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8/18/2019 3. Dr. Afiatin-simpo Dialisis Neuropati Uremikum
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MANAJEMEN NEUROPATI UREMIK
AfiatinAfiatin
UNPAD RS HASAN SADIKIN BANDUNGUNPAD RS HASAN SADIKIN BANDUNG
PERNEFRI KORWIL JAWA BARATPERNEFRI KORWIL JAWA BARAT
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NEUROPATI
NEUROPATI UREMIK
• Neuropati yang terjadi pada
pasien dengan penurunanfungsi ginjal
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KONDUKSI SYARAF PADA CKD
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FUNGSI OTONOM & CKD
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PATOFISIOLOGI NEUROPATI UREMIK
Aspek biokimia : multifaktorial
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Patofisiologi neuropati• Biasanya melibatkan axon dengan diameter besar terutama di
tungkai• Defek kehilangan axon dengan demyelinisasi sekunder
• Terjadi perlambatan trasmisi saraf
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• Gejala klinis dan parameter konduksi saraf
membaik dengan cepat beberapa hari setelah
transplantasi ginjal
PATOFISIOLOGI KHUSUS NEUROPATI UREMIK
menghambat transmisi saraf mempunyai
peranan penting dalam patofisiologi kelainan
saraf pada PGK
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aktivitas Ouabain
sensitive calcium ATPase
aktivitas Ouabain
sensitive calcium ATPase
Toksin uremik lainPolyamines, phenol
metabolites, myoinositol, and3-carboxy-4-methyl-5-propyl-2-fluranpropanoic acid, (yangmenghambat transport asam
organik )
Toksin uremik lainPolyamines, phenol
metabolites, myoinositol, and3-carboxy-4-methyl-5-propyl-2-fluranpropanoic acid, (yangmenghambat transport asam
organik )Toksin mdiddle molecule :
guanidine(methylguanidine) yang
Toksin mdiddle molecule :
guanidine(methylguanidine) yang
inhibisitransketolasi dan
pyridoxalphosphate kinase(proses yang
terjadi pada axon)
inhibisitransketolasi dan
pyridoxalphosphate kinase(proses yang
terjadi pada axon)
pumppump meng n s so umATPase pump,
hormon parathyroid
meng n s so umATPase pump,
hormon parathyroid
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METABOLISME SIANIDA
Fig. 2. Metabolic pathways of cyanide. CN, cyanide; Na2S
2O
3, sodiumthiosulphate; SCN−, thiocyanate; CN-B
12, cyanocobalamin; HCN,
hydrocyanic acid; HCNO, cyanic acid; HCOOH, f ormic acid.
Koyama et al. Nephrol Dial Transplant 1997: 12: 1622-28
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d e t o k s i f i k a s i
SCN
Enzym Rhodanese(Na2S 2O3 )
ekskresi melalui urine
methylcobalamin (CH3 – B12)
mempercepat proses detoksifikasiCNmelalui sintesis menjadiCyanocobalamin (CN – B12 )
(akumulasi SCN ) (Clearance SCN menurun)-
--
-
-PATOFISIOLOGI NEUROPATI UREMIK
konsep baru : sianida merupakan toksin uremik neurogenik
CN-B12detoksifikasiPelepasansubstansi Cyanida (CN )dalam tubuh
CN pool
(CN pool meningkat )
Penyebab utama terjadinya Neuropati
- -
-
Koyama et al. Nephrol Dial Transplant 1997: 12: 1622-28
Proporsi mecobalamin menurunProporsi mecobalamin menurun
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KADAR TIOSIANAT CKD
40
50
60
70
80
u m o l / L
p < 0.01 p < 0.01
p < 0.01
0
10
20
30
S C N
Control ESRD* Pre-HD Post-HD Pre-HD Post-HD
*
Smokers (9)Non-smokers (21)n = 13 n = 12
Koyama et al. Nephrol Dial Transplant 1997: 12: 1622-28
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PASIEN CKD DAN PEROKOK
MEMERLUKAN VITAMIN B12 LEBIH
TINGGI DIBANDINGKAN ORANG
NORMAL
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Diagnosis neuropati uremik
• Langkah pertama : hilangkan penyebab laindengan anamnesis , pemeriksaanfisik, evaluasi preskripsi dialisis danpemeriksaan penunjang sederhana
• Gold standard : Nerve conduction studies(NCS) pada EMG
• NCS : neuropati generalisata tipe axonal
dengan penurunan amplitudo sensoris >motoris
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DIABETIC NEUROPATHY :
SIGNS AND SYMPTOMS OF NEUROPATHY
SENSORY MOTOR AUTONOMIC
PositiveSpontaneous pain
Burning
Pricking
Squeezing
Negative
Numbness*
Deadness
Weakness
atrophy
Sudomotor
Pupilary
Cardiovaskular
Urinary
Gastrointestinal
Tingling*
Knife-like
Lancinating
Electric shock
Aching
Trobbing
Freezing
Tightness
Stimulus-evoked pain
Allodynia*
Hyperalgesia
Loss of sensation
Loss of balanceDistal rox ma Focal
allodynia foot ulceration
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Diagnostic Tests
• Assess symptoms - muscle weakness, musclecramps, prickling, numbness orpain, vomiting, diarrhea, poor bladder control andsexual dysfunction
• Comprehensive foot exam
– n sensa on an s n n egr y – Quantitative Sensory Testing (QST)
– X-ray
• Nerve conduction studies
• Electromyographic examination (EMG)• Ultrasound
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DIAGNOSTIC TEST
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DIAGNOSTIC TEST
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PENATALAKSANAAN
• Transplantasi ginjal : di Indonesia masih banyak
hambatan seperti sosial dan ketersediaan donor
dializer high flux atau teknik khusus seperti
Hemodiafiltrasi atau HFR tetapi biaya lebih mahal
• Medikamentosa : bisa menjadi pilihan terapi yang
mungkin dapat dilaksanakan
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Penelitian yang dilakukan oleh Koyama, yang
telah di publikasikan di urnal “Nephrol Dial
Apakah Cukup dengan melakukanHemodialisa saja ?
Disebutkan bahwa :“Tindakan hemodialisa terbukti belum dapat
menurunkan kadar Thiocyanete (SCN) secara
optimal”
Transplant tahun 1997
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VITAMIN B 12
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Peranan methylcobalamin dalam neuropati
• Mecobalamin memperbaiki efek terapi terutama untuknyeri melalui : – Meningkatkan availibilitas dan efektivitas dari noradrenalin
dan 5hydroxytryptamine pada sistem nosiseptif
– Memperbaiki nerve conduction velocity
– – Menghambat Ectopic Spontaneous Discharge.
• Schmerz, 1998, Ming Zhang, Wenjuan Han, Sanjue Hu, and Hui Xu,2013
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CN-B12
(Sianokobalamin)
OH-B12
Non aktif
TRANSPORT COBALAMIN
Non aktif
Dilepaskan
ke dalam sel
Dilepaskan
ke dalam sel
y roxoco a amn
cytosol
CH3 – B12
Mecobalamin
mitokondria
AS – B12
Adenosyn Cobalamin
Metabolisme asam amino
Dari protein dan lemak
Cycle Homocysteine
aktif
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Vitamin B12 dalam tubuh
• Dalam tubuh : 2 – 5 mg• Dewasa : 50 % ada di hati
• Serum :
• Methylcobalamin : 60 – 80 % vit B12
•• Hati :
• AdoB12 : vit B12 utama : pooling
• Liver : hanya 1 % cyanocobalamin
dikonversi menjadi methylcobalamin• Urine :• Methylcobalamin : vit B12 utama
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VITAMIN B 12 DAN DIALISIS
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VITAMIN B 12 DAN DIALISIS
• Vitamin B12 larut
dalam air
• Dalam plasma
terikat dengan
protein
transkobalamin 2
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Klirens vit B12
Dializer Low flux
Penelitian : pada high flux klirens vit B12 bisasampai 105 ml/menit saat HD
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DOSIS
• 1500 mcg - 6000 mcg/hari oral / IM
• Jangka panjang 3 hingga 6 bulan
• Neuropati perifer: + ALA
• ↑ Homocystein: + FA
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NEUROPATI UREMIK &
METHYLCOBALAMIN
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Efficacy of IV methylcobalamin and oral folic acid in the treatment of uremic
neuropathy in chronic haemodialysis patientsL.Venu Madhavi1*, D.Santha Rao2, T.Ushasree1, S.Ramesh1
1 Department of Pharmacology, Gandhi Medical College, Secunderabad-500 003, Andhra Pradesh, India2 Department of Biochemistry, Guntur Medical College, Kannavari Thota, Guntur-522 004, Andhra Pradesh, India
Received: 26 Feb 2013 / Revised: 04 Mar 2013 / Accepted: 06 Mar 2013 / Online publication: 23 Mar 2013
pu s eABSTRACT
The aim of the present study was to assess the efficacy of methylcobalamin and folic acid for the treatment of uremic
neuropathy. The study was conducted on 35 chronic renal failure patients on maintenance haemodialysis. All the patients
were given 500µg of intravenous methylcobalamin thrice weekly after each dialysis session and 5mg of folic acid orally daily
for 6 months. The following points were noted at the start and at the end of the study–(i) Serum vitamin B 12 levels (ii) Serum
folic acid levels (iii) Neuropathic pain/paresthesia grading (Modified published criteria by Dyck et al ) (iv) Neurological
disability score (v) Neurological symptom score (vi) Nerve conduction studies. High dose supplementation of
methylcobalamin and folic acid led to ultrahigh serum levels along with significant clinical and electrophysiological
improvement in neuropathy.
Key words: Folic acid, High dose, Improvement, Methylcobalamin, Nerve conduction studies, Uremic neuropathy
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Table 1
Scores before and after treatment
efore treatment
(Mean±SEM)
fter treatment
(Mean±SEM)
Value
PG 1.08±0.2 0.28±0.08 0.001**
DS 34.23±1.38 32.8±1.51 0.001**
SS 2.37±0.48 0.83±0.29 0.001**
NPG-Neuropathic pain grading, NDS-Neurological disability scores, NSS-
Neuropathic symptom scores
**highly significant
Pre
Mean
Post
Mean
Serum vit B12 647,14 77194,4
Serum asam folat 20,11 4545,86
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PENGGUNAAN LAIN METHYCOBALAMINE
PADA PASIEN DIALISIS
• Hyperhomosisteinemia : bersama asam folat
– Hiperhomosisteinemia : faktor risiko
kardiovaskular
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KESIMPULAN
• Neuropati uremik merupakan salah satu masalahpada pasien dialisis
• Penyebab : toksin middle molecule dan sianida
• Penatalaksanaan utama adalah transplantasi
• Pemberian medikamentosa salah satunya vitaminB12 bermanfaat dalam memperbaiki neuropatiuremik
• Methylcobalamin : jenis preparat vitamin B12dalam bentuk aktif mempunyai efek yang baikpada pasien dialisis
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TERIMA KASIH