Host defences in continuous ambulatory peritoneal dialysis and the genesis of peritonitis

Continuous ambulatory peritoneal dialysis (CAPD) has come to be extensively used for the treatment of end-stage renal failure in children, and especially infants, such that now more than half of children on dialysis worldwide receive treatment by this means. Peritonitis, however, is commoner in children than in adults receiving treatment, and is a major source of morbidity and treatment failure in children started on CAPD. Only recently has the immunology of the normal peritoneum been studied extensively, with the need to assess the impact of the installation of large volumes of fluid into the peritoneal sac during dialysis. The main phagocytic defences of the peritoneum depend upon a unique set of macrophages which are present free in the peritoneal fluid but also in the submesothelium and in perivascular collections together with B lymphocytes in the submesothelial area. Both the number of macrophages per unit volume and the concentration of opsonic proteins, such as IgG, complement and fibronectin, are reduced to between only 1% and 5% when dialysis fluid is continuously present in the peritoneal sac. In addition, the fluids used for CAPD are toxic to both macrophages and to mesothelial cells. Thus minor degrees of contamination frequently lead to peritonitis and in addition the majority of patients have catheters inserted in their peritoneum which become colonised with organisms capable of producing exopolysaccharide (slime), which promotes adhesion of the organism to the plastic and protects them against phagocytic attack and the penetration of antibiotics. Thus the peritoneum is in a state of continual inflammation, as well as being a markedly more vulnerable site than the normal peritoneum to the entry of organisms. Whether clinical peritonitis appears in this state of chronic contamination probably depends on perturbation in the balance between host defences and the organism. Whilst Staphylococcus epidermidis is the commonest cause of peritonitis, Staphylococcus aureus and Gram-negative organisms are much more serious and more frequently lead either to temporary catheter removal or discontinuation of dialysis altogether. This review describes the peritoneal defences in relation to the genesis of peritonitis.     

Nystatin prophylaxis: its inability to prevent fungal peritonitis in patients on continuous ambulatory peritoneal dialysis

OBJECTIVE: To evaluate the potential effectiveness of nystatin as prophylaxis for fungal peritonitis (FP) in patients on continuous ambulatory peritoneal dialysis (CAPD). DESIGN: This historically controlled study was designed to investigate the effectiveness of nystatin in the prevention of FP. For this purpose we compared the incidence of FP among 240 (new and prevalent) CAPD patients between January 1996 and November 1996 (period A) with its incidence in 240 new and prevalent CAPD patients in our program between January 1997 and November 1997 (period B) when nystatin prophylaxis was used. There were 2400 patient-months in each period. Nystatin (500,000 IU four times per day), was given orally at the beginning of other antibiotic therapy (usually for peritonitis) and continued for 5 days after the end of the antibiotic therapy. RESULTS: During period A, 133 peritonitis episodes were recorded, and during period B, 99 episodes were recorded. Six episodes of FP were identified in over 2400 patient-months of period A, and 12 in over 2400 patient-months of period B. This difference was not statistically significant. Three episodes of antibiotic-related FP were seen in period A, and four in period B. The remaining episodes arose de novo, that is, unrelated to the use of antibiotics. We observed no side effects for nystatin. CONCLUSION: In CAPD patients the use of nystatin, a nonabsorbable antifungal agent, as prophylaxis in every instance of peritonitis or other indications for antibiotics, did not lower the incidence of fungal peritonitis.     

Chylous ascites associated with acute pancreatitis in a patient undergoing continuous ambulatory peritoneal dialysis

We report on a case of chylous ascites associated with acute pancreatitis secondary to gallbladder stone disease, in a patient undergoing continuous ambulatory peritoneal dialysis. The initial clinical presentation was one of bacterial peritonitis, with later appearance of chylous peritoneal drainage. Diagnosis was suggested by abdominal computed tomography and confirmed by surgical exploration. We discuss the main diagnostic keys of peritoneal dialysis-associated pancreatitis and the possible etiologic role of this entity in chylous ascites of these patients.     

The pharmacokinetics of once-daily oral 400 mg ofloxacin in patients with peritonitis complicating continuous ambulatory peritoneal dialysis

Seven patients with end-stage renal disease requiring support by continuous ambulatory peritoneal dialysis received once-daily 400 mg oral ofloxacin for 7 days for the treatment of bacterial peritonitis. Serum and peritoneal dialysis fluid (PDF) were collected for assay throughout the course of the study and for 5 days thereafter. Ofloxacin, desmethyl ofloxacin and ofloxacin-N-oxide accumulated over the course of therapy and could still be detected in serum and PDF 5 days after the end of therapy. The mean elimination half-life of ofloxacin in serum was 32 +/- 7 h, desmethyl ofloxacin 45 +/- 26 h and for ofloxacin-N-oxide 44 +/- 15 h. The total mean recovery of ofloxacin and its metabolites from the PDF was 15.4%. This regimen results in serum and PDF concentrations likely to be effective for the treatment of infection for at least 10 days.     

A case of peritonitis caused by Roseomonas gilardii in a patient undergoing continuous ambulatory peritoneal dialysis

A case of peritonitis caused by Roseomonas gilardii in a patient receiving continuous ambulatory peritoneal dialysis is presented. The patient's domestic water supply was implicated as the probable source of infection. This is the first report of R. gilardii causing such an infection.     

IgG glycation and function during continuous ambulatory peritoneal dialysis

IgG in dialysate may have an important role in anti-infection mechanisms during continuous ambulatory peritoneal dialysis (CAPD). As Fc fragment oligosaccharidic chains are crucial for IgG effector functions, we have tested the hypothesis that IgG glycation might occur during CAPD and modify IgG properties. Purified normal IgG was incubated with glucose solutions of different concentrations and pH. Separation of glycated IgG was performed by affinity chromatography. Complement activation (C3c deposition) and phagocytosis by polymorphonuclear leucocytes (PMN) were studied in vitro using Staphylococcus aureus Wood (STAW) as antigen. In addition, we compared the percentages of glycated IgG in IgG purified from sera and dialysates of 12 CAPD patients. The percentage of glycated IgG after in vitro incubation of normal IgG with glucose solutions was directly proportional to glucose concentrations, incubation time and pH. Glycated IgG anti-STAW induced a higher C3c deposition than non-glycated IgG anti-STAW (C3c/IgG (mean +/- SD) 0.96 +/- 0.06 vs 0.79 +/- 0.08; P = 0.027). PMN phagocytosis was not affected by IgG glycation. The percentages of glycated IgG in dialysates of CAPD patients were greater than those in corresponding sera (5.38 +/- 2.36% vs 4.56 +/- 2.47%; P = 0.006). It is concluded that IgG glycation may take place in the peritoneal cavity during CAPD and lead to enhanced complement activation. This could explain the high degree of complement activation previously described in dialysate of CAPD patients and might theoretically result in a reduction of complement factors available in dialysate for adequate anti-infection mechanisms.     

Measuring the economic impact of ambulatory dialysis: the case of continuous ambulatory peritoneal dialysis

BACKGROUND: As concerns the treatment of terminal renal failure (TRF), France is characterized by a minimal use of peritoneal dialysis, even though this technique is as effective and less expensive than others and that authorities precognize to switch patients to out-of-centre techniques, like peritoneal dialysis. The purpose of the article is to estimate benefits for the Social Security induced by an incitative program leading the current structure of TRF treatment to the existing government standards defined in 1984. METHODS: We computed treatment cost differences, on the basis of an incident case of TRF followed during 7 years, between three different situations: the current French structure of TRF treatment (29.5% of patients treated by out-of-center techniques); two reference situations A and B (respectively 45% and 37% of patients treated by out-of-center techniques). We performed a sensitivity analysis on the rate of use of continuous ambulatory peritoneal dialysis (CAPD). We made assumptions on the cost of techniques, the cost of complications and the rate of CAPD treatment failure. RESULTS: Results stress the existence of benefits induced by increased use of out-of-centre techniques on the basis of a 7-year follow-up of an incident TRF patient: around 65,000 FF in situation A with a 20% rate of use of CAPD; around 5,000 FF in situation B with a 15% rate of use of CAPD. Assumptions concerning CAPD treatment lead to an underestimation of the true benefits. CONCLUSION: The study highlights the therapeutic and economic interest to transfer some patients from hemodialysis to peritoneal dialysis.     

Peritonitis in continuous ambulatory peritoneal dialysis. Culture of peritoneal dialysate fluid

Conventional aerobic and anaerobic culture of peritoneal dialysate effluent from patients in continuous peritoneal dialysis (CAPD) was compared to culture in a semiautomated blood culture system. During a two-year period 78 of 79 consecutive episodes of peritonitis among 45 Danish CAPD patients were cultured and the etiology of the infection found in 73 (94%). The sensitivity of the blood culture system was 88%, whereas the sensitivity of the conventional culture of the dialysate effluent was 81%. This difference is not significant (McNemar test; 0.5 > p > 0.3). The majority of isolates were Gram-positive bacteria dominated by coagulase-negative staphylococci (38%). In comparison, only 2% of the cultures of peritoneal dialysate effluent taken within the same period from patients without clinical signs of peritonitis were positive. All the Gram-positive aerobic bacteria were sensitive to vancomycin whereas 97% of the Gram-negative aerobic bacteria were sensitive to gentamicin. An initial empiric treatment of peritonitis with a combination of vancomycin and gentamicin is recommended.     

High serum D-lactate in patients on continuous ambulatory peritoneal dialysis

BACKGROUND: As abnormally high serum D-lactate levels may cause neurological impairment, we determined whether patients undergoing continuous ambulatory peritoneal dialysis (CAPD) with lactate-containing fluids have increased serum D-lactate concentrations. METHODS: D- and L-lactate concentrations were determined in peritoneal dialysis fluids and in serum from control subjects (n = 10), haemodialysis patients (n = 10), and CAPD patients (n = 30) before and after 1 h of dialysis. RESULTS: We found the median D-lactate concentration in Dianeal CAPD fluid to be 26 mM (range 19-27), whereas it was less than 0.5 mM in DPCA2 fluid. Control, haemodialysis, and CAPD (DPCA2) patient median serum D-lactate concentrations were below 0.07 mM. However, CAPD (Dianeal) patient serum D-lactate concentrations were 4-fold higher than controls (P < 0.0001), at 0.28 mM, an hour after instillation of D-lactate-containing fluid. Three patients, whose serum D-lactate averaged 0.59 mM, were found to have D-lactate concentrations at 0.22 mM after overnight cessation of dialysis. CONCLUSION: We conclude that CAPD with D-lactate-containing fluids raises serum D-lactate to abnormal levels.     

Outcome of HIV infected patients on continuous ambulatory peritoneal dialysis

A retrospective analysis of 39 HIV infected patients with ESRD cared for in New Haven from 1987 to June 1992 was performed. All patients had evidence for HIV infection at the start of CAPD therapy. Cumulative technique survival at one and two years was 43% and 27%, respectively. Only eight patients transferred to center dialysis. One and two year patient survival on CAPD was 58% and 54%, respectively. Mortality was higher in patients with advanced infection than in those with asymptomatic HIV infection. Hospitalization rates were also higher in patients with advanced infection. HIV infected patients had higher rates of peritonitis (3.9 episodes/outpatient CAPD year) compared to non-HIV infected patients (1.5 episodes/CAPD year), especially for pseudomonal and fungal infections. Active injection drug use and use of the "straight set" system were associated with increased rates of peritonitis. CAPD deserves consideration as a therapy for HIV infected patients with ESRD.     

Serum ionic fluoride levels in haemodialysis and continuous ambulatory peritoneal dialysis patients

High serum fluoride (F-) in patients with chronic renal failure (CRF) and end-stage renal disease (ESRD) is associated with risk of renal osteodystrophy and other bone changes. This study was done to determine F- in normal healthy controls and patients with ESRD on haemodialysis (HD) or peritoneal dialysis (PD). Seventeen healthy controls (12 males, 5 females) and 39 ESRD patients on dialysis (17 males, 22 females) were recruited in the study in a community with 47.4 +/- 3.28 microM/l (range 44-51 microM/l) of F- content in drinking water. Control subjects showed a mean serum F- concentration of 1.08 +/- 0.350 microM/l. Males in control group showed slightly higher F- levels (1.15 +/- 0.334, range 0.55-1.9 microM/l) than females (0.92 +/- 0.370, range 0.6-1.5 microM/l). Mean serum F- concentration did not correlate significantly with age and sex among control subjects, whereas such correlation was observed in patients with ESRD on dialysis. Mean serum F- concentration was significantly higher in patients on dialysis (2.67 +/- 1.09, range 0.8-5.2 microM/l) than normal controls. When grouped according to sex, the mean serum F- concentration in males (3.05 +/- 1.04, range 1.8-5.2 microM/l) was significantly higher than females (2.38 +/- 1.08, range 0.8-5.2 microM/l). When patients were grouped according to age, it was observed that F- concentration was significantly higher in patients with age groups 21-70 (2.86 +/- 1.05) than those with age group 13-20 years (1.42 +/- 0.531). Thus F- concentration correlated with age and sex, being higher in males and above 20 years. Despite appreciable clearance of F- (39-90%) across the peritoneum, patients on CAPD showed higher serum F- concentration than those on HD (3.1 +/- 1.97 vs 2.5 +/- 1.137 microM/l). Of the total 39 patients on dialysis 39% had their serum F- concentration above 3.0 microM/l, posing the risk of renal osteodystrophy.