ARE PHOSPHOLIPASE A(2) AND NITRIC-OXIDE INVOLVED IN THE ALTERATIONS IN PERITONEAL TRANSPORT DURING CAPD PERITONITIS

The alterations in peritoneal permeability characteristics during peri tonitis can only partly be explained by the increased concentrations o f prostaglandins and cytokines in the dialysate. Fifteen patients unde rgoing continuous ambulatory peritoneal dialysis (CAPD) with 16 perito nitis episodes were examined in the acute phase of the infection by us ing standard peritoneal permeability analyses (SPAs). In 9 of these pa tients, a control SPA could be performed, The contribution of nitric o xide (NO), prostaglandins, and the acute phase reactants C-reactive pr otein (CRP) and secretory phospholipase A(2) (sPLA(2)) were analyzed. The mass transfer area coefficients (MTACs) of low-molecular-weight so lutes increased during peritonitis: urea 26%, creatinine 45%, and urat e 45%. The MTAC of CO2, 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 less than or equal to .05. The periton eal protein clearances were also greater during peritonitis, but this increase was not related to the molecular weight of the protein. There fore the restriction coefficients to macromolecules were not different . The net ultrafiltration in all peritonitis episodes was lower as com pared with the control dwells: -97 mL (-196 to 19 mL) versus 25 mL (-1 32 to 216 mL), P = .03. The prostaglandin concentrations in dialysate were greater during peritonitis than after recovery. The median increa se was 199% for prostaglandin E-2 (PGE(2)), 68% for 6-keto-prostagland in F-1 alpha (6-keto-PGF(1 alpha)), and 44% for thromboxane B-2 (TxB(2 )). Plasma sPLA(2) values were 22.7 mu g/L (7.3 to 407.6) during perit onitis and 8.9 mu g/L (5.5 to 11.5) after recovery, P < .01. The incre ased plasma sPLA(2) during peritonitis correlated with plasma CRP (r = .6; P = .02). The peritoneal clearances of sPLA(2) were greater durin g peritonitis, but this could be attributed completely to the increase d peritoneal transport. Both during peritonitis and after recovery, th e sPLA(2) clearances did not exceed the predicted values based on tran sport from the circulation to the dialysate. No evidence was found for local production of nitrite or nitrate. However, the MTAC of cyclic g uanosine monophosphate (cGMP) was greater during the experiments perfo rmed 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 i n the acute phase. The activation of inducible NO synthase may occur a fter 48 hours.