title: Hyaluronan decreases peritoneal fluid absorption: effect of molecular weight and concentration of hyaluronan.
abstract: BACKGROUND
  We have recently shown that the addition of hyaluronan to peritoneal dialysis solution could decrease the peritoneal fluid absorption rate, possibly through decreasing peritoneal tissue hydraulic conductivity. The physical-chemical properties of hyaluronan were found to be both molecular weight and concentration dependent. In this study, we investigated the effects of different molecular weight as well as different concentrations of hyaluronan on the peritoneal fluid kinetics.
  
  
  METHODS
  A four-hour dwell study was performed in 48 male Sprague-Dawley rats (6 rats in each group) with 131I albumin (RISA) as an intraperitoneal volume marker. Each rat was intraperitoneally injected with 25 ml of 1.36% glucose dialysate alone (control) or with 0.01% hyaluronan (HA) with different molecular weights [85,000 (HA85K group), 280,000 (HA280K group), 500,000 (HA500K group), and 4,000,000 (HA4M group) molecular wt] or with a different concentrations of hyaluronan [(molecular wt 500,000); 0.01% (0.01% HA group), 0.05% (0.05% HA group), 0.1% (0.1% HA group), and 0.5% (0.5% HA group) hyaluronan].
  
  
  RESULTS
  The peritoneal fluid absorption rate (as assessed by the RISA elimination rate, KE) was significantly decreased in the HA500K and H4M groups as well as in all the different concentration groups (with molecular wt 500,000) as compared with the control group, resulting in significantly higher net fluid removal in these groups (except for the H4M group) as compared with the control group. In the 0.5% HA group (but not in the other hyaluronan groups), the direct lymphatic absorption (KEB) was also significantly decreased. The transcapillary ultrafiltration rate (Qu) was significantly lower in the HA4M group as compared with the control group but significantly higher in the 0.05% HA (and tended to be higher in the 0.1% HA group) as compared with the other groups. No difference in Qu was found between the 0.5% HA group as compared with the control group, despite a more marked decrease in KE in this group as compared with the H4M group. There were no significant differences in KE, Qu, and net fluid removal between the HA85K and HA280K groups and the control group.
  
  
  CONCLUSIONS
  Our results suggest that (a) the addition of hyaluronan to dialysate could decrease peritoneal fluid absorption and thus increase the net ultrafiltration; this effect appears to be both size dependent and concentration dependent. (b) High molecular weight fraction of hyaluronan may also decrease the transcapillary Qu by decreasing tissue hydraulic conductivity. (c) A higher concentration of hyaluronan in dialysate resulted in a more marked decrease in peritoneal fluid absorption (absorption to peritoneal tissues as well as direct lymphatic absorption), possibly through both decreasing tissue hydraulic conductivity and increasing fluid viscosity. (d) Decreasing tissue hydraulic conductivity by adding a high concentration of hyaluronan to dialysate does not decrease the transcapillary ultrafiltration, possibly because the osmotic effect of hyaluronan may counterbalance the decrease in transcapillary ultrafiltration because of the decrease in tissue hydraulic conductivity.
authors.affiliation: Department of Clinical Science, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Wang
authors.forename: H H
authors.initials: HH
authors.lastname: Cheng
authors.forename: O
authors.initials: O
authors.lastname: Heimbürger
authors.forename: C
authors.initials: C
authors.lastname: Chen
authors.forename: J
authors.initials: J
authors.lastname: Waniewski
authors.forename: J
authors.initials: J
authors.lastname: Bergström
authors.forename: B
authors.initials: B
authors.lastname: Lindholm
mesh_terms: D000042:Absorption / Q000187:drug effects; D000818:Animals; D001202:Ascitic Fluid / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D015314:Dialysis Solutions; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008970:Molecular Weight; D009994:Osmolar Concentration; D010530:Peritoneal Dialysis; D051381:Rats; D017207:Rats, Sprague-Dawley