Effect of Increasing Dialyzer Mass Transfer Area Coefficient and Dialysate Flow on Clearance of Protein-Bound Solutes: A Pilot Crossover Trial

Luo, Frank J.-G.; Patel, Kajal; Marquez, Ilian O.; Plummer, Natalie S.; Hostetter, Thomas H.; Meyer, Timothy W.

doi:10.1053/j.ajkd.2009.01.265

Cited by 69 publications

(61 citation statements)

References 21 publications

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“…Concentrations of PCS, IS, and hippurate (HIPP) in plasma, dialysate, and urine were measured by HPLC as described previously (22). Free, unbound solute concentrations were measured in plasma ultrafiltrates obtained using Nanosep 30K Omega separators (Pall, Ann Arbor, MI).…”

Section: Methodsmentioning

confidence: 99%

Contribution of Residual Function to Removal of Protein-Bound Solutes in Hemodialysis

Marquez

Tambra

Luo

et al. 2011

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives This study evaluated the contribution of residual function to the removal of solutes for which protein binding limits clearance by hemdialysis.Design, setting, participants, & measurements Solute concentrations were measured in 25 hemodialysis patients with residual urea clearances ranging from 0.1 to 6.2 ml/min per 1.73 m 2 . Mathematical modeling assessed the effect of residual function on time-averaged solute concentrations.Results Dialytic clearances of the protein-bound solutes p-cresol sulfate, indoxyl sulfate, and hippurate were reduced in proportion to the avidity of binding and averaged 8 Ϯ 2, 10 Ϯ 3, and 44 Ϯ 13% of the dialytic urea clearance. For each bound solute, the residual clearance was larger in relation to the residual urea clearance. Residual kidney function therefore removed a larger portion of each of the bound solutes than of urea. Increasing residual function was associated with lower plasma levels of p-cresol sulfate and hippurate but not indoxyl sulfate. Wide variation in solute generation tended to obscure the dependence of plasma solute levels on residual function. Mathematical modeling that corrected for this variation indicated that increasing residual function will reduce the plasma level of each of the bound solutes more than the plasma level of urea. ConclusionsIn comparison to urea, solutes than bind to plasma proteins can be more effectively cleared by residual function than by hemodialysis. Levels of such solutes will be lower in patients with residual function than in patients without residual function even if the dialysis dose is reduced based on measurement of residual urea clearance in accord with current guidelines.

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Section: Methodsmentioning

confidence: 99%

Contribution of Residual Function to Removal of Protein-Bound Solutes in Hemodialysis

Marquez

Tambra

Luo

et al. 2011

Clinical Journal of the American Society of Nephrology

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“…Dialytic clearance of protein-bound solutes can be increased by increasing the dialyzer mass transfer area coefficient and dialysate flow to greater than conventional levels using 2 dialyzers in series and supplying each dialyzer with a dialysate flow of 800 ml/min [25]. The magnitude of the increases in clearance was greater for bound solutes than for BUN (increase in clearance: BUN, 25%; indoxyl sulphate, 57%; p- cresyl sulphate, 66%).…”

Section: Effects Of Dialysis Modality On Protein-bound Uraemic Toxinsmentioning

confidence: 99%

Removal of Protein-Bound Uraemic Toxins by Haemodialysis

Niwa

2013

Blood Purif

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Accumulating evidence suggests that protein-bound uraemic toxins play an important role in uraemic complications, especially in cardiovascular disease. Notably, protein-bound uraemic toxins such as indoxyl sulphate, p-cresyl sulphate, and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF) have emerged as important targets of therapeutic removal. Indoxyl sulphate stimulates reactive oxygen species production in human umbilical vein endothelial cells (HUVEC) most intensely, followed by CMPF. Indoxyl sulphate and CMPF inhibit cell growth of HUVEC. Haemodialysis (HD) even with a high-flux membrane cannot efficiently remove the protein-bound uraemic toxins because of their high albumin-binding property. Especially, indoxyl sulphate, p-cresyl sulphate, and CMPF showed high protein-binding ratios (more than 95%) and low reduction rates by HD (less than 35%). Removal of indoxyl sulphate and p-cresyl sulphate can be improved to some extent by increasing the diffusion of the free forms with super-flux membrane HD, increasing the dialyzer mass transfer area coefficient and dialysate flow, haemodiafiltration, daily HD, and addition of a sorbent to dialysate. However, CMPF is more strongly bound to albumin (with a binding ratio of 99-100%) than indoxyl sulphate and p-cresyl sulphate, and cannot be removed at all by conventional HD. Uraemic toxins strongly or covalently bound to albumin such that CMPF can be removed by protein-leaking HD. Protein-leaking HD with a polymethylmethacrylate membrane BK-F dialyzer can reduce serum levels of CMPF with improvement of anaemia as well as reduce plasma levels of homocysteine, pentosidine, and inflammatory cytokines.

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“…Indoxyl sulfate and p-cresyl sulfate are perhaps the most widely used marker molecules to study the behavior of the protein-bound uremic retention solutes during hemodialysis, hemodiafiltration, peritoneal dialysis, and experimental adsorption-based blood purification devices (5)(6)(7)(8)(9)(10). In addition, both indoxyl sulfate and p-cresyl sulfate are thought to contribute directly to uremic syndrome (1).…”

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confidence: 99%

p-Cresyl Sulfate and Indoxyl Sulfate in Hemodialysis Patients

Meijers¹,

Loor²,

Bammens³

et al. 2009

Clinical Journal of the American Society of Nephrology

155

130

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Background and objectives: Indoxyl sulfate and p-cresyl sulfate are important representatives of the protein-bound uremic retention solutes. Serum levels of p-cresyl sulfate and indoxyl sulfate are linked to cardiovascular outcomes and chronic kidney disease progression, respectively. They share important features such as the albumin-binding site, low dialytic clearance, and both originate from protein fermentation. Whether serum concentrations are related is, however, not known.Design, setting, participants, & measurements: In an observational study in 75 maintenance hemodialysis patients, we studied agreement between indoxyl sulfate and p-cresyl sulfate serum concentrations, dialytic reduction rates, and dialytic clearances. Concentrations were determined by HPLC. Dialytic clearances were determined from total spent dialysate collections. In vitro spiking experiments were performed to explore protein binding characteristics.Results: Indoxyl sulfate and p-cresyl sulfate total serum concentrations were not related (r ‫؍‬ 0.02, P ‫؍‬ 0.9), whereas free serum concentrations were only moderately related (r ‫؍‬ 0.53, P < 0.001). Indoxyl sulfate and p-cresyl sulfate share the same albumin binding site, for which they are competitive binding inhibitors. Intriguingly, indoxyl sulfate and p-cresyl sulfate reduction rates (r ‫؍‬ 0.91, P < 0.001) and dialytic clearances (r ‫؍‬ 0.97, P < 0.001) correlated tightly.Conclusions: Indoxyl sulfate and p-cresyl sulfate serum concentrations are not associated, suggesting different metabolic pathways. Indoxyl sulfate and p-cresyl sulfate are both valid markers to monitor behavior of protein-bound solutes during dialysis. Finally, they are competitive binding inhibitors for the same albumin binding site.

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Effect of Increasing Dialyzer Mass Transfer Area Coefficient and Dialysate Flow on Clearance of Protein-Bound Solutes: A Pilot Crossover Trial

Cited by 69 publications

References 21 publications

Contribution of Residual Function to Removal of Protein-Bound Solutes in Hemodialysis

Contribution of Residual Function to Removal of Protein-Bound Solutes in Hemodialysis

Removal of Protein-Bound Uraemic Toxins by Haemodialysis

p-Cresyl Sulfate and Indoxyl Sulfate in Hemodialysis Patients

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