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Adequacy of Hemodialysis

Data from HENNET.

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5 ก่ค. 2556

HENNET projectHEmodialysis 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 ?

Dr. John T. Daugirdas

Dr. Daugirdas is Professor of Medicine at theUniversity of Illinois at Chicago.

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.

How do we know if a Patient is Adequately Dialyzed ?

Urea Kinetic ModelingWhy can’t I understand it ?

It can’t be that difficult !

MW 60, only slightly toxic per sea MARKER for small MW uremic toxinsUrea removal < ---> other small toxin

removal

WHY UREA ?

MW 60, only slightly toxic per sea MARKER for small MW uremic toxinsUrea removal < ---> other small toxin

removalg = rate of UREA generation

g < ---> protein catabolic rate (PCR)PCR < ---> dietary protein intake ?g can be derived from pre and post BUN

WHY UREA ?

Monitoring the patient’s ureaPredialysis BUN or Time-averaged BUN

BAD if HIGH, also BAD if too LOW!Reflect balance of urea removal vs.production

BUNpre

BUNpost

BUN(mg/dl)

Time (hour)

TAC BUN

Monitoring the patient’s ureaPredialysis BUN or Time-averaged BUN

BAD if HIGH, also BAD if too LOW!Reflect balance of urea removal vs.production

BUNpre

BUNpost

BUN(mg/dl)

Time (hour)

URR or Kt/VURR% : (Upre – Upost) x 100

Upre

Reflect removal of urea and other toxinsPRIMARY monitors of dialysis adequacy

Monitoring the patient’s urea

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 = LITERSV = LITERSKt/V = LITERS/LITERS = ratio

What is Kt/V ?

K . t

V = 40 liters

BUN = 0

BUN = 80

Holding Tank Model

K = 10 L/Hr

K . t

V = 40 liters

BUN = 0

BUN = 80

Holding Tank ModelKt/V1.0

1.0

0.63

URR

V = 40 liters

K t =

BUN = 0

BUN = 80

20 L

V = 40 liters

K t =

BUN = 0

BUN = 80

Kt/V = 20 / 40 = 0.50

20 L

V = 40 liters

K t =

BUN = 0

BUN = 80

Kt/V = 20 / 40 = 0.50

Post BUN = 40URR = (pre-post) / pre = (80-40) / 80 = 0.50

20 L

V = 40 liters

BUN = 0

BUN = 80, 70, 60

Dialyzer outlet fluid returned continually during dialysis

K . t

Relationship between Kt/V and URR

spKt/V = single pool

eqKt/V = equilibrated (Double pool)

Std Kt/V = weekly standard

Kt/V

Post-Dialysis rebound


Equilibrated Kt/V

spKt/V = single pool

eqKt/V = equilibrated (Double pool)

Std Kt/V = weekly standard

Kt/V

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

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.

K/DOQI : Methods for Post Dialysis Blood Sampling

1. Both samples should be drawn during the same session.2. Predialysis BUN should be drawn before treatment began. 3. Postdialysis BUN, Avoid access recirculation by

Slow flow to 100 ml/min for 15 seconds


Data from HENNET.

Exploring Mortality based on Kt/V among ESRD patients undergoing Twice-weekly Hemosialysis

Setting

• 11 hemodialysis centers

• Accrual period 3 months from Feb. 2011

• Follow up period 1 years

HENNET

**

**

*

***

*

**Multi-center cohort study

Part1 BaselinePart2 Follow up Part3 Hospitalization notePart4 Discharge summary

Enrollment

HD 2/wkLab record 2 monthly

Outcomes:Disease-related Death

Study design overview

• Inclusion• Age 18 – 80 years• HD > 3 months.

• Exclusion• Pregnancy, Breast feeding • Advance malignancy• Bed-ridden status

1 year

HENNET

Censor:Kidney transplantationShift to peritoneal dialysisRefer to other centersChange frequencyDeath from accident

Enrollment

504

HD 2/wk

Death33

Results

1 year

6,928 patients-months were observed.

Mortality rate 4.8 / 1,000 patient-months.

HENNET

Table1. Baseline characteristics

Characters Survivors N=471

Non-survivorsN=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%) 15 (45.5%)

HENNET

.51

1.5

22.

53

ktv_

avg

20 40 60 80age

Kt/V by Age

1.7±0.31.7±0.4

HENNET

1

21

101

158

119

80

19

5

050

100

150

Fre

quen

cy

.5 1 1.5 2 2.5spKt/V

Distribution of Kt/V

Mean1.7±0.3

Range 0.67 – 2.83

HENNET

1

21

101

158

119

80

19

5

050

100

150

Fre

quen

cy

.5 1 1.5 2 2.5spKt/V

Distribution of Kt/V

Adequate HD20.6%

Mean1.7±0.3

Range 0.67 – 2.83

HENNET

Hemodialysis patients with adequate dialysis (URR>65%)

CMS ESRD Clinical Performance Measures Project, 2001-2002.Centers for Medicare & Medicaid Services, ESRD Clinical Performance Measures Project, 2002-2006.

HENNET

0.4

0.8

1.2

1.6

2.0

2.4

Women214(42.5%)

Men290(57.5%)

Kt/V

1.9±0.3

P < 0.001

1.6±0.3

> 20< 15 No. of Reuse15

N

12765

160152

16-20

Kt/V by numbers of Dialyzer Reuse

50

100

150

44.6%200 55.4%

Range 0 – 30

HENNET

> 20< 15 No. of reuse15

N

16-20

Kt/V by numbers of Dialyzer Reuse

50

100

150

200

Kt/V

2

1

0.5

1.5

HENNET

Log

odds

of d

ead

Assessing Linearity Assumption -- Log OddsMean of c22 categories

Log odds of dead Linear prediction

10.0 15.0 20.0 25.0

-3.50

-3.00

-2.50

-2.00

Prediction of Dead by numbers of Dialyzer Reuse

< 15 15 16-20 > 20

Dead rate 0.03 0.06 0.08 0.11

No. of Reuse

HENNET

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 !

Improving Adequacy of Hemodialysis:It Takes a Team.

Kt/V : Do we really need it ?

0.0

0.5

1.0

1.5

N = 463 462 462 462 462

< 0.91 0.91-1.05 1.06-1.16 1.17-1.32 1.33 +

1.20 p=0.11

0.87 p=0.26

1.00 (rel)

0.69 p=0.01

0.71 p=0.01

RR

Mortality Risk by Kt/V Categorical and Linear Estimates, 1991

0.0

1.0

0.5

1.5

0.8 1.0 1.2 1.4 1.6

RR = 0.93 / 0.1 Kt/V ( p < 0.01)

Kt/V

Delivered Kt/V* (Quintiles)

* From the Pre/Post BUN and Pre/Post Weight. N = 2,311, Thrice Weekly only.

P = 0.53

HENNET

0.4

0.8

1.2

1.6

2.0

2.4

Survivors Non-survivors

Kt/V

1.65(1.52-1.77)

1.7(1.67-1.72)

P=0.52

0.0

00.2

50.5

00.7

51.0

0P

robabili

ty o

f su

rviv

al

0 5 10 15 20analysis time, months

Kt/V >= 2 Kt/V <2

Kaplan-Meier survival curves by Kt/V

Log rank test, P=0.41

Kt/V > 2

Kt/V < 2

HENNET

0.0

00.2

50.5

00.7

51.0

0P

robabili

ty o

f su

rviv

al

0 5 10 15 20analysis time, months

Kt/V >= 2 Kt/V <2

Kaplan-Meier survival curves by Kt/V

Log rank test, P=0.41

Kt/V > 2

Kt/V < 2

HENNET

1 year survival 94%

0.00

0.25

0.50

0.75

1.00

Pro

babi

lity

of s

urvi

val

0 5 10 15 20analysis time, month

0.00

0.25

0.50

0.75

1.00

Pro

babi

lity

of s

urvi

val

0 5 10 15 20analysis time, month

Kt/V > 2

Kt/V < 2

HR 1.64 (0.38-7.13), p=0.5*

DMNon DM

Kt/V > 2

Kt/V < 2

Survival probability among patients with Kt/V>2 and <2 according to diabetic status

HR 1.0 (0.28-3.75), p=0.9*

*adjusted for age

HENNET

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 – 2.83Kt/V

0.62

1.040.75

Haz

ard

ratio

of d

eath

Relative Risk of Death by Kt/V quartilesRelative Risk of Death by Kt/V quartilesHENNET

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.

HENNET

HENNET

Factors Unadjusted HR Adjusted HR 95%CI P-value*

Kt/V, per 1 unit decrease

1.7 1.9†1.2‡1.4¶

0.5-6.40.4-4.10.4-4.8

0.320.760.56

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 < 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

Prognostic factors of DeathsPrognostic factors of Deaths

Kt/V : Do we really need it ?

May be, there are stronger predictors of mortality.

Take Home Message !!

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


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


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


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%.

5. Data from– Only 20.6% is adequately dialyzed, Kt/V>2.

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.

HENNET



men.– Increase No. of Reuse related to an increase mortality

in a linear prediction.

HENNET




in a linear prediction.– Higher Kt/V quartiles trend to have lower RR for death.

HENNET




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.

HENNET




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.

HENNET


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


Acknowledgements : Grant supports

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

Thank you

for your

attention

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.

HENNET

Kt/V by BMI classes

Underweight

Obese

Normal

Overw

eight> 30< 18.5

BMI18.5-25

100

80

60

40

20

Percent

15.1 12.711.9

60

25-30

HENNET

Kt/V by BMI classes

Underweight

Obese

Normal

Overw

eight> 30< 18.5

BMI18.5-25 25-30

Kt/V

2

1

0.5

1.5

1.9

1.51.71.7

P=0.00P=0.00

HENNET

Factors affect spKt/V Kt/V>1.7N=245(48.6%)

Kt/V<1.7 N=259(51.4%)

P

BMI, kg/m2 20.6±2.9 22.4±3.3 0.00Incidence HD, < 12 mo. 23 (9.4%) 45 (17.4%) 0.01Dialyzer membrane: Semi-synthetic 99 (40.4%) 101 (39%) 0.75Low Flux Dialyzer 82 (33.5%) 97 (34.5%) 0.35Dialyzer Surface area 1.76±0.2 1.8±0.2 0.04No. of Dialyzer Reuse 17.1±5.5 15.6±5.1 0.00Blood Flow, ml/min 324.2±51 297.9±46.9 0.00Dialysate flow, ml/min 537.9±98.3 517.7±64 0.01DM 71 (28.9%) 107 (60.1%) 0.00Current Smoking 5 (2.0%) 12 (4.6%) 0.08

P<0.05

HENNET

Factors affect spKt/V Kt/V>1.7N=245(48.6%)

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%) 0.01Dialyzer membrane: Semi-synthetic 99 (40.4%) 101 (39%) 0.75Low Flux Dialyzer 82 (33.5%) 97 (34.5%) 0.35Dialyzer Surface area 1.76±0.2 1.8±0.2 0.04No. of Dialyzer Reuse 17.1±5.5 15.6±5.1 0.00*Blood Flow, ml/min 324.2±51 297.9±46.9 0.00*Dialysate flow, ml/min 537.9±98.3 517.7±64 0.01DM 71 (28.9%) 107 (60.1%) 0.00Current Smoking 5 (2.0%) 12 (4.6%) 0.08

*P<0.05 in Multivariate Analysis

HENNET

Factors affect spKt/V

Coef. 95%CI PBMI, kg/m2 0.20 0.13 to 0.27 0.000No. of Dialyzer Reuse -0.06 -0.02 to -0.10 0.003Blood Flow, ml/min -0.01 -0.006 to -0.014 0.000

Kt/V < 1.7

Every 1 increase in BMI will increase 20% of Kt/V<1.7

HENNET

NIH Hemo Study

URR of about 67% vs. about 75%spKt/V of 1.3 vs. 17eKt/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

HD adequacy : dose


K: dialyzer clearance t: duration of HDV: volume distribution of urea

Relationship of eKt/V to spKt/V

eKt/V = spKt/V [(t/(t+C)]C=35 min if artery, 22 min if vein

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

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

1111

3 3 3 3

Outcomes

Outcomes N %Death 33 34.7Refer to other centers 27 28.4Change frequency 13 13.7Shift to CAPD 10 10.5Kidney transplantation 6 6.3Loss to follow up 6 6.3

Indices of Urea RemovalKt/V

Reflects urea removalNCDS suggested Kt/V must be > 0.90Population studies suggest Kt/V should

be>1.2

URRAlso reflects urea removalCurrent goal is a URR > 65 %

Sample

0.8

1.0

1.2

1.4

1.6

1.8

2.0

< 0.70 0.75 0.88 1.0 1.15 1.3 >1.4

Approximate Kt/V

100

80

60

40

20

Percent

1.5

P=1.00

Incidence and Prevalence Hemodialysis

Incidence HD<= 12 mo.

Prevalence HD> 12 mo.

(13.5%)

(86.5%)

68

436

HENNET

Kt/V

2

1

0.5

1.5 1.54 (1.46 to 1.61)

P=0.00

Kt/V by Incidence and Prevalence Hemodialysis

Incidence HD<= 12 mo.

Prevalence HD> 12 mo.

1.72 (1.69 to 1.74)

HENNET

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