Accumulation of indoxyl-beta-D-glucuronide in uremic serum: suppression of its production by oral sorbent and efficient removal by hemodialysis.
We identified and quantified indoxyl-beta-D-glucuronide in uremic serum and urine to determine the metabolism of indoles including indoxyl sulfate in uremic patients. Serum levels of indoxyl-beta-D-glucuronide were markedly increased in undialyzed uremic patients, in patients on hemodialysis, and in patients on continuous ambulatory peritoneal dialysis. Urinary excretion of indoxyl-beta-D-glucuronide was also increased in undialyzed uremic patients. Urinary indoxyl-beta-D-glucuronide was significantly correlated with serum indoxyl sulfate, indicating that a high serum level of indoxyl sulfate leads to the enhanced synthesis of indoxyl-beta-D-glucuronide. Oral sorbent (AST-120) administration markedly decreased the serum and urine levels of indoxyl-beta-D-glucuronide as well as indoxyl sulfate in the undialyzed uremic patients. Serum indoxyl-beta-D-glucuronide could be efficiently removed by hemodialysis despite its high protein-binding ratio of about 50%. In conclusion, the serum level of indoxyl-beta-D-glucuronide increases in uremic patients due to renal insufficiency and its increased production. The production of indoxyl-beta-D-glucuronide can be suppressed by oral sorbent treatment, and serum indoxyl-beta-D-glucuronide can be efficiently removed by hemodialysis.
Niwa
T
T
Nagoya University Branch Hospital, Japan.
Miyazaki
T
T
Tsukushi
S
S
Maeda
K
K
Tsubakihara
Y
Y
Owada
A
A
Shiigai
T
T
D000327:Adsorption; D002244:Carbon / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005965:Glucuronates / Q000097:blood* / Q000652:urine; D006801:Humans; D007211:Indoles / Q000097:blood* / Q000652:urine; D008163:Luminescent Measurements; D008297:Male; D013058:Mass Spectrometry; D010087:Oxides / Q000494:pharmacology*; D010531:Peritoneal Dialysis, Continuous Ambulatory; D011485:Protein Binding; D006435:Renal Dialysis; D014511:Uremia / Q000097:blood* / Q000188:drug therapy*
D005965:Glucuronates; D007211:Indoles; D010087:Oxides; C059836:indoxyl glucuronide; D002244:Carbon; C040896:AST 120