simon davies university hospital of north staffordshire, stoke-on-trent institute for science and
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Controversies in EPS Bari, March 2010. Simon Davies University Hospital of North Staffordshire, Stoke-on-Trent Institute for Science and Technology in Medicine Keele University, UK. What are the controversies surrounding EPS?. Diagnostic criteria Are EPS and membrane fibrosis the same? - PowerPoint PPT PresentationTRANSCRIPT
Simon DaviesUniversity Hospital of North Staffordshire,
Stoke-on-TrentInstitute for Science andTechnology in Medicine
Keele University, UK
Controversies in EPS
Bari, March 2010
What are the controversies surrounding EPS?
• Diagnostic criteria• Are EPS and membrane fibrosis the
same?• Is EPS after transplantation the
same?• Should we screen? How?• Should all patients stop PD at 5
years?• Is surgery the only treatment?
Abdominal Cocoon
Defining EPS – learning form the Japanese experience
• clinical symptoms/signs of obstructive ileus, with or without a systemic inflammatory reaction, (e.g. CRP)
• Presence of peritoneal thickening and encapsulation, intestinal obstruction, cocooning, ± peritoneal calcification, confirmed by radiological investigations or at laparotomy, ± typical biopsy
What are the controversies surrounding EPS?
• Diagnostic criteria• Are EPS and membrane fibrosis the
same?• Is EPS after transplantation the
same?• Should we screen? How?• Should all patients stop PD at 5
years?• Is surgery the only treatment?
Davies, SJ, KI, 2004
Are EPS and SS/fibrosis the same?
EPS• Inflammatory• Visceral• Rare• No intermediate• Rapid onset• Triggers• Longevity• Fibrinous exudate
Simple Sclerosis• Non-inflammatory• Parietal• Common• Continuum• Gradual change• No triggers• Longevity• Fibrosis
0.4
0.5
0.6
0.7
0.8
0.9
1
-9 -8 -7 -6 -5 -4 -3 -2 -1 0 1 2
Years before EPS/Stopping PD
So
lute
Tra
nsp
ort
0
100
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300
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500
600
-9 -8 -7 -6 -5 -4 -3 -2 -1 0 1 2
Years before EPS/Stopping PD
UF
cap
acit
y (m
l)
* *†
* Stoke PD Study
Longitudinal changes in membrane function for 9 patients developing EPS and controls matched (x4) for duration of completed time (mean 78.5 months) on PD
* P < 0.02
† P = 0.007Lambie et al, KI in press
0
100
200
300
400
500
600
0.5 0.6 0.7 0.8 0.9 1
Solute transport (D/P creatinine)
UF
cap
acit
y (m
l)
0
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400
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700
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900
0 20 40 60 80 100 120
Months on PD
Med
ian
Uri
ne
Vo
lum
e (m
l)
Lambie et al, KI in press
Lambie et al, KI in press
Longitudinal membrane change in EPS v. patients with normal UF or UF
Failure
Sampimon, DE, Krediet R et al, awaiting publication
Solute transport Net Total UF
Longitudinal membrane change in EPS v. patients with normal UF or UF
Failure
Sampimon, DE, Krediet R et al, awaiting publication
Small pore fluid transport Aquaporin fluid transport
Start PD
Increasing solute transport
Dissociation of solute transport and
osmotic conductance
Ultrafiltration failure
EPS
Variability in membrane function
•Effective contact area
•Osmotic conductanceIncreasing vascularity
Increase in blood flow
Progressive fibrosis
Additional trigger/2nd hit
Stop PD
Peritonitis
Visceral involvement
IL-1/IL-6
VEGF
? TGF
EMT
? Impaired fibrinolysis
Loss RRF
Glucose/GDP
Peritonitis
What are the controversies surrounding EPS?
• Diagnostic criteria• Are EPS and membrane fibrosis the
same?• Is EPS after transplantation the
same?• Should we screen? How?• Should all patients stop PD at 5
years?• Is surgery the only treatment?
EPS after transplantation
• Not described in Japan – but low transplantation rates
• Recently described in Europe• Why? Time on treatment/Tx waiting
list? Immunosupression?– Manchester (Summers et al); long time on
PD, immuosupression changes CyA only to include MMF
– Netherlands (Korte et al); long time on PD
What are the controversies surrounding EPS?
• Diagnostic criteria• Are EPS and membrane fibrosis the
same?• Is EPS after transplantation the
same?• Should we screen? How?• Should all patients stop PD at 5
years?• Is surgery the only treatment?
Radiological features of EPS (CT scanning)
• peritoneal calcification• bowel distribution• bowel wall thickening and
dilatation • loculation of ascites • peritoneal thickening
0
1
2
3
4
Me
dia
n s
core
0
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2
3
Med
ian
scor
e
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dia
n s
co
re
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dia
n s
core
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Me
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n s
core
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Me
dia
n s
core
Calcification Bowel Distribution Bowel wall thickening
Loculation Peritoneal Thickening Bowel wall dilatation
Tarzi et al, CJASN, 2008
HD PD EPS HD PD EPS HD PD EPS
0
5
10
15
20
Med
ian
scor
e
HD PD EPS HD PD EPS
Tarzi et al, CJASN, 2008
CT can diagnose EPS, but...
• Early signs of EPS are not easily identified or agreed by radiologists
• In CT studies several patients had normal CT scans a short time before diagnosis was confirmed – so not useful for screening
What are the mediators/potential biomarkers?
• Protein leak = fibrosis, = inflammation/EPS
• CA125 mesothelial cell health• IL-6 local production transport• VEGF local production
transport• TGF-β driver of EMT• MCP-1, CCL18 local production ?fibrosis• Hyaluronan ? Membrane health/healing• Fibrinolytic system • CRP systemic inflammation EPS
What are the controversies surrounding EPS?
• Diagnostic criteria• Are EPS and membrane fibrosis the
same?• Is EPS after transplantation the
same?• Should we screen? How?• Should all patients stop PD at 5
years?• Is surgery the only treatment?
Comparison of estimated EPS risk in 7 studies worldwide conducted by
the Scottish Renal registryStudy
Nomotoet al1996
Rigbyet al1998
Leeet al2003
Kawanishiet al2001
Kawanishiet al2004
Summerset al2005
Brownet al
(current study)
Number of EPS Cases(those meeting ISPD 2000 criteria in brackets)
62 54 (46) 31 17 48 27 (23) 46
Dates of Study1980 - 1994 1980 - 1994 1981 – 2002 1999 - 2001 1999 - 2003 1998 – 2003 2000-2007
Study DesignRetrospectiveMulti-centre
RetrospectiveMulti-centre
RetrospectiveMulti-centre
ProspectiveMulti-centre
ProspectiveMulti-centre
RetrospectiveSingle-centre
RetrospectiveMulti-centre
Denominator Population (prevalent + incident PD Patients)
6923 7374 3888 2216 1958 810 1638
Overall Rate0.9% 0.7% 0.8% 0.8% 2.5% 3.3% 2.8%
Mean PD Exposure (yrs)5.1 4.3 5.8 10 4.3 6.1 5.4
Mortality (over study period) 43.5 % 56 % 25.8 % 35 % 37.5 % 29.6 % 56.5%
Incidence and outcome of EPS in relation to time on PD.
PD duration(yrs)
No of pts EPS incidence
Mortality Recovery
<3 337 0%
3 to <5 554 0.7% 0% 100%
5 to <8 576 2.1% 8.3% 83.3%
8 to <10 239 5.9% 28.6% 42.9%
10 to 15 223 5.8% 61.5% 15.3%
>15 29 17.2% 100% 0%
Total 1958 2.5% 37.5% 45.8%
Kawanishi H et al Am J Kid Dis 2004 44:729-37
Stoke PD Study: Risk of developing EPS
Lambie et al, KI in press
Patients are not the same... Imagine two different patients
on PD for 5 years:• 45 yrs, anuric for 2 years, requires 2
2.27% glucose exchanges per day, no live donor – an exit strategy from PD needs to be planned
• 71 yrs, 300 ml urine, 2 comorbidities, enjoys good QOL on PD, also needs 2 2.27% exchanges per day – discussion required but staying on PD is reasonable
What are the controversies surrounding EPS?
• Diagnostic criteria• Are EPS and membrane fibrosis the
same?• Is EPS after transplantation the
same?• Should we screen? How?• Should all patients stop PD at 5
years?• Is surgery the only treatment?
Cocoon Opened
Thickened Visceral Membrane Dissected
Released gut
Manchester ExperienceReferrals Jan 2000 – Dec
2008 n = 83 Local - 61
MRI (42) Hope (7) Preston (9) Wythenshawe (3)
National - 18Exeter(3) Dorset (2) London (2) Epsom
St.Helier(1) North Staffs (2) Derby (1) Cumberland (1) Sheffield (1) Bristol (1) Sunderland (1) Birmingham (1) Cardiff (1) Inverness(1)
International - 4Dublin (3) Slovenia (1)
Post Surgery Outcomes
49 ALIVE None on TPN All home 3 patients have symptoms of
colic and early satiety but on oral diet
Suggested Risk Stratification For Surgical Intervention
LENGTH OF DIALYSIS
1-4 YRS 4-8YRS 8-12YRS
SYMPTOMS Mild fullness,discomfort
Distension,fullness,early satiety,vomiting,subacute obstruction
Gross distension, Recurrent subacute obstruction, obstruction*, Peritonitis*, Major Hemoperitoneum*
ALBUMIN Normal Moderate Low
ANEMIA Hb>10gm% Hb 8-10gm%, EPO,Transfusions
Hb<8gm%, Transfusions,EPO
WEIGHT NORMAL SUB-OPTIMAL SIGNIFICANT WEIGHT LOSS
CRP <50 50-100 >100
LENGTH OF SYMPTOMS/ADMISSION
0-4 WEEKS 4-8 WEEKS >8 WEEKS
CT FINDINGS Essentially normal Thickened peritoneum, some fluid,Mild dilatation of small bowel
Thickened calcified peritoneum, retracted mesentry, encapsulation,ascites
TREATMENT OPTIONS MEDICAL MEDICAL/SURGICAL SURGICAL
ABSOLUTE SURGICAL INDICATIONS*
OBSTRUCTION* PERITONITIS* MAJOR HEMOPERITONEUM*
UK approach to EPS management
• Funded supra-regional service – 2 centres of excellence with dedicated expert
teams and funding that follows the patient
• National Guidelines (Renal Association Website)– suspected or diagnosed patients should be
referred for assessment
• UK PD Research network – EPS registry and gene/biomarker bank
• Parenteral feeding to optimise nutrition• CT scanning – diagnosis not screening