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Monitoring the Hemodialysis Dose

KDIGO Controversies ConferenceNovel techniques and innovation in blood purification:

How can we improve clinical outcomes in hemodialysis?October 14-15, 2011

Paris France

Monitoring the Hemodialysis Dose

Tom Depner, M.D.University of California, Davis

© 2001 By Default!Slide 2

Removal of accumulated smallsolutes is important

A Free sample background from www.pptbackgrounds.fsnet.co.uk

solutes is important

How long will I live if I choose to stop dialysis?

This varies from person to person. People who stop dialysis may live anywhere from who stop dialysis may live anywhere from one week to several weeks, depending on the amount of kidney function they have leftand their overall medical condition.

National Kidney Foundation web site

Art Buchwald

Famous as a syndicated humorist in life, after his death he is more notable for his reputation as the man who beat hospice and the kidney machine.

How long will I live if I choose to stop dialysis?

The median time to death after stopping The median time to death after stopping dialysis in a series of 18 patients reported by Rich was 7 days (0-17 days)

Rich A, Palliative Med 15:513-14, 2001.

The cause of death is uremia

� Principal cause: accumulation of toxic solutes normally excreted by the kidney

� Evidence: dialysis works by removing small solutes.solutes.

� Death is not due to anemia, vitamin D deficiency, hyperparathyroidism, fluid overload, accumulation of beta 2-microglobulin, etc, etc.

Minimum urea clearance for Hemodialysis

KDOQI guidelines call for a continuous equivalent Kt/Vurea of 2.0 volumes/week.

2.0 volumes per week x 35 L = 70 L/week

= 70,000 ml/L /10080 min/week

= 7 ml/min


HEMO Study: Survival by Kt/V Group

A Free sample background from www.pptbackgrounds.fsnet.co.ukEknoyan et al, N Eng J Med 2002

3

4

5

6

7

We

ek

ly D

ialy

sis

Do

se

(s

tdK

t/V

)

6

Hemodialysissessions/wk

HEMO: High

DailyDialysis

Effect of Increasing Number of Effect of Increasing Number of Effect of Increasing Number of Effect of Increasing Number of Dialysis Sessions Per WeekDialysis Sessions Per WeekDialysis Sessions Per WeekDialysis Sessions Per Week

9

0.0 0.5 1.0 1.50

1

2

3

We

ek

ly D

ialy

sis

Do

se

(s

tdK

t/V

)

3

HEMO: Standard

Dialysis dose each dialysis (eKT/V)

7 ml/min

8 ml/min

Deficiencies of Kt/V

� Residual kidney function not considered

� Solute disequilibrium is under-represented

No provision for dialysis frequency� No provision for dialysis frequency

� K and t may not be equivalent

� V is independently associated with outcome

� Non-linear correlation with outcome

Effect of Kr-urea on mortality in HD patients

12

14

16

18

20

RR

mo

rta

lity

5.0 to 62.6

Adjustments: age, Adjustments: age, comorbidity score, comorbidity score, primary kidney primary kidney disease, SGA, BMIdisease, SGA, BMI

Termorshuizen F, et al: JASN 15:1061Termorshuizen F, et al: JASN 15:1061--70, 200470, 2004

0

2

4

6

8

10

RR

mo

rta

lity

0 0 to 0.84 >0.84

KrT/V per week

reference1.1 to 2.6

Standard K (and Kt/V) - Gotch

continuous removal rate

average peak concentrationStandard K =

In a steady state, the removal rate is equal to the generation rate (G)

Standard K =G

average peak concentration


Standard Kt/V

t

e110080

Kt/V

eKt/V−

=

−


1Nt

10080

eKt/V

e1tKt/V

eKt/Vstd

−+−

=−

Gotch, FA: Nephrol Dial Transplant 13 Suppl 6:10-14, 1998

Leypoldt, JK: Seminars In Dialysis 17:142-145, 2004


Standard Kt/V adjusted for Uf and Kru

stdKt/V = S/[1 - (0.74/F) • Uf/V]

+ Kru • [0.974/(spKt/V + 1.62) + 0.4] • 10/V

A Free sample background from www.pptbackgrounds.fsnet.co.ukDaugirdas J, et al: Kidney Int 2010

S is the unadjusted stdKt/V per week

F is the number of dialyses/week

Uf is the weekly fluid removal in liters

Kru is the residual native kidney clearance of urea in ml/min

spKt/V is the single pool Kt/V per dialysis

V is the urea distribution volume in liters

4.0

5.0

6.0

7.0S

tandard

Kt/

VContinuous vs. intermittent clearance expressions

7/week

6

5

4

per

week

0.00 0.50 1.00 1.50 2.00 2.50

spKt/V per dialysis

0.0

1.0

2.0

3.0

Sta

ndard

Kt/

V

3

2

1

per

week


4.0

5.0

6.0

7.0R

e-d

efin

ed

Kt/

V (

pe

r w

ee

k)

Continuous versus peak concentration methods

Mean methodPeak method

7/week

6

5

4


0.00 0.50 1.00 1.50 2.00 2.50

spKt/V per dialysis

0.0

1.0

2.0

3.0

Re

-de

fin

ed

Kt/

V (

pe

r w

ee

k)

3

2

1


0.90

1.00

1.10

1.20K

t/V

Effect of treatment time on eKt/V

eKt/V1.09

spKt/V


2 4 6 8 10

Td (treatment time in hours)

0.60

0.70

0.80

0.90

Kt/V

0.87

Treatment time predicts mortalitySaran et al from DOPPS, Kid Int 69:1222-28, 2006

New NKF-KDOQI Hemodialysis Guidelines


1.20

1.40

Rela

tive R

isk o

f death

Mortality and Body Mass IndexUSRDS: 3607 patients enrolled in CMAS, Jan 1991

ad

juste

d f

or

ag

e,

se

x,

race

& o

the

r fa

cto

rs

quintile means ñ 95% confidence intervals


15 20 25 30 35 40 45

BMI

0.80

1.00

Rela

tive R

isk o

f death

Source: Leavey et al, AJKD 31:1002, 1998

ad

juste

d f

or

ag

e,

se

x,

race

& o

the

r fa

cto

rs


Kurea•t


urea

Vurea


Continuous risk (hazard) plane for Ktand BSA. The analysis did not include an inter-action term between Kt and BSA and was case mix adjusted.

43,334 patients


Continuous risk (hazard) plane for Ktand BSA. The analysis included an interactionterm between Kt and BMI and was case mixadjusted.

Lowrie E, et al: KI 62:1891-7, 2002

0.6

0.8

1.0R

esponse (

R)

Concentration (Dose) - Response CurveHill equation: applies to a direct reversible effect

(1/Q) + CSCS

R =

0.5 1.0 10.0

Concentration (C in arbitrary units)

0.0

0.2

0.4

Response (

R)

6.0

8.0

10.0C

on

ce

ntr

atio

n (

C in

arb

itra

ry u

nits) Concentration versus Clearance

C = 1/K

0.0 0.2 0.4 0.6 0.8 1.0

Clearance (K) in arbitrary units)

0.0

2.0

4.0

Co

nce

ntr

atio

n (

C in

arb

itra

ry u

nits)

2

2.5

3

3.5

4

4.5

5

0

0.5

1

1.5

2

0 5 10 15 20

Steady-state solute concentration

Some proposed improvements to Kt/V

• Include residual native kidney clearance (Kr)

• Account for solute disequilibrium» eKt/V

• Allow for more frequent dialysis» Standardized Kt/V

• Index to surface area instead of V

• Tighter correlation with outcome» reciprocal of Kt/V


Summary: uremia is a complex state

Comorbidity (DM, CVD, nutrition, anemia, etc)Comorbidity (DM, CVD, nutrition, anemia, etc)

Residual Syndrome:Residual Syndrome:

Slowly accumulating solutes:Slowly accumulating solutes:•• B2B2--microglobulin & other peptidesmicroglobulin & other peptides•• Calcium & phosphate depositsCalcium & phosphate deposits•• ProteinProtein--bound toxins?bound toxins?

Comorbidity (DM, CVD, nutrition, anemia, etc)

Residual Syndrome:

Slowly accumulating solutes:• B2-microglobulin & other peptides• Calcium & phosphate deposits• Protein-bound toxins?


Life threatening toxins

•• ProteinProtein--bound toxins?bound toxins?•• AGE’s ?AGE’s ?•• Carbamylated proteins ?Carbamylated proteins ?

Toxic effect of dialysis Toxic effect of dialysis -- exposure to exposure to membrane, hemodynamic effectsmembrane, hemodynamic effects

• Protein-bound toxins?• AGE’s ?• Carbamylated proteins ?

Toxic effect of dialysis - exposure to membrane, hemodynamic effects


Future of dose monitoring

Because control of small solute concentrations

must be the principal goal of replacement

therapy, future efforts should focus not on


therapy, future efforts should focus not on

whether we should measure small solute

clearance, but what else we should measure

and do for our patients.

Adequacy of Dialysis

= Removal of Toxins

= Prevention of Uremia= Prevention of Uremia

= Restoration of Health

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