Journal ArticleDOI
Albumin is the main plasma binding protein for indoxyl sulfate and p-cresyl sulfate
Liesbeth Viaene,Pieter Annaert,Henriette de Loor,Ruben Poesen,Pieter Evenepoel,Björn Meijers +5 more
TLDR
The ultrafiltration–HPLC technique reliably measures free serum concentrations of indoxyl sulfate and p‐cresyl sulfates and indicates that competition for this binding site could be used to augment free solute concentrations during dialysis, thus improving epuration.Abstract:
Indoxyl sulfate and p-cresyl sulfate are two uremic retention solutes implicated in the uremic syndrome. Removal during dialysis is limited, mainly due to protein binding. Binding characteristics to healthy albumin have recently been characterized. Whether uremia alters the binding characteristics of albumin is currently unknown. Moreover, protein binding values previously determined with ultrafiltration are in sharp contrast to recently reported values based on microcalorimetry. In the present study, indoxyl sulfate and p-cresyl sulfate binding were therefore quantified using both equilibrium dialysis and ultrafiltration. Deming regression demonstrated good agreement between equilibrium dialysis and ultrafiltration. Free serum concentrations of indoxyl sulfate (+26.6%) and p-cresyl sulfate (+19.7%) were slightly higher at body temperature compared with at room temperature. To investigate binding kinetics, the plasma of healthy individuals or hemodialysis patients was titrated with albumin solutions. Theoretical models of protein binding were fitted to observed titration curves. Binding coefficients of both toxins were highest in purified albumin, and were reduced from healthy to uremic plasma. In conclusion, the ultrafiltration-HPLC technique reliably measures free serum concentrations of indoxyl sulfate and p-cresyl sulfate. Albumin is the main binding protein, both in health and in advanced stages of chronic kidney disease. Modeling suggests that albumin contains two binding sites for both toxins, a single high affinity binding site and a second low affinity binding site. The high affinity binding site accounts for at least 90% of overall binding. Competition for this binding site could be used to augment free solute concentrations during dialysis, thus improving epuration.read more
Citations
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Journal ArticleDOI
The Uremic Toxicity of Indoxyl Sulfate and p-Cresyl Sulfate: A Systematic Review
TL;DR: A systematic approach allowed the retrieval of methodologically correct studies unbiased by erroneous conditions related to albumin binding, and the data seem to confirm the toxicity of indoxyl sulfate and p-cresyl sulfates and support their roles in vascular and renal disease progression.
Journal ArticleDOI
Meta-Analysis of the Associations of p-Cresyl Sulfate (PCS) and Indoxyl Sulfate (IS) with Cardiovascular Events and All-Cause Mortality in Patients with Chronic Renal Failure.
TL;DR: Elevated levels of PCS and IS are associated with increased mortality in patients with CKD, while PCS, but not IS, is associated with an increased risk of cardiovascular events.
Journal ArticleDOI
The gut-kidney axis.
TL;DR: An increasing body of evidence indicates that crosstalk between host and microbiota is pathophysiologically relevant in patients with chronic kidney disease (CKD); these co-metabolites are an appealing target for adjuvant therapy in CKD.
Journal ArticleDOI
Bioengineered kidney tubules efficiently excrete uremic toxins
Jitske Jansen,Michele Fedecostante,Martijn J. Wilmer,Janny G. P. Peters,U.M. Kreuser,P. van den Broek,Rens A. Mensink,Thomas J. Boltje,Dimitrios Stamatialis,Jack F.M. Wetzels,L.P.W.J. van den Heuvel,L.P.W.J. van den Heuvel,Joost G. J. Hoenderop,Rosalinde Masereeuw +13 more
TL;DR: A newly designed bioengineered renal tubule capable of active uremic toxin secretion through the concerted action of essential renal transporters, viz. organic anion transporter-1 (OAT1), breast cancer resistance protein (BCRP) and multidrug resistance protein-4 (MRP4) is presented.
Journal ArticleDOI
Exploring Protein Binding of Uremic Toxins in Patients with Different Stages of Chronic Kidney Disease and during Hemodialysis
TL;DR: Findings explain why protein-bound solutes are difficult to remove by dialysis: a combination of the fact that only the free fraction can pass the filter and the equilibrium cannot be restored during the dialysis session, as it is continuously disturbed.
References
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The Original Michaelis Constant: Translation of the 1913 Michaelis–Menten Paper
TL;DR: This reanalysis of Michaelis and Menten's data using modern computational methods revealed an unanticipated rigor and precision in the original publication and uncovered a sophisticated, comprehensive analysis that has been overlooked in the century since their work was published.
Journal ArticleDOI
Serum Indoxyl Sulfate Is Associated with Vascular Disease and Mortality in Chronic Kidney Disease Patients
Fellype C. Barreto,Daniela V. Barreto,Sophie Liabeuf,Natalie Meert,Griet Glorieux,Mohammed Temmar,Gabriel Choukroun,Raymond Vanholder,Ziad A. Massy +8 more
TL;DR: The study presented here indicates that IS may have a significant role in the vascular disease and higher mortality observed in CKD patients.
Journal ArticleDOI
The Hill equation: a review of its capabilities in pharmacological modelling
Sylvain Goutelle,Michel Maurin,Florent Rougier,X. Barbaut,Laurent Bourguignon,Michel Ducher,Pascal Maire +6 more
TL;DR: The Hill equation has many different properties which can be of great interest for those interested in mathematical modelling in pharmacology and biosciences, and is introduced as a probabilistic view of the Hill equation.
Journal ArticleDOI
Free p-cresylsulphate is a predictor of mortality in patients at different stages of chronic kidney disease
Sophie Liabeuf,Daniela V. Barreto,Fellype C. Barreto,Natalie Meert,Griet Glorieux,Eva Schepers,Mohammed Temmar,Gabriel Choukroun,Raymond Vanholder,Ziad A. Massy +9 more
TL;DR: Serum levels of free and total p-cresylsulphate (the main in vivo circulating metabolites of p- cresol) were elevated in later CKD stages, however, only free p-Cresol seems to be a predictor of survival in CKD.
Journal ArticleDOI
Free serum concentrations of the protein-bound retention solute p-cresol predict mortality in hemodialysis patients
TL;DR: The data suggest that free serum levels of p-cresol, a representative of the protein-bound uremic retention solutes, are associated with mortality in HD patients, and may encourage nephrologists to widen their field of interest beyond the scope of small water-soluble ureming solutes and middle molecules.
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