Hyaluronan decreases peritoneal fluid absorption: Effect of molecular weight and concentration of hyaluronan

Background. We have recently shown that the addition of hyaluronan to perit oneal 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 eff ects of different molecular weight as well as different concentrations of h yaluronan on the peritoneal fluid kinetics. Methods. A four-hour dwell stud y was performed in 48 male Sprague-Dawley rats (6 rats in each group) with I-131 albumin (RISA) as an intraperitoneal volume marker. Each rat was intr aperitoneally injected with 25 ml of 1.36% glucose dialysate alone (control ) or with 0.01% hyaluronan (HA) with different molecular weights [85,000 (H A85K 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 per itoneal fluid absorption rate (as assessed by the RISA elimination rate, K- E) was significantly decreased in the HA500K and H4M groups as well as in a ll the different concentration groups (with molecular wt 500,000) as compar ed with the control group, resulting in significantly higher net fluid remo val 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 (K-EB) was also significantly decreased. The tr anscapillary ultrafiltration rate (Q(u)) was significantly lower in the HA4 M 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 th e other groups. No difference in Q(u) was found between the 0.5% HA group a s compared with the control group, despite a more marked decrease in K-E in this group as compared with the H4M group. There were no significant diffe rences in K-E, Q(u), and net fluid removal between the HASSK and HA280K gro ups and the control group. Conclusions. Our results suggest that (a) the ad dition of hyaluronan to dialysate could decrease peritoneal fluid absorptio n and thus increase the net ultrafiltration; this effect appears to be both size dependent and concentration dependent. (b) High molecular weight frac tion of hyaluronan may also decrease the transcapillary Q(u) 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 increas ing fluid viscosity. (d) Decreasing tissue hydraulic conductivity by adding a high concentration of hyaluronan to dialysate does not decrease the tran scapillary ultrafiltration, possibly because the osmotic effect of hyaluron an may counterbalance the decrease in transcapillary ultrafiltration becaus e of the decrease in tissue hydraulic conductivity.