IN-VIVO AND IN-VITRO EFFECTS OF AMINO-ACID-BASED AND BICARBONATE-BUFFERED PERITONEAL-DIALYSIS SOLUTIONS WITH REGARD TO PERITONEAL TRANSPORTAND CYTOKINES PROSTANOIDS DIALYSATE CONCENTRATIONS/

Background. Increasing evidence suggests that conventional PD solution s are detrimental to host defence mechanisms of peritoneal cells. We t ested a new aminoacid-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 investig ated 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 transpor t properties (clearance, D/P ratio, MTAC) were calculated. Prostanoid and cytokine concentrations were measured in serum and the 6 h effluen t. Using an in vitro model, mononuclear leukocytes of healthy donors w ere also incubated with the test fluids. In vivo results. Peritoneal c learance and MTAC of small solutes (creatinine, urea) were not signifi cantly altered by amino acids or bicarbonate. Peritoneal permeability and transperitoneal excretion of higher-weight protein molecules (beta (2)-microglobuiin, albumin? IgG) were increased with Amino/Bic compare d 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 Am ino/Bic was accompanied by an increased effluent concentration of IL-6 : IL-8, TNF alpha, PGE(2), and 6-keto-PGF(1a) (P<0.05). Dialysate nitr ite/nitrate and cGMP concentrations (as indicators of NO generation) d id not differ between the solutions. In vitro results. Both bicarbonat e fluids demonstrated a better preservation of the mitochondrial dehyd rogenases activity (MTT assay) compared to Glu, Lac (P<0.01) (Amino/Bi c: 80.6 +/- 3.2%; Glu/Bic: 86.0 +/- 1.8%; Glu/Lac, 64.9 +/- 2.3%, refe rred to RPMI as control). Constitutive and LPS stimulated release of I L-1 beta 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 +/- 9.7% referred to RPMI). Conclusion. App lication of an amino-acid/bicarbonate solution resulted in a small but significant increase in peritoneal permeability. Also increased conce ntrations of various cytokines/prostanoids were measured in the efflue nt. According to in vitro testing with mononuclear phagocytes both bic arbonate-buffered fluids were to the same extent less inhibitory to ce rtain cell functions than lactate-buffered solution.