Adequacy of Hemodialysis Data from HENNET.

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Adequacy of HemodialysisData from HENNET.

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HENNET project
HEmodialysis Network of the North-East of Thailand
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Agenda

• What is Adequacy of HD
• Data from HENNET Project
• Kt/V Do we really need it ?

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Dr. John T. Daugirdas
Dr. Daugirdas is Professor of Medicine at
the University of Illinois at Chicago.
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What is Adequacy of Hemodialysis ?

• Adequacy of dialysis refers to how well we
  remove toxins and waste products from the
  patients blood, and has a major impact on their
  well-being.

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How do we know if a Patient is Adequately
Dialyzed ?

• Urea Kinetic Modeling
• Why cant I understand it ?
• It cant be that difficult !

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WHY UREA ?

• MW 60, only slightly toxic per se
• a MARKER for small MW uremic toxins
• Urea removal lt ---gt other small toxin removal

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WHY UREA ?

• MW 60, only slightly toxic per se
• a MARKER for small MW uremic toxins
• Urea removal lt ---gt other small toxin removal
• g rate of UREA generation
• g lt ---gt protein catabolic rate (PCR)
• PCR lt ---gt dietary protein intake ?
• g can be derived from pre and post BUN

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• Monitoring the patients urea
• Predialysis BUN or Time-averaged BUN
• BAD if HIGH, also BAD if too LOW!
• Reflect balance of urea removal vs.
• production

BUNpre
BUN (mg/dl)
BUNpost
Time (hour)
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• Monitoring the patients urea
• Predialysis BUN or Time-averaged BUN
• BAD if HIGH, also BAD if too LOW!
• Reflect balance of urea removal vs.
• production

BUNpre
BUN (mg/dl)
BUNpost
Time (hour)
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• Monitoring the patients urea
• Predialysis BUN or Time-averaged BUN
• BAD if HIGH, also BAD if too LOW!
• Reflect balance of urea removal vs.
• production

BUNpre
BUN (mg/dl)
TAC BUN
BUNpost
Time (hour)
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Monitoring the patients urea

• URR or Kt/V
• URR (Upre Upost) x 100
• Upre
• Reflect removal of urea and other toxins
• PRIMARY monitors of dialysis adequacy

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What is Kt/V ?

• Kt/V fractional urea clearance
• K dialyzer clearance (ml/min or L/hr)
• t time (min or hr)
• V distribution volume of urea (ml or L)
• K x t L/hr x hr LITERS
• V LITERS
• Kt/V LITERS/LITERS ratio

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K 10 L/Hr
V 40 liters
BUN 80
BUN 0
K . t
Holding Tank Model
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V 40 liters
BUN 80
BUN 0
K . t
Holding Tank Model
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V 40 liters
BUN 80
BUN 0
20 L
K t
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V 40 liters
BUN 80
BUN 0
Kt/V 20 / 40 0.50
20 L
K t
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V 40 liters
BUN 80
BUN 0
Kt/V 20 / 40 0.50 Post BUN
40 URR (pre-post) / pre
(80-40) / 80 0.50
20 L
K t
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V 40 liters
BUN 80, 70, 60
BUN 0
K . t
Dialyzer outlet fluid returned continually during
dialysis
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Relationship between Kt/V and URR
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Kt/V
spKt/V single pool eqKt/V equilibrated
(Double pool) Std Kt/V weekly standard
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Post-Dialysis rebound
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Post-Dialysis rebound
Equilibrated Kt/V
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Kt/V
spKt/V single pool eqKt/V equilibrated
(Double pool) Std Kt/V weekly standard
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What is the target spKt/V in 2 times/week HD
patients ?
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K/DOQI 2006 Minimum spKt/V
Schedule Krlt2 ml/min/1.73m2 Krgt2 ml/min/1.73m2
2x/wk Not recommended 2.0
3x/wk 1.2 0.9
4x/wk 0.8 0.6
6x/wk 0.5 0.4
Dialyzer clearance only not recommended unless
Kr gt 3
K/DOQI CPG for Hemodialysis Adequacy update
2006. Am J Kidney Dis 2007 37 S7-S64.
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K/DOQI Methods for Post Dialysis Blood Sampling

• Both samples should be drawn during the same
  session.
• Predialysis BUN should be drawn before treatment
  began.
• Postdialysis BUN, Avoid access recirculation by
• Slow flow to 100 ml/min for 15 seconds

K/DOQI CPG for Hemodialysis Adequacy update
2006. Am J Kidney Dis 2007 37 S7-S64.
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Data from HENNET.
Exploring Mortality based on Kt/V among ESRD
patients undergoing Twice-weekly Hemosialysis
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Setting
HENNET
Multi-center cohort study

• 11 hemodialysis centers
• Accrual period 3 months
• from Feb. 2011
• Follow up period 1 years

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Part1 Baseline Part2 Follow up Part3
Hospitalization note Part4 Discharge summary
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HENNET
Study design overview
Lab record 2 monthly
HD 2/wk
1 year
Outcomes Disease-related Death
Enrollment

• Inclusion
• Age 18 80 years
• HD gt 3 months.
• Exclusion
• Pregnancy, Breast feeding
• Advance malignancy
• Bed-ridden status

Censor Kidney transplantation Shift to
peritoneal dialysis Refer to other centers Change
frequency Death from accident
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HENNET
Results
HD 2/wk
1 year
Enrollment 504
Death 33
6,928 patients-months were observed. Mortality
rate 4.8 / 1,000 patient-months.
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Table1. Baseline characteristics
HENNET
Characters Survivors N471 Non-survivors N33
Male 276 (58.6) 15 (45.5)
Age, year 54.9 13.8 66.1 10.6
Married 365 (77.5) 24 (72.7)
ICED score 1.2 0.7 1.8 0.9
Causes of ESRD Diabetes Hypertension Glomerulonephritis Obstructive uropathy Gout Cystic disease Unknown 144 (30.6) 90 (19.1) 31 (6.6) 29 (6.2) 28 (5.9) 6 (1.3) 142 (30.2) 16 (48.5) 8 (24.2) 1 (3) - 3 (9.1) - 5 (15.2)
Time on HD, month 40.6 31.3 38.4 28.0
Anuria (lt100ml/day) 228 (48.4) 15 (45.5)
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HENNET
Kt/V by Age
1.70.3
1.70.4
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HENNET
Distribution of Kt/V
Mean 1.70.3
Range 0.67 2.83
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HENNET
Distribution of Kt/V
Adequate HD 20.6
Mean 1.70.3
Range 0.67 2.83
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Hemodialysis patients with adequate dialysis
(URRgt65)
CMS ESRD Clinical Performance Measures Project,
2001-2002. Centers for Medicare Medicaid
Services, ESRD Clinical Performance Measures
Project, 2002-2006.
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HENNET
Kt/V among women and men
Kt/V
2.4
2.0
1.90.3
1.6
1.60.3
1.2
0.8
P lt 0.001
0.4
Women 214(42.5)
Men 290(57.5)
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HENNET
Kt/V by numbers of Dialyzer Reuse
N
200
44.6
55.4
150
160
152
127
100
50
65
lt 15
15
gt 20
No. of Reuse
16-20
Range 0 30
40
HENNET
Kt/V by numbers of Dialyzer Reuse
N
200
150
100
50
lt 15
15
gt 20
No. of reuse
16-20
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HENNET
Prediction of Dead by numbers of Dialyzer Reuse
16-20
gt 20
lt 15
15
No. of Reuse
Dead rate 0.03 0.06
0.08 0.11
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Hemodialysis Prescription Determines Adequacy

• Hemodialysis component
• Duration of Treatment
• Dialyzer Urea Clearance (KOA)
• Blood Flow
• Dialysate Flow
• Heparinization
• Access

Adequacy of Treatment is Everyones Concern !
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Improving Adequacy of Hemodialysis It Takes a
Team.
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Kt/V Do we really need it ?
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Mortality Risk by Kt/V
Categorical and Linear Estimates, 1991
RR 0.93 / 0.1 Kt/V ( p lt 0.01)
RR
1.5
1.5
1.0
0.5
0.0

0.8
1.0
1.2
1.4
1.6
1.0
1.20 p0.11

Kt/V

1.00 (rel)
0.87 p0.26


0.71 p0.01
0.69 p0.01
0.5
N
463
462
462
462
462
0.0
lt 0.91
0.91-1.05
1.06-1.16
1.17-1.32
1.33
Delivered
Kt/V (Quintiles) From the Pre/Post BUN and
Pre/Post Weight. N 2,311, Thrice Weekly
only.
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P 0.53
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HENNET
Kt/V among survivors and non-survivors
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HENNET
Kt/V gt 2 Kt/V lt 2
Log rank test, P0.41
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HENNET
Kt/V gt 2 Kt/V lt 2
1 year survival 94
Log rank test, P0.41
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HENNET
Survival probability among patients with Kt/Vgt2
and lt2 according to diabetic status
Kt/V gt 2 Kt/V lt 2
Kt/V gt 2 Kt/V lt 2
HR 1.64 (0.38-7.13), p0.5
HR 1.0 (0.28-3.75), p0.9
DM
Non DM
adjusted for age
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HENNET
Relative Risk of Death by Kt/V quartiles
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HENNET
Figure 15. Cox proportional hazard ratios and
their 95 CI, adjusted for age, among women
undergoing twice-weekly HD with Kt/V lt versus gt
1.4, lt versus gt 1.6, lt versus gt 1.8, lt versus gt
2.0, lt versus gt 2.2.
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HENNET
Prognostic factors of Deaths
Factors Unadjusted HR Adjusted HR 95CI P-value

Kt/V, per 1 unit decrease 1.7 1.9 1.2 1.4 0.5-6.4 0.4-4.1 0.4-4.8 0.32 0.76 0.56

Serum albumin, per 1 g/dl decrease 3.1 2.5 1.2-5.1 0.01
Current smoker 5.3 19.3 4.8-76.9 lt 0.001

Table 9. Unadjusted and adjusted hazard ratio of
death using Cox regression model. P-value from
partial likely hood ratio test, adjusted for age,
ICED, time on dialysis and dialysis
centers. Adjusted HR considering effect of
albumin level Adjusted HR considering effect of
smoking Adjusted HR considering effects of
albumin level and smoking
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Kt/V Do we really need it ?
May be, there are stronger predictors of
mortality.
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Take Home Message !!

• 1. Adequacy of dialysis is based on Kt/V and URR.

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Take Home Message !!

• 1. Adequacy of dialysis is based on Kt/V and URR.
• 2. Kt/V and URR are mathematically linked.

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Take Home Message !!

• 1. Adequacy of dialysis is based on Kt/V and URR.
• 2. Kt/V and URR are mathematically linked.
• 3. For HD 2/week Target spKt/V 2, Kr gt 2
  ml/min/1.73m2

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Take Home Message !!

• 1. Adequacy of dialysis is based on Kt/V and URR.
• 2. Kt/V and URR are mathematically linked.
• 3. For HD 2/week Target spKt/V 2, Kr gt 2
  ml/min/1.73m2
• 4. For HD 3/week Target spKt/V 1.2, URRgt65.

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Take Home Message !!
HENNET

• 5. Data from
• Only 20.6 is adequately dialyzed, Kt/Vgt2.

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Take Home Message !!
HENNET

• 5. Data from
• Only 20.6 is adequately dialyzed, Kt/Vgt2.
• Mean Kt/V of women is significantly higher than
  that of men.

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Take Home Message !!
HENNET

• 5. Data from
• Only 20.6 is adequately dialyzed, Kt/Vgt2.
• Mean Kt/V of women is significantly higher than
  that of men.
• Increase No. of Reuse related to an increase
  mortality in a linear prediction.

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Take Home Message !!
HENNET

• 5. Data from
• Only 20.6 is adequately dialyzed, Kt/Vgt2.
• Mean Kt/V of women is significantly higher than
  that of men.
• Increase No. of Reuse related to an increase
  mortality in a linear prediction.
• Higher Kt/V quartiles trend to have lower RR for
  death.

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Take Home Message !!
HENNET

• 5. Data from
• Only 20.6 is adequately dialyzed, Kt/Vgt2.
• Mean Kt/V of women is significantly higher than
  that of men.
• Increase No. of Reuse related to an increase
  mortality in a linear prediction.
• Higher Kt/V quartiles trend to have lower RR for
  death.
• Suggested target Kt/V gt 1.8 for Thai women on
  2HD/wk.

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Take Home Message !!
HENNET

• 5. Data from
• Only 20.6 is adequately dialyzed, Kt/Vgt2.
• Mean Kt/V of women is significantly higher than
  that of men.
• Increase No. of Reuse related to an increase
  mortality in a linear prediction.
• Higher Kt/V quartiles trend to have lower RR for
  death.
• Suggested target Kt/V gt 1.8 for Thai women on
  2HD/wk.
• Predictors of death are SMOKING and ALBUMIN
  level.

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Take Home Message !!

• 6. spKt/V is a current marker for monitoring
• HD adequacy.

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Acknowledgements Grant supports

• The Royal College of Physician of Thailand
• The Medical Association of Thailand
• The Kidney Foundation of Thailand

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Thank you for your attention
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HENNET
Cox proportional hazard ratios and their 95 CI,
adjusted for age, among patients With Kt/V lt
versus gt 1.4, lt versus gt 1.6, lt versus gt 1.8, lt
versus gt 2.0, lt versus gt 2.2.
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HENNET
Kt/V by BMI classes
Percent
100
80
60
60
40
20
15.1
12.7
11.9
BMI
lt 18.5
18.5-25
gt 30
25-30
Obese
Normal
Overweight
Underweight
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HENNET
Kt/V by BMI classes
1.9
1.7
1.7
1.5
P0.00
P0.00
BMI
lt 18.5
18.5-25
gt 30
25-30
Obese
Normal
Overweight
Underweight
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Factors affect spKt/V
HENNET
Kt/Vgt1.7 N245(48.6) Kt/Vlt1.7 N259(51.4) P
BMI, kg/m2 20.62.9 22.43.3 0.00
Incidence HD, lt 12 mo. 23 (9.4) 45 (17.4) 0.01
Dialyzer membrane Semi-synthetic 99 (40.4) 101 (39) 0.75
Low Flux Dialyzer 82 (33.5) 97 (34.5) 0.35
Dialyzer Surface area 1.760.2 1.80.2 0.04
No. of Dialyzer Reuse 17.15.5 15.65.1 0.00
Blood Flow, ml/min 324.251 297.946.9 0.00
Dialysate flow, ml/min 537.998.3 517.764 0.01
DM 71 (28.9) 107 (60.1) 0.00
Current Smoking 5 (2.0) 12 (4.6) 0.08
Plt0.05
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Factors affect spKt/V
HENNET
Kt/Vgt1.7 N245(48.6) Kt/Vlt1.7 N259(51.4) P
BMI, kg/m2 20.62.9 22.43.3 0.00
Incidence HD, lt 12 mo. 23 (9.4) 45 (17.4) 0.01
Dialyzer membrane Semi-synthetic 99 (40.4) 101 (39) 0.75
Low Flux Dialyzer 82 (33.5) 97 (34.5) 0.35
Dialyzer Surface area 1.760.2 1.80.2 0.04
No. of Dialyzer Reuse 17.15.5 15.65.1 0.00
Blood Flow, ml/min 324.251 297.946.9 0.00
Dialysate flow, ml/min 537.998.3 517.764 0.01
DM 71 (28.9) 107 (60.1) 0.00
Current Smoking 5 (2.0) 12 (4.6) 0.08
Plt0.05 in Multivariate Analysis
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Factors affect spKt/V
HENNET
Kt/V lt 1.7
Coef. 95CI P
BMI, kg/m2 0.20 0.13 to 0.27 0.000
No. of Dialyzer Reuse -0.06 -0.02 to -0.10 0.003
Blood Flow, ml/min -0.01 -0.006 to -0.014 0.000
Every 1 increase in BMI will increase 20 of
Kt/Vlt1.7
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• NIH Hemo Study
• URR of about 67 vs. about 75
• spKt/V of 1.3 vs. 17
• eKt/V of about 1.05 vs. 1.45
• Also will compare small-pore (low-flux)
• vs. large-pore (high flux) membranes
• Endpoints mortality, hospitalization,
• fall in dry weight

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HD adequacy dose
K dialyzer clearance
t duration of HD V volume distribution of urea
K/DOQI CPG for Hemodialysis Adequacy update
2006. Am J Kidney Dis 2007 37 S7-S64.
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Post-Dialysis rebound
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Relationship of eKt/V to spKt/V
eKt/V spKt/V (t/(tC)
C35 min if artery, 22 min if vein
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Std Kt/V, spKt/V and Dialysis frequencies per week
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Associated causes of death
Causes of Death N
Cardiovascular 14 42.4
Infection 11 33.3
Cerebrovascular 2 6.1
Malignancy 2 6.1
Other GI bleeding Bleeding diverticulosis Dialysis withdrawal Car accident 1 1 1 1 3 3 3 3
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Outcomes
Outcomes N
Death 33 34.7
Refer to other centers 27 28.4
Change frequency 13 13.7
Shift to CAPD 10 10.5
Kidney transplantation 6 6.3
Loss to follow up 6 6.3
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• Indices of Urea Removal
• Kt/V
• Reflects urea removal
• NCDS suggested Kt/V must be gt 0.90
• Population studies suggest Kt/V should begt
• 1.2
• URR
• Also reflects urea removal
• Current goal is a URR gt 65

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Sample
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2.0






Relative Mortality Risk
1.8
R (post / pre BUN)
gt0.55
1.6
0.50-0.55
1.4
0.45-0.50
1.2
lt 0.30
0.40-0.45
0.30-0.35
0.35-0.40
1.0


0.8
lt 0.70 0.75 0.88
1.0 1.15 1.3
gt1.4
Approximate Kt/V
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HENNET
Incidence and Prevalence Hemodialysis
Percent
100
436
80
(86.5)
1.5
60
40
P1.00
68
20
(13.5)
Incidence HD lt 12 mo.
Prevalence HD gt 12 mo.
90
HENNET
Kt/V by Incidence and Prevalence Hemodialysis
1.72 (1.69 to 1.74)
1.54 (1.46 to 1.61)
P0.00
Incidence HD lt 12 mo.
Prevalence HD gt 12 mo.