P3: verso un concetto più ampio di dialisi peritoneale

Proteggere per preservareProteggere per preservare

Roberto Russo

PROTECT

PERITONEAL MEMBRANE FROM

PERITONITIS

Extra safe and easy to understand Extra safe and easy to understand PD system PD system

Peritonitis is a cause of …

Peritoneal membrane damage

Hospitalization and pain

Catheter loss

Technique failure

Death

IL-1βTNF-α

IL-8INITIATION

IL-8

IFN-γ

IL-1βTNF-α

AMPLIFICATION

TRANSITION

MCP-1

IFN-γIL-1βTNF-α

IL-6/sIL6R

sgp 130

RANTES

RESOLUTION

The sequence of events in peritoneal inflammation

Patients on CAPD who have peritonitis producelarge amounts of pro-inflammatory cytokines

Hurst SM et al Immunity 2001;14:705-714

sIL-6R IL-6

IL-8 MCP-1

Period post infectionPeriod post infection

Med

iato

r co

nce

ntr

atio

n (

pg

/ml)

MNC

PMN

Effluent VEGF correlates with peritonitis severity

0

200

400

600

800

1000

0 2000 4000 6000 8000 10000 12000

WBC/mm3

VEG

F effl

uent

ρg/

ml

Szeto et al, Perit Dial Int 2002; 22:265-274

Peritonitis is associated with a protractedinflammatory process

0

25

50

75

100

D1 D2 D3 D4 D5

MNC Neutrophils

Period post infection

% L

euko

cyte

s

0

5

10

15

20

25

0 5 10 15 20

0

20

40

60

80

100

0 5 10 15 20

0

20

40

60

80

100

0 5 10 15 20

CXCR1 expression (PMN)

CD14 expression (MNC)

CD3 expression (T-cells)

Days

% s

urfa

ce e

xpre

ssio

n

Topley and Parker, 2005

Peritonitis is associated with a protracted inflammatory process

Modified from Lai KN AJKD 2000;35:644-52

PD Effluent PD Effluent

IL-6

TGF-βFGF-β

IL-1

Peritonitis and inflammatory severity “drives” to membrane change

Davies S et al Nephrol Dial Transplant 11:498-506,1996

0

500

1000

1500

2000

2500

0 1 2 3

Thic

knes

s of

sub

mes

othe

lial c

ompa

ct z

one

()

No previousinfection

Previousinfection

Repeated peritoneal inflammation drives the fibrotic process

0

0,15

0,3

Hit 1 Hit 2 Hit3

Fibroblast proliferation

Activation cycle with infected PDE

Prol

ifera

tion

Inde

x

Topley and Parker, 2005

0

1

2

3

1 2 3

Collagen III synthesis

Activation cycle

Colla

gen

III/A

ctin

OD

ratio

Pattern of inflammation may become deregulated during PD

PMN Monocytes

Lymphocytes

PMN

Monocytes

Lymphocytes

Time (days) Time (days)

Resident leukocyte populations in PD are suggestive of chronic inflammatory phenotype

Acute Dysregulated Chronic

AlbuminAlbuminDiabetes MellitusDiabetes Mellitus

DisconnetDisconnetExit siteExit site

DepressionDepressionAdherenceAdherence

ObesityObesityEthnicityEthnicity

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 prevenzionedelle 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 prevenzionedelle 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

• 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)

PERITONEAL DIALYSIS-RELATED INFECTIONSRECOMMENDATIONS: 2005 UPDATE PREVENTION OF PD-RELATED INFECTIONS

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.

PreserveProtect