P3: verso un concetto più ampio di dialisi peritoneale Proteggere per preservare Roberto Russo PROTECT PERITONEAL MEMBRANE FROM PERITONITIS Extra safe and easy to understand PD system Peritonitis is a cause of … Peritoneal membrane damage Hospitalization and pain Catheter loss Technique failure Death The sequence of events in peritoneal inflammation IL-1β TNF-α RESOLUTION sgp 130 INITIATION AMPLIFICATION IL-8 IL-6/sIL6R IL-1β TNF-α TRANSITION IFN-γ IL-1β TNF-α IL-8 MCP-1 RANTES IFN-γ Mediator concentration (pg/ml) Patients on CAPD who have peritonitis produce large amounts of pro-inflammatory cytokines sIL-6R IL-6 MNC PMN IL-8 MCP-1 Period post infection Hurst SM et al Immunity 2001;14:705-714 Effluent VEGF correlates with peritonitis severity 1000 VEGF effluent ρg/ml 800 600 400 200 0 0 2000 4000 6000 WBC/mm3 8000 10000 12000 Szeto et al, Perit Dial Int 2002; 22:265-274 Peritonitis is associated with a protracted inflammatory process 100 CXCR1 expression (PMN) 80 60 MNC Neutrophils 40 100 20 0 0 5 10 15 20 100 75 CD14 expression (MNC) % Leukocytes 80 60 40 20 0 0 5 10 15 20 25 50 25 CD3 expression (T-cells) 20 0 15 10 D1 D2 D3 D4 D5 5 Period post infection 0 0 5 10 Days 15 20 Topley and Parker, 2005 Peritonitis is associated with a protracted inflammatory process PD Effluent PD Effluent IL-6 TGF-β FGF-β IL-1 Modified from Lai KN AJKD 2000;35:644-52 Peritonitis and inflammatory severity “drives” to membrane change Thickness of submesothelial compact zone () 2500 2000 1500 1000 500 0 0 No previous infection 1 Previous infection 2 3 Davies S et al Nephrol Dial Transplant 11:498-506,1996 Repeated peritoneal inflammation drives the fibrotic process Fibroblast proliferation Collagen III synthesis Collagen III/Actin OD ratio 0,3 0,15 0 Hit 1 Hit 2 Hit3 Activation cycle with infected PDE 3 2 1 0 1 2 3 Activation cycle Topley and Parker, 2005 Pattern of inflammation may become deregulated during PD PMN PMN Monocytes Monocytes Lymphocytes Lymphocytes Time (days) Acute Time (days) Dysregulated Chronic Resident leukocyte populations in PD are suggestive of chronic inflammatory phenotype Risk factors of peritonitis Medical Factors Patient factors Albumin Diabetes Mellitus Non medical factors System factors Modifiable Fixed Disconnet Exit site Depression Adherence Obesity Ethnicity American Journal of Kidney Diseases, Vol 45, No 2 , 2005: pp 372–380 Peritoneal Dialysis International 2005, 25: 374–37 Prevention of peritonitis • • • • • • Catheter placement Exit site care Connection method Training Antibiotic prophylaxis for procedures Prevention of bowel source peritonitis • Prevention of fungal peritonitis Strategie antimicrobiche per la prevenzione delle peritoniti in dialisi peritoneale: Linea Guida G. Amici, R. Russo, M. Feriani et al • L’uso topico giornaliero, sull’emergenza cutanea del catetere peritoneale, della gentamicina riduce il rischio di peritonite (livello 2). • L’utilizzo di antibiotici, nella profilassi perioperatoria del posizionamento dei cateteri per dialisi peritoneale, è in grado di ridurre efficacemente solo gli episodi di peritonite precoce (livello 1). • La nistatina per via orale, in associazione alla terapia antibiotica, è efficace nel prevenire le peritoniti da Candida (livello 2). Giornale Italiano di Nefrologia 2007; 24(S-37):S125-S135 Strategie correlate al catetere per la prevenzione delle peritoniti in dialisi peritoneale: Linea Guida A. De Vecchi, R. Corciulo, M. Salomone, R. Russo et al • I set a Y e i sistemi a doppia sacca riducono il rischio di peritonite nei pazienti in dialisi peritoneale rispetto al sistema convenzionale (livello 1). Giornale Italiano di Nefrologia 2007; 24 (S-37); S136-S148 PERITONEAL DIALYSIS-RELATED INFECTIONS RECOMMENDATIONS: 2005 UPDATE PREVENTION OF PD-RELATED INFECTIONS • Training methods influence the risk of PD infections (Evidence). • There is an association between both severe constipation and enteritis and peritonitis due to enteric organisms (Evidence). • Prevention of catheter infections (and thus peritonitis) is the primary goal of exit-site care. Antibiotic protocols against S. aureus are effective in reducing the risk of S. aureus catheter infections (Evidence) Perit Dial Int 25: 107–131, 2005 Effect of Peritoneal Dialysis Nurses and Training Peritonitis rates per 1,000 Patients Months Hall G et al, Nephrol Nurs J 2004 Patient re-training in PD: why and when it is needed • Multi centered italian study: 353 patients answered a questionnaire 191 patients had a home visits with score card 23% were non-compliant with exchange procedure. Russo et al KI suppl 2006: 103; S 127-32 Summary • Peritonitis remains a serious complication of peritoneal dialysis. • Most peritonitis is due to either contamination with the PD exchange or exit site infection (ESI) and can be prevented by protocols. • Training and retraining of the patients, use of the best connection technology and use of exit site antibiotic cream to prevent ESI are keys to preventing peritonitis from contamination. Protect Preserve