Carrier-status for nasal staphylococci does not predict infections in CAPD patients.

It has been reported that nasal carriage of staphylococci may contribute to infections of the continuous ambulatory peritoneal dialysis (CAPD) catheter exit site or cause peritonitis due to this pathogen. Recently, a nasal ointment to eradicate these bacteria in patients and staff has been marketed with the implication that this treatment may reduce infection rates. In this study, we investigated 37 patients treated with CAPD for a mean of 38.8 +/- 6.4 months. Presence of nasal carriage of staphylococci was assessed using standard nasal swab techniques and related to bacteria identified at the time of previous infections. Results were analyzed using Spearman rank order correlation and linear regression analysis. In 119.5 patient years at risk, 50 infections with staphylococci (24 episodes of peritonitis and 26 exit-site infections) were evaluated. Nineteen patients were carriers of S. aureus or S. epidermidis; 6 patients were carrying both species. There was no correlation of current nasal carriage of staphylococci with previous infection. Although 23 of 37 patients were carriers, 14 of these never had infections due to nasal staphylococci. Only in 14 of 50 infections were bacteria species the same in the nose and at the site of infection. We conclude that prospective trials demonstrating a reduction of CAPD-related infections are needed before general use of prophylactic nasal antibiotic treatment can be recommended in these patients.

Inhibition of C5a-induced actin polymerization, chemotaxis, and phagocytosis of human polymorphonuclear neutrophils incubated in a glucose-based dialysis solution.

Chemotaxis and phagocytosis are important functions of phagocytic cells, which are closely related to cytoskeletal reorganization. These functions may be abnormal in phagocytes of uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD). In order to examine whether these abnormalities result from treatment, we studied actin polymerization (AP), as an index of cytoskeletal alterations, chemotaxis, and phagocytosis in polymorphonuclear neutrophils (PMNs) of healthy subjects. Polymorphonuclear neutrophils were exposed to either a hepes buffer or a glucose-based dialysis solution (GBDS) of different pH's (5.2, 7.4) and different glucose concentrations (1.36%, 2.27%, 3.86%). After incubation for 0, 5, or 20 minutes, cells were activated with 10 nmol/L C5a-complement. AP was measured as filamentous (F) actin content by NBD phallacidin staining and FACS analysis. Chemotaxis of PMNs was measured in Boyden chambers. In addition, phagocytosis of zymosan particles was assessed. Prior exposure to GBDS pH 5.2 of each glucose concentration immediately and completely inhibited AP in response to 10 nmol/L C5a-complement, reduced chemotaxis (> 95%), and completely inhibited phagocytosis. The inhibition was pH-dependent, since GBDS pH 7.4 caused less inhibition of these functions. We conclude that glucose-based dialysis solutions are cytotoxic towards neutrophils and completely inhibit their ability to display responses requiring cytoskeletal reorganization.

Effect of simvastatin on qualitative and quantitative changes of lipoprotein metabolism in CAPD patients.

The efficacy of simvastatin, a competitive inhibitor of 3-hydroxy-3-methyl glutaryl coenzyme A reductase, was investigated in 12 patients treated with continuous ambulatory peritoneal dialysis (CAPD), displaying hypercholesterolemia and moderate hypertriglyceridemia. After a 4-week placebo period, simvastatin was administered in increasing doses over a period of 3 months (1st month 10 mg; 2nd month 20 mg and 3rd month 40 mg day-1). Simvastatin reduced total serum cholesterol (300.0 +/- 15.5 vs. 193.0 +/- 8.0; -35%), LDL cholesterol (203.8 +/- 13.0 vs. 104.7 +/- 6.0; -48.0%) as well as apolipoprotein B (132.3 +/- 6.6 vs. 77.8 +/- 2.7 mg/dl; -40%). Furthermore, the ratio of LDL apo B/LDL cholesterol increased significantly (0.55 +/- 0.016 vs. 0.64 +/- 0.027). Another remarkable effect was the reduction of cholesterol concentration in VLDL (47.8 +/- 5.6 vs. 30.4 +/- 5.2; -35%). Therefore, the ratio of triglycerides/cholesterol in VLDL increased (3.57 +/- 0.3 vs. 4.28 +/- 0.29), indicating VLDL formation poor in cholesterol and rich in triglycerides. However, HDL cholesterol increased significantly from 48.6 +/- 4.4 to 57.9 +/- 5.3 mg/dl (23%). Lipoprotein(a) levels were increased as compared to controls (420 +/- 73 vs. 145 +/- 26 U/l), but were not influenced significantly by simvastatin treatment (539 +/- 99 U/l, 3rd month). No evidence for notable clinical side effects and laboratory abnormalities were reported. Measurement of simvastatin plasma levels 12 h after drug administration (single dose 40 mg) showed no detectable plasma values. At present, it appears that CAPD patients with high serum cholesterol are good candidates for the treatment with HMG-CoA reductase inhibitors.

Effect of CAPD dialysate on the release of eicosanoids and cytokines from human peritoneal macrophages.

The effect of fresh peritoneal dialysis (PD) solution and effluent on the generation of eicosanoids and cytokines by human peritoneal macrophages (PMO) was studied in vitro. PMO, isolated by density gradient separation from patients undergoing intermittent peritoneal dialysis (IPD), were incubated for 2 h with PD effluent after dwell periods of 5 to 240 min or fresh PD solution. Supplemented RPMI-1640 medium served as control. PMO were stimulated by calcium ionophore A23187 (10 M). PD solution significantly inhibited the release of prostanoids (PGE2, TXB2, 6-k-PGF1), leukotrienes (LTB4, LTC4), and cytokines (11-6, TNF) from PMO by 60 to 96% (p < 0.05). Addition of A23187 increased the generation of TXB2, LTB4, and LTC4 in PD solution adjusted to pH 7.4 to 2.7 up to 28.6 times the basal level, but was ineffective in PD fluid at pH 5.2. Incubation of PMO with PD effluent of varying dwell times resulted in a rise of all assayed mediators (p < 0.05). The release of IL-6 increased continuously from 80 +/- 10 pg/10(6) PMO (0 min dwell time) to 440 +/- 104 pg/10(6) PMO (4 h dwell time, mean +/- S.E.M.). TNF generation rose from 6.0 +/- 0.1 pg/10(6) PMO (0 min dwell time) to 162 +/- 54 pg/10(6) PMO after 5 min dwell time and remained constant with effluents of longer dwell times (15 to 240 min). Exposure of PMO to PD effluents after 240 min dwell time tended to decrease the median levels of PGE2, TXB2, and 6-k-PGF1.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of amino acid based dialysis solution on peritoneal permeability and prostanoid generation in patients undergoing continuous ambulatory peritoneal dialysis.

The acute effect of amino acid based dialysis solution on peritoneal kinetics of amino acids and plasma proteins in comparison to conventional glucose-based dialysate was studied in 9 patients with end-stage renal failure on continuous ambulatory peritoneal dialysis. Instillation of 2.6% amino acid solution resulted in raised plasma concentrations of all essential amino acids included in the dialysis fluid (p less than 0.005). The amino acid solution induced an augmented leakage of plasma proteins into the dialysate at all dwell times investigated (1-8 h). After a dwell time at 8 h, the dialysate total protein increased from 2.62 +/- 0.45 g with glucose dialysate to 3.85 +/- 0.42 g with amino acid solution (p less than 0.05). Corresponding results were obtained for beta 2-microglobulin, albumin, transferrin, IgG, and for the non-essential amino acids alanine, citrulline, and glutamine (p less than 0.025) not included in the initial amino acid composition of the dialysis fluid. During the use of amino acid based dialysis fluid, the effluent prostaglandin E2 concentration increased by more than 80% in comparison to glucose dialysate (p less than 0.025). The augmented loss of proteins induced by the amino acid solution was positively correlated with increased dialysate prostaglandin E2 (r = 0.8894; p less than 0.001). Peritoneal ultrafiltration was not affected by the use of amino acid based dialysate fluid. The present results indicate that amino acid based dialysis fluid enhances the peritoneal permeability for plasma proteins and amino acids, probably mediated by locally generated prostanoids.

Effect of human recombinant erythropoietin on anaemia and dialysis efficiency in patients undergoing continuous ambulatory peritoneal dialysis.

The effect of long-term treatment with human recombinant erythropoietin (rHuEPO) has been studied in nine end-stage renal disease patients on continuous ambulatory peritoneal dialysis (CAPD). RHuEPO was administered subcutaneously twice weekly in rising doses starting with 50 Ukg-1 body weight. After 3 months of rHuEPO haemoglobin increased from 77.7 +/- 3.2 to 112.7 +/- 5.6 g l-1 (P less than 0.03), haematocrit rose from 22.8 +/- 1.2 to 30.3 +/- 1.7% (P less than 0.01). A consistent decrease in ferritin concentration was observed during this time (P less than 0.05). After 12 months of rHuEPO treatment and increased oral iron supplementation the rises of haemoglobin and haematocrit remained stable without other significant haematological changes. The rHuEPO-induced rise in haematocrit was associated with an increased peritoneal ultrafiltration (UF) without change in diuresis and body weight. UF improved from 128 +/- 28 ml 4 h-1 dwell time to 273 +/- 45 ml 4 h-1 (P less than 0.03) within 3 months of rHuEPO treatment, and remained stable during the following study period (month 12: 253 +/- 43 ml 4 h-1, P less than 0.05). The rise in UF resulted in improved peritoneal clearances of creatinine, urea, potassium, and phosphate (P less than 0.05, month 3). No change was observed in serum urea, creatinine, calcium, and potassium. Serum phosphate increased throughout the first 6 months of rHuEPO (P less than 0.05). No severe adverse effects of rHuEPO treatment could be observed. The present results demonstrate that long-term subcutaneous administration of rHuEPO is effective in correcting renal anaemia in CAPD patients and may improve dialysis efficiency by increased peritoneal ultrafiltration.

One year experience with subcutaneous human erythropoietin in CAPD: correction of renal anemia and increased ultrafiltration.

After 6 months of (recombinant human erythropoietin) rHuEPO treatment we recently observed an increased peritoneal ultrafiltration (UF) (Nephron 53: 91, 1989). The aim of the present study was to investigate the long term effect of subcutaneous (SC) on dialysis efficiency in CAPD. Fourteen patients (11 female, 3 male, mean age 42.6, range 18-65 years) with renal anemia (HCT less than 28%) took part in the study. rHuEPO was administered s.c. twice weekly in an initial dose of 50 U/kg body weight. This dose was increased by 25 U/kg body weight every 4 weeks till the target HKT of 35% had been achieved. After 12 months of mean time of treatment (range 8-14 months) hematocrits had increased from 23.3 +/- 3.2 (x +/- SD) to 36.6 +/- 5.3% (p less than 0.005). UF improved from 0.70 +/- 0.22 to 1.03 +/- 0.47 ml/min (4 hr dwell time, 1.5% glucose monohydrate) (p less than 0.03). Increased UF resulted in an augmented creatinine clearance (p less than 0.05). No changes were observed in serum chemistries, body weight, pulse rate or cardiothoracic index. The observed increase in peritoneal ultrafiltration might be due to augmented mesenteric perfusion resulting from improved cardiac function. The sustained increase in UF after rHuEPO-induced correction of renal anemia may improve the fluid balance on CAPD patients.