; 11 (7):385.
Chicago/Turabian StyleOlivier Deltombe; Griet Glorieux; Sami Marzouki; Rosalinde Masereeuw; Daniel Schneditz; Sunny Eloot. 2019. "Selective Transport of Protein-Bound Uremic Toxins in Erythrocytes." Toxins 11, no. 7: 385.
Protein-bound uremic toxins (PBUTs) play a role in the multisystem disease that children on hemodialysis (HD) are facing, but little is known about their levels and protein binding (%PB). In this study, we evaluated the levels and %PB of six PBUTs cross-sectionally in a large pediatric HD cohort (n = 170) by comparing these with healthy and non-dialysis chronic kidney disease (CKD) stage 4–5 (n = 24) children. In parallel β2-microglobulin (β2M) and uric acid (UA) were evaluated. We then explored the impact of age and residual kidney function on uremic toxin levels and %PB using analysis of covariance and Spearman correlation coefficients (rs). We found higher levels of β2M, p-cresyl glucuronide (pCG), hippuric acid (HA), indole acetic acid (IAA), and indoxyl sulfate (IxS) in the HD compared to the CKD4–5 group. In the HD group, a positive correlation between age and pCG, HA, IxS, and pCS levels was shown. Residual urine volume was negatively correlated with levels of β2M, pCG, HA, IAA, IxS, and CMPF (rs −0.2 to −0.5). In addition, we found overall lower %PB of PBUTs in HD versus the CKD4–5 group, and showed an age-dependent increase in %PB of IAA, IxS, and pCS. Furhtermore, residual kidney function was overall positively correlated with %PB of PBUTs. In conclusion, residual kidney function and age contribute to PBUT levels and %PB in the pediatric HD population.
Evelien Snauwaert; Els Holvoet; Wim Van Biesen; Ann Raes; Griet Glorieux; Johan Vande Walle; Sanne Roels; Raymond Vanholder; Varvara Askiti; Karolis Azukaitis; Aysun Bayazit; Nur Canpolat; Michel Fischbach; Nathalie Godefroid; Saoussen Krid; Mieczyslaw Litwin; Lukasz Obrycki; Fabio Paglialonga; Bruno Ranchin; Charlotte Samaille; Franz Schaefer; Claus Peter Schmitt; Brankica Spasojevic; Constantinos J. Stefanidis; Maria Van Dyck; Koen Van Hoeck; Laure Collard; Sunny Eloot; Rukshana Shroff. Uremic Toxin Concentrations are Related to Residual Kidney Function in the Pediatric Hemodialysis Population. Toxins 2019, 11, 235 .
AMA StyleEvelien Snauwaert, Els Holvoet, Wim Van Biesen, Ann Raes, Griet Glorieux, Johan Vande Walle, Sanne Roels, Raymond Vanholder, Varvara Askiti, Karolis Azukaitis, Aysun Bayazit, Nur Canpolat, Michel Fischbach, Nathalie Godefroid, Saoussen Krid, Mieczyslaw Litwin, Lukasz Obrycki, Fabio Paglialonga, Bruno Ranchin, Charlotte Samaille, Franz Schaefer, Claus Peter Schmitt, Brankica Spasojevic, Constantinos J. Stefanidis, Maria Van Dyck, Koen Van Hoeck, Laure Collard, Sunny Eloot, Rukshana Shroff. Uremic Toxin Concentrations are Related to Residual Kidney Function in the Pediatric Hemodialysis Population. Toxins. 2019; 11 (4):235.
Chicago/Turabian StyleEvelien Snauwaert; Els Holvoet; Wim Van Biesen; Ann Raes; Griet Glorieux; Johan Vande Walle; Sanne Roels; Raymond Vanholder; Varvara Askiti; Karolis Azukaitis; Aysun Bayazit; Nur Canpolat; Michel Fischbach; Nathalie Godefroid; Saoussen Krid; Mieczyslaw Litwin; Lukasz Obrycki; Fabio Paglialonga; Bruno Ranchin; Charlotte Samaille; Franz Schaefer; Claus Peter Schmitt; Brankica Spasojevic; Constantinos J. Stefanidis; Maria Van Dyck; Koen Van Hoeck; Laure Collard; Sunny Eloot; Rukshana Shroff. 2019. "Uremic Toxin Concentrations are Related to Residual Kidney Function in the Pediatric Hemodialysis Population." Toxins 11, no. 4: 235.
There is a gradual increase in serum concentrations of protein-bound colon-derived uremic toxins indoxyl sulphate (IxS) and p-cresyl sulphate (pCS) as chronic kidney disease (CKD) progresses. In acute kidney injury (AKI), up till now, the retention pattern has not been studied. In this study, 194 adult patients admitted with sepsis to the intensive care unit were included. IxS, pCS and serum creatinine (sCrea) were quantified at inclusion (D0) and at day 4, unless follow-up ended earlier (Dend). Serum levels of sCrea (P < 0.001), IxS (P < 0.001) and pCS (P < 0.05) were higher in patients with AKI according to RIFLE classification at D0. In contrast with sCrea, IxS and pCS levels only increased from stage I (IxS) and F (pCS) on. When grouped according to evolution in RIFLE class from D0 to Dend, all solute concentrations were higher (P < 0.001) in the group with unfavourable evolution. In this group, there was a marked rise in sCrea (P < 0.001), a moderate one for pCS (P < 0.05), but no change for IxS (P = 0.112). There was a decrease (P < 0.001) of all solute concentrations in the group with favourable evolution. Comparing AKI with CKD patients matched for sCrea, total levels of both IxS and pCS were higher (P < 0.01) in patients with CKD. Although concentrations of IxS and pCS both tend to rise in sepsis patients with AKI, their evolution does not conform with that of sCrea. For the same level of sCrea, IxS and pCS concentrations are lower in AKI compared with CKD.
Laurens Veldeman; Jill Vanmassenhove; Wim Van Biesen; Ziad A. Massy; Sophie Liabeuf; Griet Glorieux; Raymond Vanholder. Evolution of protein-bound uremic toxins indoxyl sulphate and p-cresyl sulphate in acute kidney injury. International Urology and Nephrology 2019, 51, 293 -302.
AMA StyleLaurens Veldeman, Jill Vanmassenhove, Wim Van Biesen, Ziad A. Massy, Sophie Liabeuf, Griet Glorieux, Raymond Vanholder. Evolution of protein-bound uremic toxins indoxyl sulphate and p-cresyl sulphate in acute kidney injury. International Urology and Nephrology. 2019; 51 (2):293-302.
Chicago/Turabian StyleLaurens Veldeman; Jill Vanmassenhove; Wim Van Biesen; Ziad A. Massy; Sophie Liabeuf; Griet Glorieux; Raymond Vanholder. 2019. "Evolution of protein-bound uremic toxins indoxyl sulphate and p-cresyl sulphate in acute kidney injury." International Urology and Nephrology 51, no. 2: 293-302.
Although the relationship between protein-bound uremic toxins (PBUTs) and cardiac structure and cardiac mortality in chronic kidney disease (CKD) has been studied in the past, the association between cardiac dysfunction and PBUTs has not yet been studied. We therefore evaluated the association between impaired peak cardiac performance and the serum free and total concentrations of potentially cardiotoxic PBUTs. In a cross-sectional study of 56 male CKD patients (stages 2–5 (pre-dialysis)) who were asymptomatic with no known cardiac diseases or diabetes we measured peak cardiac power (CPOmax), aerobic exercise capacity (VO2max), and echocardiographic parameters of cardiac morphology and evaluated their association with PBUTs. The serum total and free concentrations of indoxyl sulfate (IXS), p-cresyl sulfate (PCS), p-cresyl glucuronide, indole acetic acid, and hippuric acid showed significant negative correlation with CPOmax and VO2max. IXS and PCS were independently associated with CPOmax and VO2max even after controlling for eGFR. No correlation between left ventricular mass index (LVMI) and PBUTs was seen. The present study for the first time has demonstrated the association between subclinical cardiac dysfunction in CKD and serum levels of a panel of PBUTs. Further studies are required to evaluate the mechanism of cardiotoxicity of the individual uremic toxins.
Shanmugakumar Chinnappa; Yu-Kang Tu; Yi Chun Yeh; Griet Glorieux; Raymond Vanholder; Andrew Mooney. Association between Protein-Bound Uremic Toxins and Asymptomatic Cardiac Dysfunction in Patients with Chronic Kidney Disease. Toxins 2018, 10, 520 .
AMA StyleShanmugakumar Chinnappa, Yu-Kang Tu, Yi Chun Yeh, Griet Glorieux, Raymond Vanholder, Andrew Mooney. Association between Protein-Bound Uremic Toxins and Asymptomatic Cardiac Dysfunction in Patients with Chronic Kidney Disease. Toxins. 2018; 10 (12):520.
Chicago/Turabian StyleShanmugakumar Chinnappa; Yu-Kang Tu; Yi Chun Yeh; Griet Glorieux; Raymond Vanholder; Andrew Mooney. 2018. "Association between Protein-Bound Uremic Toxins and Asymptomatic Cardiac Dysfunction in Patients with Chronic Kidney Disease." Toxins 10, no. 12: 520.