encapsulating peritoneal dialysis update – prediction, risk factors, medical and surgical...
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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
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
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