1. Adequacy of Hemodialysis Data from HENNET.
นพ.ธนชัย พนาพุฒิ
อายุรแพทย์โรคไต รพศ.ขอนแก่น
5 กค. 2556

2. HENNET project HEmodialysis Network of the North-East of Thailand
นพ.ธนชัย พนาพุฒิ นพ.จิรศักดิ์ อนุกุลกนันต์ชัย รพ.ขอนแก่น
รศ.นพ.ทวี ศิริวงศ์ รศ.นพ.ชลธิป พงศ์สกุล รศ.พญ.ศิริรัตน์ เรืองจุ้ย รพ.ศรีนครินทร์
นพ. พิสิฐ อินทรวงษ์โชติ รพ.หนองคาย
นพ. สุรพงษ์ นเรนทร์พิทักษ์ รพ.อุดรธานี
นพ. สัจจะ ตติยานุพันธ์วงศ์ รพ.ชัยภูมิ
พญ. ลักษมณ ประเดิม รพ.ร้อยเอ็ด
นพ. ชวศักดิ์ กนกกัณฑ์พงษ์ รพ.มหาราชนครราชสีมา
พญ. กรรณิการ์ นิวัตยกุล รพ.เลย
นพ. ปกรณ์ ตุงคะเสรีรักษ์ รพ.สุรินทร์
นพ. อมฤต สุวัฒนศิลป์ รพ.มหาสารคาม
พญ. ทัดสะรัง แก้วบุนมา รพ.ท่าบ่อ
The HENNET project stand for Hemodialysis network of the North-eastern Thailand derived from the network of local nephrologist. We create research and share together.

3. Agenda
What is Adequacy of HD
Data from HENNET Project
Kt/V: Do we really need it ?

4. Dr. John T. Daugirdas
Dr. Daugirdas is Professor of Medicine at the
University of Illinois at Chicago.

5. What is Adequacy of Hemodialysis ?
Adequacy of dialysis refers to how well we remove toxins and waste products from the patient’s blood, and has a major impact on their well-being.

6. How do we know if a Patient is Adequately Dialyzed ?
Urea Kinetic Modeling
Why can’t I understand it ?
It can’t be that difficult !

7. WHY UREA ?
MW 60, only slightly toxic per se a MARKER for small MW uremic toxins Urea removal < ---> other small toxin removal

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

9. Monitoring the patient’s 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)

10. Monitoring the patient’s 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)

11. Monitoring the patient’s 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)

12. Monitoring the patient’s urea
URR or Kt/V
URR% : (Upre – Upost) x 100
Upre
Reflect removal of urea and other toxins
PRIMARY monitors of dialysis adequacy

13. 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

14. K = 10 L/Hr
V = 40 liters
BUN = 80
BUN = 0
K . t
Holding Tank Model

15. V = 40 liters K . t Holding Tank Model BUN = 80 BUN = 0 URR Kt/V 0.63
1.0
0.63
URR
BUN = 0
K . t
Holding Tank Model

16. V = 40 liters
BUN = 80
BUN = 0
K t =
20 L

17. V = 40 liters
BUN = 80
BUN = 0
Kt/V = 20 / 40
= 0.50
K t =
20 L

18. V = 40 liters 20 L BUN = 80 BUN = 0 Kt/V = 20 / 40 = 0.50 K t =
Post BUN = 40
URR = (pre-post) / pre
= (80-40) / 80
= 0.50
K t =
20 L

19. V = 40 liters
BUN = 80, 70, 60
BUN = 0
K . t
Dialyzer outlet fluid returned continually during dialysis

20. Relationship between Kt/V and URR

21. Kt/V spKt/V = single pool eqKt/V = equilibrated (Double pool)
Std Kt/V = weekly standard

22. Post-Dialysis rebound

23. Post-Dialysis rebound
Equilibrated Kt/V

24. Kt/V spKt/V = single pool eqKt/V = equilibrated (Double pool)
Std Kt/V = weekly standard

25. What is the target spKt/V in
2 times/week HD patients ?

26. K/DOQI 2006: Minimum spKt/V
Schedule
Kr<2 ml/min/1.73m2
Kr>2 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 > 3
K/DOQI CPG for Hemodialysis Adequacy: update 2006.
Am J Kidney Dis 2007; 37: S7-S64.

27. 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.

28. Data from HENNET. Exploring Mortality based on Kt/V
among ESRD patients undergoing
Twice-weekly Hemosialysis

29. Setting HENNET Multi-center cohort study * ** 11 hemodialysis centers
Accrual period 3 months
from Feb. 2011
Follow up period 1 years

30. Part1 Baseline
Part2 Follow up
Part3 Hospitalization note
Part4 Discharge summary

31. HENNET Study design overview HD 2/wk 1 year Outcomes:
Lab record 2 monthly
HD 2/wk
1 year
Outcomes:
Disease-related Death
Enrollment
Inclusion
Age 18 – 80 years
HD > 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

32. HENNET Results 504 33 HD 2/wk 1 year Enrollment Death
6,928 patients-months were observed.
Mortality rate 4.8 / 1,000 patient-months.

33. Table1. Baseline characteristics
HENNET
Table1. Baseline characteristics
Characters
Survivors
N=471
Non-survivors
N=33
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 (<100ml/day)
228 (48.4%)

34. HENNET
Kt/V by Age
1.7±0.4
1.7±0.3

35. HENNET
Distribution of Kt/V
Mean
1.7±0.3
Range 0.67 – 2.83

36. HENNET Distribution of Kt/V Adequate HD 20.6% Mean 1.7±0.3
Range 0.67 – 2.83

37. Hemodialysis patients with adequate dialysis (URR>65%)
CMS ESRD Clinical Performance Measures Project,
Centers for Medicare & Medicaid Services, ESRD Clinical Performance Measures Project,

38. HENNET Kt/V among women and men 1.9±0.3 1.6±0.3 Kt/V Women 214(42.5%)
2.4
2.0
1.9±0.3
1.6
1.6±0.3
1.2
0.8
P < 0.001
0.4
Women
214(42.5%)
Men
290(57.5%)

39. HENNET Kt/V by numbers of Dialyzer Reuse 55.4% 44.6% Range 0 – 30 160
200
55.4%
44.6%
150
160
152
127
100 50 65
< 15 15
16-20
> 20
No. of Reuse
Range 0 – 30

40. HENNET Kt/V by numbers of Dialyzer Reuse Kt/V 2 1.5 1 0.5 No. of reuse
200
150
100 50
< 15 15
16-20
> 20
No. of reuse

41. HENNET Prediction of Dead by numbers of Dialyzer Reuse No. of Reuse
< 15 15
16-20
> 20
Dead rate

42. Hemodialysis Prescription Determines Adequacy
Hemodialysis component:
Duration of Treatment
Dialyzer Urea Clearance (KOA)
Blood Flow
Dialysate Flow
Heparinization
Access
Adequacy of Treatment is Everyone’s Concern !

43. Improving Adequacy of Hemodialysis:
It Takes a Team.

44. Kt/V :
Do we really need it ?

45. Categorical and Linear Estimates, 1991
Mortality Risk by Kt/V
Categorical and Linear Estimates, 1991
RR = / 0.1 Kt/V
( p < 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
p=0.11
Kt/V
1.00
(rel)
0.87
p=0.26
0.71
p=0.01
0.69
p=0.01
0.5
N =
463
462
462
462
462
0.0
< 0.91
1.33 +
Delivered Kt/V* (Quintiles)
* From the Pre/Post BUN and Pre/Post Weight. N = 2,311,
Thrice Weekly only.

46. P = 0.53

47. HENNET Kt/V among survivors and non-survivors 1.65 1.7 Survivors
0.4
0.8
1.2
1.6
2.0
2.4
Survivors
Non-survivors
Kt/V
1.65
( )
1.7
( )
P=0.52

48. HENNET
Kt/V > 2
Kt/V < 2
Log rank test, P=0.41

49. HENNET 1 year survival 94% Kt/V > 2 Kt/V < 2
Log rank test, P=0.41

50. HENNET
Survival probability among patients with Kt/V>2 and <2
according to diabetic status
Kt/V > 2
Kt/V < 2
Kt/V > 2
Kt/V < 2
HR 1.0 ( ), p=0.9*
HR 1.64 ( ), p=0.5*
Non DM DM
*adjusted for age

51. HENNET Relative Risk of Death by Kt/V quartiles Kt/V
0.4
0.8
1.2
1.6
2.0
2.4
0.67 – 1.45
1.46 – 1.67
1.68 – 1.9
1.91 – 2.83
Kt/V
0.62
1.04
0.75
Hazard ratio of death

52. HENNET
Figure 15. Cox proportional hazard ratios and their 95% CI, adjusted for age, among women
undergoing twice-weekly HD with
Kt/V < versus > 1.4, < versus > 1.6, < versus > 1.8, < versus > 2.0, < versus > 2.2.

53. HENNET Prognostic factors of Deaths
Unadjusted HR
Adjusted HR
95%CI
P-value*
Kt/V,
per 1 unit decrease
1.7
1.9†
1.2‡
1.4¶
0.32
0.76
0.56
Serum albumin,
per 1 g/dl decrease
3.1
2.5
0.01
Current smoker
5.3
19.3
< 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

54. May be, there are stronger predictors of mortality.
Kt/V :
Do we really need it ?
May be, there are stronger predictors of mortality.

55. Take Home Message !!
1. Adequacy of dialysis is based on Kt/V and URR.

56. Take Home Message !!
1. Adequacy of dialysis is based on Kt/V and URR. 2. Kt/V and URR are mathematically linked.

57. 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 > 2 ml/min/1.73m2

58. 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 > 2 ml/min/1.73m2
4. For HD 3/week: Target spKt/V 1.2, URR>65%.

59. Take Home Message !! HENNET 5. Data from
Only 20.6% is adequately dialyzed, Kt/V>2.

60. Take Home Message !! HENNET 5. Data from
Only 20.6% is adequately dialyzed, Kt/V>2.
Mean Kt/V of women is significantly higher than that of men.

61. Take Home Message !! HENNET 5. Data from
Only 20.6% is adequately dialyzed, Kt/V>2.
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.

62. Take Home Message !! HENNET 5. Data from
Only 20.6% is adequately dialyzed, Kt/V>2.
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.

63. Take Home Message !! HENNET 5. Data from
Only 20.6% is adequately dialyzed, Kt/V>2.
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 > 1.8 for Thai women on 2HD/wk.

64. Take Home Message !! HENNET 5. Data from
Only 20.6% is adequately dialyzed, Kt/V>2.
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 > 1.8 for Thai women on 2HD/wk.
Predictors of death are SMOKING and ALBUMIN level.

65. Take Home Message !!
6. spKt/V is a current marker for monitoring HD adequacy.

66. Acknowledgements : Grant supports
The Royal College of Physician of Thailand
The Medical Association of Thailand
The Kidney Foundation of Thailand

67. Thank you for your attention

68. HENNET
Cox proportional hazard ratios and their 95% CI, adjusted for age, among patients
With Kt/V < versus > 1.4, < versus > 1.6, < versus > 1.8, < versus > 2.0, < versus > 2.2.

69. HENNET Kt/V by BMI classes 60 15.1 BMI Percent 12.7 11.9 < 18.5
100 80 60 60 40 20
15.1
12.7
11.9
BMI
< 18.5
25-30
> 30
Normal
Obese
Underweight
Overweight

70. HENNET Kt/V by BMI classes Kt/V 2 1 0.5 1.5 1.9 1.7 1.7 1.5 BMI
P=0.00
P=0.00
BMI
< 18.5
25-30
> 30
Normal
Obese
Underweight
Overweight

71. HENNET Factors affect spKt/V Kt/V>1.7 Kt/V<1.7 N=259(51.4%) P
BMI, kg/m2
20.6±2.9
22.4±3.3
0.00
Incidence HD, < 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
1.76±0.2
1.8±0.2
0.04
No. of Dialyzer Reuse
17.1±5.5
15.6±5.1
Blood Flow, ml/min
324.2±51
297.9±46.9
Dialysate flow, ml/min
537.9±98.3
517.7±64 DM
71 (28.9%)
107 (60.1%)
Current Smoking
5 (2.0%)
12 (4.6%)
0.08
P<0.05

72. HENNET Factors affect spKt/V Kt/V>1.7 Kt/V<1.7 N=259(51.4%) P
BMI, kg/m2
20.6±2.9
22.4±3.3
0.00*
Incidence HD, < 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
1.76±0.2
1.8±0.2
0.04
No. of Dialyzer Reuse
17.1±5.5
15.6±5.1
Blood Flow, ml/min
324.2±51
297.9±46.9
Dialysate flow, ml/min
537.9±98.3
517.7±64 DM
71 (28.9%)
107 (60.1%)
0.00
Current Smoking
5 (2.0%)
12 (4.6%)
0.08
*P<0.05 in Multivariate Analysis

73. HENNET Factors affect spKt/V Kt/V < 1.7 Coef. 95%CI 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 to
Every 1 increase in BMI will increase 20% of Kt/V<1.7

74. NIH Hemo Study spKt/V of 1.3 vs. 17 eKt/V of about 1.05 vs. 1.45
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

75. HD adequacy : dose K: dialyzer clearance t: duration of HD
Hemodialysis dose which reflect adequacy of dialysis Kt/V was suggested by the The National Kidney Foundation Kidney Disease Outcome Quality Initiative .
: urea clearance determined by urea kinetic modeling
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.

76. Post-Dialysis rebound

78. eKt/V = spKt/V [(t/(t+C)]
Relationship of eKt/V to spKt/V
eKt/V = spKt/V [(t/(t+C)]
C=35 min if artery, 22 min if vein

79. Std Kt/V, spKt/V and Dialysis frequencies per week

80. Associated causes of deathN %
Cardiovascular 14
42.4
Infection 11
33.3
Cerebrovascular 2
6.1
Malignancy
Other
GI bleeding
Bleeding diverticulosis
Dialysis withdrawal
Car accident 1 3

81. 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

82. Indices of Urea Removal
Kt/V
Reflects urea removal
NCDS suggested Kt/V must be > 0.90
Population studies suggest Kt/V should be>
1.2
URR
Also reflects urea removal
Current goal is a URR > 65 %

85. Sample

88. Relative Mortality Risk R (post / pre BUN)
2.0
Relative Mortality Risk
1.8
>0.55
R (post / pre BUN)
1.6
1.4
1.2
< 0.30
1.0
0.8
< >1.4
Approximate Kt/V

89. HENNET Incidence and Prevalence Hemodialysis 436 68 Incidence HD
Percent
100
436 80
(86.5%)
1.5 60 40
P=1.00 20 68
(13.5%)
Incidence HD
<= 12 mo.
Prevalence HD
> 12 mo.

90. HENNET Kt/V by Incidence and Prevalence Hemodialysis 1.72 1.54
0.5
1.5
1.72
(1.69 to 1.74)
1.54
(1.46 to 1.61)
P=0.00
Incidence HD
<= 12 mo.
Prevalence HD
> 12 mo.