Transcript complications of esrd

20/12/2016
HEMODIALYSIS PART II: PATIENT
MANAGEMENT, ACCESS, DIALYSIS
PRESCRIPTION, COMPLICATIONS
R Vanholder, University Hospital, Gent, Belgium
© 2008 Universitair Ziekenhuis Gent
TOPICS
Complications of ESRD
Sudden death
Dialysis hypotension
Vascular access
Anticoagulation
Adequacy, Kt/V
© 2008 Universitair Ziekenhuis Gent
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COMPLICATIONS OF ESRD
R Vanholder
University Hospital, Gent,
Belgium
© 2008 Universitair Ziekenhuis Gent
CHRONIC KIDNEY DISEASE: THE MORTALITY
CHALLENGE
© 2008 Universitair Ziekenhuis Gent
modified, Foley et al, AJKD, S3:S112-S119; 1998
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IN CKD VIRTUALLY ALL BIOCHEMICAL AND
ORGANS SYSTEMS ARE AFFEECTED
© 2008 Universitair Ziekenhuis Gent
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NUTRITION AND THE UREMIC
SYNDROME
R Vanholder
University Hospital, Gent,
Belgium
© 2008 Universitair Ziekenhuis Gent
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MALNUTRITION: THE RESULT
Vanholder et al, Lancet Diabetes Endocrinol, 2016,
doi: 10.2016/ S2213-8587(16)00033-4
© 2008 Universitair Ziekenhuis Gent
© 2008 Universitair Ziekenhuis Gent
Carrero et al, Am J Clin Nutr, 85, 695-701, 2007
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MALNUTRITION IS FREQUENT IN CKD ASSESSMENT PER APPETITE SCORE
MEN
(N=127)
WOMEN
(N=96)
Appetite
good
medium
poor
good
medium
poor
N
80
32
12
44
30
22
BMI
25.1±4.1 22.7±4.2 21.6±3.8 25.9±7.2 24.5±5.3 23.7±4.7
S Alb (g/L)
35.4±3.6 34.2±5.1 31.1±4.6 34.7±4.2 35.5±4.0 31.4±5.3
CRP(mg/L)
5.4
11.0
26.6
5.8
6.2
10.0
BMI: body mass index, S Alb: serum albumin,
CRP: C reactive protein
© 2008 Universitair Ziekenhuis Gent
Carrero et al, Am J Clin Nutr, 85: 695-701; 2007
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MALNUTRITION IS FREQUENT IN CKD ASSESSMENT PER APPETITE SCORE
MEN
(N=127)
WOMEN
(N=96)
Appetite
good
medium
poor
good
medium
poor
N
80
32
12
44
30
22
BMI
25.1±4.1 22.7±4.2 21.6±3.8 25.9±7.2 24.5±5.3 23.7±4.7
S Alb (g/L)
35.4±3.6 34.2±5.1 31.1±4.6 34.7±4.2 35.5±4.0 31.4±5.3
CRP(mg/L)
5.4
11.0
26.6
5.8
6.2
10.0
BMI: body mass index, S Alb: serum albumin,
CRP: C reactive protein
© 2008 Universitair Ziekenhuis Gent
Carrero et al, Am J Clin Nutr, 85: 695-701; 2007
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MALNUTRITION IS FREQUENT IN CKD ASSESSMENT PER APPETITE SCORE
MEN
(N=127)
WOMEN
(N=96)
Appetite
good
medium
poor
good
medium
poor
N
80
32
12
44
30
22
BMI
25.1±4.1 22.7±4.2 21.6±3.8 25.9±7.2 24.5±5.3 23.7±4.7
S Alb (g/L)
35.4±3.6 34.2±5.1 31.1±4.6 34.7±4.2 35.5±4.0 31.4±5.3
CRP(mg/L)
5.4
11.0
26.6
5.8
6.2
10.0
BMI: body mass index, S Alb: serum albumin,
CRP: C reactive protein
© 2008 Universitair Ziekenhuis Gent
Carrero et al, Am J Clin Nutr, 85: 695-701; 2007
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MALNUTRITION IS FREQUENT IN CKD ASSESSMENT PER APPETITE SCORE
MEN
(N=127)
WOMEN
(N=96)
Appetite
good
medium
poor
good
medium
poor
N
80
32
12
44
30
22
BMI
25.1±4.1 22.7±4.2 21.6±3.8 25.9±7.2 24.5±5.3 23.7±4.7
S Alb (g/L)
35.4±3.6 34.2±5.1 31.1±4.6 34.7±4.2 35.5±4.0 31.4±5.3
CRP(mg/L)
5.4
11.0
26.6
5.8
6.2
10.0
BMI: body mass index, S Alb: serum albumin,
CRP: C reactive protein
© 2008 Universitair Ziekenhuis Gent
Carrero et al, Am J Clin Nutr, 85: 695-701; 2007
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THE DIABOLIC TRIANGLE
MALNUTRITION
MORBI/MORTALITY
PROTEIN ENERGY
WASTING
INFLAMMATION
© 2008 Universitair Ziekenhuis Gent
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COMPLEX PATHO-PHYSIOLOGY
© 2008 Universitair Ziekenhuis Gent
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Ikizler et al, KI, 84: 1096-1107; 2013
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UREMIA
NUTRITION
© 2008 Universitair Ziekenhuis Gent
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UREMIA
NUTRITION
© 2008 Universitair Ziekenhuis Gent
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UREMIA AND THE INTESTINE
© 2008 Universitair Ziekenhuis Gent
INTESTINAL MICROBIOTA ARE MODIFIED
IN CKD
© 2008 Universitair Ziekenhuis Gent
Vaziri et al, KI, 83: 308-315;
2013
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Fig. 4 - Hierarchical clustering of probe
sets representing significantly different
operational taxonomic units (OTUs)
between groups with a minimum two-fold
change in untransformed intensities
between samples to show relative
abundance. Yellow indicates increased
abundance and red indicates decreased
abundance relative to the mean for each
OTU. Columns represent rat fecal microbiota
composition for control (CTL) and chronic
renal failure (CRF) individual rats. Rows are
OTUs with mean fold change among
samples and cluster based on the similarity
of their abundance profiles across the data
set, with similar OTUs connected at the
hierarchical tree on the left. Bars
on
the right represent (1)
OTUs from the Firmicutes
(especially
Lactobacillaceae and a
few Coprococcus within
the Lachnospiraceae),
Bacteroidetes (Prevotellaceae, two
Rikenellaceae OTUs) that had higher
abundances in CTL samples, or (2) OTUs
from the Firmicutes (unclassified
Lachnospiraceae) and other Rikenellaceae
(in Bacteroides) that have higher
abundances in CRF samples.
© 2008 Universitair Ziekenhuis Gent
Vaziri et al, KI, 83: 308-315;
2013
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CHANGES IN ASSIMILATION MODIFY THE
GENERATION OF P-CRESYLSUFATE
© 2008 Universitair Ziekenhuis Gent
Bammens et al, KI, 64: 2196-2203; 2003
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CHANGES IN ASSIMILATION MODIFY THE
GENERATION OF P-CRESYLSUFATE
Group A: GFR > 60
Group B: GFR 30-60
Group C: GFR < 30
(A) The median values of urinary pcresol output (mg/24 hours) in the three
study groups.
(B) The median values of the urinary pcresol (mg/24 hours)/urinary urea
nitrogen
(g/24 hours) ratio.
*P < 0.05 vs. group A.
© 2008 Universitair Ziekenhuis Gent
Bammens et al, KI, 64: 2196-2203; 2003
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CKD DISTURBS INTEGRITY OF THE
INTESTINAL EPITHELIUM
© 2008 Universitair Ziekenhuis Gent
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Vaziri et al, NDT, 27, 2686-2693, 2011
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CKD DISTURBS INTEGRITY OF THE
INTESTINAL EPITHELIUM
© 2008 Universitair Ziekenhuis Gent
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Vaziri et al, NDT, 27, 2686-2693, 2011
CARDIO-VASCULAR DISEASE
© 2008 Universitair Ziekenhuis Gent
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CKD PRE-DIALYSIS IS ALSO LINKED TO
CVD
y = (0.1262x) + 10.77,
r = 0.645, P < 0.001;
y = (–0.1018x) + 2.727,
r = 0.574, P < 0.004
© 2008 Universitair Ziekenhuis Gent
Vanholder et al, NDT, 20: 1048-1056; 2005
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ATHEROSCLEROSIS: AN INFLAMMATORY DISEASE
1
2
3
4
Interaction between different cell types
© 2008 Universitair Ziekenhuis Gent
1. Leukocytes
2. Endothelium
3. Platelets
4. Smooth muscle cells
Ross, NEJM 340 (2): 115-126; 1999
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UREMIC VASCULAR DISEASE
Vanholder et al, Lancet Diabetes Endocrinol, 2016, doi: 10.2016/ S22138587(16)00033-4
© 2008 Universitair Ziekenhuis Gent
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OTHER COMPLICATIONS
© 2008 Universitair Ziekenhuis Gent
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IMMUNE RESPONSE: NORMAL VS UREMIA
© 2008 Universitair Ziekenhuis Gent
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IMMUNE RESPONSE: NORMAL VS UREMIA
© 2008 Universitair Ziekenhuis Gent
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IMMUNE RESPONSE: NORMAL VS UREMIA
© 2008 Universitair Ziekenhuis Gent
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IMMUNE RESPONSE: NORMAL VS UREMIA
© 2008 Universitair Ziekenhuis Gent
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© 2008 Universitair Ziekenhuis Gent
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UREMIC BONE DISEASE – RUGGER-JERSEY
SPINE
Vanholder et al, Lancet Diabetes Endocrinol, 2016, doi: 10.2016/ S2213-8587(16)00033-4
© 2008 Universitair Ziekenhuis Gent
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UREMIC BONE DISEASE – VASCULAR
CALCIFICATION
Vanholder et al, Lancet Diabetes Endocrinol, 2016, doi: 10.2016/ S2213-8587(16)00033-4
© 2008 Universitair Ziekenhuis Gent
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UREMIC BRAIN LESIONS – SILENT
INFARCTIONS
Vanholder et al, Lancet Diabetes Endocrinol, 2016, doi: 10.2016/ S2213-8587(16)00033-4
© 2008 Universitair Ziekenhuis Gent
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UREMIC BRAIN LESIONS – MICROBLEEDS
Vanholder et al, Lancet Diabetes Endocrinol, 2016, doi: 10.2016/ S2213-8587(16)00033-4
© 2008 Universitair Ziekenhuis Gent
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KIDNEY
GISYSTEM
BONE
© 2008 Universitair Ziekenhuis Gent
IMMUNE
SYSTEM
HEART
VESSELS
LUNGS
BRAIN
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CKD: A SYSTEMIC DISORDER
THE SYSTEMIC NATURE OF CKD
Carmine Zoccali , Friedo W Dekker, Danilo Fliser, Gunnar H
Heine, Kitty J Jager, Mehmet Kanbay, Francesca
Mallamaci, Ziad Massy, Alberto Ortiz, Gianfranco Parati,
Patrick Rossignol, Pantelis Sarafidis, Raymond
Vanholder, Andrzej Wiecek, Gerard London
For the EURECA-m workgroup of ERA-EDTA
© 2008 Universitair Ziekenhuis Gent
Submitted to NRN Reviews Nephrology
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SUDDEN DEATH
© 2008 Universitair Ziekenhuis Gent
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DURING DIALYSIS
Technique failure
Error in composition dialysate
Anaphylactoid reaction
Hypocalcemia with citrate anticoagulation
Bleeding
Air embolism
Pulmonary embolism (from catheter) (VSD!)
Hypokalemia
Hypotension
Disequilibrium
© 2008 Universitair Ziekenhuis Gent
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PREFERENTIALLY OUTSIDE DIALYSIS
Hyperkalemia
Pulmonary edema
Overdose of drug
Water intoxication (pontine myelolysis)
© 2008 Universitair Ziekenhuis Gent
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DISTRIBUTION OF SUDDEN DEATH
RELATED TO DIALYSIS SESSION
Fig. 2 Ratio of actual to expected number of occurrences of sudden death
for each 12 h interval beginning with the start of HD.
© 2008 Universitair Ziekenhuis Gent
Bleyer et al, KI, 69: 2268-2273; 2006
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LONG WEEK-END INTERVAL AS KILLER
Fig. 2 Annualized Mortality and Cardiovascular-Admission Rates on the
Day after the Long Interdialytic Interval and on Other Days, According
to subgroup.
Events on the day after the long (2-day) interdialytic interval are indicated by
a black circle, and events on other days are indicated by an open circle. The
horizontal bars represent 95% confidence intervals. CVD denotes
cardiovascular disease, and ESRD end-stage renal disease
© 2008 Universitair Ziekenhuis Gent
Foley et al, NEJM, 365:1099-1107; 2011
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DISTRIBUTION OF SUDDEN DEATH
RELATED TO DIALYSIS SESSION
Characteristica
0–12 h interval
12–60 h interval 60–72 h interval P-valueb
Left ventricular ejection fraction (%)
45.416.7
46.618.0
50.016.6
0.55
Congestive heart failure (%)
62.1
56.3
35.3
0.20
Coronary artery disease (%)
55.2
62.5
41.2
0.36
Left ventricular hypertrophy (%)
25.0
40.6
50.0
0.21
Peripheral vascular disease (%)
44.8
46.9
17.7
0.11
Stroke (%)
27.6
28.1
5.6
0.16
Diabetes mellitus (%)
62.1
62.5
35.3
0.14
Frequent non-compliance (%)
17.3
21.9
23.5
0.85
Beta-blocker usage (%)
31.0
37.5
58.8
0.01
Weight gain between treatments
4.52.7
4.63.2
4.42.6
0.99
Serum potassium (mEq/l) in
previous month
4.470.73
4.300.80
4.861.0
0.18
Bleyer et al, KI, 69: 2268-2273; 2006
© 2008 Universitair Ziekenhuis Gent
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DISTRIBUTION OF SUDDEN DEATH
RELATED TO DIALYSIS SESSION
Characteristica
0–12 h interval
12–60 h interval 60–72 h interval P-valueb
Left ventricular ejection fraction (%)
45.416.7
46.618.0
50.016.6
0.55
Congestive heart failure (%)
62.1
56.3
35.3
0.20
Coronary artery disease (%)
55.2
62.5
41.2
0.36
Left ventricular hypertrophy (%)
25.0
40.6
50.0
0.21
Peripheral vascular disease (%)
44.8
46.9
17.7
0.11
Stroke (%)
27.6
28.1
5.6
0.16
Diabetes mellitus (%)
62.1
62.5
35.3
0.14
Frequent non-compliance (%)
17.3
21.9
23.5
0.85
Beta-blocker usage (%)
31.0
37.5
58.8
0.01
Weight gain between treatments
4.52.7
4.63.2
4.42.6
0.99
Serum potassium (mEq/l) in
previous month
4.470.73
4.300.80
4.861.0
0.18
© 2008 Universitair Ziekenhuis Gent
Bleyer et al, KI, 69: 2268-2273; 2006
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SOLUTIONS
Alternate day dialysis
Frequent (daily) dialysis
Extended (long) dialysis
Home dialysis
Self care
© 2008 Universitair Ziekenhuis Gent
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LOW DIALYSATE POTASSIUM
© 2008 Universitair Ziekenhuis Gent
Jadoul et al, cJASN, 7, 765-774, 2012
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DIALYSATE POTASSIUM AND MORTALITY
All Cause All cause Sudden
RR
P
death RR
Sudden
death - P
Patient
KD ≤ 1.5 vs ≥ 3.0
KD 2-2.5 vs ≥ 3.0
Instrumental
KD ≤ 1.5 vs ≥ 3.0
KD 2-2.5 vs ≥ 3.0
© 2008 Universitair Ziekenhuis Gent
Jadoul et al, cJASN, 7, 765-774, 2012
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DIALYSATE POTASSIUM AND MORTALITY
All Cause All cause Sudden
RR
P
death RR
Sudden
death - P
Patient
KD ≤ 1.5 vs ≥ 3.0
1.13
0.01
1.39
0.004
KD 2-2.5 vs ≥ 3.0
Instrumental
KD ≤ 1.5 vs ≥ 3.0
KD 2-2.5 vs ≥ 3.0
© 2008 Universitair Ziekenhuis Gent
Jadoul et al, cJASN, 7, 765-774, 2012
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DIALYSATE POTASSIUM AND MORTALITY
All Cause All cause Sudden
RR
P
death RR
Sudden
death - P
Patient
KD ≤ 1.5 vs ≥ 3.0
1.13
0.01
1.39
0.004
KD 2-2.5 vs ≥ 3.0
1.08
0.03
1.17
0.04
Instrumental
KD ≤ 1.5 vs ≥ 3.0
KD 2-2.5 vs ≥ 3.0
© 2008 Universitair Ziekenhuis Gent
Jadoul et al, cJASN, 7, 765-774, 2012
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DIALYSATE POTASSIUM AND MORTALITY
All Cause All cause Sudden
RR
P
death RR
Sudden
death - P
Patient
KD ≤ 1.5 vs ≥ 3.0
1.13
0.01
1.39
0.004
KD 2-2.5 vs ≥ 3.0
1.08
0.03
1.17
0.04
1.09
0.43
1.67
0.05
Instrumental
KD ≤ 1.5 vs ≥ 3.0
KD 2-2.5 vs ≥ 3.0
© 2008 Universitair Ziekenhuis Gent
Jadoul et al, cJASN, 7, 765-774, 2012
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DIALYSATE POTASSIUM AND MORTALITY
All Cause All cause Sudden
RR
P
death RR
Sudden
death - P
Patient
KD ≤ 1.5 vs ≥ 3.0
1.13
0.01
1.39
0.004
KD 2-2.5 vs ≥ 3.0
1.08
0.03
1.17
0.04
KD ≤ 1.5 vs ≥ 3.0
1.09
0.43
1.67
0.05
KD 2-2.5 vs ≥ 3.0
1.23
0.01
1.61
0.01
Instrumental
© 2008 Universitair Ziekenhuis Gent
Jadoul et al, cJASN, 7, 765-774, 2012
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DIALYSATE POTASSIUM AND MORTALITY
All Cause All cause Sudden
RR
P
death RR
Sudden
death - P
Patient
KD ≤ 1.5 vs ≥ 3.0
1.13
0.01
1.39
0.004
KD 2-2.5 vs ≥ 3.0
1.08
0.03
1.17
0.04
KD ≤ 1.5 vs ≥ 3.0
1.09
0.43
1.67
0.05
KD 2-2.5 vs ≥ 3.0
1.23
0.01
1.61
0.01
Instrumental
Adjusted for 14 comorbidities and Kt/V
© 2008 Universitair Ziekenhuis Gent
Jadoul et al, cJASN, 7, 765-774, 2012
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CONCLUSIONS
Sudden death due to:
Technical problems and mistakes
Pulmonary and air embolism
Hyperkalemia
Hypokalemia
Bleeding
Fluid overload
Cave
Dialysate potassium
Dialysis timeframe
© 2008 Universitair Ziekenhuis Gent
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HYPOTENSION
© 2008 Universitair Ziekenhuis Gent
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© 2008 Universitair Ziekenhuis Gent
© 2008 Universitair Ziekenhuis Gent
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BLOOD VOLUME = UF - REFILLING
© 2008 Universitair Ziekenhuis Gent
Santoro
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DIETARY SODIUM RESTRICTION
In order to control inter-dialytic weight gain (IDWG) and
reduce the risk of IDH, dietary salt intake should be
assessed and not exceed 6 g/day unless contraindicated (III).
© 2008 Universitair Ziekenhuis Gent
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INTER DIALYTIC WEIGHT GAIN AND
SURVIVAL
Interdialytic weight gain
0.99 (0.97, 1.00) per %
Unadjusted
1.02 (1.01, 1.03) per %
Adjusted
Quintiles
P = 0.05
P = 0.005
2.3 (reference
1 (reference category)
1 (reference category)
2.3 to 3.1
0.97 (0.90, 1.06)
0.96 (0.88, 1.05)
3.2 to 3.9
1.02 (0.94, 1.10)
1.03 (0.94, 1.13)
4.0 to 4.8
0.99 (0.91, 1.07)
1.03 (0.94, 1.14)
>4.8
0.92 (0.85, 1.00)
1.12 (1.02, 1.23)
(4.8%= 3.4 kg in a 70 kg person)
© 2008 Universitair Ziekenhuis Gent
Foley; USRDS. Kidney Int 2002
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DIALYSIS DURATION AND FREQUENCY
In patients with frequent episodes of IDH, a
prolongation in dialysis time or an increase in
dialysis frequency should be considered (level II-III)
© 2008 Universitair Ziekenhuis Gent
Brunet et al.; Nephrol Dial Transpl 1996
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LENGTH OF DIALYSIS MORE IMPORTANT
IN PREVENTING HYPOTENSION THAN
HDF
© 2008 Universitair Ziekenhuis Gent
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Cornelis et al, AJKD, 64: 247-256; 2015
LENGTH OF DIALYSIS MORE IMPORTANT
IN PREVENTING HYPOTENSION THAN
HDF
© 2008 Universitair Ziekenhuis Gent
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Cornelis et al, AJKD, 64: 247-256; 2015
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HOME HEMODIALYSIS AS A SOLUTION?
© 2008 Universitair Ziekenhuis Gent
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Vanholder et al, Nat Rev Nephrol, 8: 579-586; 2012
SODIUM PROFILING
HNa: high sodium; NaM: sodium profiling;
UF: ultrefiltration followed by dialysis
© 2008 Universitair Ziekenhuis Gent
Dheenan S, et al; Kidney Int 2001; 59: 1175-1181. 66
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SODIUM PROFILING (CONT)
TACNa = Time averaged
concentration of Na
© 2008 Universitair Ziekenhuis Gent
Song J et al, Am J Kidney Dis, 40: 291-301; 2002
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BIOFEEDBACK REDUCES HYPOTENSIVE
EPISODES
© 2008 Universitair Ziekenhuis Gent
68
Nesrallah et al, NDT, 28: 182-191; 2013
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BIOFEEDBACK REDUCES HYPOTENSIVE
EPISODES
Fig. 1. Study selection flow diagram
© 2008 Universitair Ziekenhuis Gent
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Nesrallah et al, NDT, 28: 182-191; 2013
BIOFEEDBACK REDUCES HYPOTENSIVE
EPISODES
Fig. 1. Study selection flow diagram
© 2008 Universitair Ziekenhuis Gent
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Nesrallah et al, NDT, 28: 182-191; 2013
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ISOTHERMIC TREATMENTS
© 2008 Universitair Ziekenhuis Gent
Maggiore Q, et al: Am J Kidney Dis 2002; 40: 280-90
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LOWERING DIALYSATE TEMPERATURE
DECREASES ISCHEMIC BRAIN INJURY
© 2008 Universitair Ziekenhuis Gent
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Eldehni et al, JASN, 26: 957-965; 2015
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LOWERING DIALYSATE TEMPERATURE
DECREASES ISCHEMIC BRAIN INJURY
© 2008 Universitair Ziekenhuis Gent
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Eldehni et al, JASN, 26: 957-965; 2015
CONCLUSIONS
Risk factors for intra-dialytic hypotension
Exaggerated salt intake and too high interdialytic weight gain
Too short dialysis
Solutions
Limit dietary salt intake
Adapt dialysis time frame
Not: Sodium profiling
Biofeedback
Cool dialysate / isothermic dialysis
© 2008 Universitair Ziekenhuis Gent
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VASCULAR ACCESS
R Vanholder,
University Hospital,
Gent, Belgium
© 2008 Universitair Ziekenhuis Gent
© 2008 Universitair Ziekenhuis Gent
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TOPICS
Access flow as predictor of thrombosis
Preventive antiaggregation / anticoagulation
Various other aspects
Central vein catheters
© 2008 Universitair Ziekenhuis Gent
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ACCESS FLOW AS A PREDICTOR OF
THROMBOSIS
© 2008 Universitair Ziekenhuis Gent
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EBPG 2007
Guideline 5.1. Prior to any cannulation, autogenous
arteriovenous fistulae and grafts should be assessed by
physical examination (Evidence level IV).
Guideline 5.2. Objective monitoring of access function should
be performed at a regular base by measuring access flow
(Evidence level II).
© 2008 Universitair Ziekenhuis Gent
Tordoir et al, NDT, 22 (suppl 2): ii88-ii117; 2007
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EFFECT MONITORING ON THROMBOSIS
AVG
AVF
© 2008 Universitair Ziekenhuis Gent
MacCarley et al, KI, 60: 1164-1172; 2001
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THROMBOSIS WITH ACCESS BLOOD FLOW
SURVEILLANCE VS. STANDARD CARE
Standard care could consist of either venous pressure monitoring or no access surveillance.
Abbreviations: RR, relative risk; CI, confidence interval; F, fistula; VP, venous pressure; G, graft;
DU, Doppler ultrasound; UD, ultrasound diluation.
© 2008 Universitair Ziekenhuis Gent
Tonelli et al, AJKD, 51: 630-640; 2008
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ACCESS LOSS WITH ACCESS BLOOD FLOW
SURVEILLANCE VS. STANDARD CARE
Standard care could consist of either venous pressure monitoring or no access surveillance.
Abbrevations: RR, relative risk; CI, confidence interval; DU, Doppler ultrasound; UD, ultrasound diluation
© 2008 Universitair Ziekenhuis Gent
Tonelli et al, AJKD, 51: 630-640; 2008
82
41
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CONCLUSIONS
For grafts, there is no controlled data favoring use of
flow measurements
For AVF: useful to prevent thrombosis, no differences in
outcome
© 2008 Universitair Ziekenhuis Gent
83
PREVENTIVE ANTIAGGREGATION /
ANTICOAGULATION
© 2008 Universitair Ziekenhuis Gent
42
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EBPG 2007
?
© 2008 Universitair Ziekenhuis Gent
85
CLOPIDOGREL AND EARLY FAILURE OF AVF
(US MULTICENTER TRIAL)
Effect of Clopidogrel on Early Failure of Arteriovenous
Fistulas for Hemodialysis
A Randomized Controlled Trial
Laura M. Dember, MD; Gerald J. Beck, PhD; Michael Allon, MD;
James A. Delmez, MD; Bradley S. Dixon, MD; Arthur Greenberg, MD;
Jonathan Himmelfarb, MD; Miguel A. Vazquez, MD; Jennifer J.
Gassman, PhD; Tom Greene, PhD; Milena K. Radeva, MS; Gregory L.
Braden, MD; T. Alp Ikizler, MD; Michael V. Rocco, MD, MSCE; Ingemar
J. Davidson, MD; James S. Kaufman, MD; Catherine M. Meyers, MD;
John W. Kusek, PhD; Harold I. Feldman, MD, MSCE; for the Dialysis
Access Consortium Study Group
© 2008 Universitair Ziekenhuis Gent
Dember et al, JAMA, 299: 2164-2171; 2008
86
43
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© 2008 Universitair Ziekenhuis Gent
Dember et al, JAMA, 299: 2164-2171; 2008
87
COCHRANE REVIEW: INCREASING PATENCY OF
AVF AND AVG
3 RCT’s
Aspirin > placebo
3 RCT’s
Ticlopidine > placebo
1 trial
Dipyridamole ± aspirin > placebo
1 trial
Fish oil > placebo
1 trial
Warfarin inefficient; prematurely stopped for
bleeding
1 trial
Sulfinpyrazone > placebo
1 trial
Clopidogrel > placebo
© 2008 Universitair Ziekenhuis Gent
Osborn et al, The Cochrane Library; 2009, issue 1
88
44
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ASPIRIN AND PATENCY GRAFTS
Figure 1. Primary unassisted patency is prolonged in patients on aspirin at baseline. Cumulative incidence of
loss of primary unassisted graft patency for baseline aspirin users (dashed line) and nonusers (solid line). The
median patency in the baseline aspirin users and nonusers was 5.8 (95% CI, 4.8 to 7.4) and 4.1 months (95%
CI, 3.5 to 5.3; P = 0.13), respectively
© 2008 Universitair Ziekenhuis Gent
Dixon et al, JASN, 22: 773-781; 2011
89
BLEEDING AS A COUNTERBALANCE
Randomized Controlled Trial of Clopidogrel
plus Aspirin to Prevent Hemodialysis Access
Graft Thrombosis
James S. Kaufman, Theresa Z. O’Connor, Jane Hongyuan
Zhang, Robert E. Cronin, Louis D. Fior*, Michael B. Ganz,
David S. Goldfarb and Peter N. Peduzzi for the Veterans
Affairs Cooperative Study Group on Hemodialysis Access
Graft Thrombosis
© 2008 Universitair Ziekenhuis Gent
Kaufman et al, JASN, 14: 2313-2321; 2003
90
45
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CONCLUSIONS
For short-term outcome, ticlopidine prevents thrombosis
without imapct on access survival (US)
Several studies show an advantage for antiaggregants
for maintaining patency; mostly, these are small studies
with debatable quality
Coumarin has little benefit
Bleeding complications seriously blur the picture
Many patients receive these drugs for other reasons
© 2008 Universitair Ziekenhuis Gent
91
VARIOUS OTHER ASPECTS
© 2008 Universitair Ziekenhuis Gent
46
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PREOPERATIVE VASCULAR
ULTRASOUND
© 2008 Universitair Ziekenhuis Gent
Ferring et al, cJASN, 5: 2236-2244; 2010
93
DAILY HEMODIALYSIS
* The
hazard ratios and P values for rates of events (including multiple events per patient) between the frequent-hemodialysis group and the conventionalhemodialysis group were calculated with the use of the Andersen–Gill model, except where otherwise noted.
† The percentage of dialysis treatments with recorded hypotensive episodes, defined as the need for a lower ultrafiltration rate, reduced blood flow, or saline
administration to ameliorate hypotension, was 10.9% in the frequent-hemodialysis group and 13.6% in the conventional-hemodialysis group (P = 0.04 with the use of
generalized estimating equations).
‡ The P values for the comparison of the number of patients with at least one event of hypokalemia or hypophosphatemia were calculated with the use of Fisher's
exact test.
§ Hypophosphatemia was defined as a phosphorus concentration of less than 2.17 mg per deciliter (0.7 mmol per liter).
© 2008 Universitair Ziekenhuis Gent
Chertow et al, NEJM, 363: 2287-2300; 2010
94
47
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DAILY HEMODIALYSIS
© 2008 Universitair Ziekenhuis Gent
Chertow et al, NEJM, 363: 2287-2300; 2010
95
DAILY HEMODIALYSIS
 Benefits
Less hazard for composite endpoint: death or increase in left
ventricular mass
Less hazard for composite endpoint: death or decrease in
physical health score
© 2008 Universitair Ziekenhuis Gent
Chertow et al, NEJM, 363: 2287-2300; 2010
96
48
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BUTTONHOLE TECHNIQUE
Figure 1 Time to first septic permanent access event in conventional hemodialysis vs. nocturnal
hemodialysis (NHD)/rope ladder and NHD/buttonhole cannulation groups (univariable analysis).
© 2008 Universitair Ziekenhuis Gent
Van Eps, Hemodial Int, 14: 451-463; 2010
97
BUTTONHOLE TECHNIQUE
Figure 1. Annual incidence of infectious events. Lines around the squares indicate 95% confidence intervals; *P < 0.05
(compared with 2001, 2002, 2003, 2004, 2005, 2006, and 2008B); **P < 0.05 (compared with 2001, 2003, 2004, 2005, and
2008B). Period 1 (January 1, 2001, to August 3, 2004): all patients using rope-ladder technique with sharp needles; period 2
(August 4, 2004, to January 31, 2005): progressive switch to buttonhole (BH) method using blunt needles; period 3 (February
1, 2005, to May 19, 2008): all patients using BH method, before educational workshops; and period 4 (May 20, 2008, to June
30, 2010): all patients using BH method, after educational workshops. Abbreviation: AVF, arteriovenous fistula.
© 2008 Universitair Ziekenhuis Gent
Labriola et al, AJKD, 57: 442-448; 2011
98
49
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CONCLUSIONS
Vascular bed mapping prior to access surgery increases
access quality
Daily dialysis may damage access
The buttonhole may be beneficial for access survival if
hygienic measures are carefully applied
© 2008 Universitair Ziekenhuis Gent
99
ERBP POSITION STATEMENT on
CATHETER RELATED BLOOD STREAM
INFECTIONS (CRBSI)
R Vanholder,
University Hospital,
Gent, Belgium
© 2008 Universitair Ziekenhuis Gent
50
20/12/2016
© 2008 Universitair Ziekenhuis Gent
© 2008 Universitair Ziekenhuis Gent
R Vanholder et al, NDT Plus, 3: 234-246; 2010
R Vanholder et al, NDT; 2010; DOI: 10.1093/ndt/gfq205
101
102
51
20/12/2016
TUNNELED VS. NON-TUNNELED CATHETERS
A.1.1: The use of non-tunneled catheters, except in Acute Kidney
Injury (AKI), is esteemed undesirable. In chronic maintenance
haemodialysis patients, it is recommended to remove temporary
catheters as soon as possible, even without or with only minor
complications, and to have them replaced preferentially by an arteriovenous fistula, or if that is impossible, an arterio-venous graft (AVG),
or, if that is impossible, a tunneled central vein catheter (CVC).
A.1.2: If haemodialysis catheters are required either due to need or
because patients refuse an AVF, the occurrence of a catheter related
complication should be a trigger to reevaluate options for alternative
access, such as AVF.
© 2008 Universitair Ziekenhuis Gent
103
CATHETER USE AND HOSPITALIZATION RISK
FOR ACCESS INFECTION
© 2008 Universitair Ziekenhuis Gent
Pisoni et al, AJKD, 53: 475-491; 2009
104
52
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NON-INFECTED ACCESS CATHETERS AND
INFLAMMATION
C-reactive protein (CRP) levels (mg per 100 ml) decrease
significantly in incident maintenance hemodialysis patients who
initially dialyze with a non-infected catheter but with a fistula at 6
months (P<0.0001). By contrast, no change in CRP is observed in
incident maintenance hemodialysis patients who initiated dialysis with
a catheter and remained with a catheter at 6 months (P=0.17). CRP
concentrations are shown as median (interquartile range) in the boxes.
© 2008 Universitair Ziekenhuis Gent
Goldstein et al, KI, 76: 1063-1069; 2009
105
SURVIVAL ADVANTAGE AVF PARTLY
PATIENT-RELATED?
Abstract
Patients needing hemodialysis are advised to have arteriovenous fistulas rather than catheters because of
significantly lower mortality rates. However, disparities in fistula placement raise the possibility that patient factors
have a role in this apparent mortality benefit. We derived a cohort of 115,425 patients on incident hemodialysis ≥67
years old from the US Renal Data System with linked Medicare claims to identify the first predialysis vascular access
placed. We compared mortality outcomes in patients initiating hemodialysis with a fistula placed first, a catheter after
a fistula placed first failed, or a catheter placed first (n=90,517; reference group). Of 21,436 patients with a fistula
placed first, 9794 initiated hemodialysis with that fistula, and 8230 initiated dialysis with a catheter after failed fistula
placement. The fistula group had the lowest mortality over 58 months (hazard ratio, 0.50; 95% confidence interval,
0.48 to 0.52; P<0.001), with mortality rates at 6, 12, and 24 months after initiation of 9%, 17%, and 31%, respectively,
compared with 32%, 46%, and 62%, respectively, in the catheter group. However, the group initiating hemodialysis
with a catheter after failed fistula placement also had significantly lower mortality rates than the catheter group had
over 58 months (hazard ratio, 0.66; 95% confidence interval, 0.64 to 0.68; P<0.001), with mortality rates of 15%,
25%, and 42% at 6, 12, and 24 months, respectively. Thus, patient factors affecting fistula placement, even when
patients are hemodialyzed with a catheter instead, may explain at least two thirds of the mortality benefit observed in
patients with a fistula.
© 2008 Universitair Ziekenhuis Gent
Brown et al, JASN 28: 2016. doi: 10.1681/ASN.2016010019
106
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PREVENTIVE ANTIMICROBIAL LOCKS
B.3.1: The preventive use of antimicrobial locks is advocated to reduce
the rate of CRBSI.
B.3.2: In view of the potential risks of spillover of the locking solution,
associated risks (arrythmias, toxicity, allergic reactions, development
of resistance to antibiotics) should be balanced with the benefits in
terms of prevention of infection. Citrate locks have for the time being
most extensively been studied. The 4% solution seems to offer at
present the best benefit/risk ratio.
B.3.3: Antimicrobial lock solutions should not replace hygienic
standards with regard to catheter care and handling.
© 2008 Universitair Ziekenhuis Gent
107
META-ANALYSIS
Antimicrobial Lock Solutions for the Prevention
of Infections
Associated with
Intravascular
Preventing
haemodialysis
catheter-related
Catheters
in
Patients
Undergoing
Hemodialysis:
bacteraemia with an antimicrobial lock
solution: a
Systematic Review
and Meta‐analysis
of trials
meta-analysis
of prospective
randomized
Randomized, Controlled Trials
Laura Labriola, Ralph Crott, and Michel Jadoul
Dafna Yahav, Benaya Rozen‐Zvi, Anat Gafter‐Gvili,
Leonard Leibovici, Uzi Gafter, and Mical Paul
Nephrol. Dial. Transplant. 2008 23: 1666-1672
© 2008 Universitair Ziekenhuis Gent
Yahav et al, Clin Infect Dis, 47: 83-93; 2008
108
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HEPARIN PROMOTES AND CITRATE
COUNTERACTS BIOFILM FORMATION
The effect of other anticoagulants on S. aureus biofilm formation
(A-D)
Gentamicin and citrate together strongly inhibit biofilm formation
© 2008 Universitair Ziekenhuis Gent
Shanks et al, NDT, 21: 2247-2255; 2006
109
CITRATE 4% - TAUROLIDINE 1.35%
RECENT STUDIES
Several recent RCTs show a positive impact of the
combination on CRBIs
All studies used heparin as a comparator, not citrate
alone
A meta-analysis showed a similar positive impact on
CRBIs
Data were insufficient with regards to thrombosis
Studies were insufficiently powered and not well
designed
© 2008 Universitair Ziekenhuis Gent
Liu et al, PLoS ONE 8, e79417, 2013
110
55
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EXIT SITE OINTMENTS
B.5.1: Application of antibiotic ointment at the exit site should be
considered after catheter placement until the insertion site has healed,
but should be discontinued after healing.
B.5.2: With long term exit site and nasal antibiotic ointment
applications, especially of mupirocin, development of resistance
should be taken into account as an effect counterbalancing the
potential benefit of infectious complications.
© 2008 Universitair Ziekenhuis Gent
111
EXIT SITE ANTIBIOTIC APPLICATION – CRBSI
FREQUENCY
© 2008 Universitair Ziekenhuis Gent
Rabindranath et al, NDT, 24: 3763-3774; 2009 112
56
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MUPIROCIN RESISTANCE
© 2008 Universitair Ziekenhuis Gent
Zakrewska-Bode, J Hosp Infect, 31: 189-193; 1995
113
MOST IMPORTANT MESSAGES
Central vein catheters as access are discouraged
If unavoidable they should be tunneled (in CKD)
Antimicrobial locks are advocated but should not replace
hygienic standards
Track records should be kept of infections and their cause
© 2008 Universitair Ziekenhuis Gent
114
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ANTICOAGULATION IN HEMODIALYSIS
R Vanholder, University Hospital, Ghent, Belgium
© 2008 Universitair Ziekenhuis Gent
OPTIMAL ANTICOAGULATION DURING
HEMODIALYSIS
Minimize premature interruption of dialysis
Minimize retention and loss of red blood cells
Maximize dialysis efficiency
Minimize bleeding risk
No adverse effects
Easy handling
Cheap
Additional beneficial effects
© 2008 Universitair Ziekenhuis Gent
116
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ADVERSE EFFECTS
Osteoporosis
Suppression aldosterone
Hyperkalemia
Dyslipidemia
Endothelial dysfunction
Heparin induced thrombocytopenia
Porcine allergy
Reaction to additives
Sulphites, benzyl alcohol, chondroitin sulfate
© 2008 Universitair Ziekenhuis Gent
117
SUMMARY
Unfractionated heparin
Low molecular weight heparin
Citrate
Anticoagulant-free regimes
Heparin-protamine
Fondaparinux
Argatroban
Orgaran/danaparoid
R-hirudin (lepirudin)
© 2008 Universitair Ziekenhuis Gent
118
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ANTI THROMBIN
FROM UPTODATE.COM
© 2008 Universitair Ziekenhuis Gent
119
ANTI THROMBIN
© 2008 Universitair Ziekenhuis Gent
FROM UPTODATE.COM
120
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KINETICS
AVERAGE
AXa/AIIa
EP RANGE
FOR AXa/AIIa
UFH
T1/2
0.5-2 H
TINZAPARIN
6500
1.5
1.5-2.5
DALTEPARIN
6000
2.5
1.9-3.2
ENOXAPARIN
4500
3.9
3.3-5.3
NADROPARIN
4300
3.3
2.5-4.0
2.3 H (HF)
13.9 H (LF)
© 2008 Universitair Ziekenhuis Gent
121
MANUFACTURER INSTRUCTIONS
TINZAPARIN
75 aXaIU/kg
DALTEPARIN
80 aXaIU/kg bolus (up to 4 h)
(30-40 aXaIU/kg bolus + 10-15/kg/h)
ENOXAPARIN
1mg/kg (up to 4 h)
NADROPARIN
<50kg: 0.3ml (2850aXa),
50-69kg: 0.4ml (3800aXa)
>70kg: 0.6ml (5700aXa) (up to 4h)
© 2008 Universitair Ziekenhuis Gent
122
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1
2
3
4
5
6
7
8
9H
© 2008 Universitair Ziekenhuis Gent
123
A META-ANALYSIS DOES NOT SHOW ANY
DIFFERENCE
© 2008 Universitair Ziekenhuis Gent
Lim et al, JASN, 15: 3192-3206; 2004
124
62
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A META-ANALYSIS DOES NOT SHOW ANY
DIFFERENCE
© 2008 Universitair Ziekenhuis Gent
Lim et al, JASN, 15: 3192-3206; 2004
125
HIT (II) IN HEMODIALYSIS
0-12 %
Acute respiratory distress (pulmonary embolism)
Chest pain
Marked clots in circuit (cave: heparin dose not to be
increased)
Thrombocytopenia
Thrombosis
© 2008 Universitair Ziekenhuis Gent
126
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HIT: LMWH (LEFT) VS. STANDARD
© 2008 Universitair Ziekenhuis Gent
Martel et al, Bllod, 106, 2710-2715, 2005
127
ANTICOAGULATION IN CASE OF
BLEEDING TENDENCY
Heparin-free dialysis with saline flushing
Check blood lines
Remove all air from circuit
Easier if coagulation disturbances
Heparin-free dialysis with replacement of filter and blood lines
Heparin-free dialysis with heparin-coated membranes
Evodial
Heparin dialysis neutralized by protamine
Discouraged because of different pharmacokinetics + bleeding
post-dialysis
Citrate dialysis
Necessitates strict protocols and strict adherence to those
protocols
© 2008 Universitair Ziekenhuis Gent
128
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REGIONAL ANTICOAGULATION WITH
CITRATE
1/ Calcium dialysate concentration = 0 mmol/L
2/ Calcium containing dialysate
© 2008 Universitair Ziekenhuis Gent
129
CITRATE: ADVERSE EFFECTS
Hypocalcemia (with PTH increase)
Hypomagnesemia
Metabolic alkalosis
Hypernatremia
Aluminum overload (glass containers)
© 2008 Universitair Ziekenhuis Gent
130
65
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CITRATE: CONTRA-INDICATIONS
LIVER FAILURE, ANHEPATIC PHASE
HYPOCALCEMIA (POST-PTX)
HYPOMAGNESEMIA
© 2008 Universitair Ziekenhuis Gent
131
CONCLUSIONS
Optimal anticoagulation should allow efficient
hemodialysis without adverse effects for a reasonable
cost
LMWH has a more specific effect on the coagulation
system than UFH
Some LMWHs are more short acting and more
convenient for short dialyses (e.g. tinzaparin)
Some are more long acting and more convenient for
long dialyses (e.g. enoxaparin)
There are no differences in complication profile between
LMWH and UFH
Cost of LMWH is considered higher
© 2008 Universitair Ziekenhuis Gent
132
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HAS THE END COME FOR KT/Vurea AS A
MARKER FOR ADEQUACY OF DIALYSIS?
R Vanholder,
University Hospital,
Gent, Belgium
© 2008 Universitair Ziekenhuis Gent
PRO-CON DEBATE KIDNEY INTERNATIONAL
© 2008 Universitair Ziekenhuis Gent
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PRO Kt/V
Titel, logo journal etc
© 2008 Universitair Ziekenhuis Gent
Daugirdas, KI, 88: 466-473; 2015
135
CON Kt/V
© 2008 Universitair Ziekenhuis Gent
Vanholder et al, KI, 88: 460-465; 2015
136
68
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© 2008 Universitair Ziekenhuis Gent
© 2008 Universitair Ziekenhuis Gent
137
138
69
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PRO-CON
PRO
© 2008 Universitair Ziekenhuis Gent
139
PRO-CON
PRO
© 2008 Universitair Ziekenhuis Gent
CON
140
70
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REALITY
PRO
REALITY
CON
© 2008 Universitair Ziekenhuis Gent
141
THE CONCEPTION OF KT/V
© 2008 Universitair Ziekenhuis Gent
Gotch & Sargent, KI, 28: 526-534; 1985
142
71
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KT/V AVOIDS MISCLASSIFYING INADEQUATELY
DIALYZED MALNOURISHED PATIENTS
© 2008 Universitair Ziekenhuis Gent
143
KT/V: CONCEPT
© 2008 Universitair Ziekenhuis Gent
144
72
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KT/V: CONCEPT
© 2008 Universitair Ziekenhuis Gent
145
KT/V: CONCEPT
© 2008 Universitair Ziekenhuis Gent
146
73
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KT/V: CONCEPT
© 2008 Universitair Ziekenhuis Gent
147
KT/V RELATED TO OUTCOMES IN
OBSERVATIONAL STUDIES - DOPPS
© 2008 Universitair Ziekenhuis Gent
Held et al, KI, 50: 550-556; 1996
148
74
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KT/V RELATED TO OUTCOMES IN
OBSERVATIONAL STUDIES - DOPPS
© 2008 Universitair Ziekenhuis Gent
Held et al, KI, 50: 550-556; 1996
149
ALBUMIN AS A STRONGER PREDICTOR
OF RISK OF DEATH THAN KT/V
© 2008 Universitair Ziekenhuis Gent
Owen et al. New Engl J Med 329: 1001-6; 1993
150
75
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ALBUMIN AS A STRONGER PREDICTOR
OF RISK OF DEATH THAN KT/V
© 2008 Universitair Ziekenhuis Gent
Owen et al. New Engl J Med 329: 1001-6; 1993
151
MORTALITY INCREASES WITH SHORTER
DIALYSIS IRRESPECTIVE OF KT/V
© 2008 Universitair Ziekenhuis Gent
Saran et al, KI, 69: 1222-1228; 2006
152
76
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MORTALITY INCREASES WITH SHORTER
DIALYSIS IRRESPECTIVE OF KT/V
© 2008 Universitair Ziekenhuis Gent
Saran et al, KI, 69: 1222-1228; 2006
153
HEMO-STUDY: PRIMARY AND
SECONDARY OUTCOMES
© 2008 Universitair Ziekenhuis Gent
Eknoyan et al, NEJM, 25: 2010-2019; 2002
154
77
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HEMO-STUDY: PRIMARY AND
SECONDARY OUTCOMES
© 2008 Universitair Ziekenhuis Gent
Eknoyan et al, NEJM, 25: 2010-2019; 2002
155
KEY QUESTION: IS UREA KINETICS
REPRESENTATIVE FOR THE KINETIC
BEHAVIOR OF OTHER UREMIC RETENTION
SOLUTES?
© 2008 Universitair Ziekenhuis Gent
78
20/12/2016
THE CONCEPTION OF KT/V
Titel
© 2008 Universitair Ziekenhuis Gent
Gotch & Sargent, KI, 28: 526-534; 1985
157
BASIC PRINCIPLES OF SOLUTE KINETICS
IN DIALYSIS
© 2008 Universitair Ziekenhuis Gent
Vanholder et al, KI, 88: 460-465; 2015
158
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BASIC PRINCIPLES OF SOLUTE KINETICS
IN DIALYSIS
© 2008 Universitair Ziekenhuis Gent
Vanholder et al, KI, 88: 460-465; 2015
159
THREE PHYSICO-CHEMICAL TYPES
Small water soluble (prototype urea): < 500D
Protein-bound (prototype phenols, indoles)
The larger “middle molecules” (prototype ß 2microglobulin): > 500D
© 2008 Universitair Ziekenhuis Gent
160
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MIDDLE MOLECULES
© 2008 Universitair Ziekenhuis Gent
Β2M KINETICS CAUSE HIGH-FLUX POSTDIALYSIS REBOUND
© 2008 Universitair Ziekenhuis Gent
Leypoldt et al, KI, 56: 1571-1577; 1999
162
81
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Β2M KINETICS CAUSE HIGH-FLUX POSTDIALYSIS REBOUND
© 2008 Universitair Ziekenhuis Gent
Leypoldt et al, KI, 56: 1571-1577; 1999
163
MPO-STUDY: SURVIVAL ADVANTAGE
FOR HIGH-FLUX HEMODIALYSIS
© 2008 Universitair Ziekenhuis Gent
Locatelli et al, JASN, 20: 645-654; 2009
164
82
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MPO STUDY
Kaplan-Meier Survival Analysis
© 2008 Universitair Ziekenhuis Gent
Locatelli et al, JASN, 20: 645-654; 2009
165
MPO
© 2008 Universitair Ziekenhuis Gent
Locatelli et al, JASN, 20: 645-654; 2009
166
83
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MPO
© 2008 Universitair Ziekenhuis Gent
Locatelli et al, JASN, 20: 645-654; 2009
167
MPO-STUDY: SURVIVAL ADVANTAGE
FOR HIGH-FLUX HEMODIALYSIS
© 2008 Universitair Ziekenhuis Gent
Locatelli et al, JASN, 20: 645-654; 2009
168
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WHAT DO WE NOT REGISTER BY Kt/V
Concentration changes attributable to:
Increase in dialyser pore size/convection for larger and
protein bound molecules
Intercompartmental shifts due to longer or more frequent
dialysis
Different removal due to different compartmental shift
pattern
Metabolic factors
Intestinal generation/absorption
© 2008 Universitair Ziekenhuis Gent
169
CAN WE DISCARD Kt/Vurea?
NO, WE CAN’T!
© 2008 Universitair Ziekenhuis Gent
170
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CAN WE DISCARD Kt/Vurea?
NO, WE CAN’T!
Because of:
- Relation of urea removal to
potassium removal
- Own toxicity of urea
- Relation of urea to carbamylation
- Detection of novel small water
soluble uremic toxins
© 2008 Universitair Ziekenhuis Gent
171
RELATION UREA AND POTASSIUM
REMOVAL
© 2008 Universitair Ziekenhuis Gent
Gutzwiller et al, Clin Nephrol, 59: 130-136; 2003
172
86
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RELATION UREA AND POTASSIUM
REMOVAL
© 2008 Universitair Ziekenhuis Gent
Gutzwiller et al, Clin Nephrol, 59: 130-136; 2003
173
UREA DISRUPTS INTESTINAL WALL
PROTECTIVE BARRIER
© 2008 Universitair Ziekenhuis Gent
Vaziri et al, Am J Nephrol, 37: 1-6; 2013
174
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UREA DISRUPTS INTESTINAL WALL
PROTECTIVE BARRIER
Figure 1
Bar graphs depicting the
TER (transepithelial
electrical resistance) in
intestinal epithelial T84
cell monolayers
incubated for 24 h in
regular media and those
incubated in media
containing 42 or 72
mg/dl urea. *** p <
0.001.
© 2008 Universitair Ziekenhuis Gent
Vaziri et al, Am J Nephrol, 37: 1-6; 2013
175
UREA IS RELATED TO CARBAMYLATION
© 2008 Universitair Ziekenhuis Gent
Velasquez et al, KI, 87, 1092-1094, 2015
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UREA IS RELATED TO CARBAMYLATION
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TMAO ENHANCES ATHEROGENESIS
© 2008 Universitair Ziekenhuis Gent
Wang et al, Nature, 472: 57-63; 2011 178
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TMAO ENHANCES ATHEROGENESIS
Metabolomic analysis unraveled
TMAO as linked to vascular
disease
Sources of TMAO: Choline,
fosfatidyl choline, betaine
Red meat, shellfish, eggs, dairy
products
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CONCLUSIONS
Kt/V urea is used as an index of dialysis adequacy since
several decades
Its relevance has been debated for many reasons
The relatively weak proof of toxicity of urea
The different kinetics of several solutes with proven toxicity as
compared to urea
Its incompetence to grasp all aspects that influence uremic
solute concentration in dialysis patients
Yet, Kt/V cannot be discarded as adequacy marker, but
we have to take into account its weaknesses
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