DISTURBED HOST-DEFENSE IN PERITONEAL-CAVITY DURING CAPD - CHARACTERIZATION OF RESPONSIBLE FACTORS IN DWELL FLUID

In this study, the factors in overnight dwell fluid (8 to 10 hr dwell) depressing granulocyte (GC) NAD(P)H-oxidase dependent radical species production are characterized. At present, most studies have essential ly focused on fresh, unspent dialysate and on peritoneal macrophages. The response to Staphylococcus aureus (Staph A) was dose-dependently d epressed for both GC CO2 production (from 91.3 +/- 8.4 to 9.0 +/- 1.5 dpm/10(3) GC, P < 0.91) and chemiluminescence (CL) (peak from 7.3 +/- 0.8 to 1.6 +/- 0.8 cps x 10(3)/GC, P < 0.01). Stimulation with formyl- methionine-leucine-phenylalanine (f-MLP), phorbol myristic acid (PMA), Staphylococcus epidermidis (Staph Epi),E. coli, latex and zymosan rev ealed a parallel depression, pointing to an intrinsic metabolic defect , rather than failure of particle ingestion. The addition of glucose t o the normal cell medium to obtain the same concentration as in the CA PD effluent (2.9 +/- 0.3 mg/dl) depressed function but nor to the same extent as the genuine PD effluent. Opsonization of Staph A and E. col i induced a partial correction. No effect of pH or osmolality was obse rved. HPLC fractionation of CAPD effluent on a polarity based gradient revealed an elution of depressive factors in hydrophobic fractions wi th a nadir in F7 and F12. Analysis of the elution pattern of various u remic solutes revealed elution in F12 of p-cresol, a solute with known inhibitory effect on GC function. These events may be related to rece nt peritonitis (CL in response to Staph A 0.3 +/- 0.1 in effluent of 6 patients with recent peritonitis versus 2.6 +/- 0.8 cps x 10(3)/GC in 12 patients without recent peritonitis (P < 0.01). We conclude that t he GC response is depressed in the presence of CAPD effluent due to ex cess glucose, lack of opsonization, and uremic solutes of which p-cres ol is one of the responsible compounds.