Protein-bound uraemic toxin removal in haemodialysis and post-dilution haemodiafiltration

Krieter, Detlef H.; Hackl, Andrea; Rodriguez, Annie; Chénine, Leïla; Moragues, Hélène Leray; Lemke, Horst‐Dieter; Wanner, Christoph; Canaud, Bernard

doi:10.1093/ndt/gfp437

Cited by 173 publications

(125 citation statements)

References 23 publications

Supporting

Mentioning

114

Contrasting

Unclassified

Order By: Relevance

“…Although the β 2 -microglobulin reduction rate improved by only 4%, the main benefit was observed with molecular weight solutes between 17 and 33 kDa; the reduction rate of myoglobin (17.2 kDa), prolactin (22.9 kDa) and α 1 -microglobulin (33 kDa) increased by 28.4, 28.2 and 53.6%, respectively. The results obtained are consistent and supported by those of other studies that have evaluated the reduction rate of low molecular weight proteins with new-generation dialyzers [5,16,17]. …”

Section: Discussionsupporting

confidence: 90%

Elimination of Large Uremic Toxins by a Dialyzer Specifically Designed for High-Volume Convective Therapies

Maduell¹,

Arias‐Guillén²,

Fontseré³

et al. 2014

Blood Purif

View full text Add to dashboard Cite

Background: Unlike conventional hemodialysis treatments, which rely almost solely on diffusion-related mechanisms for solute removal, hemodiafiltration (HDF) allows more efficient removal of higher molecular weight toxins due to convective transport mechanisms. To facilitate the removal of these toxins in HDF treatment modalities, dialyzers with highly efficient high-flux membranes are necessary. This study assessed the large uremic toxin removal ability of a high-flux dialyzer (FX CorDiax 60) specifically designed to facilitate convective therapies compared with a standard high-flux dialyzer (FX 60). Methods: In an open, randomized, cross-over, single-center, controlled, prospective clinical study, 30 adult chronic hemodialysis patients were treated by post-dilution online HDF with the FX 60 or the FX CorDiax 60 dialyzer. All other dialysis parameters were kept constant in both study arms. The reduction rate (RR) of blood urea nitrogen, phosphate, β₂-microglobulin (β₂-m), myoglobin, prolactin, α₁-microglobulin, α₁-acid glycoprotein, albumin and total protein as well as the elimination into dialysate was intraindividually compared for the two dialyzer types. Results: For FX CorDiax 60 versus FX 60, the RR was significantly higher for blood urea nitrogen (86.23 ± 4.14 vs. 84.89 ± 4.59%, p = 0.015), β₂-m (84.67 ± 3.79 vs. 81.30 ± 4.82%, p < 0.0001), myoglobin (75.23 ± 10.48 vs. 58.60 ± 12.1%, p < 0.0001), prolactin (72.96 ± 9.68 vs. 56.91 ± 13.01%, p < 0.0001) and α₁-microglobulin (20.89 ± 18.27 vs. 13.60 ± 12.50%, p = 0.016). There were no significant differences in the RR for phosphate, α₁-acid glycoprotein, albumin and total protein. Mass removal was significantly higher with the FX CorDiax 60 than with the FX 60 for β₂-m (0.26 ± 0.09 vs. 0.24 ± 0.09 g, p = 0.0006), myoglobin (1.83 ± 0.89 vs. 1.51 ± 0.76 mg, p = 0.0017), prolactin (0.17 ± 0.13 vs. 0.14 ± 0.08 mg, p = 0.02) and albumin (4.25 ± 3.49 vs. 3.01 ± 2.37 g, p = 0.03). Conclusions: This study demonstrates that treating patients with an FX CorDiax 60 instead of an FX 60 dialyzer in post-dilution HDF mode significantly increases the elimination of middle molecules.

show abstract

Section: Discussionsupporting

confidence: 90%

Elimination of Large Uremic Toxins by a Dialyzer Specifically Designed for High-Volume Convective Therapies

Maduell¹,

Arias‐Guillén²,

Fontseré³

et al. 2014

Blood Purif

View full text Add to dashboard Cite

show abstract

“…Because insulin resistance is an important cardiovascular risk factor, novel therapeutic approaches such as prebiotics, which could decrease PCS more substantially than with the currently available strategies, must be developed, especially because this toxin is not very efficiently removed by hemodialysis. 53 …”

Section: Discussionmentioning

confidence: 99%

p-Cresyl Sulfate Promotes Insulin Resistance Associated with CKD

Koppe

Pillon

Vella

et al. 2013

Journal of the American Society of Nephrology

232

175

View full text Add to dashboard Cite

The mechanisms underlying the insulin resistance that frequently accompanies CKD are poorly understood, but the retention of renally excreted compounds may play a role. One such compound is p-cresyl sulfate (PCS), a protein-bound uremic toxin that originates from tyrosine metabolism by intestinal microbes. Here, we sought to determine whether PCS contributes to CKD-associated insulin resistance. Administering PCS to mice with normal kidney function for 4 weeks triggered insulin resistance, loss of fat mass, and ectopic redistribution of lipid in muscle and liver, mimicking features associated with CKD. Mice treated with PCS exhibited altered insulin signaling in skeletal muscle through ERK1/2 activation. In addition, exposing C2C12 myotubes to concentrations of PCS observed in CKD caused insulin resistance through direct activation of ERK1/2. Subtotal nephrectomy led to insulin resistance and dyslipidemia in mice, and treatment with the prebiotic arabino-xylo-oligosaccharide, which reduced serum PCS by decreasing intestinal production of p-cresol, prevented these metabolic derangements. Taken together, these data suggest that PCS contributes to insulin resistance and that targeting PCS may be a therapeutic strategy in CKD.

show abstract

“…The elimination of protein-bound compounds depends particularly on diffusion [26]. Lack of enhanced removal in online post-dilution haemodiafiltration (HDF) emphasizes the minor significance of convection for the clearance of these solutes.…”

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

confidence: 99%

Removal of Protein-Bound Uraemic Toxins by Haemodialysis

Niwa

2013

Blood Purif

View full text Add to dashboard Cite

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.

show abstract

Protein-bound uraemic toxin removal in haemodialysis and post-dilution haemodiafiltration

Cited by 173 publications

References 23 publications

Elimination of Large Uremic Toxins by a Dialyzer Specifically Designed for High-Volume Convective Therapies

Elimination of Large Uremic Toxins by a Dialyzer Specifically Designed for High-Volume Convective Therapies

p-Cresyl Sulfate Promotes Insulin Resistance Associated with CKD

Removal of Protein-Bound Uraemic Toxins by Haemodialysis

Contact Info

Product

Resources

About