Evaluation of peritoneal membrane

Evaluation of
Peritoneal Membrane
Dr. Muhammad Mohsin Riaz
FCPS (Nephrology)
ISN Fellow
Fatima Memorial Hospital,
Lahore, Pakistan.

Intracorporeal vs Extracorporeal

Natural functions of the peritoneum
• Facilitate motion
• Minimize friction.
• To conduct vessels and nerves to the viscera.

During peritoneal Dialysis
• Solute transfer and exchange.
• Regulation of fluid dynamics and UF

Anatomy of Peritoneal Membrane
• Blood supply from the
superior mesenteric and
celiac arteries,
• Drainage into the portal
vein.
Visceral peritoneum
60 % of total peritoneum
10% Liver
Khanna, R. and Krediet, R.T. eds., 2009. Nolph and Gokal's textbook of peritoneal dialysis. Springer Science & Business
Media.
Mesentry & Omentum
30%
Peritoneal/body
surface area averaged
0.6–0.8 in adults
1 – 1.3 m2
in total
Surface area involved
in active exchange
varies
Only 25–30% of the
visceral peritoneum

• Blood supply from the abdominal wall
(lumbar, intercostals, and epigastric
arteries )
• Drainage into the inferior vena cava,
Parietal peritoneum
10 % of total peritoneum
(3 – 8% diaphragmatic)
Khanna, R. and Krediet, R.T. eds., 2009. Nolph and Gokal's textbook
of peritoneal dialysis. Springer Science & Business Media.

Lymphatic drainage though
surrounding lymphatics
•Mainly sub diaphragmatic
lymphatics (80%)
•Removal of macromolecules and
foreign substances
•In stable PD patients the rate of
lymphatic flow 0.5 – 1 ml/min
The total peritoneal blood flow
•50–150 mL/min.
J Bras Nefrol. 2014 Jan-Mar;36(1):74-9.

Resistance vessels
Regulation of blood flow
to capillaries
Solute and
fluid exchange
( principle site)
Leukocyte adhesion
Permeability under
inflammatory
conditions
Media.

• Structural elements of a typical
mesenteric microcirculatory
bed.
• A-arteriole
• B-venule
• C-thoroughfare channel
• D-capillary
• E-capillary sphincter
A
B
C
D
E

• Peritoneal clearance is not blood flow limited as long as blood flow is
>30% of normal
• UF also does not appear to be blood flow limited.
• Vasoactive agents can affect peritoneal clearance by means of
capillary recruitment & increasing the micropore diameters.
• Peritoneal dialysis fluid is also vasoactive and causes increased blood
flow and capillary recruitment
Media.

Schematic Representation
of Peritoneal Membrane
Pathways & Barriers

Anatomy of Peritoneal Membrane;
Barriers to movement
1
2
3
4
5
6
Flessner MF. Solute and water transport across the peritoneal membrane. In: Ronco C, Bellomo R,
Kellum JA, eds. Critical Care Nephrology. 2nd ed. Philadelphia, PA: Saunders Elsevier; 2009:1472-1478

Semin Nephrol. 2011 Mar;31(2):127-37

• Several theoretical constructs to determine the solute
transport across the peritoneal capillary bed
• Most discussed models are the
• Three pore model
• The distributed model
• Pyle – Popovich model (two compartment model)
• The Pore-Matrix Model
Model of peritoneal transport

Curr Opin Nephrol Hypertens. 2015 Sep;24(5):434-43
The three-pore model
(a) Cross-section of the human
parietal peritoneum
Willebrand factor (vWf).
m, mesothelium; bar, 100 µm.
(b) The three-pore model for
peritoneal transport.
A °, angstro¨m (10-10
m);
r, functional radius

• Large pores (100 - 200 Å)
• Few in number (3% of surface area)
• Transport macromolecules
• Clefts between endothelial cells
• Small pores (40 - 60 Å)
• Most numerous (95% of surface area)
• Allow transport of small solutes and water
• Postulated to be clefts in the endothelium; have not been
• Demonstrated anatomically

• Ultrasmall (transcellular) pores (4 - 6 Å)
• Many in number (but only 2% of surface area)
• Transport water only (Na sieving)
• Demonstrated to be AQP 1

Flessner MF. Peritoneal ultrafiltration: physiology and failure. Contrib Nephrol 2009;163:7-14
The
Distributed
Model

J. Am. Soc. Nephrol. 1991; 2:122-135)
Effective
Peritoneal
Surface Area

Effective Peritoneal Surface Area
• Increased “effective” peritoneal surface area may occur:
• During peritonitis
• After prolonged exposure to high glucose-containing fluids

Pyle – Popovich Model
• Just two homogeneous compartments (body and dialysate) separated
by an ideal homoporous semi-permeable membrane with constant
characteristics and nil thickness.
• Peritoneal membrane similarly to a hemodialyzer membrane .
• The mass transfer area coefficient (MTAC) : is determined without
taking into consideration the specific anatomic factor such as the
interstitium or capillaries
ASAIO Journal: April-June 199

J. Am. Soc. Nephrol. 1991; 2:122-135)
Membrane Model

The Pore – Matrix Model
Flessner MF. Peritoneal ultrafiltration: physiology
and failure. Contrib Nephrol 2009;163:7-14

The Pore – Matrix Model
• The small and large pores represent different functional
states of a single entity that depends on the density of the
glycocalyx.
• The glycocalyx density is decreased by:
• Oxidized LDL
• Adenosine
• Ischemia reperfusion injury
• TNF α

Components of Peritoneal Dialysis &
Physiological processes involved
• Solute Clearance
• Diffusion
• Convection
• Fluid management
• Osmosis

Diffusion
`
• Mol wt
• MTAC
• Peritoneal blood flow
• Kinetic energy
Surface area, Resistance, C
Patient Activity

Diffusion & Molecular weight of solutes
> 90% equilibrated by 4 hours
60 Da
>60% equilibrated by 4 hours
113 Da
Middle Molecules
500 - 5000 Da

Factors influencing diffusion
• Surface Area
• Peritoneal Permeability
• Solute Characteristics
• Concentration Gradient
• Temperature of Dialysis Solution
• Blood Flow
• Dialysis Solution Volume in 24 hrs.
• Dwell Time

Diffusion Kinetics
• Diffusive flux is highest in the first hour
• Further small solute removal is modest
• Long dwells are more important for the removal of the larger
molecular weight (MW) solutes such as β-2 microglobulin and
albumin
• More number of dwells needed for clearance of small molecules.
Teitelbaum I. Anatomy and Physiology of the peritoneum.

Ultrafiltraion
A B
Increased osmotic pressure
or
increased colloid oncotic pressure

Osmotic gradient & Ultrafiltration
Computer simulation of the net ultrafiltration obtained with the use of various
dextrose concentration PD solutions and with polyglucose over a 14-hour
600 ml at
12 hours
400 ml at 06 hours

Factors influencing Ultrafiltration
• Hydraulic conductance of the peritoneal membrane
• Reflection coefficient for the osmotic agent
• Reflects the osmotic agent’s effectiveness to diffuse out of the dialysis solution
into the peritoneal capillaries
• Ranges from 0 – 1
• Osmotic agent used/ osmotic concentration and gradient
• Effective peritoneal surface area
• Dwell time
• Hydrostatic pressure gradient

Colloid Osmotic Pressure with Glucose
Polymers

Clearance equations
Clearance of solutes through Diffusion
• JsD = (Df/ Δx ) x A x ΔC
• Where JsD = Clearance through diffusion
• Df = diffusion coefficient of solute
• Δx = diffusion distance
• A = area of the membrane
• ΔDf ⁄ x A = MTAC
• MTAC has the dimensions of a clearance and can be understood as the
theoretical maximal clearance by diffusion at time zero (ie, when the
concentration gradient has not yet started dissipating)
• JsD = MTAC x ΔC
Semin Nephrol 31:127-137 © 2011 Elsevier Inc

Clearance equations
Clearance of solutes through Convection
•
• Js = clearance of solute through convection
• = water flux through the membrane; Membrane dependant
• = mean concentration of solute on both sides
• = Staverman’s reflection coefficient; ranges from 0 – 1
•
Semin Nephrol 31:127-137 © 2011 Elsevier Inc

Effect of Size of molecules
Relationship between parameters of solute transport and
permeability characteristics of the peritoneal membrane

Nat Rev Nephrol.
2012 Sep;8(9):542-50
Factors influencing Peritoneal Membrane

Flessner MF. Peritoneal ultrafiltration: physiology
and failure. Contrib Nephrol 2009;163:7-14
Scarred Peritoneum

Differences in Peritoneal Membrane
characteristics
Grade 1, subendothelial hyaline zone <7μ m;
Grade 2, subendothelial hyaline zone >7μ m;
Grade 3, the lumen is distorted or narrowed;
Grade 4, the vascular lumen is obliterated
KI 2003 May;(84):S158-61.

Curr Opin Nephrol Hypertens. 2015 Sep;24(5):434-43.

Clinical assessment of
Peritoneal Membrane (PM)
Characteristics
• Peritoneal membrane is a living tissue
• Vulnerable to changes in many medical conditions
• In order to find appropriate PD modality based on patients peritoneal
membrane characteristics
• Document changes in transport characteristics
• Solute
• Fluid
J Am Soc Nephrol. 1998;9(7):1285-92
Clin J Am Soc Nephrol. 2015 Nov 6;10(11):1990-2001

Various methods to assess PM
characteristics
• Peritoneal equilibrium test (PET)
• Peritoneal dialysis capacity (PDC)
• 24-hour batch dialysate test
• Dialysis adequacy and transport test (DATT)
• Accelerated peritoneal examination (APEX)
• Standard peritoneal permeability analysis (SPA)
• Peritoneal function test (PFT)
Journal of nephrology. 2010;23(6):633-47.

Computer based software for PM
assessment
• PD Adequest1 (Baxter Healthcare Corporation, Deerfield, Illinois,
USA)
• Personal Dialysis Capacity test (PDC1) (Gambro, Lund, Sweden)
• Patient On Line (POL1) (Fresenius Medical Care, Bad Homburg,
Germany).

Why Peritoneal Equilibrium Test (PET)
• Reference test for other more complex tests
• Simple to perform
• First shown that there is considerable variability in the
transport of small solutes through the peritoneal membrane
Perit Dial Int. 1997;17:144-150
Perit Dial Bull. 1987;7:138-147
Adv Perit Dial. 1990;6:186-191

• Results can be used to prescribe most suitable PD
prescription in terms of
• Solute clearance
• Fluid removal (ultrafiltration)
• Can be used for patient follow up
• Monitoring membrane characteristics
• After any acute illness
Usefulness of PET

Historical points of PET
• More than 20 years ago
• Twardowski proposed the peritoneal equilibration test (PET)
• Evaluate the capacity of the peritoneal membrane to
• Transport solutes
• Ability to generate UF
Perit Dial Bull. 1987;7:138-147

Types of PET
• 2.27% PET – Standardized PET
• 3.86% PET – Modified PET
• Mini – PET
• Double Mini – PET
• Combined 3.86% - PET
• Uni – PET

Standardized PET – Procedure
• Overnight dwell:
• 2 litre 2.5% dextrose (8 to12 hr dwell)
• Morning of Test:
• Drain overnight dwell with patient in sitting position over 20
minutes, record the amount drained
• Infuse 2 litres of 2.5% dextrose with patient supine, record time
completed
• This is the 0 Hr Dwell time (zero hour)

• At 0 hour(Zero hour)
• Drain back 200cc of dialysate and gently mix by inverting bag twice
• Collect dialysate samples. Send 10ml of dialysate for zero hour
specimen
• Re-infuse the remaining 190ml
• Repeat above at the 2 hour dwell time.
• At the 2 hour dwell time, draw the serum sample for BUN,
Creatinine, and glucose

• At 4 hours, with the patient sitting up, drain completely at
least for 20 minutes
• Obtain 10 ml dialysate sample, record volume of drained effluent.

Time Dialysate Sample Serum Sample
Overnight Creatinine, BUN (urea)
Glucose
0 Hours Creatinine, BUN (urea)
Glucose
Glucose
Creatinine, BUN (urea)
Glucose
Glucose
Sampling Time

• It is essential to assess the vital signs of the patients,
especially those old and with low BP.
• Blood glucose should be monitored in patients with diabetes
mellitus.
Patient Monitoring

• Possible errors:
• Sampling
• Data entry
• Calculations
• Lab
• Incorrect labelling of specimen tubes
• Incorrect patient instructions
• Patient collection errors
• High serum blood sugar ( > 300mg/DL) may alter glucose
interpretation
Caution

• How easily does solute (creatinine) cross from the blood to the
peritoneal cavity?
• Quantified as = Dialysate creatinine concentration
Plasma creatinine concentration
OR
D/P creatinine (at t = 4 hours)
Standardized PET
What we calculate ?

• How long is glucose retained in the peritoneal cavity?
• Quantified as: Dialysate concentration of glucose at t = 4hrs
Dialysate concentration of glucose at t = 0 hr
OR
D/ D0 glucose (at t = 4 hours)
• Cannot use D/P glucose as a surrogate since glucose entering the plasma
from dialysate is rapidly metabolized
Standardized PET
What we calculate ?

Standardized PET – Results
Twardowski et al. PDB 7; 138, 1987

interpretation
Slow transporters

interpretation
Fast transporters

interpretation
Patient classification & Modality
Adv Perit Dial. 1990;6:186-91

Standardization of PET
• Reproducible
• Variability coefficient
• 10 % for solutes
• May reach up to 25% - 50% for ultrafiltration volume
Kidney Int. 2004;66:2437-2445

I. Duration of the exchange (usually overnight) before the
PET
II. Volume of infusion and infused solution,
III. Position of patient during the infusion and the drainage,
IV. Duration of the infusion and drainage
V. Methods of sampling and storage of blood and dialysate
samples
VI. Laboratory methods

Duration of exchange before PET
D/P ratios of creatinine were greater during PET dry
Am J Kidney Dis. 1999 Aug;34(2):247-53.

Type of exchange before PET
• Polyglucose (Icodextrin)
• D/P ratios of creatinine
were greater
• Dt/Do ratio of glucose is
low
AJKD 2001, 38: 118

• For APD
• Patient arrive at the dialysis centre with a full peritoneal cavity
• Dwell before the test (if APD) should not last less than 45-60
minutes
• For CAPD
• Any dwell time between 3 and 12 hours is acceptable for the
preceding exchange
• Type of Fluid
• It is necessary that the night dwell immediately preceding the PET
is performed with a solution containing glucose (1.36% or 2.27%).
Recommendations of exchange before PET
Adv Perit Dial. 2003;19:53-8. Perit Dial Int. 2000;20(Suppl 4):S5-S21

• The lack of quantification of the volume used for the “flush before
fill,” which on average is 200 mL
• The actual volume of bags always differ when measured.
• No difference in results were observed when test was performed
with 1500 ml instead of 2000 ml.
• Due to lack of quality data, it is suggested to do study with 2000 ml
Infusion Volume
Perit Dial Int. 2006;26:503-506
Perit Dial Int. 2005;25:92-93

Almost all the fresh PD bags were overfilled
316 PETs using 3.86% glucose solution
in 119 patients
Perit Dial Int. 2006;26:503-506

W = weighed volume
N = nominal volume
Underestimation of UFF without weighing the bag Perit Dial Int. 2006;26:503-506

• Drain the overnight bag in supine position
• Allows maximum drainage
• During infusion
• Supine
• Rotate from side to side
• 2 minutes on each side after infusion of every 400 ml
• Must rotate before draining the first 200 ml
• No scientific studies
Position of Patient

• Drainage of overnight bag = 20 min
• Infusion as quick as possible = usually not more than 10 min
• 0 hour = at the end of first infusion
• Drainage at the end = 20 min
• All the drainage in upright position
Duration of infusion and drainage

• One sample from overnight drained effluent
• Time 0 from infusion
• Time 120 from infusion and from drainage
• Volume of dialysate = 10 ml
• Technique for drawing dialysate sample
• 200 ml drained at 0 hours and 2 hours, 190 ml infused back
• 10 ml should be taken into account when calculating
ultrafiltration
Sampling technique – Dialysate

Type of PET Timing of Sample
Classic PET 2 blood samples
At the end of the drainage for the night
At the end of PET immediately after the drainage
The average was used for calculation of D/P
Mid – PET At 120 minutes of the test
Currently in practice
New PET 2 blood samples are taken
At 60 minute into test
same as in modified PET; to calculate Na sieving
At the end of PET
Sampling technique – Blood

• Creatinine
• Measurements to be corrected for level of glucose
• Sodium
• Flame photometry or indirect ion selective electrodes (ISEs)
Laboratory Method
Perit Dial Int. 1990;10:89-92
Nephrol Dial Transplant. 2004;19:1849-
1855

• Characteristics of small solutes peritoneal transport changed
significantly during the first month of peritoneal dialysis
treatment, and remained stable thereafter
• The first PET should be performed 4-8 weeks after the start
of PD
• PET should be performed at least 1 month after any episode
of peritonitis
• PET should be performed at least once a year
• As many times as there are clinical problems related to
peritoneal transport
Timing of PET
Am J KidneyDis. 2006;48(Suppl 1):S138-S142
Perit Dial Int. 2000;20(Suppl 4):S5-S21

Modified PET
• Similar to the standard PET
• Different concentration of dialysate fluid used
• Performed with 3.86% dextrose
• Helps diagnosing ultrafiltration failure (UFF).
• Patients classification based on D/P creat remains same using the
various types of solution for the PET
Perit Dial Int. 2000;20(Suppl 4):S5-S21

Perit Dial Int. 2000;20:734-741

D/P creatinine
Data of 47 patients, all of whom had a 2.5% PET and
4.25% PET performed with in 1 week of each other. Perit Dial Int. 2002;22:365-370

D/P Urea

D/Do Glucose

Ultrafiltration

• Ultrafiltration failure is defined as net ultrafiltration < 400 cc at 4
hours
• Allows the assessment of the Na sieving coefficient during the first
part of the test
• D/P of Na at 60 minutes
• Indirect expression of the free water transport of the peritoneal
membrane
Modified PET

Type of test Test procedure
details
Measurement of
small solute
clearance
Measurements
obtained
2.27%-PET
Standardized
4-hour test
exchange
2.27% glucose
solution
D/PCreat; Dt/D0
glucose
3.86%-PET
Modified
4-hour test
exchange
3.86% glucose
solution
D/PCreat; Dt/D0
glucose
Maximal UF
capacity after 4
hours
Measures of Na
sieving:
D/PNa(60)
D/PNa(60) –
D/PNa(0)
D/PNa(60) /
D/PNa(0)
ΔDNa

• A PET using 4.25% dextrose may be substituted for the standard 2.5%
PET. This allows for simultaneous evaluation of both the small solute
transfer and ultrafiltration capacities of the peritoneal membrane.
• However, commercially available programs for modelling peritoneal
adequacy have not been standardized to the 4.25% PET.
Modified PET

details
Measurement of
small solute
clearance
Measurements obtained
Mini-PET 1-hour test
exchange 3.86%
glucose solution
D/PCreat;
Dt/D0 glucose
after 1
hour
Maximal UF capacity after
1 hour
Measures of Na sieving
(all)
FWT = free water
transport (aquaporin-1
transport);
UFSP = ultrafiltration
through the small pores

details
Measurement of
small solute
clearance
Double Mini-
PET
Two 1-hour test
exchanges
(performed
consecutively)
1st exchange 1.36%
2nd exchange
3.86%
D/PCreat;
Dt/D0 glucose
after 1
hour
Minimal and maximal UF
capacity after 1 hour
(all)
FWT = free water
transport)
OCG = osmoticJournal of nephrology. 2010;23(6):633-47.

details
Measurement of
small solute
clearance
Combined
3.86%-PET
4-hour test
exchange
3.86% glucose
solution.
Temporary
drainage of
dialysate after 1
hour to
assess the volume
by weighing and
taking a
dialysate sample.
Then reinfusion of
dialysate
(left in place for
D/PCreat;
Dt/D0 glucose
1 and 4 hours
(all)
FWT = free water
transport)

Type of
test
Test procedure details Measurement
of small
solute
clearance
Uni-PET Two test exchanges
(performed consecutively)
1st exchange 1.36% lasting
1 hour
2nd exchange 3.86% lasting
4 hours:
Temporary drainage of
dialysate after 1 hour to
assess the volume by
weighing and taking a
dialysate sample.
Then reinfusion of dialysate
(left in place for another 3
hours)
D/PCreat;
Dt/D0 glucose
1 and 4 hours
(all)
FWT = free water
transport)
OCG = osmotic
Journal of nephrology.
2010;23(6):633-47.

Take Home Message
• Peritoneal Membrane is a living tissue
• Success of peritoneal dialysis depends upon a healthy
peritoneal membrane
• Periodic evaluation of peritoneal membrane is mandatory to
tailor the peritoneal dialysis prescription according to patient
needs.

Evaluation of peritoneal membrane

Evaluation of peritoneal membrane

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Similar to Evaluation of peritoneal membrane

Similar to Evaluation of peritoneal membrane (20)

Recently uploaded

Recently uploaded (20)

Evaluation of peritoneal membrane