Peritoneal dialysis solution calcium concentration regulates peritoneal fibroblast proliferation in CAPD

Peritoneal fibrosis remains one of the major causes of dropout in continuous ambulatory peritoneal dialysis (CAPD), by reducing ultrafiltration capacity. Since studies in vitro have shown that cytoplasmic Ca2+ regulates the proliferation of most cell lines and the release of cytokines from immune cells, eight uremics and four controls at the start of CAPD were evaluated for the in vitro effects of different peritoneal dialysis solution (PDS) Ca2+ concentrations (1, 1.25, 1.75, and 2 mmol/L) on: 1) peritoneal fibroblast (PF) proliferation; 2) peritoneal macrophage (PM) and peritoneal lymphocyte (PL) release of interleukin-1 (IL-1) and interferon-gamma (IFN-gamma)--cytokines that are known to induce PF proliferation; and 3) cytoplasmic Ca2+ concentrations in PF, PM, and PL. Results showed that in both the uremics and controls, increasing the dose of Ca2+ in the medium induced a dose-dependent rise in PF proliferation, and in the release of IL-1 and IFN-gamma from PM and PL. Meanwhile, the cytoplasmic Ca2+ concentration of PF, PM, and PL also increased. With a PDS containing 1 mmol/L of Ca2+ in the uremics, these parameters were below normal; they exceeded the norm with a Ca2+ concentration of 1.75 and 2 mmol/L, and were normal with a Ca2+ concentration of 1.25 mmol/L. These data suggest that in CAPD patients, the use of a low Ca2+ PDS (1 and 1.25 mmol/L) may be useful in reducing the proliferation of PF and the production of IL-1 and IFN-gamma from PM and PL, thereby preventing peritoneal sclerosis.