HEMODIALYSIS ADEQUACY

Kolonel CKM dr.Dwi Edi Wahono,SpPD,K-GH,MH.

SMF Ginjal Hipertensi

Dept. Penyakit Dalam RSPAD Gatot Subroto
Jakarta
 Definition of CKD
CKD is defined as abnormalities of kidney structure or
function, present for ≥3 months, with implications for
health

Kidney Disease: Improving Global Outcomes

www.kdigo.org
Function of the Kidney
 Symptoms and Signs of Uremia

Symptoms Signs
• Fatigue • Seizures/change in seizure
• Lethargy threshold
• Confusion • Amenorrhea
• Anorexia • Reduced core body temperature
• Nausea • Protein-energy wasting
• Alterations in senses of smell • Insulin resistance
and taste • Heightened catabolism
• Cramps • Serositis (pleuritis, pericarditis)
• Restless legs • Hiccups
• Sleep disturbances • Platelet dysfunction
• Pruritus • Somnolence
Conceptual model of CKD.
 GFR categories

Kidney Disease: Improving Global Outcomes

www.kdigo.org
Timing of Hemodialysis Initiation
• Education about different forms of renal replacement
therapy (RRT) should be started once eGFR reaches <30
mL/min/1.73m2 or the eminent need for RRT approaches.

• The timing of therapy should be driven by signs and

symptoms of uremia, evidence of protein-energy wasting,
or metabolic abnormalities/volume overload refractory to
medical management. The 2015 guideline removes any
suggested eGFR (which was previously given as 15
mL/min/1.73m2 in 2006).

Am J Kidney Dis. 2015;66(5):884-930

Overview
1. How to asses the adequacy of delivered HD ?
2. Factors Affecting of Hemodialysis Adequacy
3. Recommendations for Dialysis Dose Adequacy
4. Prescription of Dialysis Dose
5. Conclusion
 1. HOW TO ASSES THE
ADEQUACY OF DELIVERED HD
?
 The Concept of Dialysis Adequacy

The minimum dose of dialysis needed

to survive

Dialysis doses are needed so that

patients can live optimally

Lacson E, Wish J B.
In: Dialysis, 2nd. Ed: WilliamL.Henrich. Lippincott Williams & Wilkins, Philadelphia. P. 99-113
 What is ‘adequate’ hemodialysis ?

Adequate HD is treatment regimen that is acceptable

to the pts and dialysis provider in term of:
• Control of uremic symptoms and pts well-being
• BP control
• Biochemical markers of uremia and nutrition
• Achieved dialysis dose based on small solute
clearance
• Inconvenience and cost

(Basic Clinical Dialysis, 2015)

Two central issues in the management of
patients undergoing maintenance hemodialysis
:

Determining the optimal amount

of dialysis that should be
prescribed

Quantifying the amount of

dialysis that is actually
delivered to individual patients
 Clinical Dialysis Adequacy Criteria
• Subjective assessment
• How well are the symptoms of uremia controlled in the
patients (e.g. Appetite, nausea, tiredness, itch) ?
• Objective assessment
• Volume/BP control
• Is the patients still acidotic (as indicated by a low
mid-week predialysis bicarbonat level)?
• How well are blood phosphate level controlled?
• Is the serum albumin level normal (an indicator of
nutrition strongly associated with survival)?
• Dialysis dose assessment
• Is the desired level of urea removal being met?
 Assessment of dialysis adequacy
• Two methods are commonly used to assess the adequacy
of dialysis, is URR and Kt / V.
• Against dialysis blood samples at the beginning and at the
end of dialysis
• Urea levels in the two blood samples were then compared.
• The recommended frequency of assessment is:
• Every 3 months in patients who are stable
• Every month in patients who are unstable or after
changes in prescription dialysis
• If there are signs of decreased clearance (symptoms of
uremia)
(Basic Clinical Dialysis, 2015)
 URR :
Advantages:
• Practical / simple
Limitations:
• Does not take into account the
situation, nutrition, urea generation,
etc.
Lacson E, Wish J B.
- URR ~ Kt / V
In: Dialysis, 2nd. Ed: WilliamL.Henrich. Lippincott Williams & Wilkins, Philadelphia. P. 99-113
19

URR ?
• URR: urea reduction ratio, which means a reduction in

urea as a result of dialysis.

• URR: one measure of how effectively the dialysis

procedure removes waste products (urea) from the body

and is generally expressed as a percentage.
20

Reasons for using urea removal

• a material used to mark small size solute

buildup in kidney failure

• easily measured

• a product of protein catabolism & is 90% of

residual nitrogen that can be dialyzed
Reasons for using urea removal

• Residual renal functions can be measured in

various formulas (very important for new
dialysis patients)
• The use of formulas facilitates ongoing
monitoring of dialysis doses given to each
patient
• Measuring urea removal shows the results of
dialysis in patients
22

Limitations of urea removal as a

measure of adequate hemodialysis
• Measuring the adequacy of a given dialysis dose
should not only use urea discharge

• The removal of urea is not always related to the

disposal of other uremic poisons

• The accuracy of measurement depends on the

accuracy and timing of blood sampling after dialysis
23

How to take post HD samples

1. At the end of HD:
a) Turn off the dialysate flow (Flow off)
b) Lower the speed of blood flow (Qb) to 50 ml
/ minute
c) Wait 15 seconds for the machine to alarm,
take blood from the arterial line
2. Continue with the procedure for ending
hemodialysis
3. Blood samples are labeled with the patient's
name and the label "post HD"
24

Metode Daugirdas
• Set UF rate to O
• Lower Qb 100 ml / minute for 10-20
seconds
• Turn off the blood pump
• Take a blood sample from the arterial
blood line port
25

Estimated urea clearance using a formula

Urea reduction ratio (URR)

predialisisUrea – post dialisis urea

URR = ------------------------------------------------- x 100
Pre-dialysis Urea

The minimum recommended

URR for HD is 65-70%.
26

CASE :
• Mrs. S, 50 years old
• BW pre-HD 52 kg
• Dry weight 50 kg
• HD 2x a week
• Time duration of HD 5 hours
• Qb 250 ml / minute
• F7 Dializer
• Ureum pre 200 mg / dl
• Ureum post 60 mg / dl

• What is the URR Ny. S?

27

Example calculation with URR

Known :
• Urea pre HD = 200 mg / dl
• Ure post HD = 60 mg / dl
How much is the URR?
Answer:
200 mg / dl - 60 mg / dl
URR = ---------------------------- x 100%
200 mg / dl

= 140 mg / dl
--------------- x 100% = 70%
200 mg / dl
Definition and calculation Kt/V

• Kt/V is defined as the dialyzer clearance of urea (K)

multiplied by the duration of the dialysis treatment (t, in
minutes) divided by the volume of distribution of urea
in the body (V, in mL), which is approximately equal to
the total body water, corrected for volume lost during
ultrafiltration
Definition and calculation Kt/V
• The Daugirdas equation is validated for a Kt/V range of
0.8 - 2.0 and is widely used because of its simplicity and
accuracy

R = the postdialysis-predialysis serum urea ratio,

t = treatment time (hours),
UF = ultrafiltration volume (liters), and
W = the patient’s postdialysis body weight (kilograms)
Sp = single pool
 Kt / V

• KT/V
• K: clearance in L / minute, dializer coefficient (KoA),
blood flow rate (Qb), and dialysate (Qd) flow rate
• t: dialysis time in minutes
• V: is the volume of urea distribution (in liters), male urea
distribution volume is around 58% of BW while female is
55% of BW
• If a BW male patient is 70 kilograms (kg), dry weight is 65
kg
• Then the volume of urea distribution (V) = 70 kg multiplied
by 58/100 = 40.6 liters
 Estimated urea clearance using a formula

Estimated single pool Kt/V (Dougirdas Formulation)

Post-dialysis urea
Kt/V = - log e [ ----------------------------- - 0,08 x t ]
Pre-dialysis urea

Post-dialysis urea
+ [ 4 – 3,5 x --------------------------- ]
Pre-dialysis urea

Pre-dialysis BW– Post-dialysis BW

x [-------------------------------------------------------------- ]
Pre-dialysis BW

t = dialysis time in hours

Kasus

• Tn. R, 35 tahun • Jawab :

Kt/V = 183 x 240
• BB Pre HD 60 Kg
34800
• HD 2x seminggu
= 43920
• Lama HD 4 jam 34800 ml
• QB 200 ml/menit = 43,9
• Dializer F6 (K. 183 ) 34.8 L
58%x60=34,8 L= 34800 = 1,26
● Target Kt/V = 1,8
• Berapakah Kt/ V Tn R ? ● Bagaimana untuk
meningkatkan klirens?
Contoh perhitungan waktu dialisis (t):

• Diketahui : • Jawab :
• Kt/V yang diinginkan t = 1,8 x V
(target) = 1,8 K
• V = 34800 ml (34,8 L) = 1,8 x 34800 ml
• K = 183 (F6) 183
= 62640 ml
• Berapa t dibutuhkan ? 183
= 342,30 menit
= 5 Jam 42 menit

Jadi pasien tsb membutuhkan 1 jam 42 menit lagi

untuk mendapatkan HD yang adekuat.
UREMIC TOXINS

• Theretention in the body of compounds (are called uremic

retention solutes or uremic toxins) results in the uremic
syndrome.

• Uremic toxins include a small group of inorganic

compounds, such as water, potassium, phosphate, and
trace elements, and a much larger group of organic
compounds that are further subdivided into
• small water-soluble solutes (<500 d)

• middle molecules (>500 d)

• protein-bound solutes
Comprehensive Clinical Nephrology 5ed.
 Urea as a Surrogate Marker of Uremic Toxicity
Freely diffusible
Standard Solute through cell
Translocation membranes

allows rapid
✓ Small molecular weight equilibration of urea
✓ Can move freely from
concentration within
extra cellular to intra
cellular and dialysate whole body water
compartments after urea has been
removed from the
blood compartment

Urea removal does not closely parallel

that of other small water-soluble
compounds, protein-bound solutes, or
middle molecules
 INTRADIALYCTIC UREA KINETICS
konsentrasi urea
intradialisis dalam darah
selalu lebih rendah
daripada dalam jaringan
Equilibrasi penuh di antara
Dialiser sangat effisien
antar kompartemen
mengurangi konsentrasi
tercapai dalam 30-60
urea sampai 80-90%.
menit setelah akhir dialisis

INTRADIALYCTIC
UREA
2. FACTORS AFFECTING OF
HEMODIALYSIS ADEQUACY
41

Factors Affecting of Hemodialysis Adequacy

• HD prescription
• Made by nephrologists before hemodialysis is done
• Individual
• The dializer selection
• Material:
• Cellulose: cuprophan
• Cellulose substituted: Cellulose acetate, Diacetate,
Triacetate
• Synthetic: Polysulfone, Polycarbonate, polyamide and
• polymethylmethacylate (PMMA)
• Others:
• Low Flux
• High flux dialyzer
• High efficiency dialyzer
43

Factors Affecting of Hemodialysis Adequacy

• Surface area :
o KoA (Coefficient Mass Transfer Urea)
o KUF (Coefficient Ultrafiltration)

• Dialysis frequency
• HD 2 times a week (mild BW, there is still
residual kidney function)
• HD 3 times a week
44

Factors Affecting of Hemodialysis Adequacy

• Kecepatan aliran darah (Qb)

• > 300 ml/menit

• Kecepatan aliran dialisat (Qd)

• 2x Qb

• Dialiser pakai Ulang (dialyzer reuse)

• TCV (total cell volume) > 80%
Dosis Minimum Hemodialisis

Hemodialisis 3 x / minggu
•Kt/V minimal 1.2 (DOQI)
•URR minimal 65% (DOQI)
Diukur
Hemodialisis 2 x / minggu 1 x/bulan
• Kt/V minimal 1.8 – 2
( Tidak direkomendasikan oleh NKF-DOQI)

• URR : 80%
NKF-KDOQI 2015
Agar dapat mencapai hemodialisis
yang adekuat, maka target
adekuasi ditentukan lebih tinggi
Kt/V 1.3, URR 70%
47

Penyebab Hemodialisis Tidak Adekuat

❖ Underprescription
❖ Akses vaskular yang inadekuat
❖ Waktu dialisis yang diperpendek
❖ Darah membeku
❖ Penggunaan reuse dialyzer
❖ Variabel lain :
~ Pasien, staf medis, masalah mekanik

Lacson E, Wish J B.
In: Dialysis, 2nd. Ed: WilliamL.Henrich. Lippincott Williams & Wilkins, Philadelphia. P. 99-113
 Approach to the patient with suspected inadequate
dialysis
(Basic Clinical Dialysis,2015)
Are prescribed dialysis
times being met?

YES NO

Is blood flow rate >300 Increase to

Reasses in
mL/min and asses prescribed
1 month
resirculation <10%? time

YES NO

Is there another cause of poor health or •

Temporary increase
poor dialysis ? delivered dose
• Cardiac failure • Evaluate for acces stenosis
• Malignancy
• Infection

NO YES

• Treat underlying disease if

Are desired target for
possible
small removal being
• Increase delivered dialysis
met?
dose

YES NO

• Increase delivered
Reasses in 1 month dialysis dose
49

Risiko Relatif Kematian Meningkat pada

Kt/V dan URR yang Lebih Rendah
1.5 1.
RR = 0.93/0.1 Kt/V 5 RR = 0.89/5 URR, %

1.0 (P < 0.01) 1.0 (P < 0.01)

RR

RR
0.5 0.5

0.0 0.
0.8 1.0 1.2 1.4 1.6 0 50 6 70 8 90
0 0
Kt/V URR (%)

Ket. : Sampel diambil secara random dari pasien U.S. yang telah menjalani
dialisis selama lebih dari 1 tahun pada 31 Des’1990.
(N=2,311)
Modifikasi dari N.K. Man, J. Zingraff, P. Jungers.
In: Long –term Hemodialysis. Kluwer Academic Publisher, The Netherlands. pp. 49-60
Luaran Hemodialisis

• Luaran terbaik pasien dalam terapi HD

• Efek terhadap mortalitas
• Efek terhadap angka perawatan di RS
• Kualitas hidup pasien

• -Comprehensive clinical nephrology, fifth edition

3. RECOMMENDATIONS FOR
DIALYSIS DOSE ADEQUACY
Recommendation of KDOQI 2015

• For patients with minimal residual kidney function (<2

ml / minute / 1.73)
• Dialysis 3 times / week
• Minimum dose single pool Kt / V = 1,2 or URR = 65%
• Target dose single pool Kt / V = 1.4 or URR = 70%
• Dialysis 2 times / week is not recommended unless
there is still significant residual kidney function (GFR>
= 5ml / minute)
Konsensus Pernefri 2003

Inisiasi HD
1. LFG < 10 mL/m dengan gejala uremia/malnutrisi
2. LFG < 5 mL/m walaupun tanpa gejala
3. Indikasi khusus :
•Terdapat komplikasi akut (edema paru, hiperkalemia,
asidosis metabolik berulang)
•Pada pasien nefropati diabetik dapat dilakukan lebih
awal.
Konsensus Pernefri 2003

• Target Kt/V yang ideal adalah 1,2 (URR 65%)

untuk HD 3x perminggu selama 4 jam perkali HD
dan 1,8 untuk HD 2x perminggu selama 4-5 jam
perkali HD.

• Frekuensi pengukuran adekuasi HD sebaiknya

dilakukan secara berkala (idealnya 1 kali tiap
bulan) minimal tiap 6 bulan.
Ideal dialysis patient:

• Kt/V > 1.3.

• Time Average Urea Consentration < 52.
• Protein Catabolic Rate >1.1 gm/kg/day.
• Good nutritional indices:
• plasma albumin >4 gm%.
• pre DxBUN= 70-90mg%.
• Hemoglobin level >11 gm.
• Minimal degree of dialysis complications.
4. PRESCRIPTION OF DIALYSIS
DOSE
Hemodialysis Prescription

Determines Adequacy
• Hemodialysis Prescription Components:
• Duration of Treatment min 4 hours
• Dialyzer Urea Clearance (KOA)
• Blood Pump Speed min 250 ml/min
• Dialysate Flow Rate 500-800 ml/min
• Heparinization
• Access
Frequency and Duration of Dialysis
• Observational and controlled nonrandomized studies had
suggested that more frequent and/or longer dialysis
improves the patient’s
• quality of life,
• controls hyperphosphatemia,
• reduces hypertension, and
• results in regression of left ventricular hypertrophy (LVH)

Clin J Am Soc Nephrol. 2006;1(1):33-42.

TECHNICAL REQUIREMENTS FOR
DELIVERY OF ADEQUATE
DIALYSIS:
• Vascular access:blood flow ≥ 300 ml/min .
• Dialysis fluid: bicarbonate buffered, sterile, pyrogen-free.
• Dialyzer:-Highly permeable, biocompatible membrane.
• -Surface area: ≥1.3 m2.
• Dose of dialysis:
• Minimum Kt/V urea: 1.2–1.3
• Minimum URR : 65–70%.
• Measurement of dialysis dose: once / month.
• Weekly dialysis time: 12 hr
FAKTOR FAKTOR YANG
MEMPENGARUHI DELIVERED Kt/V

• Pembersihan urea dializer yang efektif (Kd) tergantung

pada kecepatan aliran dalam ruang penampungan darah
dan dialisat, dialyzer KoA, area permukaan membrane
efektif, hematokrit, antikoagulation, dan resirkulasi.
• Lama waktu HD , t sangat penting untuk mencapai target
Kt/V .
• V tidak berubah banyak selama satu sesi, tetapi bisa
berubah seiring waktu.
• Dosis HD perlu disesuaikan bila ada kenaikan V.
Sebaliknya, jika ada kehilangan massa tubuh, yang
biasanya terjadi karena penurunan V, Kt/V tidak boleh
dikurangi melainkan disesuaikan ke angka yang lebih
tinggi, V ideal pasien, atau seperti yang diminta
sebelumnya, ke BSA.
• Penyebab yang sering mengakibatkan dosis HD yang
rendah dan tidak layak adalah masalah akses vaskular
yang mengarahkan resirkulasi.
FAKTOR FAKTOR YANG
MEMPENGARUHI DELIVERED Kt/V

• Pembersihan urea dializer yang efektif (Kd)

tergantung pada kecepatan aliran dalam ruang
penampungan darah dan dialisat, dialyzer KoA,
area permukaan membrane efektif, hematokrit,
antikoagulation, dan resirkulasi

• Lama waktu HD, t sangat penting untuk mencapai

target Kt/V

• V tidak berubah banyak selama satu sesi, tetapi

bisa berubah seiring waktu.
FAKTOR FAKTOR YANG MEMPENGARUHI
DELIVERED Kt/V

• Pengambilan sampel darah yang tidak tepat harus juga

dipertimbangkan karena sampling post HD yang terlambat
akan mengurangi hasil Kt/V.
• Jika nilai Kt/V yang rendah tetap tak bisa dijelaskan, treatment
harus ditingkatkan dan harus dipertimbangkan penggunaan
dialiser yang lebih efisien, aliran darah dan dialisat yang lebih
cepat.
selama HD meningkatkan Kt/V
• Simulasi otot aktif atau pasif
dengan cara meningkatkan suplai darah ke jaringan otot
dan juga memfasilitasi pembuangan urea dan phosphate.
• Nilai Kt/V pemberian harus di cek kapanpun resep HD diubah
secara substantial.
67

The method for raising the delivered

dialysis dose

• The most effective method

• Increase dialysis time (frequency and
time HD)
• Using a dialysis membrane that has a
larger size or permeability
• Another method
• Increases the blood flow
• Increase the dialysate flow
Optimal Dialysis
 Terapi Dialisis yang Optimal

Penilaian
Konseling Diet Status Nutrisi

Pelaksanaan
Penilaian Terapi
Dialisis

Perencanaan Dialisis yang Dilakukan

Dialisis vs
Dialisis yang
Direncanakan

Modifikasi dari Renal Division, Baxter Healthcare Corporation

Kesimpulan

• Adekuasi HD adalah kecukupan dosis HD yang diberikan

kepada pasien dengan tujuan untuk meningkatkan kualitas
hidup pasien sehingga mempunyai harapan hidup yang sama
dengan orang sehat.
• Secara klinis adekuasi HD memperlihatkan ; pasien aktif
secara fisik,status nutrisi baik, tidak anemis,tidak hipertensi
dan euvolemik.
• Dua metode yang umumnya digunakan adalah Kt /V dan
URR.
• Peresapan HD meliputi , lama HD, UF Goal ,jenis dialiser,
antikoagulan,Qb,Qd, temperatur.
Membranes and Hemodiafiltration
Versus HD
• Cardiovascular (CV) disease is the leading cause of death
in patients with CKD stage with uremic toxins and the
kidney failure milieu including volume expansion likely
important contributing factors.
• Compared to low-flux dialysis, high-flux dialysis and
convective therapies such as hemofiltration and
hemodiafiltration provide higher clearance of larger
solutes, removal of which might improve CV outcomes.
Small-Solute Clearance
• Assessment of dialysis requires measurement of the
dialysis dose.
• Included herein are the current recommended methods for
measuring what dialysis does best, the purging of small
dialyzable solutes, with the assumption that this function is
the essence of the life-prolonging effect of dialysis.
Adverse Effects of Dialysis
• exposure of the blood to a large foreign surface for several
hours would cause an inflammatory response in the patient and
deplete vital constituents of the blood, such as platelets and
clotting factors.
• Removal of low-molecular-weight hormones, vitamins, and
other vital molecules.
• Membranes were developed to be “biocompatible,” causing
less interaction with blood constituents
• transient intra- and postdialysis alkalosis and
dialysis-associated reductions in blood pressure (BP), serum
potassium, and serum phosphorus and changes in other
electrolytes and proteins that may amount to a “perfect storm”
of stress potentially responsible for acute cardiac events, as
well as longterm effects on the brain and CV system
• Timing of Hemodialysis Initiation
• Frequent and Long Duration Hemodialysis
• Measurement of Dialysis—Urea Kinetics
• Volume & BP Control—Treatment Time & UF Rate
• Hemodialysis Membranes
• Hemodialysis Membranes
Frequent and Long Duration
Hemodialysis
In-center Frequent HD

• Suggest: Patients with ESRD should be offered in-center

short frequent HD as an alternative to thrice weekly HD,
with discussion of patient preference and risk/benefit.

• Recommend:All patients need to be informed of risk of

in-center frequent HD, including increase in vascular
access complications and potential hypotension during
HD.
Measurement of Dialysis: Urea Kinetics
• Recommend:Target single pool Kt/V of 1.4 and minimum
Kt/V of 1.2 per HD session in thrice weekly HD.

• Dose may be reduced in patients with significant

residual kidney function provided residual kidney
function is measured periodically.
Volume and Blood Pressure Control:
Treatment Time and Ultrafiltration Rate
• Reduce dietary sodium intake and ensure adequate
sodium/water removal with HD to manage HTN and
volume. Grade of 1B.

• Prescribe UF rate balancing risk of hemodynamic

instability with benefit of volume removal. No change from
2006.No grade
Volume and Blood Pressure Control:
Treatment Time and Ultrafiltration Rate
• Recommend:Patients with low residual kidney function
(<2mL/min) undergoing thrice weekly dialysis need a
minimum of 3 hours per treatment. No change from 2006.
Grade of 1D.

• •Consider longer session or extra session if large

weight gains, high BP, high UF rates, metabolic
complications, or inability to achieve dry weight. No
change from 2006. No grade given for this
Basic goals of adequate dialysis:

• Fluid removal to expected 'dry weight' at end of dialysis.

• Predialysis BP < 140/90 mmHg with or without
antihypertensive drugs.
• Predialysisplasma concentrations:
• Potassium: ≤5.5 mmol/l without using ion exchange resins.
• Bicarbonate: ≥24 mmol/l .
• Inorganic phosphate: ≤5.5 mg/dl without oral binding agents.
• Urea: <35 mmol/l with daily protein-intake1.2 g/kg/BW .
• Albumin: ≥40 g/l & Cholesterol= 200-300 mg%
• Haemoglobin: 11–12 g/dL with or without ESA.

Rodriegaz handbook of dialysis 2012