Intraperitoneal Hyaluronan Production in Stable Continuous Ambulatory Peritoneal Dialysis Patients

Abstract

Objective Several cytokines and proteins are excreted intraperitoneally during the course of peritonitis and stable states in continuous ambulatory peritoneal dialysis (CAPD) patients. Dialysate hyaluronan (HYA) is also regarded as a marker of peritoneal healing during bacterial peritonitis. We examined here, intraperitoneal HYA production in stable CAPD patients and compared the results to those of the peritoneal equilibration test (PET), the length of time on dialysis, and other marker proteins. Design We determined the concentration of HYA and other marker proteins in the 4-hour-dwell dialysate at 1-year intervals. Setting CAPD unit in Hitachi General Hospital. Patients The subjects were 46 stable CAPD patients who underwent 104 PETs. Results A correlation was found between the length of time on dialysis and the amount of HYA excretion in the 4-hr-dwell dialysate ( r = 0.403, p < 0.001). A positive but weak correlation was found between the dialysate-to-plasma ratio of the creatinine concentration and dialysate HYA excretion ( r = 0.229, p < 0.05). Seven patients were over the 90th percentile in both the concentration of HYA (>349.2 ng/mL) and the amount of HYA (>743.6 μg/4-hr dwell). Five patients exceeded 1000 μg of HYA excretion in the 4-hr-dwell dialysate, 4 of whom showed an abrupt increase of HYA excretion to more than 1000 μg/4-hr dwell, and discontinued CAPD within 6 months due to ultrafiltration failure. Two of these 4 patients were diagnosed with sclerosing encapsulating peritonitis at autopsy. Conclusion Intraperitoneal HYA production increased with both higher permeable membrane and the length of time on CAPD. Monitoring of HYA in the peritoneal dialysate may be useful as a marker to assess functional and morphological changes in the peritoneum in long-term CAPD patients.

2009 Japanese Society for Dialysis Therapy Guidelines for Peritoneal Dialysis

“…Morphological changes of the peritoneum can be identified via laparoscopy (114,115), peritoneal biopsy of the parietal wall (116), and cytological examination of mesothelial cells in drained PD solution (117), commonly displaying specific alterations. Humoral factors in the drained PD solution, such as cancer antigen 125, hyaluronic acid, matrix metaprotease‐2 (MMP‐2), interleukin‐6, vascular endothelial cell growth factor, and clotting and fibrinolytic factors, have been reported to be useful as markers of peritoneal deterioration (118–122). Moreover, there have been reports that an increase in the circulating β 2 ‐microglobulin level (123) and gene polymorphisms (124) are involved in tissue damage.…”

Clinical indices of in vivo biocompatibility: The role of ex vivo cell function studies and effluent markers in peritoneal dialysis patients

“…It is now becoming clear, however, that in addition to the acute effects of peritonitis, chronic local inflammation also is a feature of the peritoneal cavity of PD patients. Studies of inflammatory markers such as hyaluronic acid (HA) and IL-6 have demonstrated that their levels in the dialysis effluent increase with therapy duration [50,51]. Although the precise factors responsible for this apparent progressive rise in local inflammation are unclear, there is some preliminary evidence that it may be related to dialysis solution exposure [52].…”

“…These studies were seminal to our understanding of acute inflammation and underpin our current understanding of the control of these events [31,41]. At the same time, it was realized that evaluation of effluent markers in stable PD patients might also permit the description of inflammatory and fibrogenic changes that occur over time in the peritoneal membrane [51,[78][79][80].…”

“…The interpretation of the data on intraperitoneal markers of inflammation would seem more definitive. The process of chronic inflammation is activated within the peritoneal cavity, as evidenced by time-dependent increases in the levels of inflammatory markers such as IL-6, HA, and TNFa in dialysis effluent [50,51]. The regulation of each of these mediators is well understood, and in the case of IL-6 and TNFa, their role within both acute and chronic inflammation is clearly documented [31,94,95].…”

Regulation of Synthesis and Roles of Hyaluronan in Peritoneal Dialysis

“…The therapeutic application of the addition of HA to PD fluid is based on the assumption that HA is lost from the peritoneal cavity during PD [ 97 ]. In PD patients, IP production of HA increases during episodes of peritonitis [ 41 , 98 ], and with the duration of PD therapy the HA concentration rises in the effluent of PD patients [ 99 ]. Consequently, the first animal studies were performed to determine the role of HA in peritoneal function during PD [ 97 ].…”