Increased production of hyaluronan by peritoneal cells and its significance in patients on CAPD

Hyaluronan (HA) is a polysaccharide that forms a critical component of extr acellular matrices. HA is present in high concentrations in tissues undergo ing remodeling and morphogenesis, and it appears to have an important role in the early stages of wound healing. Here, we studied the level of HA in t he peritoneal dialysate effluent (PDE) from 116 stable continuous ambulator y peritoneal dialysis (CAPD) patients. Longitudinal studies over a period o f 6 weeks were performed in seven of these patients who developed peritonit is, The median HA level in PDE from these patients was 154.6 mu g/L (range, 29.7 to 820.2 mu g/L). Dialysate level of HA increased with age of the pat ients, but no such correlation was shown between HA level in PDE and durati on of CAPD treatment or previous episodes of peritonitis. Patients with hig h or average peritoneal membrane transport of small solutes had a higher HA level in the PDE than those with a low peritoneal membrane transport (P = 0.046). A significant correlation was observed between PDE level of HA and interleukin-1 beta (IL-1 beta) or IL-6. The plasma level of HA in these pat ients was significantly greater than that of healthy controls (P < 0.0001), yet the plasma concentration of HA was only 85% that of the PDE concentrat ion, In CAPD patients with peritonitis, there was a sharp increase in the P DE levels of HA, IL-l P, and IL-6. These values decreased progressively wit h resolution of peritonitis. The changes in the PDE levels of HA closely fo llowed those of IL-1 beta or IL-6, In vitro [H-3]-glucosamine incorporation studies suggest that the main bulk of HA is derived from synthesis by the peritoneal mesothelial cells, whereas the amount synthesized by macrophages is trivial, We conclude that elevated levels of HA found in the PDE of sta ble CAPD patients originate from increased synthesis by peritoneal mesothel ial cells. This event may serve as a marker of regeneration and remodeling of the peritoneal lining. (C) 1999 by the National Kidney Foundation, Inc.