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“ Adequacy in PD prescription What, How, When? Wim Van Biesen.
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Transcript of “ Adequacy in PD prescription What, How, When? Wim Van Biesen.
“Adequacy in PD prescription What, How, When?
Wim Van Biesen
Overview
• What is “adequacy”?
• How to measure adequacy?
• How much is enough?:impact of adequacy
• How to improve adequacy?
Aims of dialysis • Remove uremic toxins
• Remove salt and water ( blood-pressure, fluid control)
• Avoid toxic side effects (glucose, hyperlipidemia; obesitas)
• At the lowest cost and inconvenience for patient and society (decrease incompliance, increase quality of life, decrease cost)
THREE PHYSICO-CHEMICAL TYPES OF TOXINS
• The small water soluble compounds (prototype urea): < 500D
• The protein-bound compounds (prototype p-cresol)
• The larger “middle molecules” (prototype ß2-microglobulin): > 500D– Some of these exceed 12,000 D (prototype leptin)
Quantified measurement of adequacy• Biochemical parameters
– Urea:* influenced by protein intake, hydration *low urea correlated with high mortality(Degoulet et al,
Nephron, 31-103-110, 1982)
– Creatinine: * influenced by nutritional status, muscle mass
* inverse correlation Screa-mortality (Lowrie et al, AJKD, 15, 458-482,1990)
Conclusion: “Static” biochemical markers are no good markers of adequacy
Quantified measurement of adequacyUrea kinetic modelling:
1) Kt/V: sum of the peritonal clearance of urea and the residual renal urea clearance, multiplied by 24 hours and divided by the volume of distribution.
Quantified measurement of adequacyUrea kinetic modelling:
1) Kt/V: sum of the peritonal clearance of urea and the residual renal urea clearance, multiplied by 24 hours and divided by the volume of distribution.
Total urinary volume * urinary urea concentrationplasma urea concentration * V
Kt/V renal=
Total DRAINED dialysate volume * dialysate urea concentration
plasma urea concentration * VKt/Vper =
BCM – Body Composition Monitor…
quantifies individual overhydration
determines urea distribution volume V for dialysis dose assessment
provides a basis for nutritional assessment
measures non-invasively, fast and easy
0
200
400
600
800
1000
urea CREA UA P B2M HA IS IAA PCS free HA free IS free IAA
free PCS
TP
Dia
lytic m
ass r
em
ova
l
0
200
400
600
800
1000
urea CREA UA P B2M HA IS IAA PCS free HA
free IS free IAA
free PCS
TP
Re
na
l m
ass re
mo
va
l
Removal of Uraemic Toxins CAPD vs high volume APD
Eloot et al, PDI, 2014
Quantified measurement of adequacyUrea kinetic modelling:
1) Kt/V: sum of the peritonal clearance of urea and the residual renal urea clearance, multiplied by 24 hours and divided by the volume of distribution.
Total urinary volume * urinary urea concentrationplasma urea concentration * V
Kt/V renal=
Total DRAINED dialysate volume * dialysate urea concentration
plasma urea concentration * VKt/Vper =
PET test.
Quantified measurement of adequacy
Ratio’s of D/P for creatinine and urea
Dwell-time(hrs)
1 3 6
Lowtransporter
0.48 0.50 0.57
Low averagetransporter
0.57 0.62 0.70
High averagetransporter
0.68 0.74 0.82
Hightransporter
0.79 0.87 0.93
Phosphate clearance in CAPDvs CCPD
0
2
4
6
8
10
12
14
16
CAPD CCPD PhCAPD PhCCPD
Liters dialysatePhosphate clearance ml/min
Sedlacek et al, AJKD 2000, 36, 1020-1024
P-cresol and Beta 2 microglobulin clearance in CAPDvs CCPD
0
1
2
3
4
5
6
7
P cresol B2 Microglobulin
Evenepoel et al, KI, 2006
P<0.001
P<0.001
Time
IP volume Drain
Dwell time
fill
A PD dwell
DRAIN PROFILE APD :
0
500
1000
1500
2000
2500
3000
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
MIN
ML
Drain # 1
Drain # 2
Drain # 3
Drain # 4
• More (shorter) exchanges: • steeper transperitoneal transport rate• more « no exchange time » due to in and outflow• Inefficient use of fluid volume• Take care for « larger » molecules: Kt/V urea and creatinine clearance tell different stories
•Less (longer) dwells• at the end, slower transperitoneal transport rate• risk of lower drained volume
Efficient use of solution in APD.
0
10
20
30
40
50
60
70
80
90
100
Low LA HA High
20L APD (8 x 2.5L (Dry Day))20L APD (7 x 2.5L + 2.5L)12.5L APD (4 x2.5 + 2.5L)15L APD (4 x 2.5L + 2.5L + 2.5L (Mid-day exchange))
CrC
l/L/W
k/1
.73
m²
Blake et al, PDI, 16, 1996.
BSA 1.71 - 2.0m²RRF = 0 mL
Efficient use of solution in APD.
0
10
20
30
40
50
60
70
80
90
100
Low LA HA High
20L APD (8 x 2.5L (Dry Day))20L APD (7 x 2.5L + 2.5L)12.5L APD (4 x2.5 + 2.5L)15L APD (4 x 2.5L + 2.5L + 2.5L (Mid-day exchange))
CrC
l/L/W
k/1
.73
m²
Blake et al, PDI, 16, 1996.
BSA 1.71 - 2.0m²RRF = 0 mL
Demetriou et al, KI 2006
APD and adequacy
Demetriou et al, KI 2006
Impact of normal vs high volume APD
0,70,80,9
11,11,21,31,41,51,61,71,81,9
2
volume Glucose uptake Cost
normal dose high dose
Demetriou et al, KI 2006
More is not always better!
Survival
Peritoneal Kt/V péritoneale and survival
Rumpsfeld et al, PDI, 2009
Peritoneal Kt/V péritoneale and survival
Rumpsfeld et al, PDI, 2009
If you push too far, you get into trouble…
ADEMEX: Causes of dropout
0123456789
10
discomfort hernia peritonitis uremia
controltreated
%
AGE’s and GDP
0
20
40
60
80
100
120
Low GDP Classic
Unused1.5%
Unused2.5%
Spent 2hrs
Spent 8hrs
• Zeier et al, Kidney Int, 63, 298-305
Pyrraline (pmol/mgprotein) in fluid
Effect of dwell number on compliance
0
5
10
15
20
25
4 e/jour 5 e/jour 2litres >2litres
tousCANADAUSA
p=0.001 p=NS
Blake et al, AJKD, 35, 3, 506-514, 2000
Peritonitis free survival
Impact of volume on intraperitoneal pressure
Dejardin et al, NDT, 2007
2
Figure 2.Gastrointestinal microcirculation and cardiopulmonary function during experimentally increased intra-abdominal pressure *.Olofsson, Pia; Berg, Soren; MD, PhD; Ahn, Henrik; MD, PhD; Brudin, Lars; MD, PhD; Vikstrom, Tore; MD, PhD; Johansson, Kenth; MD, PhD
Critical Care Medicine. 37(1):230-239, January 2009.DOI: 10.1097/CCM.0b013e318192ff51
Figure 2. Microcirculatory organ blood flow (mean +/- sem). Micorcirculatory flow (% of baseline) measured by laser Doppler flowmeter at each pressure level (mm Hg). The blood flow is reduced progressively with increased intra-abdominal pressure. This reduction is less pronounced in small bowel mucosa. x = statistically significant difference (p o = statistically significant difference (p < 0.05) compared with the previous value.
Impact of intra abdominal pressure
Adequate dialysis
• Remove uremic toxins
• Remove salt and water ( blood-pressure, fluid control)
Male Female
PD HD pre HD TAVO
Vo
lum
e S
tatu
s [L
]
-4
-2
0
2
4
6
8
10
PD HD pre HD TAVO
Volu
me S
tatu
s [
L]
-4
-2
0
2
4
6
8
10
PD HD pre HD TAVO
Vo
lum
e S
tatu
s / E
CV
[%
]
-20
-10
0
10
20
30
40
PD HD pre HD TAVO
Volu
me S
tatu
s /
EC
V [
%]
-20
-10
0
10
20
30
40
p=0.004p<0.0001 p=0.71
p<0.0001
p=0.07p<0.0001
p=0.19p<0.0001
I am preserving my residual renal function
Icodextrin and residual renal function
GFR ml/min
Konings et al, KI, 2003
P=0.001
Icodextrin and residual renal function
-140
-120
-100
-80
-60
-40
-20
0
1
icodextrin hypertonic glucose
Davies et al, JASN 2003
Change in daily diuresis
Aims of dialysis
• Remove uremic toxins
• Remove salt and water ( blood-pressure, fluid control)
• Avoid toxic side effects (glucose, hyperlipidemia; obesitas)
PD HD
BM
I [k
g/m
²]
10
15
20
25
30
35
40
PD HD
BM
I [k
g/m
²]
10
15
20
25
30
35
40
PD HD
FT
I [k
g/m
²]
0
5
10
15
20
25
30
PD HD
FT
I [k
g/m
²]
0
5
10
15
20
25
30
MalePD HD
LT
I [k
g/m
²]
0
5
10
15
20
25
30
FemalePD HD
LT
I [k
g/m
²]
0
5
10
15
20
25
30
p=0.18 p=0.75
p=0.90 p=0.30
p=0.001p<0.0001
Body Composition PD vs HD: the EuroBCM trial
Van Biesen et al, NDT, 2013
-
5
10
15
20
25
30
20 40 60 80
LTI [
kg/m
²]
Age [years]
PD
HD
-
5
10
15
20
25
30
20 40 60 80
LTI [
kg/m
²]
Age [years]
PD
HD
-
5
10
15
20
25
30
20 40 60 80
FTI [
kg/m
²]
Age [years]
PD
HD
-
5
10
15
20
25
30
20 40 60 80
FTI [
kg/m
²]
Age [years]
PDHD
male
male female
female
Van Biesen et al, NDT, 2013
Body Composition PD vs HD: the EuroBCM trial
Relation inflammation, nutrition, fluid overload
Verger, ISPD, 2014
Albumin [g/L]<35.0 35.0-40.0 >40.0
N Mean ± SD N Mean ± SD N Mean ± SD
BMI [kg/m2] 314 25.0±4.6333 26.3±4.9 302 26.5±4.8
LTI [kg/m2] 311 13.1±3.1329 13.5±3.2 300 14.2±3.5
FTI [kg/m2] 310 7.8±3.8329 8.9±4.2 300 7.7±4.0
FO [L] 314 2.9±2.6 333 1.6±2.1 302 1.0±1.7
CRP [mg/L] 267 13.7±24.1276 10.0±21.0 257 5.8±10.4
Relation inflammation, nutrition, fluid overload
Verger, ISPD, 2014
