Accumulation of Indoxyl-β-D-Glucuronide in Uremic Serum: Suppression of Its Production by Oral Sorbent and Efficient Removal by Hemodialysis

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Abstract
We identified and quantified indoxyl-β-D-glucuronide in uremic serum and urine to determine the metabolism of indoles including indoxyl sulfate in uremic patients. Serum levels of indoxyl-β-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-β-D-glucuronide was also increased in undialyzed uremic patients. Urinary indoxyl-β-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-β-D-glucuronide. Oral sorbent (AST-120) administration markedly decreased the serum and urine levels of indoxyl-β-D-glucuronide as well as indoxyl sulfate in the undialyzed uremic patients. Serum indoxyl-β-D-glucuronide could be efficiently removed by hemodialysis despite its high protein-binding ratio of about 50%. In conclusion, the serum level of indoxyl-β-D-glucuronide increases in uremic patients due to renal insufficiency and its increased production. The production of indoxyl-β-D-glucuronide can be suppressed by oral sorbent treatment, and serum indoxyl-β-D-glucuronide can be efficiently removed by hemodialysis.

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