Markers of peritoneal mesothelial cells during treatment with peritoneal dialysis

Loss of peritoneal mesothelial cells and decrease of mesothelial cell mass have been described in peritoneal dialysis (PD) patients. Longitudinal follow-up in individual PD patients cannot be performed by serial peritoneal biopsies. Markers of mesothelial integrity, measured in the effluent, may therefore be a valuable approach to detect changes in the mesothelium in vivo. In the present study, markers that are known to be produced by mesothelial cells were followed in individual patients: cancer antigen 125 (CA125), phospholipids (PHL), and hyaluronan (HA). CA125 is considered to be a reflection of mesothelial cell mass or stable mesothelial cell turnover. Appearance rates (AR) were determined in the effluents of 30 PD patients on a yearly basis. Median AR (range) were: CA125: 111 U/min (10-610), PHL: 15 mg/min (3-46), HA: 666 mg/min (135-6200). Cross sectionally, the AR for CA125 was negatively related to duration of PD (r = -0.47, p < 0.0001) and weakly related to peritonitis incidence (r = -0.20, p < 0.05). Patients treated with PD for more than 4 years had lower CA125 appearance than patients treated less than 4 years (p < 0.0004). HA was also related to the incidence of peritonitis, but positively (r = 0.32, p < 0.004). PHL were not related to either parameter. A significant negative trend with time of PD treatment was observed for CA125 only [mean regression coefficient (t) -3.75, SD 1.2]. No trend in time of PD treatment could be detected for HA and PHL. These data indicate a gradual loss of mesothelial cell mass during PD by the decrease of CA125 with time. The lack of a decrease in HA and its positive relation to incidence of peritonitis suggest an additional release of HA by cells other than the mesothelial cells, such as fibroblasts and leukocytes. Alternatively, an activation of (mesothelial) cells with duration of PD and possibly with increased peritonitis incidence cannot be excluded. The relation between PHL and duration of PD suggested by others was not confirmed in this study. PHL are probably released by a number of different cells, and therefore changes in PHL cannot be used as a reflection of changes in mesothelial cell mass. It is concluded that CA125 is the most specific marker for the follow-up of mesothelial cell mass in vivo.