Contributions of hippurate, indoxyl sulfate, and o-hydroxyhippurate to impaired ligand binding by plasma in azotemic humans

Gulyassy, Paul F.; Jarrard, Elizabeth A.; Stanfel, Linda A.

doi:10.1016/0006-2952(87)90661-7

Cited by 32 publications

(13 citation statements)

References 22 publications

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“…The description of its protein binding was first reported in studies investigating the reduced drug binding caused by endogenous solutes in uremic plasma [4,5,6]. Being bound to proteins affects the dialytic behavior of indoxyl sulfate.…”

Section: Characteristicsmentioning

confidence: 99%

Indoxyl Sulfate—Review of Toxicity and Therapeutic Strategies

Leong

Sirich

2016

Toxins

210

178

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Indoxyl sulfate is an extensively studied uremic solute. It is a small molecule that is more than 90% bound to plasma proteins. Indoxyl sulfate is derived from the breakdown of tryptophan by colon microbes. The kidneys achieve high clearances of indoxyl sulfate by tubular secretion, a function not replicated by hemodialysis. Clearance by hemodialysis is limited by protein binding since only the free, unbound solute can diffuse across the membrane. Since the dialytic clearance is much lower than the kidney clearance, indoxyl sulfate accumulates to relatively high plasma levels in hemodialysis patients. Indoxyl sulfate has been most frequently implicated as a contributor to renal disease progression and vascular disease. Studies have suggested that indoxyl sulfate also has adverse effects on bones and the central nervous system. The majority of studies have assessed toxicity in cultured cells and animal models. The toxicity in humans has not yet been proven, as most data have been from association studies. Such toxicity data, albeit inconclusive, have prompted efforts to lower the plasma levels of indoxyl sulfate through dialytic and non-dialytic means. The largest randomized trial showed no benefit in renal disease progression with AST-120. No trials have yet tested cardiovascular or mortality benefit. Without such trials, the toxicity of indoxyl sulfate cannot be firmly established.

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Section: Characteristicsmentioning

confidence: 99%

Indoxyl Sulfate—Review of Toxicity and Therapeutic Strategies

Leong

Sirich

2016

Toxins

210

178

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“…Subsequent fluid overload and extracellular fluid volume expansion in turn increase volumes of distribution for hydrophilic drugs, such as aminoglycosides. Acutely ill subjects frequently have decreased plasma protein concentrations, and, additionally, uremic solutes such as hippurate and indoxyl sulfate alter drug binding to albumin in chronic renal failure, and might do so in acute renal failure, although this has not been tested (32, 33). The free fraction of many drugs – phenytoin, digoxin, and others is increased in renal failure, even though the volume of distribution for total drug may increase due to movement of unbound drug into interstitial or total body water (34, 35).…”

Section: Brief Review Of Pharmacokinetic and Pharmacodynamic Princmentioning

confidence: 99%

Antimicrobial Dosing in Acute Renal Replacement

Fissell

2013

Advances in Chronic Kidney Disease

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“…Binding of many acidic drugs and hormones to serum albumin is decreased in patients with renal failure (8)(9)(10)(11). A number of endogenous ligand substances in uremic serum inhibit the binding of drugs to serum proteins (12)(13)(14)(15)(16). In particular, 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) (Scheme 1) in an endogenous, ligand is tightly bound to serum protein (17,18) and, there-fore, the concentration of CMPF in uremic plasma is not significantly decreased by hemodialysis (19).…”

mentioning

confidence: 99%

Production of antiserum for sensitive enzyme‐linked immunosorbent assay of 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid by chemiluminescence

Tanaka

Ikebuchi

Sawada

et al. 1998

Lipids

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To obtain a specific antiserum for use in enzyme-linked immunosorbent assay (ELISA) of 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), we prepared a hapten-carrier conjugate in which the CMPF hapten was linked to a carrier protein through the 5-(1-hydrazopropyl) group. The antisera raised against this antigen in guinea pigs had excellent specificity for CMPF, showing little cross-reactivity with closely related compounds and no significant cross-reactivities with other furan compounds. The results indicated that a specific antiserum to CMPF could be produced by an antigen whose CMPF moiety is linked to a carrier protein through a position remote from the inherent functional groups. A standard curve of CMPF by ELISA using a chemiluminescence system showed a high sensitivity and a linearity in the range of 5-100 ng/mL.

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Contributions of hippurate, indoxyl sulfate, and o-hydroxyhippurate to impaired ligand binding by plasma in azotemic humans

Cited by 32 publications

References 22 publications

Indoxyl Sulfate—Review of Toxicity and Therapeutic Strategies

Indoxyl Sulfate—Review of Toxicity and Therapeutic Strategies

Antimicrobial Dosing in Acute Renal Replacement

Production of antiserum for sensitive enzyme‐linked immunosorbent assay of 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid by chemiluminescence

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