SINDROM NEFROTIK PADA ANAK

Prof.Dr.dr.Syarifuddin Rauf,SpA(K)
Prof.dr.Husein Albar,SpA(K)
dr.Jusli Aras,M.Kes,SpA(K)

Divisi Nefrologi, Departemen Ilmu Kesehatan Anak,Fakultas

Kedokteran Unhas /RSUP.Dr.Wahidin Sudirohusodo
2019
Tingkat kemampuan yang harus dicapai

• Tingkat 2
• Peserta didik mampu mendiagnosis dan merujuk penyakit sindrom nefrotik pada
anak.

04/02/2021 2
Tujuan Umum

Setelah mengikuti pembelajaran ini, peserta didik memiliki pengetahuan tentang

penyakit Sindrom Nefrotik pada anak.

04/02/2021 3
Tujuan khusus

Setelah mengikuti pembelajaran Sindrom Nefrotik pada anak, peserta didik

akan memiliki kemampuan untuk:
• Menjelaskan definisi sindrom nefrotik
• Menjelaskan etiologi dan klasifikasi sindrom nefrotik
• Menjelaskan patologi dan patogenesis sindrom nefrotik
• Menjelaskan gejala klinis dan laboratorium pasien sindrom nefrotik
• Menegakkan diagnosis dan diagnosis banding pasien sindrom nefrotik
• Melakukan pengobatan pasien sindrom nefrotik
• Mengetahui dan mencegah komplikasi pasien sindrom nefrotik
• Menjelaskan prognosis sindrom nefrotik

04/02/2021 4
 PENDAHULUAN
Richard Bright, 1829
Bright Disease
Edema-Proteinuria- penyakit ginjal

Fredrich Von Muller, 1905

Nefrosis - Nefritis -

Munk, 1913
Lipid Nephrosis Henry Christian, 1929
Terapi • Klinik
• Laboratorium
. 1940 Antibiotik “ SN ”
. 1950 Steroid sintetik
Protokol ISKDC 1978, APN 1979, KDIGO 2012
04/02/2021 5
04/02/2021 6
 MEMBRAN FILTRASI

Glicoprotein,
podocalycin

(Heparin sulfate,proteoglycans, sialoproteins)

[Sialoprotein]

04/02/2021 7
04/02/2021 8
DEFINISI
• Proteinuria Massif
• ≥ 40 mg/m2 /jam; 1 g/m2/24 jam
• ≥ 50 mg/BB/hari
• Semikuantitatif (dipstik) > 2+
• Rasio Protein/kreatinin >2 (mg/mg)

• Hipoalbuminemia ≤ 2,5 mg/dL

• Edema
• Hiperkolesterolemia ≥ 250 mg/dl

04/02/2021 9
 KLASIFIKASI

SINDROM NEFROTIK (SN)

Etiologi Histopatologis
1) SN Kongenital (< 1%) 1) SN Kelainan Minimal
2) SN Primer/Idiopatik (90%) 2) SN Kelainan Non-Minimal
3) SN Sekunder (10%)

Respon terhadap pengobatan

1) SN Sensitif Steroid
2) SN Resisten Steroid
3) SN Dependen steroid

04/02/2021 10
ISTILAH
• Respons terhadap terapi steroid
• Initial responder
• Initial non-responder
1) SN sensitif steroid.
2) SN resisten steroid
3) SN dependen steroid
• Remisi
• Relaps
1) SN relaps jarang (Infrequent relaps)
2) SN relaps sering (Frequent relaps)

04/02/2021 11
 INSIDENS
• Negara berkembang : 2 – 4 / 100.000 /tahun
• India : 9 – 10 /100.000 (Arvind Bangga,RN Srivastava)
• Indonesia : 6 / 100.000 Age < 14 tahun (Wila Wirya IGN)
• RS.Wahidin Sudirohusodo 1-2 kasus baru/bulan
• SN 15 kali lebih sering pada anak dibanding dewasa
• Terutama anak umur 2-6 tahun
• Rerata umur 4 tahun
• Rasio ♂ : ♀ : 2 : 1
• Mortalitas 1 – 7,2% (sepsis & trombosis vaskuler)

04/02/2021 12
ETIOLOGI(ISKDC 1978)
1. SN Primar /idiopatik
• SN Kelainan Minimal (76%)
• SN Bukan Kelainan
• Focal Segmental Glomerulosclerosis(FSGS) (7%)
• Focal Global Sclerosis (FGS) (2%)
• Mesangeal Proliferative Glomerulonephritis (4%)
• Membranoproliferative Glomerulonephritis (8%)
• Membranous Nephropathy (2%)
2. SN Sekunder
• penyakit Autoimun : Nefritis lupus, nefritis HSP
• penyakit Infeksi : Hepatitis B, C, HIV
• Obat-obat (Logam berat :merkuri)
04/02/2021 13
 PATOGENESIS

 Teori elektokemis / ion (-) MBG hilang (SNKM)

 Soluble antigen- antibody complex (Non SNKM)

04/02/2021 14
 Soluble Antigen-Antibodi Complex (Non SNKM)
Faktor pencetus (Antigen)

IgG + Kompleks Antigen - Antibodi ( SAAC )

Deposite di membrana basalis glomerulus (MBG)

Aktivasi Komplemen (C3)

Kompleks Imune di MBG (Antigen,IgG+C3)

Simtom ginjal
04/02/2021 15
PATOMEKANISME (SNKM)
1) Electrochemic theory ( fixed negative ion
• Primary disorder
Decrease serum protein
Loss of glomerular
BM sialoprotein hypoalbuminemia

Decrease plasma oncotic

Loss of normal pressure
negative charge

Fluid shift from vascular Edema

Increase to interstitial
glomerular
permeability
Contraction of plasma
volume
Massive
proteinuria
Hypovolemia Shock

04/02/2021 16
MANIFESTASI KLINIS

• Edema
• palpebra, moon face, asites, efusi pleura, edema skrotum/vulva,
edema pretibial dan dorsum pedis
• Gejala komplikasi
• Infeksi sekunder: kulit, peritonitis
• Syok hipovolemik/hipoalbuminemia
• Gangguan Ginjal Akut /Acute kidney injury
• Trombosis vena
• Kejang /tetani (hipocalcemia)
• Anemia
• Retardasi pertumbuhan
04/02/2021 17
 PROTEINURIA MASIF
Edema: Teori underfill
Hipoalbuminemia
• Tekanan onkotik plasma
(80%) Tekanan Onkotik intravaskular
menurun
• Albumin <2.5 g/dL
Perpindahan cairan ke ekstravaskuler

Deplesi volume intravaskuler

Inhibisi ANP Aktivasi SNS Aktivasi RAAS sekresi ADH

Retensi Natrium dan Air

EDEMA

Asupan Makan
04/02/2021 Natrium dan air 18
 Edema : Teori PROTEINURIA
underfill
- Transferine  IgG 
- Glob.Thyroxin  Factor B 
- Glob. Vit. D 
- Antithrombin III 
HYPOALBUMINAEMIA

B-lipoprot   hyperlipidaemia
ONCOTIC PRESSURE 
OEDEMA
HYPOVOLAEMIA
Circulation collaps
Hb  Death
Aldosteron  
 Packed cell vol  Renal perfusion 
Na and H2O
retention  Viscocity  renin plasma  Renal
 failure
Vein thrombosis
04/02/2021 20
“Pitting edema”
pada pretibial

04/02/2021 21
• Edema Genital
- Edema skrotum / vulva

04/02/2021 22
 • Striae pada dinding abdomen

• Efek samping steroid

04/02/2021 23
MANIFESTASI LABORATORIUM
 Urinalisis:
• BJ , pH 
• proteinuria masif (selective - albumin 85-95%)
• leukosituria
• hematuria (22,7% SNKM)
• oval fat bodies
• lipiduria
• hyaline and lipid cast
•

04/02/2021 24
 MANIFESTASI LABORATORIUM
 Plasma :
• Hb , Ht
• hipoalbuminemia, rasio alb/glob terbalik
• hiperkolesterolemia:
•  LDL, VLDL, trigliserida and Lp(a)
• normal: ureum, kreatinin ( 33%)
• Imunoglobulin:
• IgG , IgM 

04/02/2021 25
Plasma : Hiperlipidemia
• Sintesa kolesterol meningkat, trigliserida and lipoprotein
• Katabolisme lipoprotein menurun
• Aktivasi lipoprotein lipase 
• Penurunan : aktivasi reseptor LDL
• Ekskresi HDL meningkat via urine
• Konsentrasi Lp(a) meningkat

04/02/2021 26
Indikasi biopsi ginjal
1. Resisten steroid
2. Umur < 1 tahun dan > 10 tahun
3. Gross hematuria
4. Hipertensi
5. Hipokomplementemia persisten
6. Gagal ginjal
7. Riwayat keluarga gagal ginjal dan ketulian

04/02/2021 27
DIAGNOSIS BANDING

1) Kwashiorkor
2) SNA / GNA
3) Gagal Jantung Kongestif
4) Protein losing enteropathy
5) Hepatic failure

04/02/2021 28
 Tata laksana
1. Terapi imunosupresi
• Prednisone
• Levamizole
• Cyclophosphamide
• Cyclosporine A (CsA)
• Mycophenolate Mofetil (MPA) /Tacrolimus/ Rituximab
2. Terapi non-imunosupresi
• Hipovolemia Nutrsi
• Antiproteinuric agent Anti infection strategy
• Hiperlipidemia Trombosis
• Tfungsi tiroid

04/02/2021 29
 Tata laksana
1) Prednisone
Indication :first episode of NS and subsequent relapses

2) Levamizole
Indication : Frequent relapsing or steroid dependent NS with
unacceptable steroid side-effects, due to MCNS

3) Cyclophosphamide
Indication : Frequent relapsing and steroid dependent NS with
unacceptable steroid side-effects, due to MCNS

04/02/2021 30
 Management
4) Cyclosporine A (CsA)
Indication :
1. Steroid resistance and steroid dependent patients with MCNS who has
failed cytotoxic therapy with alkylating agent such as
cyclophosphamide and with normal renal function
2. NS due to FSGS with normal renal function

5) Mycophenolate Mofetil (MPA)

Indication : Patients who are still relapsing while on prednisone and CsA
alternative drug in those with CsA Toxicity

04/02/2021 31
 Management
6) Tacrolimus
Indication : Patients who fail to respond within 2 months to CsA ± MPA
therapy

7) Rituximab
Indication : Steroid dependent and steroid resistant NS not responding
well to conventional treatment.

04/02/2021 32
 Management – First episode

1. ISKDC
CD = 4 weeks

AD/ID = 4 weeks
Tap. Off

6 Bln- 1 thn
1 2 3 4 5 6 7 8
remission remission

04/02/2021 33
 Management – First episode

2. Arbeitsgemeinschaft fur Paediatrische Nephrologie (APN)

CD = 6 weeks

AD/ID = 6 weeks
Tap. off

1 2 3 4 5 6 7 8 9 10 11 12 1 year

remission remission

04/02/2021 34
 Management – Relapse

CD

AD/ID
CD until remission Tap. Off
( 1 - 4 minggu )

1 year
1 2 3 4

remission remission

04/02/2021 35
 Frequent Relapse Nephrotic Syndrome
or Steroid Dependent

Prednisone FD
Remission Prednisone AD + CPA
Decrease until treshoid doses
0.1 – 0.5 mg/kgBWAD
6-12 months

(1)
Relapse using Relapse using
Prednisone> 0.5 mg/kgBW AD Prednisone> 1 mg/kgBWAD
(2) or
Side effect ↑↑
Levamisol 2.5 mg/kgBW AD
(4-12 months) CPA 2-3 mg/kgBW
(3)
8-12 Weeks
04/02/2021 36
 CPA

Relapse Prednisone standard

Relapse using Prednisone

> 0,5 mg/kgBW AD

Cyclosporine A 5 mg/kgBW/day
1 year

Treatment of Frequent relapses /steroid dependent Nephrotic Syndrome

04/02/2021 37
04/02/2021 38
 Supportive Care
in Nephrotic Syndrome

• Management of Edema
• Management of Infection
• Management of Hypertension
• Management of Thrombosis
• Management of Hyperlipidemia
• Nutritional support
• Stress Dose of steroid
• Parent Education and Counseling

04/02/2021 39
 Supportive Care in Nephrotic Syndrome
Control of Edema
1. Salt restriction
2. Albumin infusion 20% 1 g/kg over 4 hours followed by IV
furosemide 1-2 mg/kg mid-way and at end of infusion
3. Consider chronic diuretic therapy in patients with intractable
edema, using combination of:
• Furosemide 1-2 mg/kg
• Spironolactone
0-10 kg : 6,25 mg
11-20 kg : 12,5 mg
21-40 kg : 25 mg
> 40 kg : 25 mg 8H
• Bumetanide 25-50 mcg/kg (max 3 mg) daily, increasing to
8-12H
04/02/2021 40
 Management of Edema
in Nephrotic Syndrome
Evidence of hypovolemia
Yes
Normal saline,
Albumin infusion*
No

Oral furosemide 1-3 mg/kg/day

No response#
Add spironolactone 2-4 mg/kg/day

No response#
Increase furosemide to 4-6 mg/kg/day

No response#
Add hydrochlorthiazide 1-2 mg/kg/day or mitolazone 0,1 – 0,3 mg/kg/day

No response#
Furosemide IV bolus 1-3 mg/kg/dose or infusion 0,1 – 1 mg/kg/hour

No response#

20% albumin 1 g/kg followed by IV Furosemide

04/02/2021 41
 Supportive Care in
Nephrotic Syndrome

Diet
1. Normal calorie, Low saturated fats (10-14% Protein, 40-45%
poly- and mono-unsaturated fats, 40-50% carbohydrate)
2. Salt restriction only if edema is present
3. Fluid restriction to 50% of maintenance if edema present.
4. Protein requirements
High protein intake : no evidence of benefit unless there is
massive loss preventing growth
to avoid malnutrition, increase protein intake to compensate
for protein loss

04/02/2021 42
 Protein requirements
Age RDA Protein intake to compensate for protein loss
(years) (g/kg/day) (g/kg/d)

Infants 0-0.5 2.2 3.0-4.0

0.6-1.0 1.6 2.3-2.4
Children 1-3 1.2 1.9-2.0
4-6 1.2 1.9-2.0
7-10 1.0 1.7-1.8

Males 11-14 1.0 1.7-1.8

15-18 0.9 1.4-1.5
19-21 0.8 1.3

Females 11-14 1.0 1.7-1.8

15-18 0.8 1.4-1.5
19-21 0.8 1.3
04/02/2021 43
 Supportive Care in
Nephrotic Syndrome

Decrease proteinuria
1. ACE Inhibitor :
• Captopril 0,3 mg/kg/day 12H or 24H
• Enalapril 0.1-1.0 mg/kg daily (maxi 40 mg daily)
• Ramipril 0.05-0.2 mg/kg once daily (max 10 mg)

2. Angiotensin II Receptor Blocker :

Losartan 0,5-2 mg/kg daily (max 100 mg)

04/02/2021 44
 Supportive Care in
Nephrotic Syndrome

Decrease Hypercholesterolemia
1. Dietary restriction
2. HMG CoA Reductase inhibitor :
o Lovastatin 0.4-0.8 mg/kg nightly.dose can be increase
monthly. (max 40 mg 12H)

o Atorvastatin 0.2-1.6 mg/kg nightly. Dose can be increase

monthly (max 80 mg nightly)

o Simvistatin has the highest risk of rhabdomyolysis

o Monitor liver function test and serum creatine kinase

monthly for first 3 months then 3-monthly
04/02/2021 45
 Supportive Care in
Nephrotic Syndrome

Decrease hypercoagulopathy
1. Avoid hypovolemia

2. Aspirin 3-5 mg/kg (max 100 mg) daily or

antiplatelet agents such as dipyridamole 1-2
mg/kg (max 100 mg) 8H

3. Heparin dan warfarin (if there has been a

thrombotic event)

04/02/2021 46
 Parent Education and Counseling

• Explained the natural history of the disease and it’s

outcome.
• Explained adverse effects high dose steroid therapy and
other medication.
• The patient should return for follow up at 4 weeks of
therapy.
• The need to examine urine protein at home.
• A diary recording the protein excretion, intake of
medications and intercurrent illness.

04/02/2021 47
 KOMPLIKASI
• Infeksi
• Syok hipovolemia
• Acute kidney injury
• Chronic Kidney Desease /ESRD
• Steroid Toxicity
• Trombosis

04/02/2021 48
• Komplikasi Infeksi
Penyebab :
Konsentrasi IgG ↓
Konsentrasi Faktor B ↓
Gangguan opsonisasi
Disfungsi limfosit.
• Infeksi bakteri
• Peritonitis, Sepsis
• Selulitis
• Relaps karena infeksi bakteri
• Infeksi virus
• Pencetus relaps SN misalnya campak, varicella
• Relaps karena infeksi virus

04/02/2021 49
Trombosis vena
• Risiko trombosis
1) Fibrinogen meningkat dalam darah
2) Faktor koangulasis V,VII,VIII,X meningkat
3) Kadar Antitrombin III menurun
4) Hiperagregasi trombosit
5) Viskositas darah meningkat
6) Trombositosis vena

04/02/2021 50
Penyebab anemia pada SN
1) Defisiensi Protein
2) Transferrin 
3) Infeksi (anemia penyakit kronik)
4) Eritropoietin menurun

04/02/2021 51
Retardasi Pertumbuhan
Etiologi:
1) IGF binding protein
2) IGF I and II serum
3) IF-receptor mRNA
4) Efek samping steroid

04/02/2021 52
 Prognosis

• Mortalitas
• Mortalitas 1940: 40% dalam 1 tahun pertama
• Mortalitas saat ini 1-2%
• Penyebab utama kematian
• Infeksi
• Trombosis
• CKD /ESRD
• MCNS dalam 20 tahun: 4-5%
• GSFS dalam 5 tahun: 25%

04/02/2021 53
 PROGNOSIS

Idiopathic NS

Steroid sensitive (90%) Steroid resistant (10%)

Frequent
relapses/S.dependend (50%) ESRD

Infrequent relapses (33%)

No relapses (25%)
04/02/2021 54
 KESIMPULAN
1. SN pada anak bersifat idiopatik dan umumnya sensitif
kortikosteroid.
2. Pengobatan SN pada anak sebaiknya dimulai dengan
prednison/ prednisolon yang setelah mencapai remisi,
prednison / prednisolon dilanjutkan sampai mencapai dosis
“threshold” selama 6 – 12 bulan.
3. Bila terjadi relaps, apakah itu bersifat resistent atau dependen
steroid maka dapat diberikan obat-obat immunosupresif lain,
yang diberikan secara bersama-sama dengan steroid atau
sebagai single treatment.
4. Selain pemberian obat maka pada penatalaksanaan SN harus
diperhatikan terapi penunjang.
04/02/2021 55
 TERIMA KASIH

04/02/2021 56