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.
Moberly
James B
JB
Renal Division, Baxter Healthcare Corporation, McGaw Park, Illinois, USA. jmoberly@sankyopharma.com
Sorkin
Michael
M
Kucharski
Andrew
A
Ogle
Kristen
K
Mongoven
James
J
Skoufos
Line
L
Lin
Lawrence
L
Bailey
Susan
S
Rodela
Helen
H
Mupas
Lou
L
Walele
Aziz
A
Ogrinc
Francis
F
White
Darci
D
Wolfson
Marsha
M
Martis
Leo
L
Breborowicz
Andrzej
A
Oreopoulos
Dimitrios G
DG
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D001202:Ascitic Fluid / Q000378:metabolism / Q000503:physiopathology*; D018592:Cross-Over Studies; D015314:Dialysis Solutions; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010530:Peritoneal Dialysis; D011446:Prospective Studies
D000276:Adjuvants, Immunologic; D015314:Dialysis Solutions; D006820:Hyaluronic Acid