HOW TO MEASURE DIALYSIS ADEQUACY

Mochammad Sja'bani
Department of Internal Medicine, Faculty of Medicine
Gadjah Mada University, Yogyakarta

KONAS XIII AND ANNUAL MEETING PERNEFRI 2017 - MALANG

KONAS XIII AND ANNUAL MEETING PERNEFRI 2017 - MALANG
 Quality of life
and Survival
(Optimal Dialysis
Adequacy)

Dialysis
Adequacy
(Kt/V)

KONAS XIII AND ANNUAL MEETING PERNEFRI 2017 - MALANG

 Dialysis Adequacy =
Simple Adequacy
(Kt/V)

ONLY MEASURES UREMIC TOXINS REMOVAL

KONAS XIII AND ANNUAL MEETING PERNEFRI 2017 - MALANG

UREMIC TOXICITY
Yesterday

CKD

Uremic Toxins
Accumulation

Uremic Toxicity

Uremic Syndrome

Poor Outcomes

KONAS XIII AND ANNUAL MEETING PERNEFRI 2017 - MALANG

UREMIC TOXICITY
Today, much more than Toxins Accumulation

CKD Hemodialysis

Diet Uremic Milieu

Uremic Toxins Internal
Life Style
Accumulation Metabolism
Comorbidity
Inflammation
Genetic- Uremic Toxicity
Epigenetic Microbota

Gut Barrier Salt metabolism

Uremic Syndrome
Residual Kidney Cross-Talk
Function Function

........ ........
Improve Outcomes

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 SUBDIVISION UREMIC TOXINS

A. Small Water Soluble Compounds

< 500 Dalton
Prototype urea
Easily removed by any type of dialysis
B. Large Middle Molecules
> 500 Dalton
Prototype 2-microglobulin, FGF 23, Cardiac biomarkers
Removed only by large pore dialyzers (high flux)
C. Protein Bound Compounds
Mostly < 500 Dalton
Prototypes indoles, phenols
Difficult to remove by any type of dialysis

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 POTENTIAL TOXINS
Small Water Soluble Compounds

Urea
Uric Acid
Methylguanidine
Guanidinosuccinic Acid
Asymmetric Dimethylarginine (ADMA)
Symmetric Dimethylarginine (SDMA)
Oxalate
Phosphate
Potassium
Trimethylamine-N-oxide (TMAO)

KONAS XIII AND ANNUAL MEETING PERNEFRI 2017 - MALANG

 POTENTIAL TOXINS
Small Water Soluble Compounds

Urea
Uric Acid
Methylguanidine
Guanidinosuccinic Acid
Asymmetric Dimethylarginine (ADMA)
Symmetric Dimethylarginine (SDMA)
Oxalate
Phosphate
Potassium
Trimethylamine-N-oxide (TMAO)

KONAS XIII AND ANNUAL MEETING PERNEFRI 2017 - MALANG

UREA DISRUPTS INTESTINAL WALL PROTECTIVE BARRIER

Vaziri et al. Am J Nephrol, 37: 1-6. 2013

KONAS XIII AND ANNUAL MEETING PERNEFRI 2017 - MALANG

 POTENTIAL TOXINS
Small Water Soluble Compounds

Urea
Uric Acid
Methylguanidine
Guanidinosuccinic Acid
Asymmetric Dimethylarginine (ADMA)
Symmetric Dimethylarginine (SDMA)
Oxalate
Phosphate
Potassium
Trimethylamine-N-oxide (TMAO)

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 TMAO ENHANCES ATHEROGENESIS

Wang et al. Nature, 472: 57-63. 2011

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 Uremic toxin removal

until 50
until until kDa
6 kDa 40 kDa

Low Flux High Flux Hemodiafiltration

- Urea (60 Da)
- Creatinine (113 Da) - FGF-23 -FGF-23
- Uric acid (168 Da) -Cardiac marker -Cardiac marker
- FGF-23 - 2MG - 2MG
-Cardiac marker - PTH - PTH
- 2MG - BNP - BNP
- PTH
- BNP
- TnT - TnT
- TnT -Nt-proBNP - Nt-proBNP
-Nt-proBNP
-Hypertension
DANGEROUS - Chronic Cardiovascular
- Stroke
- > Mortality
- Low quality of life
Sjabani 2016
 THEN, HOW TO MEASURE DIALYSIS
ADEQUACY?

LET SEE OUTLINE OF PRESENTATION

KONAS XIII AND ANNUAL MEETING PERNEFRI 2017 - MALANG

OUTLINE OF PRESENTATION
1) Basic equation to estimate dialysis adequacy

2) Limitations of common formula to estimate

quality of dialysis adequacy

3) Optimal dialysis adequacy assesment related to

quality of life and survival

KONAS XIII AND ANNUAL MEETING PERNEFRI 2017 - MALANG

 PART 1

KONAS XIII AND ANNUAL MEETING PERNEFRI 2017 - MALANG

1) Basic equation to estimate dialysis adequacy

Qunibi WY and Henrich WL. UpToDate. 2017

KONAS XIII AND ANNUAL MEETING PERNEFRI 2017 - MALANG

 Kt/V URR

Basic equation to
estimate dialysis
adequacy

Other Measurements
KONAS XIII AND ANNUAL MEETING PERNEFRI 2017 - MALANG
 Kt/V
Definition

Kt/V is urea kinetic equation used to predict clearance

- K: urea dialyzer clearance
- t : dialysis time, and
- V: urea distribution volume adjusted to total body water

Formula

(Eq. 1) Kt/V = -ln (R - 0.03) + [(4 - 3.5R) x (UF W)]

where:
UF ultrafiltration volume (liter), W post dialysis mass (kg), and R post dialysis
ratio to pre dialysis Blood Urea Nitrogen (BUN)

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Nomogram to estimate Kt/V (Data from Daugirdas et al., 1993)

KONAS XIII AND ANNUAL MEETING PERNEFRI 2017 - MALANG

Changes in blood urea nitrogen measured at different times after dialysis
(Data from Depner, 1994)

KONAS XIII AND ANNUAL MEETING PERNEFRI 2017 - MALANG

 Main Benefits of Kt/V

Urea is easily measurable

Reflects protein intake in stable patients

Very large observational database regarding

serum UN and URR in HD and PD patients

Removal (as Kt/V) has been studied in two randomized

trials (NCDS and HEMO) of 3 times/week dialysis and
also in FHN trials (as stdKt/V)

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 Urea Reduction Ratio (URR)
Definition

- URR is fractional Blood Urea Nitrogen (BUN) reduction

during single dialysis session
- Less accurate compared to Kt/V

Formula

(Eq. 2) URR = (1 - [postdialysis BUN predialysis BUN])

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 Other Measurements
Tabel Perhitungan Dosis Dialisis: Hasil Diperoleh dari Perbedaan Persamaan Model
Rumus Hasil Komentar
URR=(1-Ct/C0)x100% 67% Urea mendadak tinggi, generasi urea, dan ultrafiltrasi
tidak diperhitungkan

Kt/V=ln (C0/Ct) 1,10 Urea mendadak tinggi, generasi urea, dan ultrafiltrasi
tidak diperhitungkan

spKt/V=-ln(R-0,008xt)+(4- 1,33 Model single-pool; urea mendadak tinggi tidak

3,5R)xUF/W diperhitungkan

eKT/V=spKt/V-0,6xspKt/V/t+0,03 1,16 Model double-pool untuk akses arteri vena

melibatkan peningian mendadak urea

eKt/V=spKt/V-0,47xspKt/V/t +0,02 1,20 Model double-pool untuk akses vena sentral

melibatkan peninggian mendadak urea

Perhitungan berdasarkan pada durasi dialisis(t) = 4 jam; NUD pra dialisis (C0)=90 mg/dl; NUD pasca dialisis tidak seimbang
(Ct)=30 mg/dl; volum ultrafiltrasi (UF)=3 liter; berat badan pasca dialisis (W)=72 kg; R=Ct/C0. URR: rasio penurunan urea

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 STRATEGIES TO IMPROVE FLUID REMOVAL

Dialysis Session Tolerance

Dialysis Session Length

Dialysis Frequency

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 Improved Session Tolerance with Convective Therapies

Maduell F et al. JASN 2013; 24: 487-497

KONAS XIII AND ANNUAL MEETING PERNEFRI 2017 - MALANG
IMPACT OF DIALYSIS LENGTH ON MORTALITY

Saran et al., KI, 69:1222-8. 2006

KONAS XIII AND ANNUAL MEETING PERNEFRI 2017 - MALANG

Frequent dialysis has beneficial effects on death or change in LV mass

The FHN Trial Group. N Engl J Med 2010. 363:2287-2300

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KDOQI 2015 Recommendation : Measurements of
Dialysis Dose

3.1 We recommend a target single pool Kt/V (spKt/V) of 1.4 per hemodialysis
session for patients treated thrice weekly, with a minimum delivered
spKt/V of 1.2. (1B)

3.2 In patients with signicant residual native kidney function (Kru), the dose
of hemodialysis may be reduced provided Kru is measured periodically to
avoid inadequate dialysis. (Not Graded)

3.3 For hemodialysis schedules other than thrice weekly, we suggest a target
standard Kt/V of 2.3 volumes per week with a minimum delivered dose of
2.1 using a method of calculation that includes the contributions of
ultraltration and residual kidney function. (Not Graded)
 BUT Kt/V HAVE MANY LIMITATIONS

SEE

PART 2
KONAS XIII AND ANNUAL MEETING PERNEFRI 2017 - MALANG
2) Limitations of common formula to estimate
quality of dialysis adequacy

Qunibi WY and Henrich WL. UpToDate. 2017

KONAS XIII AND ANNUAL MEETING PERNEFRI 2017 - MALANG

Limitations of Kt/V

a. Kt/V was developed in an era when dialysis utilized small-pore cellulosic

dialyzers (low flux)

b. Evidence of the toxicity of urea is limited, and its impact on patients'

outcomes has not been documented.

c. Kt/V measures urea clearance in a single session, with the implicit

assumption that the session is representative of all other sessions.

d. Kt/V cannot be used to compare treatments among patients when dialysis

frequency is delivered more than three times weekly.

e. The Kt/V disregards a possible effect of total body water on patient

outcomes independent of its effect on urea

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 The Last Days of Kt/V?

Vanholder et al. KI. 88: 460-465. 2015

KONAS XIII AND ANNUAL MEETING PERNEFRI 2017 - MALANG

 Another Limitations of
Kt/V by Vanholder et al

KONAS XIII AND ANNUAL MEETING PERNEFRI 2017 - MALANG

According to many limitations above, does this
mean that we have to discard the concept of
Kt/V completely?

SEE

PART 3
KONAS XIII AND ANNUAL MEETING PERNEFRI 2017 - MALANG
3) Optimal dialysis adequacy assesment related to
patients quality of life and survival

Perl et al. Clin J Am Soc Nephrol 2017; 12: 839 47

KONAS XIII AND ANNUAL MEETING PERNEFRI 2017 - MALANG

KONAS XIII AND ANNUAL MEETING PERNEFRI 2017 - MALANG
 Alternative/supplemental measurements
beside of Kt/V

Convective volume removal (with HDF)

Time: Weekly time

Square meter x hour
HD Index

Frequency (1,2,3, or more per week)

Volume control : Post dialysis ECF Volume

Phasic component (UF Volume, UF rate)

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 Is adequate dialysis = optimal dialysis?

Multi Dimension Assesment of Optimal Dialysis

Potential Strategies
Patient reported outcomes
Goals of ESRD Care
Small solute removal
Residual Kidney Function
Left ventricular geometry Treatment duration
Ultrafiltration rate and Treatment frequency
extracellular fluid volume Incremental dialysis
management Maximize Quality of Liffe
Preservation of RKF
Middle Molecules Removal Consideration of Home HD
Phosphorus Maximize Survival
HR and BP vaiability
Serum potassium control

Perl et al. Clin J Am Soc Nephrol, 12: 839-847. 2017

KONAS XIII AND ANNUAL MEETING PERNEFRI 2017 - MALANG

 CONCLUSION

It is useful to have a parameter of minimum adequacy,

especially in the start phase of dialysis

Kt/V can be kept as guard of minimal dialysis adequacy,

without forgetting that many other factors not explained
by Kt/V have a key role as well

Multi Dimension Assesment is suggested to measure

optimal dialysis adequacy

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ALHAMDULILLAAH

Thank you
Any Question?