Encapsulating Peritoneal DialysisUpdate – prediction, risk factors, medical

and surgical treatment

Simon Davies

Scope• Definition and Diagnosis

• Macroscopic and microscopic

• Risk Factors• Age• Time on treatment• Progressive membrane injury

• Prognostic model• Treatment

Definition• BOTH:• Obstructive bowel syndrome – leading to pain,

vomiting, fear of eating and progressive malnutrition demonstrated to be due to…

• Cocooning of the bowel by a thickened, fibrotic membrane as demonstrated on CT imaging or at laparotomy or laparoscopy

• Frequently associated with systemic inflammation

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

Macroscopical differences

Histological criteria for EPSconflicting data….

Nephrol Ther 2011

Histological criteria for EPSconflicting data….

Nephrol Ther 2011

Histological criteria for EPSA standardized approach

www.rbk.de

What are the identifiable risk factors/early indicators for EPS?• Time on therapy• Factors associated with increased survival on PD –

young age, less comorbidity, poor Tx chances• UF failure• High glucose exposure• Biomarkers of membrane injury

Scottish Renal Registry, Brown MC et al, CJASN, 2009

Risk of developing EPS – Stoke PD Study

Lambie, M et al, KI , 2010

ANZDATA: Johnson DW, KI, 2010

* * †

* 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 = 0.007

Lambie M, KI, 2010

Longitudinal membrane change in EPS v. patients with normal UF or UF Failure

Sampimon, DE et al, NDT, 2011

Solute transport Net Total UF

Longitudinal membrane change in EPS v. patients with normal UF or UF Failure

Sampimon, DE et al, NDT, 2011

Small pore fluid transport Aquaporin fluid transport

Habib, A-M et al , NDT, 2010

Royal Free experience...

Dutch EPS Registry Study – cases matched by date of starting PDPD related variable EPS Control P value

n 63 126

Time on PD (months)Peritonitis episodes episodes/year

78.84.10.7

32.82.41.1

0.00010.0020.009

Transport Status slow slow average fast average fast

25

1725

2293312

NS0.001

NS0.0001

UF Failure (%) Yes No Unknown

60.322.211

15.167.517.5

0.00010.0001

Dialysis Fluids Dianeal (ever used) Physioneal Icodextrin Time on Icodextrin Icodextrin/pat year

583149

32.70.47

1072028

18.10.53

NS0.00010.00010.006

0.6

Korte, M et al, PDI, 2011

Lambie et al, KI , 2010

Glucose exposure as a risk factor for EPS

JASN, 2015

Red area is collagen

Sampimon, D; PDI, 2010

Dependent Variable

EPS Age Time Till PD End

Coefficient (95% CI) p value Coefficient(95% CI) p value Coefficient

(95% CI) p value

Dialysate

IL-6 0.79 (0.03, 1.56)* 0.043 0.009 (-0.014, 0.033) 0.43 0.27 (0.13, 0.42)* <0.001

IL-1β 1.06 (-0.11, 2.23) 0.075 0.022 (-0.012, 0.056) 0.20 0.19 (-0.08, 0.47) 0.17

IFN-γ 0.62 (-0.06, 1.29) 0.073 0.016 (-0.005, 0.036) 0.14 0.085 (-0.045, 0.215) 0.20

TNF-α 0.64 (0.23, 1.05)* 0.002 0.019 (0.007, 0.031)* 0.001 0.048 (-0.026, 0.123) 0.20

Plasma

IL-6 0.42 (0.07, 0.78)* 0.020 0.016 (0.005, 0.026)* 0.003 0.13 (0.05, 0.21)* 0.001

IL-1β 0.66 (-0.65, 1.97) 0.33 -0.023 (-0.064, 0.017) 0.26 -0.21 (-0.55, 0.13) 0.23

IFN-γ -0.30 (-0.69, 0.09) 0.14 0.014 (0.001, 0.027)* 0.036 0.12 (0.02, 0.22)* 0.017

TNF-α 0.13 (-0.13, 0.39) 0.31 0.010 (0.002, 0.017)* 0.011 0.45 (-0.007, 0.098) 0.090

Solute Transport D/P Cr 0.024(-0.054, 0.102) 0.55 -0.0017

(-0.0039, 0.0006) 0.14 0.035 (0.023, 0.047) * <0.001

GLOBAL Fluid Study: Determinants of Inflammatory Cytokine Levels by EPS Status, Age and Time to end of PD

Lambie, M. et al., NDT under revision

What are the risks?• Can we develop a prognostic risk calculator?• Competing risks that change with time on

treatment• Complex modeling methods required• Dynamic Landmark approach with bootstrapping• Will require external validation/calibration

ANZDATA Registry

Aged 40, low risk PRD, non-diabetic 0.0196 0.278

Aged 60 , low risk PRD, non-diabetic 0.0118 0.408

Aged 80, high risk PRD, diabetic 0.00354 0.875

Scottish Renal Registry

Aged 40, low risk PRD, non-diabetic 0.135 0.195

Aged 60 , low risk PRD, non-diabetic 0.0832 0.295

Aged 80, high risk PRD, diabetic 0.0257 0.751

Probability of EPS or death at 5 year follow up for patients 3 years after commencing PD

1. Risk competed with death2. The underlying risk was 5-8 time greater in Scotland – likely

reflects ascertainment bias3. Internal models for EPS and death had high validity,

(C-statistic 0.89-91 and 0.8-82 respectively).4. PD-CRAFT cohort (external validation) 1450 patients – so far

6 cases, but requires 3 more years follow up

Treatment• Medical

• Decide if on PD whether to stop. Consider hybrid dialysis – Japanese experience is anecdotal but might be quite effective. Some evidence that inflammation declines.

• Most will present after PD has already stopped• Nutrition in key; if tolerated, use small frequent meals. Avoid enteral

feeding as this makes pain worse.• Parenteral feeding may be necessary as bridge to surgery or long term• Tamoxifen – no conclusive evidence• Steroids – as adjunct to surgery during acute inflammatory

exaccerbations

Treatment• Surgery

• Assessment and treatment as specialised centre• Facilitates diagnostic confirmation

• Other conditions occur – e.g. TB, small bowel lymphoma, adhesions, including from pancreas transplant

• Planned procedures – 80%+ success rate• Indications are severe pain, obstructive episodes, failure

to maintain nutrition (e.g. patient who avoids eating due to pain)

• Emergency procedures success rate <50%, e.g. for perforation or bowel infarction

Treatment• Surgical procedure and management

• Careful pre-operative assessment, including nutrition, which should be stabilised with parenteral nutrition of needed

• Operative time may be from 3 to 14 hours, so full surgical theatre day should be booked, with proper breaks planned

• Extreme patience required. Primary closure is not always advisable – use of vacuum seal and closure 2-3 days later

• Recurrent disease can be operated on (recurrence rate ~30%)

Treatment• Post-operative care and management

• Gut usually starts to work immediately• High post-operative infection risk due to debilitation• Post-transplant cases have best course; steroids

continued in these cases and may be used intermittently in others – e.g. during episodes of recurrent disease associated with mild obstructive symptoms and rise in the inflammatory markers (after excluding infected collections)

• Full recovery achievable in 75%+ (95% in Japan)• Patients can proceed to transplant

Psychological• This is a distressing illness which takes its toll• Patients report the greatest problem is failure to

recognise their symptoms and problems for what they are

• Delayed diagnosis• Prolonged admission with poorly experienced clinicians• Frustration; not taken seriously• Appreciation of honesty – relief at being referred to

experienced centre

Summary• EPS is a serious but relatively rare complication of PD• It is more than just progressive membrane injury associated

with fibrosis, but this is a risk factor• Time on PD, poor UF (reduced osmotic conductance identified

by reduced sodium sieving) are the main risk factors• Risk competes with death – so younger, less comorbid

patients are more likely to get EPS• Outcomes have significantly improved with better medical and

surgical management; early recognition is important