Clinical Investigation

Kidney International (1996) 50, 643–652; doi:10.1038/ki.1996.360

Disturbed host defense in peritoneal cavity during CAPD: Characterization of responsible factors in dwell fluid

Raymond Vanholder, Norbert Lameire, Marie Anne Waterloos, Nadine van Landschoot, Rita de Smet, Pascale Vogeleere, Marie Christine Lambert, Denise Vijt and Severin Ringoir

Correspondence: Raymond Vanholder MD, Nephrology Department, University Hospital, De Pintelaan 185, B9000 Gent, Belgium.

Received 22 July 1994; Revised 6 March 1996; Accepted 7 March 1996.

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Abstract

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 essentially focused on fresh, unspent dialysate and on peritoneal macrophages. The response to Staphylococcus aureus (Staph A) was dose-dependently depressed for both GC CO2 production (from 91.3 plusminus 8.4 to 9.0 plusminus 1.5 dpm/103 GC, P < 0.01) and chemiluminescence (CL) (peak from 7.3 plusminus 0.8 to 1.6 plusminus 0.8 cps times 103/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 revealed a parallel depression, pointing to an intrinsic metabolic defect, rather than failure of particle ingestion. The addition of glucose to the normal cell medium to obtain the same concentration as in the CAPD effluent (2.9 plusminus 0.3 mg/dl) depressed function but not to the same extent as the genuine PD effluent. Opsonization of Staph A and E. coli induced a partial correction. No effect of pH or osmolality was observed. HPLC fractionation of CAPD effluent on a polarity based gradient revealed an elution of depressive factors in hydrophobic fractions with a nadir in F7 and F12. Analysis of the elution pattern of various uremic solutes revealed elution in F12 of p-cresol, a solute with known inhibitory effect on GC function. These events may be related to recent peritonitis (CL in response to Staph A 0.3 plusminus 0.1 in effluent of 6 patients with recent peritonitis versus 2.6 plusminus 0.8 cps times 103/GC in 12 patients without recent peritonitis (P < 0.01). We conclude that the GC response is depressed in the presence of CAPD effluent due to excess glucose, lack of opsonization, and uremic solutes of which p-cresol is one of the responsible compounds.

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