Are phospholipase A 2 and nitric oxide involved in the alterations in peritoneal transport during CAPD peritonitis?

Abstract

The alterations in peritoneal permeability characteristics during peritonitis can only partly be explained by the increased concentrations of prostaglandins and cytokines in the dialysate. Fifteen patients undergoing continuous ambulatory peritoneal dialysis (CAPD) with 16 peritonitis episodes were examined in the acute phase of the infection by using standard peritoneal permeability analyses (SPAs). In 9 of these patients, a control SPA could be performed. The contribution of nitric oxide (NO), prostaglandins, and the acute phase reactants C-reactive protein (CRP) and secretory phospholipase A 2 (sPLA 2) were analyzed. The mass transfer area coefficients (MTACs) of low-molecular-weight solutes increased during peritonitis: urea 26%, creatinine 45%, and urate 45%. The MTAC of CO 2, calculated to estimate peritoneal blood flow, was 71 mL/min (34 to 254 mL/min) during peritonitis and 55 mL/min (42 to 63 mL/min) after recovery, P <- .05. The peritoneal protein clearances were also greater during peritonitis, but this increase was not related to the molecular weight of the protein. Therefore the restriction coefficients to macromolecules were not different. The net ultrafiltration in all peritonitis episodes was lower as compared with the control dwells: −97 mL (−196 to 19 mL) versus 25 mL (−132 to 216 mL), P = .03. The prostaglandin concentrations in dialysate were greater during peritonitis than after recovery. The median increase was 199% for prostaglandin E 2 (PGE 2), 68% for 6-keto-prostaglandin F 1α (6-keto-PGF 1α), and 44% for thromboxane B 2 (TxB 2). Plasma sPLA 2 values were 22.7 μg/L (7.3 to 407.6) during peritonitis and 8.9 μg/L (5.5 to 11.5) after recovery, P < .01. The increased plasma sPLA 2 during peritonitis correlated with plasma CRP (r = .6; P = .02). The peritoneal clearances of sPLA 2 were greater during peritonitis, but this could be attributed completely to the increased peritoneal transport. Both during peritonitis and after recovery, the sPLA 2 clearances did not exceed the predicted values based on transport from the circulation to the dialysate. No evidence was found for local production of nitrite or nitrate. However, the MTAC of cyclic guanosine monophosphate (cGMP) was greater during the experiments performed 48 to 72 hours after the onset of peritonitis, which suggests the synthesis of NO. It can be concluded that peritonitis does not induce detectable local release of sPLA 2 and that the inflammation-induced increase in the vascular surface area could not be attributed to NO in the acute phase. The activation of inducible NO synthase may occur after 48 hours.