présentation powerpoint - bvnbvn-sbn.be/downloads/peritoneal dialysis_e goffin.pdf · 20/03/2013 3...

20/03/2013

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Cliniques Universitaires St-Luc

Université Catholique de Louvain

Bruxelles

Prof Eric Goffin

Peritoneal dialysis : principles, techniques,

materials and quality control

UCL

March 23rd, 2013 Cliniques St Luc, Brussels

CONTENT

• General Principles of PD

• The Peritoneal Membrane : Anatomy

• Physiology of Peritoneal Dialysis : Diffusion,

Convection, UF and PD prescription

• Take home messages

Schematic Principles of Peritoneal dialysis

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Overview : how to start a PD patient

• Having a PD program

• Select patients for PD

• Pre-ESRD education program

• Pro/con evaluation of suitability of an individual

patient

• Catheter placement

• How to start ?

Overview : Having a PD program

Overview : Having a PD program

Courtesy of L Van Overmeire

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Objectives of a Pre-dialysis education Program

Decrease mystique around dialysis

Provide objective information

Help make treatment choice

Promote self care

Pre-dialysis education Program at St Luc

Information provided by nurses in charge of self-care

Individual

In-house DVD

Brochures

Contact with experienced patients

Pre-dialysis education Program at St Luc

All incident patients (n = 242) – 185 informed (57

not informed in-centre HD)

First RRT modality

Inclusion period : 12/94 – 3/00 (64 months)

Exclusion criteria :

Transfer

Graft failure

Goovaerts T et al Nephrol Dial Transplant 2005

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Our Pre-dialysis education program

Goovaerts T et al Nephrol Dial Transplant 2005

31%

16%

9%

4%

40%

Contra-indications to PD

- Stomias

- Enormous ADPKD kidneys

- Loss of integrity of the peritoneal membrane

The PD catheter

Courtesy of L Van Overmeire

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The PD catheter

Right parietal access is preferable

PD catheter migration

The PD catheter

No evidence for superiority of one single type of

catheter

Use of cuffed catheters to be preferred ; no

difference single vs double cuff

Use of Swann neck to be preferred

No preference for straight line or curled

Surgical or bed-site placement

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Pre-sternal PD catheter in obese patients

Continuous Ambulatory Peritoneal Dialysis

Vidange

Glucose

Infusion

Glucose

Déconnection Connection

Glucose

sac vide

Continuous Ambulatory Peritoneal Dialysis

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Automated Peritoneal Dialysis



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Anatomy of the Peritoneal Membrane

The Peritoneal Membrane

• Mesothelium

• Interstitium - MPS hydrogel + collagen

• Capillary network - endothelial barrier

Peritoneal cavity – Reflections of the

peritoneum

C 1999 Wesley Norman

Virtual cavity (<100 ml of viscous fluid)

between visceral and parietal sheets

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Nature of the Peritoneal Membrane

Serous membrane : reduces friction between moving organs

Components : Monolayer of mesothelial cells

Connective tissue : matrix of collagen

- Blood vessels - capillaries

- Lymphatics

- Cells : leukocytes, mastocytes

- Nerve fibers

Thin membrane : 30-40 m omentum (thicker in PP – VP)

1.0 – 1.3 square-meter

Contribution to transport : PP >> VP

Peritoneal membrane : the mesothelium

• Flat cells that form a monolayer : 2.5 - 3 m thick (mesentery)

• Transitional mesothelium (parietal peritoneum) : 10 - 15 m thick

• Discontinuous basement membrane : type IV collagen

• Ultrastructure : Intercellular junctions (tight - gap)

Basolateral invaginations

Microvilli and primary cilium

Rich in organelles

Peritoneal membrane : the Mesothelium

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Role of the Mesothelium

• Not a barrier for water and solutes transport

• Protection, host-defense mechanisms

• Regulation of inflammation, angiogenesis, healing - fibrosis

• Secretion of lipids : surfactant - phosphatidylcholine

• Secretion of cytokines, growth factors, PGs

• Secretion of collagen, fibronectin, elastin

• Marker : CA125

Mesothelial cell mass and CA 125

The submesothelial layer

• Matrix of collagen (bundles) and elastic fibers

• Many different cell types :

Mast cells, macrophages, leukocytes

Fibroblasts

Adipocytes

Blood vessels

Lymphatics

Nerve fibers

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Vascularization of the Peritoneum

• Visceral peritoneum :

• Upper mesenteric artery

• Venous return via the portal system

• Parietal peritoneum :

• Intercostal, epigastric and lumbar

arteries

• Venous return via vena cava system

• Lymphatic network (fluid reabsorption)

Miller FN, Peritoneal Dialysis 1981

The capillary network in the PM

Blood Flow to the Peritoneal Membrane

• Splanchnic blood flow rate : 25% of cardiac output

1200 ml/min

• Peritoneal blood flow rate: 70-80 ml/min

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Lymphatics in the peritoneal Membrane

Gokal et al. Textbook of PD 2000

Changes in the Peritoneal Membrane

Exposed to Peritoneal Dialysis

Structure of the Peritoneal Membrane

Factor VIII

staining

Control

m

Submesothelial fibrosis Vascular proliferation

Long-term PD

m

m

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Laparoscopy : 7 years of peritoneal dialysis

Loss of mesothelial cells after 40 days of PD

CA 125 and long-term (conventional) PD

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The Peritoneal Membrane in the long-term PD

Submesothelial

fibrosis

Vascular

proliferation

Combet et al. JASN 11, 2000 Factor VIII staining

Biopsy Registry : submesothelial Fibrosis

Th

ickn

ess

su

bm

eso

the

lial z

on

e (

mm

)

0-24 25-48 49-72 73-96 96+

Peritoneal Dialysis (months)

Williams JD et al. JASN 13 : 470-9, 2002

Mateijsen et al. PDI 19, 1999

Correlation between Vascular Proliferation

and Fibrosis in Long-term PD

0

10

20

30

40

50

60

70

80

Num

ber

of

ves

sels

/fie

ld

0 0-25 > 25 Peritoneal

Sclerosis Months CAPD

p=0.00002

p=0.00009

p=0.01

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Simple peritoneal sclerosis

Modest sclerosis - restricted to submesothelial area

No involvement of abdominal viscera and vessels

Sometimes inflammatory infiltrate

Sclerosing peritonitis

Sclerosis of the whole peritoneum

Involves abdominal viscera and affecting large vessels

Fibroblasts proliferation - collagen hyperplasia - inflammation

VEGF distribution in the peritoneum

Control

Long-term PD

Combet S et al. JASN 11, 2000

Monoclonal

anti-VEGF 165

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Deposition of AGE’s (pentosidine staining)

Combet S et al. JASN 11, 2000

Accumulation in mesothelium and endothelium

Changes in the Peritoneal Membrane

during an Acute Peritonitis

Acute peritonitis : structural changes

Combet et al. JASN 10: 2185-96, 1999

Inflammatory infiltrate Vascular proliferation

Control

Peritonitis

Control

Peritonitis

Rat model - Catheter-induced peritonitis - 5 days

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Nicola Di Paolo and Giovanni Sacchi

Atlas of Peritoneal Histology

Peritoneal Dialysis International 20, 2000

Peritoneal Dialysis : principles and

physiology


Source: Gambro

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Source : Gambro


the three-pore model

water

small

solutes

macro

molecules

capillary lumen

interstitium

Ultrasmall pores

r < 3Å

Small pores

r 30- 50 Å

Large pores

r > 150 Å

Rippe B et al. Kidney Int 40, 1991

endothelium

Mechanisms of Solute and Water Transport

across the Peritoneal Membrane

1. Diffusion : passive movement along the concentration gradient

2. Solvent drag : convective transport of solutes with water

3. Net ultrafiltration : results of starling forces:

- transcapillary ultrafiltration

- backfiltration into capillaries + uptake by lymphatics

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Diffusion across the Peritoneal Membrane

Diffusion: passive movement along the concentration gradient

Rate of solute transfer (Js) depends from

- Diffusive permeability of the PM to that solute (Df/x)

Df : free diffusion coefficient

x : diffusion distance

- Surface area (A)

- Concentration gradient (C = P - D)

MTAC: diffusive permeability x surface area

Js = Df/ x x A x C

MTAC = Df/ x x A

Js = MTAC x (P - D)

Convective transport across the Peritoneal

Membrane

Convection: Solvent drag, transport of solutes with water

Rate of solute transfer (Js) depends from :

- Water flux (Jv)

- Solute concentration in the membrane (C)

- Solute reflection coefficient ()

Js = Jv x C x (1 - )

varies between 0 : no resistance of the PM to transport

1 : ideal semi-permeable membrane

Relationship between MW and MTAC

Log Molecular weight 100 1000 10000

Log MTAC . Urea

Creatinine. Urate.

.Inulin

.beta 2 - M

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Kabanda et al Kidney Int 1995


- Small solutes (urea, glucose, creatinine) diffuse freely

across the PM

- Maximal transport determined by the surface area

- Notion of Effective Peritoneal Surface Area (EPSA)

Number of perfused capillaries - pores

Basal state only 25 % capillaries perfused

The MTAC of small solutes = functional measurement of

EPSA

Transport of Macromolecules (e.g. Albumin)

- Much lower rate than LMW solutes and sodium

- Size-selective restriction

- Depends from surface area and size-selective pores

- Convection/restricted diffusion + large pores

- Increased during acute peritonitis : vasoactive mediators

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Evaluation of the diffusive properties of

the Peritoneal Membrane : the Peritoneal

Equilibration Test

The Peritoneal Equilibration Test Twardowski

0 30 60 120 240 0.00

0.25

0.50

Dwell Time (min)

0.75

D/P

cre

at

The Peritoneal Equilibration Test

0 30 60 120 240 0.00

0.25

0.50

Dwell Time (min)

0.75

D/P

cre

at

0 30 60 120 240 0.0

0.5

1.0

Dwell Time (min)

D/D

0 G

luco

se

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0 30 60 120 240 0.00

0.25

0.50

Dwell Time (min)

D/P

cre

at

0 30 60 120 240 0.0

0.5

1.0

Dwell Time (min)

D/D

0 G

luco

se

0.75

Hyperpermeability-Fast transporte status:

good clearances

poor UF

Use APD & icodextrin


0 30 60 120 240 0.00

0.25

0.50

Dwell Time (min)

D/P

cre

at

0 30 60 120 240 0.0

0.5

1.0

Dwell Time (min)

D/D

0 G

luco

se

0.75

Hypopermeability-Low transporter status:

low clearances

high UF


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Inverse Correlation between Ultrafiltration and

Blood Vessels (Chronic Infusion Rodent Models)

Margetts et al. JASN 13: 721-8, 2002

0 5 10 15 20 25 30

-15

-10

-5

0

5

10

Peritoneal-associated blood vessels (vessels/mm)

Factor VIII staining

r : -0.61

P < 0.001

What would be your preferred type of

Peritoneal Membrane ?

The problem of the Fast Transporters

Churchill et al CANUSA Study JASN 1998

0 6 12 18 24

High

High Average

Low Average

Low

40

100

90

80

70

60

50

Time in Months

Per

cen

t S

urv

ivin

g

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The problem of the Fast Transporters

Early glucose absorption; i.e. rapid dissipation of the

osmotic gradient and, fluid retention.

Important protein loss within the dialysate.

Association with markers of inflammation, diabetes and

co-morbid conditions.

Inherent Fast Transport Status

Patients with older age, diabetes, higher BMI and comorbid conditions are more

likely to be fast transporters:

- Rumpsfeld et al; Am J Kid Dis 2004

ANZDATA registry (n: 3188)

- Davies Kidney Int; 2004 (n: 574)

- Gillerot et al Kidney Int 2005 (n: 152)

- Clerbaux et al NDT 2006 (n: 72)

- …

ANOVA, P = 0.003

Comorbidity grade

Low Medium High 1 0

1 1

1 2

1 3

1 4

1 5

0 1 2 3 4 5 6

0

1 0

2 0

3 0

4 0

MTA

Cc

rea

t

(ml/m

in/1

.73

m2)

Serum albumin (g/dl) Pearson r = -0.22

P = 0.005 Gillerot et al Kidney Int 2005

Inherent Fast Transport Status

Gillerot et al Kidney Int 2005

MTA

Ccre

at

(ml/m

in/1

.73m

2)

IL-6 genotype

ANOVA, P = 0.006

CC

N = 20 GC

N = 72

GG

N = 60

1 0

1 1

1 2

1 3

1 4

N=152

Polymorphism IL-6 G-174C

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Ultrafiltration in Peritoneal Dialysis

Ultrafiltration in Peritoneal Dialysis

Net UF = Cumulative TCUF – fluid uptake by lymphatics

Starling Forces and Fluid Transport

Transcapillary ultrafiltration rate = UFC (P - + O)

UFC : peritoneal UF coefficient

P : hydrostatic pressure gradient

: colloid pressure gradient

: reflection coefficient : index of osmotic effectiveness (0 to 1)

O : crystalloid osmolality gradient

Glucose = 0.02 – 0.05

(ultrasmall pores = 1 large pores = 0)

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Water Transport across the Peritoneal

Membrane

Small pores : radius 30 – 50 A° (water + small solutes)

Paracellular pathway (interendothelial clefts)

50 % UF : hydrostatic + colloid forces

Ultrasmall pores : radius < 3 A° (selectivity for water)

Transcellular pathway : endothelial cell

50 % UF : crystalloid osmosis

Predicted to mediate sodium sieving

Rippe et al Kidney Int 40; 1991

The Sodium Sieving

m

Free-water movement : fall in dialysate sodium

Zweers et al; PDI 1999; 15: 65-72

Aquaporin-1 distribution in the PM

m

lumen

Am J Physiol 275, 1998 ; Kidney Int 67, 2005

Structure : narrow pore 3.0 Å

Specificity for water only (no

urea, glucose)

Distribution in endothelium

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The role of Aquaporin-1 in the PM

0.75

0.80

0.85

0.90

0.95

1.00

Aqp1 (+/+) (n=6) Aqp1 (+/-) (n=6)

0 30 60 90 120

Aqp1 (-/-) (n=6)

*#

*#

*#

Dwell Time (min)

D/P

So

diu

m

Aqp1 (+/+) (n=6)

Aqp1 (+/-) (n=6)

Aqp1 (-/-) (n=6)

58

± 3.1 57

± 2.0 *#

27

± 1.8

(+/+) (-/-) Ni et al; Kidney Int 2006

Crystalloid vs Colloid Osmosis

or

Glucose-based dialysates vs Icodextrin

The Osmotic Gradient across the PM

Courtesy of Dr J Morelle

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Physiopathological evolution of the

Peritoneal Membrane with time on PD

Khosla S and Melton L. N Engl J Med 2007;356:2293-2300

Lifestyle Measures Recommended for Patients with Osteopenia

Peritoneal cavity

TGF-

FGF

Invading MC

VEGF

MC released

to PD effluent

- Peritonitis

- Hemoperitoneum

- PD Fluids:

- Glucose (AGEs, - GDPs)

- Lactate, low pH

VEGF

Angiogenesis

Myofibroblasts

ECM

Accumulation

Peritoneal membrane

Adapted from Lopez-Cabrea et al. (2006)

UF

FAILURE

EMT

Solute Transport increases with Time on PD

Davies et al. Kidney Int 54 : 2207-17, 1998

Combet et al J Am Soc Nephrol 2000

Clerbaux et al Nephrol Dial Transplant 2006

0.8

Solu

te tra

nsp

ort

(D

/P C

r)

* *

1 6 12 18 24 30 36 42 48 54 60

0.7

0.6

0.5

Time on peritoneal dialysis (months)

* *

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Peritonitis induce functional and structural

peritoneal membrane alterations

Davies et al Nephrol Dial Transplant 1996 Williams et al Kidney Int 2003

Peritoneal alterations with time on PD :

Ultrafiltration failure

Increased vascularization – EPSA

Deficit – dysfunction in AQP1 (nb ? Quality ?)

Both together

Ultrafiltration failure : Aquaporin dysfunction

Walz T et al. Nature 1997

Murata et al Nature 2OOO

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The role of Aquaporin-1 in the PM

Loss of sodium sieving AQP1 dysfonction

(normal expression)

Goffin et al Am J Kidney Dis 1999

Peritoneal alterations with time on PD :

Ultrafiltration failure

Increased vascularization – EPSA

Deficit – dysfunction in AQP1 (nb ? Quality ?) :

Both together

Increased lymphatic absorption

Changes in extracellular matrix : alteration of glucose

conductance

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How to monitor the Peritoneal Membrane

Properties


Properties ?

Peritoneal Equilibration Test

Using 3.86 % glucose-based dialysate for UF volume and

sodium sieving determinations

At PD onset

Yearly

After a « bad » peritonitis


Properties ? The mini-PET

How ?

Idem PET 3,86% with dialysate samplings at 0 et 60

min

Advantages

Calculation :

Free Water Transport (FWT) within the total UF

at 60 min

Na removal

D/P creat and D/D0 glucose

Length : 60 min

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Properties ? The mini-PET

La Milia et al: Mini-peritoneal equilibration test Kidney Int, Vol. 68

(2005), pp. 840–846


Properties ? The Osmotic conductance

Determine the power of glucose to generate an UF

2 successive Mini-PET :

1° glucose 1.36%

2° glucose 3.86%

How to monitor the Dialysis efficacy

Ademex study

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Ademex study


Ademex study


Lo WK et al Kidney Int 2003

Total Kt/V targets (randomized !!!)

A : 1.5 to 1.7

B : 1.7 to 2.0

C : > 2.0

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PD

adequacy

Nutritional status

Prevention of osteodystrophy

Control of BP

Control of anemia Toxins epuration

Prevention of amyloidosis

Prevention of neuropathy

Prevention of acid-

base disorders

Quality of life

Adapted from PY Durand

The PD prescription

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The PD prescription

Residual renal function ?

CAPD vs APD ?

Number of dwells ? Length of dwells ? Tonicity of dwells ?

Volume of dialysate ?

Use of icodextrin from the start ?

Residual renal function

Provides endocrine functions - Erythropoietin production

- Ca++, phosphorus and vitamin D

homeostasis

Contributes to total solute

cearance (1 ml/min CrCl = 10 liter

CrCl/week)

Reduces

Mortality

Improves

QOL

Increases

nutritional

status

Allows for more

liberal diet and

fluid intake

Facilities

volume control

Improves

2-microglobulin

and middle

molecule clearance

Courtesy of B Bammens


0 30 60 120 240 0.00

0.25

0.50

Dwell Time (min)

D/P

cre

at

0 30 60 120 240 0.0

0.5

1.0

Dwell Time (min)

D/D

0 G

luco

se

0.75

Hyperpermeability-Fast transporte status:

good clearances

poor UF

Use APD & icodextrin

20/03/2013

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0 30 60 120 240 0.00

0.25

0.50

Dwell Time (min)

D/P

cre

at

0 30 60 120 240 0.0

0.5

1.0

Dwell Time (min)

D/D

0 G

luco

se

0.75

Hypopermeability-Low transporter status:

low clearances

high UF

The Intra Peritoneal Pressure

Midaxillary line

IPP (cmH2O)

0

Dialysat

PD catheter

0.68

13.1 ± 2.6

13.5 ± 3.5

9

52

Diabetes +

–

0.87

13.2 ± 3.8

13.7 ± 3.3

12.5 ± 2.1

14.2 ± 1.9

23

31

2

5

Surgery –

light

heavy

hernia

p IPP 2000ml n

0.44

0.16

0.10

0.18

61 Age (yrs)

61 Weight (kg)

0.57 -0.07 61 Height (CM)

0.92

13.5 ± 3.1

13.5 ± 4.0

46

15

Gender M

F

0.38 0.11 61 BSA (m²)

0.03 0.28 61 BMI (kg/m²)

Relationship between IPP and IPV

0

5

10

15

20

25

0 1000 2000 3000

IPV (ml)

IPP

(cm

H20

)


Kaplan-Meier estimation of survival free

of peritonitis when IPP day < or ≥ 13 cm

H2O

months

60 50 40 30 20 10 0

Cu

mu

lative

Su

rviv

al

1.1

1.0

.9

.8

.7

.6

.5

.4

Kaplan-Meier estimation of survival

free of peritonitis when IPP night <

or ≥ 14 cm H2O

months

60 50 40 30 20 10 0

1.1

1.0

.9

.8

.7

.6

.5

.4

IPP >14 cm H2O

IPP <14 cm H2O

p=0.03

Dejardin A et al Nephrol Dial Transplant 2007

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Avoid > 17 cm H2O !!!

(at rest)


Fluid control: icodextrin vs

glucose based dialysates

Davies J Am Soc Nephrol 2003

Preservation of the peritoneal

membrane: the EAPOS study :

icodextrin vs no icodextrin

By using APD, it is possible to achieve sufficient small

solute clearance and UF to treat successfully even anuric

patients.


présentation powerpoint - bvnbvn-sbn.be/downloads/peritoneal dialysis_e goffin.pdf · 20/03/2013 3...

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