Impaired outcome of continuous ambulatory peritoneal dialysis in immunosuppressed patients

BACKGROUND.: Although immunodeficiency predisposes to CAPD peritonitis withfungal or unusual organisms, the role of immunosuppression asa predisposing factor for CAPD peritonitis, as well as the outcomeof such episodes, remains uncertain. METHODS.: The incidence, spectrum of infectious organisms, and outcomeof CAPD peritonitis was retrospectively reviewed in 39 immunosuppressedand 146 non-immunosuppressed patients treated with CAPD overthe calendar year 1993. RESULTS.: Immunosuppressed patients were younger (mean 44 vs 57 years,P<0.001) and had an increased incidence of previous transplantation,glomerulonephritis, systemic lupus erythematosus, and vasculitis.Immunosuppressed patients had more episodes of peritonitis (69/39patients vs 99/147, P<0.001), required more frequent hospitaladmission (25/39 vs 33/146, P<0.001), had more days off CAPD(331 vs 242, P< 0.001), and required more laparotomies toremove infected CAPD catheters (11/39 vs 14/146, P<0.01).Immunosuppression was associated with increased infection dueto S. aureus and fungi, which may have contributed towards increasedmorbidity in this group. Current immunosuppression or a recenthistory of immunosuppression appeared to be equally potent riskfactors for infection. There was a trend for the incidence ofinfection to parallel the aggressiveness of immunosuppression. CONCLUSIONS.: Immunosuppression is an important risk factor for CAPD peritonitis.A high index of suspicion for infection and aggressive chemotherapyare mandatory. CAPD may not be the initial therapy of choicein this high-risk group.     

Antibacterial peritoneal defence in automated peritoneal dialysis: Advantages of tidal over continuous cyclic peritoneal dialysis?

In tidal peritoneal dialysis (TPD) only a part of the infuseddialysate is drained with each exchange, leaving a residualvolume on top of which fresh fluid is cycled. As the persistentpresence of a buffered intraperitoneal reserve volume mightfavour peritoneal macrophage (PMO) function, PMO obtained fromeight patients during a 3-h continuous cyclic peritoneal dialysis(CCPD) or TPD session were studied in a randomized cross-overtrial. PMO were studied for uptake of E. coli (complement-dependent)and S. epidermidis (antibody-dependent), as well as for theirkilling capacity and peak chemiluminescence response. In addition,dialysate was sampled during both treatment sessions and studiedfor pH, osmolality, and effect on the viability of donor phagocytesand mesothelial cells. TPD-derived PMO were significantly better able to phagocytoseE. coli than CCPD-PMO (48 ±8 versus 33±6% uptake,P<0.05), whereas the other tested functional capacities revealedno significant difference between TPD- and CCPD-PMO. DuringTPD dialysate pH ranged from 6 to 7 as compared to a pH rangefrom 5 to 7 in CCPD. The presence of a residual dialysate volumeresulted in less wash-out of cells and opsonins early in thetreatment, and to some extent blunted the noxious effects offresh dialysis solutions. Overall, however, tidal PD appearedto have no advantage over CCPD regarding preservation of peritonealdefences.     

Streptococcus agalactiae: A rare peritoneal infection in a continuous ambulatory peritoneal dialysis patient

Streptococcus agalactiae causes a rare and often fatal peritonitis in continuous ambulatory peritoneal dialysis (CAPD). A 52-year-old white female with Alport and chronic kidney disease was initiated on CAPD treatment. Nineteen months later she had a S. agalactiae peritonitis identified and received initially gentamicin–cephalothin, which was changed to ceftazidime, tobramycin, and vancomycin. Recovery started after peritoneal catheter removal. After 3 weeks, severe leucopenia occurred. Granulokine and steroids were given. Six weeks later, she felt well and an abdominal video laparoscopic procedure disclosed a diffuse peritoneal fibrosis, precluding CAPD resumption. She is now doing well on hemodialysis (HD).     

Dialysis fluid cytotoxicity and inhibition of host defence in cultured human mesothelial cells are neutralized rapidly with incubation in the peritoneum

BACKGROUND.: A recent survey puts the global dialysis population at 535 100;of those on peritoneal dialysis, 85% are on continuous ambulatoryperitoneal dialysis. Current hyperosmolar dialysis fluids aretoxic to peritoneal cells and inhibit certain host-defence functions.An alternative preparation, glucose polymer, has recently beendeveloped. METHODS.: Mesothelial cell viability, interleukin-6 and prostacyclin synthesis,after exposure to 7.5% glucose polymer, 1.36% glucose or 3.86%glucose peritoneal dialysis effluent solution was assessed. RESULTS.: In its neat form, at an original pH of 5.4, glucose polymerwas as toxic as hyperosmolar solutions (P <0.01). Synthesisof interleukin-6 and prostacyclin were significantly inhibitedby neat dialysis fluid, (P <0.01). However, after an in vivointraperitoneal incubation of only 15 min the toxicity of allsolutions tested in vitro was lost. CONCLUSFONS.: Despite rapid in situ neutralization of dialysis fluid toxicity,mesothelial injury and inhibition of host-defence function,early in the dialysis cycle, may affect peritoneal physiologygiven the complex network of pathways to which these cells contribute.Although recent trials indicate improved ultrafiltration isachievable with glucose polymer, it is not a biocompatible dialysisfluid in its current manufactured form.     

Cancer antigen 125: a bulk marker for the mesothelial mass in stable peritoneal dialysis patients

Mesothelial cells that line the peritoneal cavity are capableof producing several proinfiammatory cytokines such as interleukin-6and interleukin-8. Since they are the most numerous cell inthe peritoneal cavity when the lining mesothelial cells areincluded, they may play a major role in the local antibacterialdefence mechanism. Cancer antigen (CA)125 is expressed by mesothelialcells (as by other coelomic epithelium-derived cells) and mighttherefore be considered a marker of the mesothelium. The aimof this study was to determine whether CA125 is a bulk or anactivation stage mesothelial cell marker. A positive correlation was found between the mesothelial cellnumber and the CA125 concentration in dialysate of stable PDpatients (P = 0.03). CA125 release by mesothelial cell culturesduring confluence showed that the release per cell was constantin time. Stimulation of mesothelial cells in a confiuential phase withIL1ß, TNF, IFN and TGFß did not result inan increase in CA125 release. Cell lysis showed that CA125 isalso present intracellularly. This implies that release of intracellularCA125 can be a disturbing factor in interpreting the CA125 concentrationof dialysate in situations where mesothelial cell death mayoccur, such as in peritonitis. It can be concluded, that our data show that dialysate CA125is a bulk marker for the mesothelial cell mass in stable PDpatients and can thus provide data on the state of the peritonealmembrane in the follow-up of the individual patient.     

The impact of topical mupirocin on peritoneal dialysis infection in Singapore General Hospital.

BACKGROUND: Peritonitis and exit-site infections (ESI) are major causes of morbidity in peritoneal dialysis (PD) patients. The application of topical mupirocin to exit sites reduces such complications, and prolongs life in PD. Since the year 2000, this topical treatment has been used in our hospital on new PD patients. We analysed the results of this protocol, and studied the effects of comorbidities on the incidence of peritonitis. METHODS: We studied 740 incident PD patients, who were divided into two groups based on year of entry into PD (Group 1 from January 1998 to December 1999 inclusive, topical mupirocin not used, and Group 2 from January 2000 to March 2004 inclusive, topical mupirocin used). The variables we studied included gender, age, diabetic status, ischaemic heart disease, peripheral vascular disease, cerebrovascular disease and serum albumin. RESULTS: The application of topical mupirocin at the exit site led to a significant reduction in the rate of peritonitis (0.443 vs 0.339 episodes per patient-year; P<0.0005) and in ESI (0.168 vs 0.156 episodes per patient-year; P<0.005), results attributed primarily by the significant (P<0.005) reduction in Staphylococcus aureus infection. There was also an unexpected lowering of Pseudomonas aeruginosa peritonitis in the mupirocin group (P<0.005). Stepwise multiple logistic regression analysis revealed that only the application of mupirocin and serum albumin levels were significant predictors of peritonitis. CONCLUSIONS: Our study, although retrospective, has demonstrated that the topical use of mupirocin was associated with a significant reduction in ESI and peritonitis and, unexpectedly, with findings of fewer incidences of Pseudomonas peritonitis. Serum albumin level before the initiation of PD was a strong predictor of subsequent peritonitis. Mupirocin, with its low toxicity, ease of application and demonstrable beneficial effect in reducing ESI and peritonitis is now used on all of our incident PD patients.     

The impact of topical mupirocin on peritoneal dialysis infection rates in Singapore General Hospital.

BACKGROUND: Peritonitis and exit-site infections (ESI) are major causes of technique failure and morbidity in peritoneal dialysis (PD) patients. Topical mupirocin on the exit-site has been shown to reduce such complications and prolong life in PD. Since the year 2000, such an approach has been adopted for our new incident PD population. We now report the results of this new protocol. We also studied the effect of co-morbidity on peritonitis occurrence. METHODS: A total of 740 incident PD patients were studied. Patients were divided into two groups based on year of entry into PD (Group 1 from January 1998-December 1999 without topical mupirocin and Group 2 from January 2000-March 2004 with topical mupirocin). Variables studied included gender, age, diabetic status, ischaemic heart disease, peripheral vascular disease, cerebrovascular disease and serum albumin. RESULTS: Topical mupirocin at the exit-site has led to a significant reduction in peritonitis rate (0.443 vs 0.339 episodes/patient-year; P<0.0005) and ESI (0.168 vs 0.156 episodes/patient-year; P<0.005) attributed primarily to the significant reduction in Staphylococcus aureus infections. There was an unexpected finding of lower Pseudomonas aeruginosa peritonitis in the mupirocin group (P<0.005). Stepwise multiple logistic regression analysis revealed that only mupirocin application and serum albumin were significant predictors of peritonitis. CONCLUSIONS: Our study, although limited by its retrospective nature, demonstrated that topical mupirocin was associated with a significant reduction in ESI and peritonitis with unexpected findings of lower Pseudomonas peritonitis. Serum albumin prior to the initiation of PD was a strong predictor of subsequent peritonitis. Mupirocin, with its low toxicity, ease of application and demonstrable beneficial effect in reducing ESI and peritonitis is now used on all incident PD patients.     

Serum concentrations and peritoneal loss of growth hormone and growth-hormone-binding protein activity in older adults undergoing continuous ambulatory peritoneal dialysis: comparison with haemodialysis patients and normal subjects

Serum concentrations and peritoneal losses of growth hormone(GH) and of growth-hormone-binding protein (GH-BP) activityin 13 patients undergoing continuous ambulatory peritoneal dialysis(CAPD) were compared with those of 13 patients on haemodialysisand 13 normal subjects. The individuals in the three groupswere matched by age (40–83 years), gender, and serum glucoseconcentration. In addition CAPD and haemodialysis patients werematched by haematocrit, serum creatinine and albumin concentrations,and period of time on dialysis (0.5–127 months). GH inthe serum and in the peritoneal effluent were measured by radioimmunoassay(RIA) and NB2 bioas-say. GH-BP activity was analysed by bindingassay and expressed as a percentage of the specific bindingof GH. In the haemodialysis patients, serum GH was significantlygreater and serum GH-BP activity significantly less than inthe CAPD patients and control subjects. Between the two lattergroups no significant differences in GH or in GH-BP activitywere observed. GH bioactive/immunoactive ratios in the threegroups were similar. Both GH and GH-BP were detected in theperitoneal effluent of CAPD patients, in whom an overnight (8-h)peritoneal loss of GH (8.0±1.4x 10^–3 ug/h/1.73m2) was strongly correlated with serum GH (r= 0.840). CirculatingGH and GH-BP activity were influenced by serum creatinine andhaematocrit. In addition a positive relationship was observedbetween GH-BP activity and body mass index and between GH andtime on dialysis. These data reaffirm that older adults undergoinghaemodialysis, unlike CAPD patients, exhibit persistent abnormalitiesin GH-GH-BP axis. The peritoneal losses of GH and GH-BP thatoccur during CAPD do not affect their respective serum concentrations.     

Peritoneal catheter colonization by Penicillium sp : Case report and review of penicillium-related complications in peritoneal dialysis

Fungal peritonitis is an uncommon, serious complication of peritoneal dialysis, usually caused by Candida sp . Asymptomatic fungal colonization of the peritoneal catheter is less frequent. Penicillium sp have only rarely been reported as a cause of peritoneal complications in peritoneal dialysis. We report a case of fever and peritoneal catheter malfunction associated with catheter colonization by Penicillium sp , in the absence of signs or symptoms of acute peritonitis. Cultures of the dialysate grew Penicillium sp, and histological examination showed penetration of the catheter by hyphae. The peritoneal catheter was removed, and the patient was maintained on hemodialysis and oral itraconazole for 6 weeks before successfully returning to continuous cycling peritoneal dialysis (CCPD). One case of Penicillium catheter colonization and seven of Penicillium peritonitis in peritoneal dialysis patients have been previously published in the English literature. Detailed data were provided in five reports. Delayed diagnosis was frequent (mean ± SD 31 ± 24 days after the onset of symptoms). Peritonitis cases were treated with catheter removal and antifungal medications, and the outcome was always satisfactory. We conclude that Penicillium should be considered a pathogenic fungus, not a contaminant, when isolated from peritoneal dialysis specimens, and should be treated accordingly. However, Penicillium may colonize the peritoneal catheter in the absence of peritonitis, and the prognosis of Penicillium peritonitis is good despite a frequent delay in diagnosis.     

Fungal peritonitis caused by Curvularia species in a child undergoing peritoneal dialysis

We report the first case of peritonitis caused by Curvularia species in a child undergoing peritoneal dialysis. He presented with gray-black proteinaceous material obstructing the lumen of his Tenckhoff catheter. Although the peritoneal fluid was cloudy, the patient suffered neither significant abdominal tenderness nor systemic symptoms. Catheter removal and treatment with amphotericin B allowed complete recovery and return to peritoneal dialysis within 7 days. Outdoor play in a wooded environment may have allowed contact of this saprophytic fungus with the child’s indwelling catheter transfer set. Received: 6 March 2000 / Revised: 7 June 2000 / Accepted: 11 August 2000     

Disruption of low density lipoprotein receptor pathway is involved in peritoneal fibrosis induced by high glucose peritoneal dialysis solution

Objective To explore the potential mechanisms of low density lipoprotein receptor (LDLr) in high glucose peritoneal dialysis solution (PDS)-induced peritoneal fibrosis. Methods Human peritoneal mesothelial cells (PMCs) were applied. In pre-experiment, human PMCs were cultured with 1.5% PDS, 2.5% PDS and 4.25% PDS for 6 h, 12 h and 24 h. 4.25% mannitol was used as high osmotic pressure control. In formal experiment, PMCs were divided into the control group (treated with phosphate buffer saline) and the high glucose PDS group (treated with 4.25% PDS for 24 h). Morphological change of PMCs was observed by inverted microscope. The mRNA and protein expressions of extracellular matrix proteins such as α-smooth muscle actin (α-SMA), fibroblast specific protein-1 (FSP-1) and collagenⅠ in PMCs were respectively measured by real-time PCR and Western blotting. The lipid accumulation was observed by oil red O staining and filipin staining, and the content of intracellular cholesterol ester was detected by high-performance liquid chromatography. The co-expression of the sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) with golgin was observed with immunofluorescent staining. The mRNA and protein expressions of LDLr, SREBP-2 and SCAP were respectively detected by real-time PCR and Western blotting. The mRNA and protein expressions of mammalian target of rapamycin (mTOR), eukaryotic initiation factor 4E-binding protein 1 (4EBP1), and p70 S6 kinase (S6K1) were respectively detected by real-time PCR and Western blotting. Results (1) Compared with the 1.50% PDS stimulation, 4.25% PDS for 24 h intervention significantly increased the expression of LDLr in PMCs (P＜0.05), and high osmotic pressure control at 6 h, 12 h and 24 h had no statistical difference (P＞0.05). (2) Compared with those in the control group, in high glucose PDS group PMCs showed notable elongation consistent with the morphology of myofibroblasts, the expressions of α-SMA, FSP-1 and collagen Ⅰ were increased (all P＜0.05), and the intracellular cholesterol were enhanced (P＜0.05). Meanwhile, the co-expression of SCAP with golgin was enhanced, and the mRNA and protein expressions of LDLr, SREBP-2 and SCAP were up-regulated in high glucose PDS group (all P＜0.05). Further, the mRNA and protein phosphorylation of mTOR, 4EBP1 and S6K1 were increased (all P＜0.05). Conclusions The disruption of LDLr feedback regulation is involved in high glucose PDS-mediated cholesterol accumulation in PMCs by mammalian target of rapamycin complex 1 (mTORC1) pathway, which promotes the accumulation of extracellular matrix and peritoneal fibrosis.