Exploring binding characteristics and the related competition of different protein-bound uremic toxins

Deltombe, Olivier; Loor, Henriëtte de; Glorieux, Griet; Dhondt, Annemieke; Biesen, Wim Van; Meijers, Björn; Eloot, Sunny

doi:10.1016/j.biochi.2017.05.010

Cited by 21 publications

(15 citation statements)

References 41 publications

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“…Incomplete clearance of uremic solutes and the generation of urea from both dialysis-induced tissue degradation and dietary proteins contribute to uremic solute accumulation [ 104 ]. Excessive uremic solute burden influences amino-acid and protein metabolism by inhibiting transamination activities of enzymes such as threonine dehydratase and alanine and aspartate transferases [ 104 ], impairing membrane transport [ 105 ], inhibiting protein binding [ 106 ], and promoting muscle wasting [ 104 ].…”

Section: Iatrogenic Factors Of Malnutritionmentioning

confidence: 99%

Understanding Development of Malnutrition in Hemodialysis Patients: A Narrative Review

et al. 2020

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Hemodialysis (HD) majorly represents the global treatment option for patients with chronic kidney disease stage 5, and, despite advances in dialysis technology, these patients face a high risk of morbidity and mortality from malnutrition. We aimed to provide a novel view that malnutrition susceptibility in the global HD community is either or both of iatrogenic and of non-iatrogenic origins. This categorization of malnutrition origin clearly describes the role of each factor in contributing to malnutrition. Low dialysis adequacy resulting in uremia and metabolic acidosis and dialysis membranes and techniques, which incur greater amino-acid losses, are identified modifiable iatrogenic factors of malnutrition. Dietary inadequacy as per suboptimal energy and protein intakes due to poor appetite status, low diet quality, high diet monotony index, and/or psychosocial and financial barriers are modifiable non-iatrogenic factors implicated in malnutrition in these patients. These factors should be included in a comprehensive nutritional assessment for malnutrition risk. Leveraging the point of origin of malnutrition in dialysis patients is crucial for healthcare practitioners to enable personalized patient care, as well as determine country-specific malnutrition treatment strategies.

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Section: Iatrogenic Factors Of Malnutritionmentioning

confidence: 99%

Understanding Development of Malnutrition in Hemodialysis Patients: A Narrative Review

et al. 2020

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“…However, the free fraction of the bound solutes in patients with AKI increased to the degree previously observed in patients on hemodialysis, whereas the absolute levels of these solutes were much lower in patients with AKI than in patients on hemodialysis, as shown in Supplemental Table 3. This suggests modification of plasma albumin may contribute more importantly to reduction in protein binding than competition by accumulating solutes, as has recently been demonstrated for solutes, including p-cresol sulfate and indoxyl sulfate, in patients with end-stage renal failure (18). The reduction in albumin concentration in patients with AKI would not by itself cause a notable reduction in solute binding unless the aggregate levels of bound solutes were causing competition for binding sites.…”

Section: Discussionmentioning

confidence: 87%

Impaired Tubular Secretion of Organic Solutes in Acute Kidney Injury

et al. 2020

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BackgroundImpairment of kidney function is routinely assessed by measuring the accumulation of creatinine, an organic solute cleared largely by glomerular filtration. We tested whether the clearance of solutes that undergo tubular secretion is reduced in proportion to the clearance of creatinine in humans with AKI.MethodsFour endogenously produced organic solutes (phenylacetylglutamine [PAG], hippurate [HIPP], indoxyl sulfate [IS], and p-cresol sulfate [PCS]) were measured in spot urine and plasma samples from ten patients with AKI and 17 controls. Fractional clearance relative to creatinine was calculated to assess tubular secretion. Fractional clearance values were calculated in terms of the free, unbound levels of HIPP, IS, and PCS that bind to plasma proteins.ResultsFractional clearance values for PAG, HIPP, IS, and PCS were >1.0 in patients with AKI as well as controls, indicating that these solutes were still secreted by the tubules of the injured kidneys. Fractional clearance values were, however, significantly lower in patients with AKI than controls, indicating that kidney injury reduced tubular secretion more than glomerular filtration (AKI versus control: PAG, 2.1±0.7 versus 4.6±1.4, P<0.001; HIPP, 10±5 versus 15±7, P=0.02; IS, 10±6 versus 28±7, P<0.001; PCS, 3.3±1.8 versus 10±3, P<0.001). Free plasma levels rose out of proportion to total plasma levels for each of the bound solutes in AKI, so that calculating their fractional clearance in terms of their total plasma levels failed to reveal their impaired secretion.ConclusionsTubular secretion of organic solutes can be reduced out of proportion to glomerular filtration in AKI. Impaired secretion of protein-bound solutes may be more reliably detected when clearances are expressed in terms of their free, unbound levels in the plasma.

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“…This might imply that BCP has affinity for the same albumin binding site as PCS has (Sudlow's site II), in contrast to CMPF (Sudlow's site I). From previous binding competition experiments, clearly showing superior binding capacity of PCS versus IxS, IAA and HA, it is however hard to explain that the correlation between BCP and PCS is due to mutual competition [34]. The in vivo results were confirmed by in vitro spiking of PCS to human serum.…”

Section: Discussionmentioning

confidence: 93%

Binding of bromocresol green and bromocresol purple to albumin in hemodialysis patients

Delanghe

Biesen

Velde

et al. 2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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Exploring binding characteristics and the related competition of different protein-bound uremic toxins

Cited by 21 publications

References 41 publications

Understanding Development of Malnutrition in Hemodialysis Patients: A Narrative Review

Understanding Development of Malnutrition in Hemodialysis Patients: A Narrative Review

Impaired Tubular Secretion of Organic Solutes in Acute Kidney Injury

Binding of bromocresol green and bromocresol purple to albumin in hemodialysis patients

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