Effects of intraperitoneal hyaluronan on peritoneal fluid and solute transport in peritoneal dialysis patients.

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.

A rapid assay for icodextrin determination in plasma and dialysate.

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.).