title: High correlation between clearance of renal protein-bound uremic toxins (indoxyl sulfate and p-cresyl sulfate) and renal water-soluble toxins in peritoneal dialysis patients.
abstract: Peritoneal dialysis (PD) is characterized by a slow continuous removal of solutes. Traditionally, dialysis adequacy is quantified by referring to the kinetics of urea nitrogen (UN) and creatinine (Cr) clearance. The efficacy of middle molecular substances and protein-bound solutes as markers for peritoneal dialysis adequacy is not clear. The aim of this cross-sectional study was to investigate correlations between the clearance of indoxyl sulfate (IS), p-cresyl sulfate (PCS), UN, and Cr in the peritoneum and kidneys and to compare the overall clearances of IS and PCS between non-anuric and anuric groups in PD patients. We recruited a total of 175 patients who had been undergoing continuous ambulatory PD (CAPD) or automated PD (APD) for at least 4 months. We measured total IS and PCS concentrations in serum, dialysate, and urine samples. Free IS and PCS concentrations were measured in all serum samples. IS and PCS clearances via both kidney and peritoneum were measured. The mean concentration of IS in the urine samples was 9.2-fold higher than that in the dialysate samples, and concentration of PCS in the urine samples was 8.5-fold higher than that in the dialysate samples. Peritoneal UN and Cr clearances were not correlated with peritoneal PCS clearance (P > 0.05) but were mildly correlated with peritoneal IS clearance. The peritoneal IS and PCS clearances in the different peritoneal equilibration test groups were similar. The renal UN and Cr clearances were strongly correlated with renal PCS and IS clearances (P > 0.89, P < 0.001). In addition, non-anuric patients showed better elimination of total PCS (10.3 mg/day [range, 1.6-19.8] vs. 5.2 mg/day [range, 0-14]; P < 0.001] and IS (37.9 mg/day [range, 25.6-56.7] vs. 24.8 mg/day [range, 17.1-41.6]; P < 0.001) than anuric patients. This cross-sectional study showed that peritoneal clearance of water-soluble solutes is not correlated with that of PCS but is mildly correlated with that of IS. However, the renal clearances of IS and PCS show strong positive correlation with the renal clearances of UN and Cr. This study confirms the important role of residual renal function in the removal of protein-bound uremic toxins.
authors: Department of Nephrology, Chang Gung Memorial Hospital, Linkou             Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors: Wen-Hung
authors: WH
authors: Huang
authors: Cheng-Chieh
authors: CC
authors: Hung
authors: Chih-Wei
authors: CW
authors: Yang
authors: Jeng-Yi
authors: JY
authors: Huang
mesh_terms: D003408:Cresols / Q000493:pharmacokinetics*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007200:Indican / Q000493:pharmacokinetics*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D010530:Peritoneal Dialysis / Q000379:methods; D010531:Peritoneal Dialysis, Continuous Ambulatory; D013463:Sulfuric Acid Esters; D014118:Toxins, Biological / Q000493:pharmacokinetics; D014511:Uremia / Q000378:metabolism*; D014867:Water
chemical_list: D003408:Cresols; D013463:Sulfuric Acid Esters; D014118:Toxins, Biological; D014867:Water; C408690:4-cresol sulfate; D007200:Indican