المؤلفون: Vanholder, Raymond, Pletinck, Anneleen, Schepers, Eva, Glorieux, Griet

المصدر: TOXINS ; ISSN: 2072-6651

مصطلحات موضوعية: Medicine and Health Sciences, CHRONIC KIDNEY-DISEASE, CHRONIC-RENAL-FAILURE, GLYCATION END-PRODUCTS, RETINOL-BINDING-PROTEIN, COLONY-STIMULATING FACTOR, ATRIAL-NATRIURETIC-PEPTIDE, CORONARY-ARTERY-DISEASE, FURAN, DICARBOXYLIC-ACID, TOXIN PHENYLACETIC ACID, NITRIC-OXIDE SYNTHASE, uremic toxins, uremic toxicity, uremia, Chronic Kidney Disease, CKD, cardiovascular disease, inflammation, fibrosis, patho-physiology CKD, middle molecules, protein bound uremic solutes, water-soluble uremic, solutes

الوصف: In this narrative review, the biological/biochemical impact (toxicity) of a large array of known individual uremic retention solutes and groups of solutes is summarized. We classified these compounds along their physico-chemical characteristics as small water-soluble compounds or groups, protein bound compounds and middle molecules. All but one solute (glomerulopressin) affected at least one mechanism with the potential to contribute to the uremic syndrome. In general, several mechanisms were influenced for each individual solute or group of solutes, with some impacting up to 7 different biological systems of the 11 considered. The inflammatory, cardio-vascular and fibrogenic systems were those most frequently affected and they are one by one major actors in the high morbidity and mortality of CKD but also the mechanisms that have most frequently been studied. A scoring system was built with the intention to classify the reviewed compounds according to the experimental evidence of their toxicity (number of systems affected) and overall experimental and clinical evidence. Among the highest globally scoring solutes were 3 small water-soluble compounds [asymmetric dimethylarginine (ADMA); trimethylamine-N-oxide (TMAO); uric acid], 6 protein bound compounds or groups of protein bound compounds [advanced glycation end products (AGEs); p-cresyl sulfate; indoxyl sulfate; indole acetic acid; the kynurenines; phenyl acetic acid;] and 3 middle molecules [(2)-microglobulin; ghrelin; parathyroid hormone). In general, more experimental data were provided for the protein bound molecules but for almost half of them clinical evidence was missing in spite of robust experimental data. The picture emanating is one of a complex disorder, where multiple factors contribute to a multisystem complication profile, so that it seems of not much use to pursue a decrease of concentration of a single compound.

وصف الملف: application/pdf

العلاقة: https://biblio.ugent.be/publication/8569371Test; http://hdl.handle.net/1854/LU-8569371Test; http://dx.doi.org/10.3390/toxins10010033Test; https://biblio.ugent.be/publication/8569371/file/8569372Test

الإتاحة: https://doi.org/10.3390/toxins10010033Test
https://biblio.ugent.be/publication/8569371Test
http://hdl.handle.net/1854/LU-8569371Test
https://biblio.ugent.be/publication/8569371/file/8569372Test

المؤلفون: Delanghe, Sigurd, Van Biesen, Wim, Van de Velde, Nadeige, Eloot, Sunny, Pletinck, Anneleen, Schepers, Eva, Glorieux, Griet, Delanghe, Joris, Speeckaert, Marijn

المصدر: CLINICAL CHEMISTRY AND LABORATORY MEDICINE ; ISSN: 1434-6621

مصطلحات موضوعية: Medicine and Health Sciences, albumin, bromocresol green, bromocresol purple, carbamylation, para-cresyl sulfate, uremic toxins, CHRONIC KIDNEY-DISEASE, BOUND UREMIC SOLUTES, P-CRESYL SULFATE, SERUM-ALBUMIN, INDOXYL SULFATE, ALPHA-1-ACID GLYCOPROTEIN, PROTEIN CARBAMYLATION, ENDOGENOUS LIGANDS, RENAL-FAILURE, TOXINS

الوصف: BACKGROUND: Colorimetric albumin assays based on binding to bromocresol purple (BCP) and bromocresol green (BCG) yield different results in chronic kidney disease. Altered dye binding of carbamylated albumin has been suggested as a cause. In the present study, a detailed analysis was carried out in which uremic toxins, acute phase proteins and Kt/V, a parameter describing hemodialysis efficiency, were compared with colorimetrically assayed (BCP and BCG) serum albumin. METHODS: Albumin was assayed using immunonephelometry on a BN II nephelometer and colorimetrically based on, respectively, BCP and BCG on a Modular P analyzer. Uremic toxins were assessed using high-performance liquid chromatography. Acute phase proteins (C-reactive protein and α1-acid glycoprotein) and plasma protein α2-macroglobulin were assayed nephelometrically. In parallel, Kt/V was calculated. RESULTS: Sixty-two serum specimens originating from hemodialysis patients were analyzed. Among the uremic toxins investigated, total para-cresyl sulfate (PCS) showed a significant positive correlation with the BCP/BCG ratio. The serum α1-acid glycoprotein concentration correlated negatively with the BCP/BCG ratio. The BCP/BCG ratio showed also a negative correlation with Kt/V. CONCLUSIONS: In renal insufficiency, the BCP/BCG ratio of serum albumin is affected by multiple factors: next to carbamylation, uremic toxins (total PCS) and α1-acid glycoprotein also play a role.

وصف الملف: application/pdf

العلاقة: https://biblio.ugent.be/publication/8542865Test; http://hdl.handle.net/1854/LU-8542865Test; http://dx.doi.org/10.1515/cclm-2017-0444Test; https://biblio.ugent.be/publication/8542865/file/8542866Test

الإتاحة: https://doi.org/10.1515/cclm-2017-0444Test
https://biblio.ugent.be/publication/8542865Test
http://hdl.handle.net/1854/LU-8542865Test
https://biblio.ugent.be/publication/8542865/file/8542866Test

المؤلفون: Vanholder, Raymond, Schepers, Eva, Pletinck, Anneleen, Nagler, Evi, Glorieux, Griet

المصدر: JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY ; ISSN: 1046-6673

مصطلحات موضوعية: Medicine and Health Sciences, NF-KAPPA-B, REGULATES RENAL EXPRESSION, CHRONIC KIDNEY-DISEASE, PROXIMAL TUBULAR CELLS, ALL-CAUSE MORTALITY, HEMODIALYSIS-PATIENTS, OXIDATIVE STRESS, ENDOTHELIAL-CELLS, CARDIOVASCULAR-DISEASE, HYPERTENSIVE-RATS

الوصف: A growing number of publications supports a biologic effect of the protein-bound uremic retention solutes indoxyl sulfate and p-cresyl sulfate. However, the use of unrealistically high free concentrations of these compounds and/or inappropriately low albumin concentrations may blur the interpretation of these results. Here, we performed a systematic review, selecting only studies in which, depending on the albumin concentration, real or extrapolated free concentrations of indoxyl sulfate and p-cresyl sulfate remained in the uremic range. The 27 studies retrieved comprised in vitro and animal studies. A quality score was developed, giving 1 point for each of the following criteria: six or more experiments, confirmation by more than one experimental approach, neutralization of the biologic effect by counteractive reagents or antibodies, use of a real-life model, and use of dose-response analyses in vitro and/or animal studies. The overall average score was 3 of 5 points, with five studies scoring 5 of 5 points and six studies scoring 4 of 5 points, highlighting the superior quality of a substantial number of the retrieved studies. In the 11 highest scoring studies, most functional deteriorations were related to uremic cardiovascular disease and kidney damage. We conclude that our systematic approach allowed the retrieval of methodologically correct studies unbiased by erroneous conditions related to albumin binding. Our data seem to confirm the toxicity of indoxyl sulfate and p-cresyl sulfate and support their roles in vascular and renal disease progression.

وصف الملف: application/pdf

العلاقة: https://biblio.ugent.be/publication/5805901Test; http://hdl.handle.net/1854/LU-5805901Test; http://dx.doi.org/10.1681/ASN.2013101062Test; https://biblio.ugent.be/publication/5805901/file/5805909Test

الإتاحة: https://doi.org/10.1681/ASN.2013101062Test
https://biblio.ugent.be/publication/5805901Test
http://hdl.handle.net/1854/LU-5805901Test
https://biblio.ugent.be/publication/5805901/file/5805909Test

المؤلفون: Neirynck, Nathalie, Vanholder, Raymond, Schepers, Eva, Eloot, Sunny, Pletinck, Anneleen, Glorieux, Griet

المصدر: INTERNATIONAL UROLOGY AND NEPHROLOGY ; ISSN: 0301-1623

مصطلحات موضوعية: Medicine and Health Sciences, HIGH-FLUX HEMODIALYSIS, CHRONIC KIDNEY-DISEASE, CHRONIC-RENAL-FAILURE, CORONARY-ARTERY-DISEASE, PROTEIN-BOUND SOLUTES, P-CRESYL SULFATE, FRACTIONATED PLASMA SEPARATION, LEFT-VENTRICULAR HYPERTROPHY, RANDOMIZED CONTROLLED-TRIAL, NITRIC-OXIDE SYNTHASE, Indoxylsulfate, Cardiovascular disease, Uremic toxins, Uremia

الوصف: In the last decade, uremic toxicity as a potential cause for the excess of cardiovascular disease and mortality observed in chronic kidney disease gained more and more interest. This review focuses on uremic toxins with known cardiovascular effects and their removal. For protein-bound solutes, for example, indoxylsulfate and the conjugates of p-cresol, and for small water-soluble solutes, for example, guanidines, such as ADMA and SDMA, there is a growing evidence for a role in cardiovascular toxicity in vitro (e.g., affecting leukocyte, endothelial, vascular smooth muscle cell function) and/or in vivo. Several middle molecules (e.g., beta-2-microglobulin, interleukin-6, TNF-alpha and FGF-23) were shown to be predictors for cardiovascular disease and/or mortality. Most of these solutes, however, are difficult to remove during dialysis, which is traditionally assessed by studying the removal of urea, which can be considered as a relatively inert uremic retention solute. However, even the effective removal of other small water-soluble toxins than urea can be hampered by their larger distribution volumes. Middle molecules (beta-2-microglobulin as prototype, but not necessarily representative for others) are cleared more efficiently when the pore size of the dialyzer membrane increases, convection is applied and dialysis time is prolonged. Only adding convection to diffusion improves the removal of protein-bound toxins. Therefore, alternative removal strategies, such as intestinal adsorption, drugs interfering with toxic biochemical pathways or decreasing toxin concentration, and extracorporeal plasma adsorption, as well as kinetic behavior during dialysis need further investigation. Even more importantly, randomized clinical studies are required to demonstrate a survival advantage through these strategies.

وصف الملف: application/pdf

العلاقة: https://biblio.ugent.be/publication/4082496Test; http://hdl.handle.net/1854/LU-4082496Test; http://dx.doi.org/10.1007/s11255-012-0258-1Test; https://biblio.ugent.be/publication/4082496/file/4082506Test

الإتاحة: https://doi.org/10.1007/s11255-012-0258-1Test
https://biblio.ugent.be/publication/4082496Test
http://hdl.handle.net/1854/LU-4082496Test
https://biblio.ugent.be/publication/4082496/file/4082506Test

المؤلفون: Pletinck, Anneleen, Glorieux, Griet, Schepers, Eva, Cohen, Gerald, Gondouin, Bertrand, Van Landschoot, Maria, Eloot, Sunny, Rops, Angelique, Van de Voorde, Johan, De Vriese, An, van der Vlag, Johan, Brunet, Philippe, Van Biesen, Wim, Vanholder, Raymond

المصدر: JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY ; ISSN: 1046-6673

مصطلحات موضوعية: Medicine and Health Sciences, FREE P-CRESOL, CHRONIC-RENAL-FAILURE, INDOXYL SULFATE, HEMODIALYSIS-PATIENTS, HEPARAN-SULFATE, CARDIOVASCULAR-DISEASE, OXIDATIVE STRESS, IN-VIVO, GLOMERULAR ENDOTHELIAL-CELLS, CHRONIC KIDNEY-DISEASE

الوصف: Leukocyte activation and endothelial damage both contribute to cardiovascular disease, a major cause of morbidity and mortality in CKD. Experimental in vitro data link several protein-bound uremic retention solutes to the modulation of inflammatory stimuli, including endothelium and leukocyte responses and cardiovascular damage, corroborating observational in vivo data. However, the impact of these uremic toxins on the crosstalk between endothelium and leukocytes has not been assessed. This study evaluated the effects of acute and continuous exposure to uremic levels of indoxylsulfate (IS), p-cresylsulfate (pCS), and p-cresylglucuronide (pCG) on the recruitment of circulating leukocytes in the rat peritoneal vascular bed using intravital microscopy. Superfusion with IS induced strong leukocyte adhesion, enhanced extravasation, and interrupted blood flow, whereas pCS caused a rapid increase in leukocyte rolling. Superfusion with pCS and pCG combined caused impaired blood flow and vascular leakage but did not further enhance leukocyte rolling over pCS alone. Intravenous infusion with IS confirmed the superfusion results and caused shedding of heparan sulfate, pointing to disruption of the glycocalyx as the mechanism likely mediating IS-induced flow stagnation. These results provide the first clear in vivo evidence that IS, pCS, and pCG exert proinflammatory effects that contribute to vascular damage by stimulating crosstalk between leukocytes and vessels.

وصف الملف: application/pdf

العلاقة: https://biblio.ugent.be/publication/4267941Test; http://hdl.handle.net/1854/LU-4267941Test; http://dx.doi.org/10.1681/ASN.2012030281Test; https://biblio.ugent.be/publication/4267941/file/4298443Test

الإتاحة: https://doi.org/10.1681/ASN.2012030281Test
https://biblio.ugent.be/publication/4267941Test
http://hdl.handle.net/1854/LU-4267941Test
https://biblio.ugent.be/publication/4267941/file/4298443Test

المؤلفون: Gondouin, Bertrand, Cerini, Claire, Dou, Laetitia, Sallée, Marion, Duval-Sabatier, Ariane, Pletinck, Anneleen, Calaf, Raymond, Lacroix, Romanic, Jourde-Chiche, Noémie, Poitevin, Stéphane, Arnaud, Laurent, Vanholder, Raymond, Brunet, Philippe, Dignat-George, Fran§oise, Burtey, Stéphane

المصدر: KIDNEY INTERNATIONAL ; ISSN: 0085-2538

مصطلحات موضوعية: Medicine and Health Sciences, CHRONIC KIDNEY-DISEASE, FACTOR UP-REGULATION, uremic solutes, tissue factor, aryl hydrocarbon receptor, FACTOR EXPRESSION, OXIDATIVE STRESS, CARDIOVASCULAR-DISEASES, HEMODIALYSIS-PATIENTS, RESPONSE ELEMENT, GENE-EXPRESSION, ACTIVATION, INFLAMMATION

الوصف: In chronic kidney disease (CKD), uremic solutes accumulate in blood and tissues. These compounds probably contribute to the marked increase in cardiovascular risk during the progression of CKD. The uremic solutes indoxyl sulfate and indole-3-acetic acid (IAA) are particularly deleterious for endothelial cells. Here we performed microarray and comparative PCR analyses to identify genes in endothelial cells targeted by these two uremic solutes. We found an increase in endothelial expression of tissue factor in response to indoxyl sulfate and IAA and upregulation of eight genes regulated by the transcription factor aryl hydrocarbon receptor (AHR). The suggestion by microarray analysis of an involvement of AHR in tissue factor production was confirmed by siRNA inhibition and the indirect AHR inhibitor geldanamycin. These observations were extended to peripheral blood mononuclear cells. Tissue factor expression and activity were also increased by AHR agonist dioxin. Finally, we measured circulating tissue factor concentration and activity in healthy control subjects and in patients with CKD (stages 3-5d), and found that each was elevated in patients with CKD. Circulating tissue factor levels were positively correlated with plasma indoxyl sulfate and IAA. Thus, indolic uremic solutes increase tissue factor production in endothelial and peripheral blood mononuclear cells by AHR activation, evoking a 'dioxin-like' effect. This newly described mechanism of uremic solute toxicity may help understand the high cardiovascular risk of CKD patients.

وصف الملف: application/pdf

العلاقة: https://biblio.ugent.be/publication/4217060Test; http://hdl.handle.net/1854/LU-4217060Test; http://dx.doi.org/10.1038/ki.2013.133Test; https://biblio.ugent.be/publication/4217060/file/4217077Test

الإتاحة: https://doi.org/10.1038/ki.2013.133Test
https://biblio.ugent.be/publication/4217060Test
http://hdl.handle.net/1854/LU-4217060Test
https://biblio.ugent.be/publication/4217060/file/4217077Test