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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 and • Insulin resistance
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)


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.
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):


• Jawab :
Diketahui :
• 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

• The retention 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
through cell
Standard Solute
membranes
Translocation

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 • Temporary increase


or 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
1.5 Rendah
1.
5
RR = 0.93/0.1 Kt/V 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.
Optimal Dialysis 
Terapi Dialisis yang Optimal

Penilaian
Penilaian
Konseling
Konseling Diet
Diet Status
Status Nutrisi
Nutrisi

Pelaksanaan
Pelaksanaan Penilaian
Penilaian Terapi
Terapi
Dialisis
Dialisis

Perencanaan
Perencanaan Dialisis
Dialisis yang
yang Dilakukan
Dilakukan
Dialisis vs
vs
Dialisis
Dialisis
Dialisis yang
yang
Direncanakan
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

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