Ultrafiltration in PD: Physiologic...
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Ultrafiltration in PD: Physiologic Principles
Ali K. Abu-Alfa, MD, FASNProfessor of Medicine
Head, Division of Nephrology and HypertensionAmerican University of Beirut
Beirut, Lebanon
Adjunct FacultySection of NephrologyYale School of Medicine
New Haven, CT
Version Date: February 2012
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DISCLOSURES
Dr Abu-Alfa has served as a Consultant for Baxter Healthcare, and has received research grants and
honoraria for speaking engagements and/or organization of PD educational conferences from Baxter Healthcare.
Dr Abu-Alfa is the immediate past co-President for the North American Chapter of the International
Society for Peritoneal Dialysis.
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Educational Objectives
Review physiologic basis of ultrafiltration Review the impact of membrane
transport characteristics in UF volume. Compare osmotic and oncotic forces
and effect on UF. Discuss Na sieveing and Na removal. Review membrane changes over time.
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Physiology of Ultrafiltration:Mechanisms at Play
Trans-capillary fluid movement: Osmotic / Oncotic gradient (first and foremost). Hydrostatic pressure (much less so). Membrane function / surface area.
Lymphatic re-absorption.
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Physiology of Ultrafiltration:Structure of Peritoneal Membrane
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Physiology of Ultrafiltration:Normal Human Peritoneum
Mesothelium
Endothelium
Interstitium
Adapted from Lai et al: J Am Soc Nephrol 12: 1036–1045, 2001
RBCs
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Physiology of Ultrafiltration:Structure of Peritoneal Membrane
Intercellular: 50%
Aquaporin mediated: 50%
CapillaryH2O
Peritoneal Space Glucose
Intercellular: >90%
Glucose transporter mediated: minimal
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Physiology of Ultrafiltration:Sodium Sieving with 4.25% Glucose
LaMilia et al, Nephrol Dial Transplant (2004) 19: 1849-1855
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Physiology of Ultrafiltration:Role of Aquaporins: Aqp1-/- mouse
Ni J et al: Kidney International (2006) 69, 1518–1525
AQP: Aquaporin
V(t): Volume versus time
UF: Ultrafiltration
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Physiology of Ultrafiltration:Three-pore model
Rippe et al: Microcirculation 8, 303–320, 2001
= Osmotic
P = Hydraulic
r = Radius
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Physiology of Ultrafiltration:Small Pores and Aquaporins
LaMilia et al, Kidney Int 72:643-50, 2007
4.25%
PET: Peritoneal Equilibration test
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Physiology of Ultrafiltration:Crystalloid Osmosis
Normal serum osmolality = 270 mOsm/L Uremic serum osmolality = 305 mOsm/L
Dialysate Glucose mOsm/L1.5 % 3452.5 % 3954.25 % 484
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13Van’t Hoff Law: Osmolar gradient * 19.3 * reflection coefficient (0.03)
Krediet R et al: Peritoneal Dialysis International 1997: 17, 35-41
Physiology of Ultrafiltration:UF with 4.25% Glucose: Small Pores
Capillary Pressure
Dialysate Pressure
Pressure Gradient
Hydrostatic (mmHg)
17 12-18 0 - 6
Colloid (mmHg)
26 0.1 -26
Osmolality(mosm/kg H2O)
305 (Glu) 486
Crystalloid(mmHg)
- - 105
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Capillary Pressure
Dialysate Pressure
Pressure Gradient
Hydrostatic (mmHg)
17 12-18 0 - 6
Colloid (mmHg)
26 0.1 -26
Osmolality(mosm/kg H2O)
305 486
Crystalloid(mmHg)
Across Small poresAcross Aquaporins
1053559
Krediet R et al: Peritoneal Dialysis International 1997: 17, 35-41
Physiology of Ultrafiltration:UF with 4.25% Glucose: Aquaporins
Van’t Hoff Law: Osmolar gradient * 19.3 * reflection coefficient (0.03)
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Physiology of Ultrafiltration:Sodium Sieving and Na Removal
Rodriguez-Carmona, PDI 2003 (22): 705-713.
0
50
100
150
200
250
Na removal meq
CAPDAPDIcodextrin
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0 60 120 180 240 300 360
Time, min
100
80
60
40
20
0
Intra
perit
onea
l glu
cose
amou
nt, %
of i
nitia
l 0
20
40
60
80
100
Amou
nt o
f glu
cose
abso
rbed
% o
f ini
tial
intra
perit
onea
l am
ount
4.25 % (n=23)2.5 % (n=9)1.5 % (n=9)
Heimbürger et al. Kidney Int 1992: 41: 1320-32Krediet R et al: Peritoneal Dialysis International 1997: 17, 35-41
Physiology of Ultrafiltration:Glucose Absorption and UF Profile
4.25 % Glucose
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-600
-400
-200
0
200
400
600
800
-30 0 30 60 90 120 150 180 210 240
Time (min)
Cum
ulat
ive
tran
spor
t (m
L)
Absorption Transcapillary UF Net UF
Adapted from Mactier RA, et al. J Clin Invest. 1987;80:1311-1316. UF: Ultrafiltration
Physiology of Ultrafiltration:Net Ultrafiltration Profile
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Effect of dwell time Effect of fill volume Effect of membrane transport profile Effect of larger molecules
Physiology of Ultrafiltration:Variables to Consider
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Physiology of Ultrafiltration:Effect of Fill Volume: Net UF Volume
0
50
100
150
200
250
300
350
400
2000 2500 3000
UF
ml
Dwell Volume, 2.5% Glucose, 4 hours
Abu-Alfa, American Society of Nephrology, Abstract 2001
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20D/P: Dialysate / Plasma
L: Low Transporter LA: Low Average TransporterHA: High Average TransporterH: High Transporter
0.20.30.40.50.60.70.80.9
1
0 1 2 3 4
Hours
D/D
0 G
luco
se LLAHAH
Physiology of Ultrafiltration:Glucose Kinetics by Transport Status
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21Adapted from Krediet R et al: Peritoneal Dialysis International 17, 35-41; 1997
Blood in Peritoneal Capillaries
Dialysate filled Peritoneal Cavity
Endothelium
Mesothelium
ureacreatinine
glucose
macromolecules
crystalloidosmosis
colloidosmosis
Physiology of Ultrafiltration:Crystalloid versus colloid osmosis
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Corn Starch
Malto-Dextrin
Icodextrin
Enzymatic hydrolysis
Membrane fractionation
Colloid Osmosis:Source and Structure of Icodextrin
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Capillary Pressure
Dialysate Pressure
Pressure Gradient
Hydrostatic (mmHg)
17 12-18 0 - 6
Colloid (mmHg)
26 66 40
Osmolality(mosm/kg H2O)
305 285
Crystalloid(mmHg)
- - –12
Krediet R et al: Peritoneal Dialysis International 1997: 17, 35-41
Physiology of Ultrafiltration:UF with 7.5% Icodextrin
Van’t Hoff Law: Osmolar gradient * 19.3 * reflection coefficient (0.03)
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Physiology of Ultrafiltration:Transport Status and Icodextrin
Krediet R et al: Peritoneal Dialysis International 1997: 17, 35-41
TCUFR: Transcapillary UF rate
MTAC: Mean Transport Area Coefficient
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Physiology of Ultrafiltration:Transport Status: Icodextrin vs 2.5%
Lin A et al: Clin J Am Soc Nephrol 2009: 4: 1799–1804
D/P: Dialysate/PlasmaICO: IcodextrinGLU: GlucoseCr: Creatinine
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26Courtesy of Dr Salim Mujais, Baxter Healthcare 2002
0102030405060708090
Low Low Ave. High Ave. High
Peritoneal Transport Type
Glu
cose
abs
orbe
d (g
/8 h
rs) 1.50%
2.50%4.25%
Widening differential
Physiology of Ultrafiltration:Glucose absorption: Caloric Cost
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27Davies et al. J Am Soc Nephrol. 2001;12:1046-51
3000040000500006000070000
Year 1 Year 2 Year 3 Year 4 Year 5
Group 1Group 2
0.50.550.6
0.650.7
0.750.8
Start Year 1 Year 2 Year 3 Year 4 Year 5
Group 1Group 2
Physiology of Ultrafiltration:Changes in Transport Profile
Glu
cose
exp
osur
e (g
ram
s/ye
ar)
Time on Treatment
Solu
te T
rans
port
(D/P
cre
atin
ine
at 4
hou
rs
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Physiologic Principles for UF in PDSummary UF in PD is primarily driven by osmotic (Glucose) or
oncotic (icodextrin) forces across the membrane.
Sodium sieving is maximal at about 60 – 90 minutes of a dwell, and will result in and decreased Na concentration in the dialysate if dwell is drained, as with cyclic PD.
Na sieving negatively impacts total Na removed.
Many factors modulate UF volume such as glucose concentration, dwell time, dwell volume and intrinsic membrane transport type of each patient.
Higher transport rates result in less UF with glucose solutions but not with icodextrin solution.
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Question 1
The removal of sodium with PD is dependent on convection
and diffusion. Calculate the approximate amount of Na
removed during a dwell for each of the following conditions:
1) No net ultrafiltration after a 4 hours dwell using 2 liters of 2.5% dextrose solution with [Na]=132 meq/L and plasma [Na]=140 meq/L.
2) 500 cc of net ultrafiltration after a 10 hours dwell using 2 liters of 7.5% icodextrin solution with [Na]=132 meq/L and plasma [Na]=140 meq/L.
3) 250 cc of net UF after a 1 hour dwell using 2 liters of 2.5% dextrose solution with [Na]=132 meq/L and 60 mins dialysate [Na]=128 meq/L, with a short APD cycle.
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Answer 1
The removal of sodium with PD is dependent on convection and diffusion. Calculate the approximate amount of Na removed during a dwell for each of the following conditions:
1) No net ultrafiltration after a 4 hours dwell using 2 liters of 2.5% dextrose solution with [Na]=132 meq/L and plasma [Na]=140 meq/L. Answer: 16 meq
2) 500 cc of net ultrafiltration after a 10 hours dwell using 2 liters of 7.5% icodextrin solution with [Na]=132 meq/L and plasma [Na]=140 meq/L. Answer: 16+70=86 meq
3) 250 cc of net UF after a 1 hour dwell using 2 liters of 2.5% dextrose solution with [Na]=132 meq/L and 60 mins dialysate [Na]=128 meq/L, with a short APD cycle.. Answer: 24 meq