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Monday 01 December 2003

[Intracellular pH changes induced by sclerosing agents in peritoneal fibroblasts]

By: Soria M, Arrieta J, Ugarte I, Moina I, Guerra M, Escanero J.

Nefrologia 2004;24(2):158-66

Sclerosing encapsulating peritonitis secondary to peritoneal dialysis has been associated to acetate-containing dialysis fluids, hypertonic glucose and disinfectants. Physiopathologic mechanisms of fibrotic proliferation that implicate those agents are not totally explained. With an experimental approach using cultured peritoneal fibroblasts, we have studied intracellular pH changes and Na+/H+ antiporter activity under cells perfusion with peritoneal dialysis liquids containing acetate, lactate, hypertonic glucose and interleukin-1. All experiments were performed at extracellular pH 7.4 and physiologic HCO3/CO2 concentration. RESULTS: 35 mM acetate produced a huge intracellular acidosis (ipH = 6.80 +/- 0.08). Lactate effect was less important (6.95 +/- 0.07), with a slow ipH recovery in about 30 min in both cases. IL-1, 10(-6) M also reduced ipH to 7.10 +/- 0.03. Acidosis was linked to Ca2+ outflow via Ca/H exchange and was blocked with Cd 20 nM. Extracellular Na = 0 and amiloride totally inhibited ipH recovery after acetate, lactate, or interleukin-induced acidosis. Hypertonic glucose perfusion increased ipH (7.31 +/- 0.06) for 5-7 min. This increase was also inhibited by amiloride or extracellular Na absence. Na+/H+ exchanger activity increased to 58%, and kept activated after ipH recovery. In conclusion, acetate, hypertonic glucose and IL-1 showed the common effect of stimulating the sodium-proton exchanger by different mechanisms, giving a possibility of potentiation. Activated Na+/H+ exchanger may act as a signal-transduction increasing fibroblast proliferation and explaining the cellular mechanism of sclerosing peritonitis.

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