In vivo and in vitro effects of amino-acid-based and bicarbonate-buffered peritoneal dialysis solutions with regard to peritoneal transport and cytokines/prostanoids dialysate concentrations.

Background. Increasing evidence suggests that conventional PD solutions are detrimental to host defence mechanisms of peritoneal cells. We tested a new amino-acid-based and bicarbonate-buffered PD solution under in vivo and in vitro conditions. Methods. During a prospective, cross-over randomized, intraindividual study 10 CAPD patients were investigated with three different solutions: Amino/Bic, 1% amino acid, 34 mmol/l bicarbonate; Glu/Bic, 1.5% glucose, 34 mmol/l bicarbonate; and Glu/Lac, 1.5% glucose, 35 mmol/l lactate. A PET was performed and transport properties (clearance, D/P ratio, MTAC) were calculated. Prostanoid and cytokine concentrations were measured in serum and the 6h effluent. Using an in vitro model, mononuclear leukocytes of healthy donors were also incubated with the test fluids. In vivo results. Peritoneal clearance and MTAC of small solutes (creatinine, urea) were not significantly altered by amino acids or bicarbonate. Peritoneal permeability and transperitoneal excretion of higher-weight protein molecules (β 2 -microglobulin, albumin, IgG) were increased with Amino/Bic compared to Glu/Lac (P<0.05) (D/P ratio albumin: Amino/Bic, 0.027 ± 0.003; Glu/Bic, 0.023 ± 0.003; Glu/Lac, 0.022 ± 0.002). Application of Amino/Bic was accompanied by an increased effluent concentration of Il-6, Il-8, TNFα, PGE 2 , and 6-keto-PGF 1a (P<0.05). Dialysate nitrite/nitrate and cGMP concentrations (as indicators of NO generation) did not differ between the solutions. In vitro results. Both bicarbonate fluids demonstrated a better preservation of the mitochondrial dehydrogenases activity (MTT assay) compared to Glu/ Lac (P<0.01) (Amino/Bic: 80.6 ± 3.2%; Glu/Bic: 86.0 ± 1.8%; Glu/Lac, 64.9 ± 2.3%, referred to RPMI as control). Constitutive and LPS stimulated release of Il-1β and Il-6 was less suppressed with both bicarbonate fluids (P<0.05) (LPS-stim. Il-6 release: Amino/Bic, 33.0 ± 6.6%; Glu/Bic, 65.5 ± 10.3%; Glu/Lac, 1.5 ± 0.7% referred to RPMI). Conclusion. Application of an amino-acid/bicarbonate solution resulted in a small but significant increase in peritoneal permeability. Also increased concentrations of various cytokines/prostanoids were measured in the effluent. According to in vitro testing with mononuclear phagocytes both bicarbonate-buffered fluids were to the same extent less inhibitory to certain cell functions than lactate-buffered solution.