Peritoneal Dialysis Fluid and Some of its Components Potentiate Fibrocyte Differentiation

Abstract

Long-term peritoneal dialysis (PD) often results in the development of peritoneal fibrosis. In many other fibrosing diseases, monocytes enter the fibrotic lesion and differentiate into fibro-blast-like cells called fibrocytes. We find that peritoneal tissue from short-term PD patients contains few fibrocytes, while fibrocytes are readily observed in the peritoneal membrane of long-term PD patients. The PD fluid Dianeal (Baxter Healthcare Corporation, Deerfield, IL, USA) contains dextrose, a number of electrolytes including sodium chloride, and sodium lactate. We find that PD fluid potentiates human fibrocyte differentiation in vitro and implicates sodium lactate in this potentiation. The plasma protein serum amyloid P (SAP) inhibits fibrocyte differentiation. Peritoneal dialysis fluid and sodium chloride decrease the ability of human SAP to inhibit human fibrocyte differentiation in vitro. Together, these results suggest that PD fluid contributes to the development of peritoneal fibrosis by potentiating fibrocyte differentiation.

Oxidative stress in peritoneal dialysis patients: Association with the dialysis adequacy and technique survival

“…In our view, the fact of a decrease in ferroxidase activity of CP in PD patients and its correlation with the dialysis adequacy is explained by PD solutions' uses which contain dextrose as an osmolyte, lactate as a buffer, and different electrolytes, including chloride. [31]…”

“…Considering the fact that most patients included in the present study (89%) received commercial glucose-containing PD fluids, the low-serum CP level might be mediated by the following mechanisms: (1) an increase in oxidative status due to the accumulation in the peritoneum of GDP with formation of free radicals, and[32] (2) the presence of chloride in the abdominal cavity (96 mmol/l in each 1000 ml of dianeal PD solution)[31] whereas its presence is not found in other pathological conditions.…”

“…demonstrated that 125 mM chloride potentiated human fibrocyte differentiation in vitro . [31] Cox et al . hypothesized that elevated serum concentration of NaCl, observed at least for a few hours after eating a high-salt meal, could contribute to fibrosis.…”

“…So, the authors have concluded that the chloride concentration in PD fluid could not be directly responsible for PD fluid potentiation of fibrocyte differentiation. [31] On the other hand, chloride ions are able to suppress the ferroxidase activity of CP, especially in low pH conditions. [37] As a result, the level of Fe 2+ is increased and leads to the stimulation of free radical reactions under elevated levels of H 2 O 2 .…”

The Development of Serum Amyloid P as a Possible Therapeutic

“…One compound that may be clinically relevant is NaCl, which when added to increase the medium NaCl concentration by 25 mM (this level of increase can be seen in the serum after a very salty meal) potentiates fibrocyte differentiation and inhibits the SAP effect, possibly explaining why high salt intake is associated with a propensity for cardiac fibrosis ( 137 ). Peritoneal dialysis can lead to peritoneal fibrosis, and we found that peritoneal dialysis fluid and dialysis fluid components such as NaCl also promote fibrocyte differentiation and impede SAP ( 139 ). In support of this connection between salt and fibrocytes, low dietary salt reduces the severity of bleomycin-induced pulmonary fibrosis in mice, suggesting that low salt diets may be beneficial for fibrosis patients ( 143 ).…”