Review on uraemic toxins III: recommendations for handling uraemic retention solutes in vitro towards a standardized approach for research on uraemia

Cohen, Gerald; Glorieux, Griet; Thornalley, Paul J.; Schepers, Eva; Meert, Nathalie; Jankowski, Joachim; Jankowski, Vera; Argilés, Àngel; Anderstam, Björn; Brunet, Philippe; Cérini, Claire; Dou, Laetitia; Deppisch, Reinhold; Marescau, Bart; Massy, Ziad A.; Perna, Alessandra F.; Raupachova, Jana; Rodríguez, Mariano; Stegmayr, Bernd; Vanholder, Raymond; Hörl, Walter H.

doi:10.1093/ndt/gfm210

Cited by 72 publications

(71 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ectopic lipids disrupt the insulin signaling pathway, which induces a reduction in tyrosine phosphorylation of IRS1. 44 We demonstrated that PCS in concentrations observed in ESRD (40 mg/ml) 1,24,45,46 can impair glucose uptake as well as insulin pathway at the level of IRS-1 and p-PKB/Akt in C2C12 myotubes. In type 2 diabetes, insulin resistance is related to a defect in elements involved in insulin signal transduction, such as IRS-1, which are modulated by several kinases (serine and tyrosine kinases).…”

Section: Discussionmentioning

confidence: 80%

“…1 The potassium salt of PCS was synthesized as described by Feigenbaum and Neuberg. 54 In the in vitro study, concentration of PCS was 40 mg/ml (212 mM), which is the concentration found in humans with ESRD.…”

Section: Pcsmentioning

confidence: 99%

“…At least 90 compounds, often referred to as uremic toxins, were described to accumulate in ESRD 1 and to be harmful for biologic systems. In recent years, the dialysis community has paid great attention to improve clearance of water-soluble molecules, such as urea.…”

mentioning

confidence: 99%

See 2 more Smart Citations

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

Section: Discussionmentioning

confidence: 80%

Section: Pcsmentioning

confidence: 99%

See 1 more Smart Citation

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

show abstract

“…EUTox recently published basic protocols for the in vitro screening of uremic retention solutes, providing information about their availability, solubility, and the appropriate preparation of stock solutions. 9 The use of the correct concentrations of solutes is a precondition to obtaining relevant conclusions, 10,11 and it is recommended that the highest reported concentration in uremic plasma be used as a starting point, with evaluation of concentration dependence in cases in which a significant biologic effect is observed. The application of appropriate control conditions is necessary for the correct interpretation of the observed effects.…”

Section: Complexity Of Uremic Toxicity and Uremic Toxin Researchmentioning

confidence: 99%

A Bench to Bedside View of Uremic Toxins

Vanholder¹,

Baurmeister²,

Brunet³

et al. 2008

Journal of the American Society of Nephrology

314

231

View full text Add to dashboard Cite

“…CKD is characterized by the progressive retention of metabolites normally excreted by the kidney, collectively termed "uremic toxins," many of which have adverse effects on numerous organs (8,9). The major uremic metabolite, urea, is usually considered to have negligible toxicity.…”

Section: Introductionmentioning

confidence: 99%

Urea impairs β cell glycolysis and insulin secretion in chronic kidney disease

Koppe¹,

Nyam²,

Vivot³

et al. 2016

Journal of Clinical Investigation

122

105

View full text Add to dashboard Cite

of the Rodent Metabolic Phenotyping core facility of the CRCHUM for metabolic studies in mice; M. Guévremont, J. Morin, and the Cellular Physiology Service core of the CRCHUM for quantification of β cell mass and αLISA assay; C. Tremblay (CRCHUM) for valuable technical assistance; E. Joly for technical advice; and M. Ferdaoussi for fruitful discussions.Address correspondence to: Vincent Poitout, CRCHUM, 900 Saint-Denis Street, Montreal, Quebec, H2X 0A9, Canada. Phone: 514.890.8044; E-mail: vincent.poitout@umontreal.ca.the CHUM (protocols ND-05-035 and 16-048, respectively). Written consent for research was obtained from all donors.

show abstract

Review on uraemic toxins III: recommendations for handling uraemic retention solutes in vitro towards a standardized approach for research on uraemia

Cited by 72 publications

References 30 publications

p-Cresyl Sulfate Promotes Insulin Resistance Associated with CKD

p-Cresyl Sulfate Promotes Insulin Resistance Associated with CKD

A Bench to Bedside View of Uremic Toxins

Urea impairs β cell glycolysis and insulin secretion in chronic kidney disease

Contact Info

Product

Resources

About