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Transport of cholytaurine (C-tau) across single layers of differentiated colonic adenocarcinoma (Caco-2) cells produced on diffusible filter inserts, is saturably and time linearly dependent on Na+. This transport in the apical to the basolateral direction is demonstrated to be 17 times more efficient than that in the reverse direction, and is inhibited by low incubation temperature, metabolic deactivators and unidentified bile acids. The mechanism of transport of bile acids is equivalent to that of ileal brush-border membrane vessicles and isolated ileal enterocytes, thus serving as a tool for the ascertaining of the molecular basis of ileal bile acid transport.

Progressive renal failure is accompanied by dyslipidemia, which is reflected in an abnormal apolipoprotein profile. It is characterized by increased concentrations of intact and partially metabolized triglyceride-rich apoB-containing lipoproteins. They occur preferentially in very-low density lipoprotein (VLDL) and low-density lipoprotein (LDL) as a result of impaired metabolism and clearance. Hemodialysis can moderately attenuate the renal dyslipidemia. In contrast, peritoneal dialysis is associated with further aggravation, including an increase of cholesterol-rich apoB-containing lipoproteins.

Background: Hyaluronan (HA) is a glycosaminoglycan found in connective tissues and tissue spaces, including the peritoneal cavity. In vivo studies in a rat model of peritoneal dialysis (PD) have shown that addition of HA to PD solution during an intraperitoneal dwell can alter peritoneal fluid transport and protect the peritoneal membrane from the effects of inflammation and repeated infusions of dialysis solution. The current study sought to evaluate the safety of intraperitoneal HA and its effect on peritoneal fluid and solute transport when administered during a dialysis dwell in humans., Methods: 13 PD patients were enrolled in a prospective, randomized crossover study involving three dialysis treatments using the following PD solutions: (1) a commercially available PD solution (Dianeal PD-4, 1.36% glucose; Baxter Healthcare Corporation, Alliston, Ontario, Canada); (2) Dianeal PD-4 containing 0.1 g/L HA, and (3) Dianeal PD-4 containing 0.5 g/L HA. Each 6-hour dialysis exchange was separated from the other exchanges by a 2-week washout period. Radioiodinated human serum albumin (RISA) was administered with the dialysis solution to evaluate intraperitoneal volume, net ultrafiltration (UF), and fluid reabsorption. Peritoneal clearances, dialysate/plasma ratios (D/P), and mass transfer area coefficients (MTACs) were determined for sodium, urea, creatinine, albumin, and glucose. Safety was evaluated by monitoring adverse events and changes in serum chemistries. Ten patients completed all three dialysis exchanges and two additional patients completed at least one treatment exchange., Results: There were no reported adverse events related to HA administration and no significant changes in serum chemistries. There were no significant differences in net UF or peritoneal volume profiles among the three treatments. Mean net UF calculated using residual volumes, estimated by RISA dilution, tended to be slightly higher during treatment with solution containing 0.1 g/L HA and 0.5 g/L HA [74 +/- 86 (SE) and 41 +/- 99 mL, respectively] compared to control treatment (-58 +/- 129 mL). Although not statistically significant, there was a trend toward decreased fluid reabsorption during treatment with HA. Solute clearances, D/P ratios, and MTACs were similar for the three treatments. Serum levels of HA were also unaffected by the two treatment solutions., Conclusions: These data support the acute safety of HA when administered intraperitoneally with the dialysis solution to PD patients. Due to the small sample size and variability in net UF and fluid reabsorption, statistically significant differences were not demonstrated for these parameters. However, a trend toward decreased fluid reabsorption was observed, suggesting that HA may act by a mechanism similar to that observed in animal studies. Further studies are necessary to evaluate whether the beneficial effects of HA observed in animal studies can be shown in humans.

Objective: Dyslipidemia is common among patients with end-stage renal disease, whether treated by hemodialysis (HD) or peritoneal dialysis (PD). To better understand the specific lipoprotein abnormalities in PD patients, we measured the lipid and apolipoprotein (Apo) composition of the four major classes of plasma lipoproteins in PD patients, HD patients, and healthy control subjects: very low density (VLDL), intermediate density (IDL), low density (LDL), and high density lipoproteins (HDL)., Design: Fasting plasma samples were obtained from 15 nondiabetic PD patients, 15 nondiabetic HD patients, and 16 healthy control subjects, all from a cross section of patients and subjects in the region of Göteborg, Sweden. Lipoproteins were isolated by preparative ultracentrifugation, and lipid and apolipoprotein concentrations were measured by gas chromatography and electroimmunoassay, respectively., Results: Alterations in lipoprotein composition were apparent in all four lipoprotein density classes from PD and HD patients. VLDL contained a significantly higher concentration of ApoCIII in both HD and PD patients, and an elevation of free cholesterol, triglyceride, ApoB, ApoCII, and ApoE in PD patients. IDL from both PD and HD patients contained an excess of free and esterified cholesterol and triglyceride and significantly elevated levels of ApoB, ApoCII, ApoCIII, and ApoE. LDL had a higher concentration of ApoB in PD patients and elevated triglyceride and ApoCIII in both PD and HD patients. HDL isolated from PD patients had lower free cholesterol and ApoAI levels compared to control subjects, but these were not significantly different from HD patients., Conclusions: An increase in lipid and apolipoprotein mass in IDL, and an enrichment of ApoCIII in VLDL, IDL, and LDL were observed in both HD and PD patients. The predominant alteration in lipoprotein composition distinguishing PD patients from HD patients was an elevation of ApoB in LDL. Further study of these alterations in lipoprotein composition in PD patients will be helpful in understanding the underlying causes of dyslipidemia and, ultimately, to the selection of hypolipidemic drugs or other treatments to reduce the cardiovascular risks associated with dyslipidemia in these patients.

Patients treated with Extraneal peritoneal dialysis solution (Baxter Healthcare Corporation, Deerfield, IL, U.S.A.) have a significant decrease in serum amylase activity. The decline is reported to be due to interference of icodextrin in a routinely used laboratory assay. The present study was designed to investigate the kinetics of icodextrin interference in the amylase activity assay and to determine whether assay interference can account for the total decline in amylase activity. Plasma obtained from healthy volunteers was spiked with 0, 0.21, 0.71, and 3.6 mg/mL icodextrin. Amylase activity was determined using Sigma kit 577-10 (Sigma Diagnostics, St. Louis, MO, U.S.A.). Amylase activity in plasma samples spiked with 3.6 mg/mL icodextrin was also monitored while varying the concentration of the substrate (ET-G7-PNP) from the assay kit. Amylase activity decreased with increasing amounts of icodextrin and decreasing amounts of assay substrate. A 72.6% decrease in amylase activity was observed in samples spiked with 3.6 mg/mL icodextrin as compared with samples without icodextrin at a substrate level similar to that in the assay kit (0.71 mmol/L). Double reciprocal and Dixon plots indicate competitive inhibition of amylase activity by icodextrin. Icodextrin functions as a competitive inhibitor in the assay for amylase activity, as predicted by the structural similarities between icodextrin and the amylase assay substrate. The degree of icodextrin interference suggests that the entire decline in amylase activity observed in patients using Extraneal can be accounted for qualitatively by icodextrin interference. The amylase activity decline in patients treated with Extraneal is an artifact attributable to assay interference.

Icodextrin is a glucose polymer osmotic agent used to achieve sustained ultrafiltration during long peritoneal dialysis dwells. Previous assays for icodextrin in plasma and dialysate samples involved laborious methods, such as gel permeation chromatography with post-column derivatization of the eluted glucose polymers. We developed and validated a simple and more rapid assay for icodextrin using amyloglucosidase to hydrolyze all glucose polymers to glucose. Glucose was determined pre- and post-hydrolysis using a glucose hexokinase assay, and icodextrin concentration was calculated as the difference between glucose levels before and after hydrolysis. The complete hydrolysis of icodextrin to glucose was confirmed using anion exchange chromatography. Recovery studies using icodextrin powder added to plasma or dialysate showed 100% +/- 15% recovery for plasma concentrations from 10 mg/dL to 800 mg/dL and for dialysate concentrations from 50 mg/dL to 800 mg/dL. The percent relative standard deviation (%RSD) based on multiple replicates was within 6%, except at plasma icodextrin concentrations of 10 mg/dL and below. This simple and reliable assay has been used routinely in our laboratory to analyze thousands of plasma and dialysate samples from patients using Extraneal peritoneal dialysis solution (Baxter Healthcare Corporation, Deerfield, IL, U.S.A.).