HIGH D ALLELE FREQUENCY OF ACE I/D GENE

POLYMORPHISM IN FAMILIAL HYPERTENSION

IN JAVANESE INDONESIAN

Fredie Irijanto
Division of Nephrology and Hypertension,
Gadjah Mada University, Yogyakarta, Indonesia
Division of Nephrology, Department of Internal Medicine,
Juntendo University, Faculty of Medicine, Tokyo, Japan
 HD Initiation
HD Initiation and and
Prescription
Prescription

By Fredie Irijanto

By Fredie Irijanto

Nephrology and Hypertension Division

Academic Hospital Universitas Gadjah
Nephrology andMada
Hypertension
Division
Academic Hospital Universitas
 Pengertian Inisiasi
Pengertian Inisiasi
Adalah tindakan
Adalah tindakanuntuk memulai dialisis
untuk
pada pasien dengan gagal ginjal kronik
memulai
(GGK)
dialisis pada pasien
dengan gagal ginjal kronik
(GGK)
Tujuan :
Mengatasi kegawatan yang terjadi akibat
Tujuan :
gagal ginjal kronik dan mencegah
Mengatasi kegawatan
kerusakan ginjal yang lebihyang
lanjut.
terjadi akibat gagal ginjal
kronik dan mencegah
kerusakan ginjal yang lebih
lanjut.
Secara ideal
Secara semua
ideal semuapasien-pasien GGK
pasien-pasien GGK
dengan
denganLFG<15mL/menit
LFG<15mL/menit dapat mulai
dapat mulai
menjalani dialisis. Namun dalam
menjalani dialisis. Namun dalam
pelaksanaan klinis pedoman yang dapat
pelaksanaan klinis pedoman yang dapat
dipakai adalah :
dipakai adalah :
LFG<10mL/menit dengan gejala
LFG<10mL/menit dengan gejala
uremia/malnutrisi
uremia/malnutrisi
LFG<mL/menit walaupun tanpa gejala
LFG <5mL/menit walaupun tanpa gejala

Indikasi Khusus
Indikasi Khusus
Pada pasien Nefropati diabetik dapat
Pada pasien nefropati diabetik dapat
dilakukan lebih awal yaitu
dilakukan lebih awal yaitu
LFG<15mL/manit.
LFG<15mL/menit.
 Indikasi Absolut
Indikasi absolut : :
Perikarditis
Perikarditis
Asidosismetabolik
Asidosis metabolikberulang
berulang
Overloadcairan
Overload cairanatau
atauedema
edemaparu
paruyang
yang refrakter
refrakter
terhadapdiuretik
terhadap diuretik
Hipertensiberat
Hipertensi beratdan
danprogresif
progresifyang
yangtidak
tidak respon
respon
denganobat.
dengan obat.
Ensefalopatiatau
Ensefalopati atauneuropati
neuropatiuremikum,
uremikum, dengan
dengan
gejalaseperti
gejala sepertibingung,
bingung,klonus
klonusotot,
otot,drop
drop foot,
foot, atau
atau
kejang;
kejang;
Pendarahanyang
Pendarahan yangsignifikan
signifikanyang
yangdisebabkan
disebabkan oleh
oleh
diatesisuremikum
diatesis uremikum
Nauseadan
Nausea danVomitus
Vomitusyang
yangpersisten
persisten
Kadarkreatinin
Kadar kreatininplasma
plasmadidiatas
atas12mg/dl
12mg/dl atau
atau BUN
BUN
didiatas
atas100mg/dl
100mg/dl
Progression
Progressionofofchronic
Chronicrenal
Renalfailure
Failure
Factors causing
Factors causingprogression
progression
Sustaining
Sustainingprimary
primarydisease
disease
Systemic
Systemichypertension
hypertension
Intraglomerular
Intraglomerularhypertension
hypertension
Proteinuria
Proteinuria
Nephrocalcinosis
Nephrocalcinosis
Dyslipidaemia
Dyslipidaemia
Imbalance
Imbalancebetween
between renal energy
renal energy
demands
demands and supply
and supply
Indikasi dialisis pada gagal ginjal akut
Severe fluid overlad
Rafractory hypertension
Uncontrollable hyperkalemia
Nausea, vomiting, poor appetite, gastritis
with hemorrhage
Lethargy, malaise, somnolence, stupor,
coma, delirium, astherixis, tremor, seizures,
Pericarditis (risk of hemorrhage or
tamponade)
Bleeding diathesis (epistaxis – GI bleeding
and etc..)
Severe metabolic acidosis
BUN >70-100mg/dl
Indikasi dialisis pada gagal ginjal kronik
Pericarditis
Fluid overload or pulmonary edema
refractory to diuretics
Accelerated hypertension poorly responsive
to antihypertensives
Progressive uremic encephalopathy or
neuropathy such as confusion, asterixis,
myoclonus, wrist or foot drop, seizures.
Bleeding diathesis attributable to uremia
Persistent nausea and vomiting
Plasma creatinine concentration >10-12
mg/dl or BUN>100 mg/dl
Anorexia
Depression, decresed attentiveness and
cognitive tasking
Severe anemia unresponsiveness to
erythropoietin
Persistent pruritus or restless leg syndrome
HD Prescription

Renal replacement therapy (RRT) = Terapi pengganti ginjal

(TPG):
• Transplantation
• Dialysis: HD, PD
acute intermitent
Terminology
Acute HD : HD session specifically for ARF/AKI continuous

• Short daily HD
• Daily nocturnal (nightly) HD
• Intermittent nocturnal HD = 3 x weekly
• Long intermittent
• Chronic HD
• Continuous HD
Dialysis prescription for short daily HD
Short, daily HD : 1.5 – 2.5 hours for 6-7/week
Best : 3 hrs short daily HD - high blood flow
- high dialysate flow
NB : Dialysate composition ~ conventional HD

Daily nocturnal HD : 5-7 d/week; night sleep ± 8 hrs

Blood flow (qb) : 200-300mL/min
Children : 100mL/min
Dialysate flow : 300mL/min
Bicnat 30 mEq
Ca : 3-3.5 mEq
Dialysate composition :
- Lactat : 40-45 mEq/L
-K : 1 mEq/L
- Na : 140 mEq/L
- Ca : 3.0mEq/L
- Mg : 1mEq/L
- Cl : 105 mEq/L
- Glucose : 100 g/dL
Factors related to HD prescription
1. HD membran (dialyser/ holofiber/ ginjal
buatan)
2. Dialysate composition
3. Buffer solution
4. BFR (qb)
5. Dialysate temperature
6. Ultrafiltration (UF)
7. Anticoagulation (heparinisasi)
Acute HD prescription
Acute HD treatment : HD session for
ARF/AKI
Indications :
- Volume overload (diuretic failure)
- Hyperkalemia
- Metabolic acidosis
- Uremia
- Toxic overdose : alcohol, drug. Lain2 :
leptospirosis, intok jengkol
ARF/AKI
Death rate  : ICU/hospital ±50%
First dialysis
Lama sesi HD: lama sesi HD dan blood flow
merupakan faktor utama
Aware: dialysis disequilibrium syndrome, too
fast reduce ureum (over correction ureum)
DDS dapat terjadi pada akut or kronik HD
A first dialysis reduce blood urea by 30%
First HD: 2 jam
2nd HD: 3 jam
3rd HD: 3,5-4 jam
 Blood flow rate (BFR): 150-200 mL/min
Pada pasien lebih besar s/d 250 mL/min
 Lama HD bisa 2,5 jam

Ultra filtration (UF): maks 2 L.

Pada psn oedema paru berat: additional UF
 Dialysate flow: 500 mL/min
1) HD membran
Outcome (clinical outcome)
2 types
- low flux : small pores
- high flux : large pores
Suggest :
- water quality ok: high flux
- water quality poor : low flux
2) Dialysate composition
Contains : potasium (K), Na, HCO3, Ca, Mg,
Cl, glucose

Acute vs chronic :
Acute : rapidly correct metabolic
abnormalities such as hyperkalemia,
metabolic asidosis.
Setting Na, K, Ca, bicnat (HCO3)
2a. Dialysate K concentration
No standard dialysate potasium consentration in
acute HD,
thus need to know K pre HD.
The goal of an acute HD : normalizing the K serum
for 24 hours
The level of K concentration in the dialysate for
acute HD 2-4 mEq/L

◦ Acute or severe hyperkalemi

◦ Signs acute/severe hyperkalemi
- muscle weakness
- cardiac conduction abnormalitis
◦ Failed medication  RRT : HD or PD
General approach (no consensus)
Predialysis K < 4 : dialysat K 4 mEq/L
Predialysis K 4-5.5 : dialysat K 2-4
mEq/L (3.5 mg/L)
Predialysis K > 5.5 – 8 : dialysat 2
mEq/L
Predialysis K > 8 : dialysat 1 mEq/L
(caution for
hypokalemia!!)

NB : Check K every 60’

2b. Dialysate glucose concentration
 modulate K removal (with insulin)
- Lower dialysate glucose concentration :100
mg/dL
mild – modest hyperkalemia : 200 mg/dL
Complication with K removal (see emergency
in Nephrology)
2c. Dialysate Na concentration ( important !! )
choice of dialysate sodium concentration
depends on:
- pre dialysis Na serum
- hemodynamic status, etc
 High Na dialysate for majority patient :
141 mEq/L
 Low Na dialysate : 137 mEq/L
 In general : 137 mEq/L
Disnatremias
Avoid rapid correction of abnormal Na serum
Caution : neurogenic complication of cerebral
edema

Hyponatremia, correction 1.5-2 mEq/L per hour

to increase 10-18mEq/L in first 48 hours.

Hypernatremia, correction with dialysate Na

concentration
within 2mEq/L of plasma Na
3. Buffer solution
Acetate is presenting not routinely used : cardiac
hemodynamic problem.
Bicarbonat : precipitate with Ca – Mg separate
rare : altered mental status, weakness,
cramping,
(due to metabolic alkalosis)
The dialysate bicnat vary based on acid-base
patients.
Range is usual on chronic HD : 33-35 mEq/L.
for metabolic acidosis moderate to severe : 40
mEq/L
If bicnat predialysis >28 (alkalosis) : lower bicnat
dialysate
Calcium
In chronic HD : calcium dialysate
concentration 2.5mEq/L
Acute HD : 3-3.5mEq/L
High vs low : (3.5 vs 2.5mEq/L)
High dialysate Ca  post HD MAP
High dialysate Ca improved the lowest
intradialytic MAP (NS)
Treatment of hypocalcemia in sepsis p
may improve outcome
Do not administering Ca to treat
hemodynamic instability on acute HD.
Conclusion :
 Hypocalcemia (Ca < 8mg/dl) : Ca dialysate 3-
3.5 mEq/L
 Hypercalcemia (Ca.12mg/dl) : Ca dialysate 2-
2.5mEq/L
 Mild – normo Ca : 2.5mEq/L

 To treat intradialystic hypotension : Ca

dialysate + sodium profiling
+ lower dialysate temperature.
4. Blood Flow Rate = quick blood (QB)
 Determined by various factors :
- For chronic HD : BFR incrementally
- For ARF/AKI depend on catheter, length, and
location (central vein catheter)
 Prefer for best BFR : femoral vein, right side IJ
cath
 Acute HD vascular access discussed
separately
 Principle :
- Higher blood flow : IHD/short daily HD
- Lower blood flow : CRRT
 Usually BFR : 200-400mL/min
 Hemodynamic unstable such as : septic shock,
decomp cordis, bleeding usually by SLED or
CRRT for 6-12 hours or
24-48 hours.
 Commonly : 100mL/min for 8-24 hours/day 
SLED
(Sustained low efficiency dialysis or hybrid
hemodialysis)
Note :
HD initiation, BUN 80-100mg/dL
IHD : 3 times per week
CRRT : 25 mL/per hour
5. Dialysate temperature : vasoconstriction: BP
cool temperature : 35C
Hyperthermia : function myocard, blood
clothing, end organ perfusion
Benefit : - fewer intradialystic hypotension
- Higher post HD MAP

K/DOQI 2005 & 2007 European :

cool temperature in frequent hipo
intradialystic patient.
6. Ultrafiltration & Blood Pressure Control
Hypotension (intradialytic) can occur during UF HD :
Reduce UF
Stop UF
And/or BFR (Qb)
Prevent intradialytic hypotension during IHD:
Minimize UF rate by increasing frequency and/or
duration
Sodium/ultrafiltration (UF) profiling
Cool temperature dialysate
Higher dialysate Ca
Vasopressor
Hemodynamic instability during HD (Emergency in
Nephrology)
HT in dialysis pts
 Pathogenesis?
 HT defined?
 Target goal BP?
 How to treat?
Pathogenesis:
Sodium and volume excess, RAAS activation, ET,
NO, EPO, Ca,
calcification artery, pre exist HT, sympathetic
activity.

Target: pre HD < 140/90

post HD < 130/80
7. Anticoagulation
Type of anticoagulation :
1. Traditionally standard heparin
effective
shorter half life
cheaper
easier to tailor dose
2. Low molecular weight heparin (LMWH)
Easy and convenience
Expensive
Not every patients suitable
Standard anti-coagulation :
Routine HD : standard dose heparin IV at the start
then mid treatment dose,
or heparin initial IV, followed by constant size infusion.
 Heparin for anticoagulan (Heparinisasi)
1. Dosis heparin
- Dosis awal : 25-50 U/kg BB
- Maintenance : 500-1000 U/jam
2. Cara pemberian
- Continuous
- Intermittent
3. Teknik pemberian heparin
Heparinisasi umum/standar
a. continuous
b. intermittent
Heparinisasi minimal
a. continuous
b. intermittent
Heparinisasi Regional
perbandingan protamin dan heparin
1 mg protamin dgn 100 IU heparin
Bebas/free heparin
Restricted heparin = heparinisasi minimal
(ketat)

Who required restricted heparin?

recent surgery
recent injury or trauma
recent blood loss (ulcers)
coagulation disorders
Method

Doses :
New patient : 250-500U for loading dose
500-800U per hour for
maintenance
Known patient : ½ usual loading dose
normal maintenance infusion
Heparin for high risk patients
Regional Heparin
heparin/protamin infusion : difficult, rarely
used
Regional citrate : rarely used today
Heparin Free Dialysis
Blood circuit is flushed with 100-200mL
NaCl/20-30 min
Depend on:
BFR
Hb
Status anticoagulation
Other medication
Pts who require Heparin Free HD?
Head injury (high risk)
Pericarditis, recent MI
New pts with unknown status coagulation
Immediately pre operation (<24 hours)
Recent/major trauma
Recent major or vascular surgery
 Dialysis Coagulation
a. Heparinisasi standard
Infusion method
Initial bolus 2000 U ( ±50U/kg)
continuous heparin infusion into arterial line :
500-2000 U/hour
stop heparin 30-60 min before end HD

Bolus method
initial bolus 4000 U
second bolus 1000-2000 U
stop heparin 1 hour before end HD
b. Tight (or minimal) heparin
 for patients with moderate risk of bleeding
- 30 min bolus 5000 U heparin or
constant infusion 250-2000 U/hr (usually 600
U/hr)
- heparin continue until the end of dialysis (HD)
c. Heparin free dialysis
 for pts with actively bleeding : coagulopathy,
trombocitopenia, ICH, recent surgery,
ulcer/bleeding
 rinse circuit with heparinized saline (3000-
5000U/L saline)
flush the rinse to drain
high blood flow (300 mL/min)
rinse circuit every 15-30 min with 25-200mL
saline
increase UF to remove extra saline
avoid blood transfusion
HD prescription for acute
First Dialysis
Hours : 2hrs
Dialyser : small to average
BFR : 150-180 mL/min (qb)
Dialysate: common, bicnat
Heparin depends on indication, usually
free/restricted
UF : maks 2L, maintenance ±5% BW
NB: pada HD kronik yg lama tdk HD,
prescription seperti
HD akut
Maintenance (regular)
4-5 h0urs
Dialyser : standard
BFR : 300-500mL/min (Qb)
Dialysate, common, bicnat
Heparin, usually standard, depend on
underlying.
UF : equal to BW; ±5%BW
max 4kg/HD (1kg ~ 1L)
average : 2-3 kg/HD
Method : high UF for 2 hrs, then reduced to
stop.
Target: dry wet (without edema)
 No gold standard for dry wet assessment
 PadaHD kronik dgn 2 kali sesi HD dlm
seminggu, Kt/V : 1,8-2.

Impossible to achieve adequate solute

clearence with 2x/week
Thus, increasing time of HD is the best way to
reach the maximum clearance
In France (Tassin et al): HD 3x8 jam
menurunkan morbidity dan mortality
 Blood fow
High koA dialyzer: BFR bisa lebih tinggi, 350-
400 mL/min
 Ultrafiltrasi (UF)
- Maksimum 4L in one session
- Average: 2-3 L/ session

Dialyzer rate: 500 mL/min, pd high koA:

800mL/min
Reuse. Kontraindikasi absolute pd HBV, KI
relative pd HIV, HCV
Complication during HD
Hypotension 20-60%
Cardial arrhytmias 5-60%
Cramps 5-25%
Nausea and vomiting 5-15%
Back pain 2-5%
Chest pain 2-5%
Itching 1-5%
Fever 1%
Other complication (rare) :
Air embolism
Seizures
Hemolisis
Dialysis disequilibrium
1st use syndrome
acute urticaria
cardiac tamponade
 Dialysis disequilibrium syndrome (DDS)

dapat terjadi pada akut maupun kronik HD

sign: headache, nausea, disorientasi,
restlessness, blurred vision, asterixis
Mild syndrome: cramps, nausea, dizzines
Patofisiologi: edema serebral karena influks
osmotik air ke dalam otak setelah penarikan
urea

Thus, slow removal urea to minimize the risk

 Manajemen hipotensi intradialitik
- Head down
- Nacl 0,9% 100 ml
- Reduce UF to 0
- Tambah nacl 0,9%

Bila persisten, evaluasi sbb:

- Dry wet too low?
- Short acting anti HT?
- UF rate
- Naikkan dialisat na
- Lower dialysate temp to 34-36
- Increase Hb
HD in children
Principle ~ adult
Dialysis characteristics : - flat plate dialyzer
- smaller HF dialysis
Low blood flow rate
Shorter time

Access: AV fistula
RESUME
Dialysis Prescription :
1. Selection of the dialysis
2. Selection of the tubing
3. BFR
4. Length and frequency of dialysis (HD)
section
5. Determination of fluid removal amount
6. Heparinisation
1. Dialyzer : low flux is prefer (debatable?)
2. BFR : body weight x 8 mL/min
3. Length & frequency : 4 hrs, 3x/week
4. best : 2-3 hrs for 6-7x/week
home HD is not option for very small
children due to safety
4. Fluid removal : 10mL/kg/hour, < 5% body
weight
Body weight > 40kg : 600mL/hours
Some patients : <5% BW for 3x/week is OK
5. Anticoagulation
Heparin infus slowly continuous during HD
session 5-50 U/kg/hour.
LMWH : bolus 1 mg kg at beginning HD
session
Thank you for your
attention
THANK YOU very much

ARIGATO Gozaimashita