(GLOMERULOPATHY)

Division Nephrology
Child Health Department
Faculty of Medicine – University of Syiah Kuala
 GLOMERULOPATHY

 MAIN CAUSE OF KIDNEY FAILURE IN CHILDREN

DEFINITION:
 INFLAMATORY CHANGES IN GLOMERULUS
DUE TO IMMUNOLOGIC MECHANISM

CLINICAL MANIFESTATIONS
# ISOLATED PROTEINURIA
# PROTEINURIA + OEDEMA (i.e.nephrotic syndrome)
# ISOLATED HAEMATURIA
# HYPERTENSION +/- proteinuria/haematuria
# RENAL FAILURE
 CLASSIFICATION

1. CONGENITAL
• Alport syndrome
• Congenital nephrotic syndrome
2. ACQUIRED – PRIMARY / IDIOPATHIC
1. Minimal change
2. Focal segmental glomerulosclerosis
3. Mesangial proliferative glomerulonephritis
4. Membrano-proliferative glomerunephritis
5. Membranous glomerulonephritis
6. IgA Nephropathy
7. Glomerulonephritis others
3. SECONDARY
• POST INFECTION – POSTSTREPTOCOCCAL GLOMERULONEPHRITIS
• MULTISYSTEM DISEASES : Lupus erythematosus, haemolytic uraemic synd
• INTOXICATION: drugs, metal
• NEOPLASMS
• Etc
 DEFINITION
NEPHROTIC SYNDROME is defined as
A clinical state characterized by the combination of
- heavy proteinuria
- hypoproteinaemia
- oedema
- hyperlipidaemia

Heavy proteinuria : > 50 mg/kg BW/day or >40mg/m2/h

creatinine/protein ratio > 2 mg/mg
selective proteinuria

Hypoalbuminaemia : < 2.5 g/dl

Hyperlipidaemia : variable degree

invariably present
 Epidemiology
• Incidence
– Incidence 2-7 new cases per 10,000
– Prevalence 15.7 cases per 10,000
• Age
– MCD 2.5 years median age
– FSGS 6 years median age
• Sex
– 3:2 Boys; Girls in children <6 yo
– Equal ratio in those older
 CLASSIFICATION

1. CONGENITAL NEPHROTIC SYNDROME

2. IDIOPATHIC NEPHROTIC SYNDROME
3. SECONDARY NEPHROTIC SYNDROME
CONGENITAL NEPHROTIC SYNDROME
 clinical onset in the first 3 months of life
 proteinuria in utero or at birth
 elevated amniotic fluid level of alpha-fetoprotein

before 20 weeks’ gestation

 Classification :
 Primary
 Finnish type
 Diffuse mesangial sclerosis

 Minimal changes NS

 Focal segmental glomerulosclerosis

 Secondary
 congenital syphilis, toxoplasmosis, cytomegalovirus
 XY gonadal dysgenesis and Wilms tumour

 nephroblastoma

 etc
CONGENITAL NEPHROTIC SYNDROME
 the majority of cases

 autosomal recessive inheritance

 incidence in Finland: 12 cases/100 000 births

 born prematurely 35-38 weeks

 small for gestational age

 placenta weighing > 25% birth weight

 breech presentation, fetal asphyxia

 widened cranial sutures, large fontanelles, pliable

cartilagenous tissue
 small nose, wide-set eyes, low-set ears

 Prognosis : infaust
 SECONDARY NEPHROTIC SYNDROME
Causes of secondary nephrotic syndrome

1. Extrinsic antigens, drugs, •Penicillamine •Gold

•Mercury •Trimethadione
and toxins •Probenecid •Volatile hydrocarbon
•Bee’s sting •snake venom

•Hepatitis B •Syphilis
2. Infections •Malaria •Filariasis
•Leprosy •Schistosomiasis

•Lupus erythematosus •Syorgen’s syndrome

3. Intrinsic antigens •Sarcoidosis •Renal tubular antigen
•Transplantation •vasculitis syndrome

4. Neoplasms •Carcinoma •Lymphoma

•Leukemia

5. Associations, possibly doubtful •Diabetes mellitus •Renal vein thrombosis

•Rheumatoid arthriris •Sickle cell disease
•Guillan Barre synd.
PATHOPHYSIOLOGY

1. PROTEINURIA
2. PERMEABILITY IMPAIRMENT
• MOLECULE IONIC CHARGE
• MOLECULE SIZE
 Glomerular Capillary Membranes
Mechanism of Proteinuria
A SIZE-SPECIFIC BARRIER
A CHARGE-SPECIFIC BARRIER
The action is at the slit diaphragm

Podocyte
Slit Diaphragm Podocyte

Podocin
CD2 associated
protein Nephrin
 PROTEINURIA

- Transferine  IgG 
- Glob.Thyroxin  IgE 
- Glob. Vit. D  IgA 
- Coagulation factors  IgM 
F VII, IX, XII  Fibrinogen 

HYPOALBUMINAEMIA

B-lipoprot   hyperlipidaemia

ONCOTIC PRESSURE 
Lipiduria
OEDEMA
HYPOVOLAEMIA

Peripheral circulation collaps

Hb  Death
Aldosteron  
 Packed cell vol  Renal perfusion 
Na and H2O
retention  Viscocity  renin plasma  Ureum 
 +
Vein thrombosis K
CLINICAL MANIFESTATIONS
Oedema (uptill 40% BW), ascites, hydrothorax,
scrotal oedema
Secondary infections : skin, peritonitis
Anaemia
Growth disturbances
Tetany (hypocalcaemia)
Hypovolemic shock
Vein thrombosis
Acute renal failure: oliguria/anuria, metabolic acidosis,
potassium
Nephrotic syndrome
Generelised edema
(anasarca)
Older child with
nephrotic syndrome

Pitting peripheral
oedema
Nephrotic Syndrome

Ascites
 Nephrotic syndrome

SCROTAL EDEMA LABIAL EDEMA

LABORATORY FINDINGS
Urinary analysis:
specific gravity , pH 
proteinuria massive
(selective - albumin 85-95%)
qualitative/semiquantitative > 2+
quantitative : Esbach
leukocyturia
haematuria
double refractile lipoid bodies
hyaline cast

Plasma :
Hb , Ht
hypoalbuminaemia, reverse ratio alb/glob
hypercholesterolaemia
normal: ureum, creatinine
 IDIOPATHIC NEPHROTIC SYNDROME

The Morphologic Spectrum of primary nephrotic

syndrome (Churg, Habib & White, 1970)

1. Minimal change
2. Focal segmental glomerulosclerosis
3. Proliferative glomerulonephritis
Mesangial
With crescent formation

Focal
Diffuse exudative

Mesangiocapillary (membrano-proliferative)

4. Membranous glomerulonephritis
5. Advance chronic glomerulonephritis
EPIDEMIOLOGY
MINIMAL DISEASE
PROLIFERATIVE DISEASE
MEMBRANOUS DISEASE
TREATMENT
1. Medication
1. STEROID
2. DIURETICS
3. IMMUNOSUPRESSIVE AGENTS

2.Dietary (nephrotic diet)

LOW SALT (1-2 g/day)
high PROTEIN 2-3 g/kg/day
3. OPTIMIZING CONDITION
(physic,psychology,social)
- Activity : not limited
- Immunization: as scheduled
- Psychological support : the child + parents

FOLLOW UP
 OUT PATIENT CLINIC:
- Symptomatic : weekly - monthly
- Asymptomatic : every 3-6 months (renal
function evaluation)
 ADMISSION :
generelized oedema, severe hypertension,
severe infection, shock, acute renal failure
 STANDARD TREATMENT
CORTICOSTEROID (PREDNISON)

INITIAL TREATMENT
FULL DOSE ALTERNATING

4 MINGGU 4 MINGGU
Prednison FD: 60 mg/m2/day
Prednison AD: 40 mg/m2/day

REMISSION (+) REMISSION (-) STEROID

SENSITIVE

STEROID RESISTANT

IMMUNOSUPRESSIVE AGENTS

THE INTERNATIONAL COMMITTEE OF KIDNEY DISEASE IN CHILDREN (1967)

RECOMMENDED DOSAGES
PREDNISON
DAILY : 60 mg/m2/day in 3 divided dose
Intermittent : 40 mg/m2/day in 3 divided dose,
3 executive days in a week
Alternatively : 35 mg/m2/day single dose

CICLOPHOPHAMIDE
2-3 mg/kg/day for 8 – 12 weeks in combination with steroid
intermittent

CHLORAMBUCILE
0,1-0,2 mg/kg/day in divided dose with steroid AD
1. Imunosupresan
2. Terapi suportif
3. Terapi komplikasi
4. Tata laksana lain
34
 1. Imunosupresan

1. Kortikosteroid:
 Prednison/prednisolon
 Metilprednisolon
 Deflazakort
2. Imunosupresan non steroid
 Siklofosfamid, klorambusil, methorexat, vinkristin
 Siklosporin, takrolimus
 MMF (mikofenolat mofetil)
 Rituximab
 Sirolimus
 Mizoribin
3. Imunomodulator:
1. Levamisol

35
 Prednison

SN inisial:

Protokol ISKDC (1970) atau modifikasinya:

– Prednison full dose 60 mg/m2 LPB/h atau 2 mg/kgbb/hari (maksimal

80 mg/h) 4 minggu.
– Diikuti prednison 40 mg/m2LPB/h atau 2/3 full dose (1,5
mg/kgbb/h) selama 4 minggu dengan intermitten dose (3 hari
berturut-turut) atau alternating dose (selang sehari pagi hari)
• Remisi : 80% setelah prednison 2 minggu
94% setelah prednison 4 minggu

• Terapi inisial : remisi total pada 94% pasien,

relaps 60-70% dan relaps sering 50%
36
 TATA LAKSANA SINDROM NEFROTIK
IDIOPATIK
MENURUT KONSENSUS UKK NEFROLOGI IDAI
2008

37
a. Sindrom nefrotik: terapi
inisial

38
 4 minggu 4 minggu

Remisi (+) Dosis alternating

Proteinuria (-) (AD)
Edema (-)
Remisi (-): Resisten steroid

Imunosupresan lain
Prednison FD: 60 mg/m2 LPB/hari
Prednison AD: 40 mg/m2 LPB/hari

Gbr. Pengobatan inisial dengan kortikosteroid 39

b. Sindrom nefrotik relaps

40
 Remisi
FD AD

Prednison FD: 60 mg/m2 LPB/hari

Prednison AD: 40 mg/m2 LPB/hari

Ket.: prednison full dose sampai remisi (max 4

minggu)
dilanjutkan prednison 2/3 full dose 4
Gbr. Pengobatan sindrom nefrotik relaps
41
c. Sindrom nefrotik relaps
sering/dependen steroid

42
 Remisi
FD AD 8 minggu

Prednison FD: 60 mg/m2 LPB/hari

Prednison AD: 40 mg/m2 LPB/hari

CPA oral:2-3 mg/kgbb/h

Gbr. Pengobatan sindrom nefrotik relaps sering 43

 Remisi
FD
AD 12 minggu
Tapering off
1 2 3 4 5 6 7
atau
FD AD 12 minggu
Tapering off
12 minggu

Prednison FD: 60 mg/m2 LPB/hari

Prednison AD: 40 mg/m2 LPB/hari (1 kali pagi hari)
CPA oral: 2-3 mg/kgbb/hari
CPA puls: 500-750 mg/m2 LPB/bulan
Tapering off 1 mg/kgbb/hari (1 bulan)  0.5 mg/kgbb/hari (1 bulan)
44
Gbr. Pengobatan sindrom nefrotik dependen steroid
 Sindrom nefrotik relaps sering
atau dependen steroid
Prednison FD Remisi
(2)
Prednison AD + CPA
Diturunkan sampai dosis treshold
0.1 – 0.5 mg/kgbb AD
6-12 bulan
(1)
Relaps pada Relaps pada
Prednison > 0.5 mg/kgbb AD Prednison > 1 mg/kgbb AD
atau
Efek samping steroid meningkat
(3)

Levamisol 2.5 mg/kgbb AD CPA 2-3 mg/kgbb

(4-12 bulan) 8-12 minggu

Relaps prednison standar

Relaps pada prednison

> 0.5 mg/kgbb AD
(4)
Siklosporin 5 mg/kgbb/hari
selama 1 tahun
45
Gbr. Diagram pengobatan SN relaps sering atau depe
d. Sindrom nefrotik
resisten steroid

46
• Imunosupresan
– Siklofosfamid : puls atau oral kombinasi dengan prednison
– Metilprenisolon puls
– Siklosforin
– MMF
– Takrolimus
– Rituximab
• Imunomodulator: levamisol
• Antiproteinuria
• Cari faktor risiko: infeksi

47
 Prednison AD 6 bulan
Tap off
CPA oral 3 – 6 bulan

atau
Prednison AD 6 bulan
Tap off
CPA puls 6 bulan

Prednison AD: 40 mg/m2 LPB/hari

CPA oral: 2-3 mg/kgbb/hari
CPA puls: 500-750 mg/m2 LPB/bulan
Tapering off 1 mg/kgbb/hari (1 bulan)  0.5 mg/kgbb/hari (1 bulan)

Gbr. Pengobatan sindrom nefrotik resisten steroid 48

 Metilprednisolon

• SNFR/SNDS dan SNRS

• Oral atau puls
• Puls: dosis: 30 mg/kgbb (max. 1 g) ke dalam
50 – 100 ml dextrose 5%, infus 2 – 4 jam
• Efek samping MP:
• katarak : 22%
• gangguan pertumbuhan : 17%
• hipertensi : 17%
• leukopenia : 19%
• gangguan saluran cerna : sering

49
 Pulse methylprednisolone
(Mendoza protocols)

Week Methylprednisolone Oral prednisone

1 -2 30 mg/kgbw, 3 x per week -
3 - 10 30 mg/kgbw, every 1 week 2 mg/kgbw AD
11 - 18 30 mg/kgbw, every 2 weeks tapering
19 - 50 30 mg/kgbw, every 4 weeks Tapering slowly
51 - 82 30 mg/kgbw, every 8 weeks Tapering slowly

Mendoza SA, Reznik VM, et al. Pediatr Nephrol

 Siklofosfamid
• Oral 2-3 mg/kgbb selama 8-12 minggu.
• Mengurangi relaps:
67-93% pada thn pertama 36-66% selama 5 tahun
• Puls intravena: 500 mg/m2 LPB dalam 250 ml infus NaCl
0,9% dalam 3-4 jam

• Efek samping:
depresi sumsum tulang, alopesia, sistitis hemoragik,
gangguan saluran cerna, azospermia, keganasan

• Periksa Hb, leukosit, trombosit, 1-2 kali/minggu

• Sitostatik dihentikan:
leukosit < 3.000/uL, Hb < 8 g/dL, trombosit <
100.000/uL 51
 Siklosporin

• Memodifikasi fungsi sel T

• Menghambat pengeluaran IL-2 dari sel T helper
• Menghambat induksi dan proliferasi sel T efektor
• Dosis 5 mg/kgbb/h
• Bila CyA dihentikan, relaps (dependen siklosporin).
• Efek samping:
hipertensi, hiperkalemia, hipertrikosis,
hipertrofi gingiva, nefrotoksik

52
 MMF (Mofetil mikofenolat)

• Menghambat enzim inosine monophosphate

dehydrogenase (IMPDH) pada metabolisme
purin
• Menginhibisi proliferasi limfosit B dan T
• Dosis: 15-30 mg/kgbb atau 500 - 1200 mg/m2
LPB/h 2 kali sehari (max 2 g/h)
• Efek samping: mual, diare, anoreksia, lekopenia

53
 Rituximab

• Antibodi monoklonal CD20

• Deplesi limfosit B  hambat aktivasi sel
T
• Dosis:
• 375 mg/m2/kali, 4 kali selang waktu 1 minggu
• 750 mg/m2kali, 2 kali, selang waktu 2 minggu

54
 Levamisol

 Imunomodulator
 Antihelmintik, merangsang sel T
 Dosis: 2,5 mg/kgbb selang sehari dapat
spi 6 bulan
 mempertahankan remisi 50%
 Efek samping: mual, muntah, neutropenia,
agranulositosis, ruam kulit,
insomnia, hiperaktif &
kejang

55
 2. Terapi suportif

a. Dietetik
 Protein normal sesuai dengan RDA:2-3 g/kgbb/h
 Rendah garam (1-2 g/h)
b. Mengatasi edema
 Pembatasan cairan jika edema berat
 Diuretik: furosemid 1-2 mg/kgbb/h
spironolakton 2-3 mg/kgbb/h
 Edema tidak berkurang: infus albumin 1 g/kgbb
selama 4 jam diikuti furosemid 1-2 mg/kgbb
 Albumin tidak ada: plasma 20 ml/kgbb/h
 Asites berat: pungsi asites
c. Aktivitas
 Edema anasarka: tirah baring
 Aktivitas tidak perlu dibatasi
 Bila edema tidak berat anak boleh sekolah
56
 3. Pengobatan komplikasi
a. Hipovolemia
- NaCl fisiologik dan albumin 1 g/kgbb atau plasma
20 mL/kgbb
- Bila hipovolemia telah teratasi dan oliguria:
furosemid

b. Infeksi
- Peritonitis: gol. penisilin parenteral & sefalosporin
(sefotaksim atau seftriakson) 10-14 hari

c. Tromboemboli
- Asetosal dosis rendah (80 mg) dan dipiridamol
- Heparin diberikan bila sudah terjadi trombosis
57
d. Hiperlipidemia
- Peningkatan kolesterol sementara, terapi dengan
pengurangan diit lemak
- Pada SNRS/SNDS: obat penurun lipid: derivat fibrat, statin

e. Kelainan elektrolit
- Hiponatremia ringan : tidak perlu pengobatan
Hiponatremia berat : pembatasan cairan
penyesuaian dosis diuretik
koreksi hiponatremia
- Hipokalemia: K oral/parenteral
diuretik hemat kalium: spironolakton
- Hipokalsemia: Ca per oral atau parenteral
Ca glukonas 50 mg/kgbb
Pada SNFR/SNDS dan SNRS: suplementasi Ca dan vit.D
58
 4. Tata laksana lain

a. Obat mengurangi proteinuria

1. Inhibitor ACE: -mengurangi proteinuria
-menghambat GGT (renoprotektif)
 kaptopril 0,3 mg/kgbb/kali
 enalapril 0,5 mg/kgbb/h
 lisinopril 0,1 mg/kgbb/hari (maks. 5
mg/h)

2. ARB: losartan 0,75 mg/kgbb/h (maks. 50 mg/h)

59
b. Antibiotik
 tidak dianjurkan antibiotik profilaksis
 antibiotik diberikan bila ada infeksi

c. Psikologis
• Penjelasan terhadap orangtua atau pasien
• Pendekatan psikologis

d. Rujukan
• SN < 1 tahun
• SNFR dan SNDS, SNRS
• SN dengan nefritis atau komplikasi
60
 Indikasi rawat

• SN dengan:
- syok
- edema anasarka
- hipertensi berat
- muntah-muntah
- gagal ginjal
- infeksi berat: peritonitis

61
 Indikasi biopsi ginjal

• SN dengan:
- hematuria nyata
- hipertensi
- kreatinin dan ureum plasma meninggi
- komplemen plasma menurun

• Sindrom nefrotik resisten steroid

• Sindrom nefrotik dependen steroid

62
SECONDARY
 Classification
Idiopathic nephrotic syndrome
• Steroid sensitive nephrotic syndrome
– SSNS
• Steroid resistant nephrotic syndrome
– SRNS
 Definitions
• Remission-
– Urinary protein < 4 mg/ m2*hr or Albustix
= 0/Trace for 3 consecutive days
• Steroid Responsive
– Remission with steroids alone
• Relapse
– Urinary protein > 40 mg/m2*hr or Albustix
> 2+ for 3 consecutive days
• Frequent Relapses
– Two or more relapses within 6 months of
initial response or 4 or more relapses
within any 12 month period
 Definitions
• Steroid Dependence
– Two consecutive relapses occurring during
corticosteroid treatment or within 14 days
of its cessation
• Steroid Resistance
– Failure to achieve response in spite of 4
weeks of prednisone 60 mg/m2*day
THE CLINICAL RESPONS OF MINIMAL CHANGES
PATIENTS TO STEROID (ISKDC)

Minimal Change 100%

Responsive 93% Early Non responsive 7%

No- Infrequent Frequent

relaps Relapser Relapser Late responsive Non-responsive
36% 18% 39% 5% 2%

Non responsive
5%

(Kidney Int. 13-43, 1978)

 PROGNOSIS

RENAL FUNCTION gradually

failure

rapid, about
5 – 10 years
 DEFINITION

ACUTE POST INFECTION GLOMERULONEPHRITIS

 IMMUNOLOGICAL REACTIONS IN KIDNEY

UPON EXTRA RENAL INFECTION
CAUSED BY AGENTS

The most common :

Extra renal infection with group A beta-hemolytic
streptococci

ACUTE POST STREPTOCOCCAL

GLOMERULONEPHRITIS
 EPIDEMIOLOGIC CHARACTERISTICS

 Actual incidence hard to ascertain

large % of cases : subclinical in nature

 Developing countries : a common form of GN in children

the disease is self-limited in most

 Advent of antibiotics and better public health 

influence incidence
ACUTE POSTSTREPTOCOCCAL GLOMERULONEPHRITIS
(APSGN)

NEPHRITOGENIC STRAINS OF STREPTOCOCCI

GROUP A
Beta-hemolytic
 Respiratory tract – M 1,2,4,12,18,25
 Skin – M 49, 55, 57, 60

GROUP C
Streptococci
Streptococcus zooepidermicus

Site of infection:
upper respiratory tract: pharynx, tonsilles, middle ear
skin
 Upper Respiratory
• Sore Throat
• Tonsillar exudate
• Fever
• Chills
• 20% school children
carriers
 Skin
• Impetigo
– Lesions on
extremities
– Commonly on face
– Pustular and crusty
INFECTIONS PRECEDING ACUTE GN
BACTERIAL
Group A, Beta-hemolityc streptococci
Streptococcus viridans
Streptococcus pneumoniae
Streptococcus grup C (Streptococcus zooepidermicus)
Staphylococcus aureus
Staphylococcus epidermidis
Salmonella typhosa
Gonococcus
Mycoplasma
Staphylococcus albus
Treponema pallidum
Corynebacterium bovis
Klebsiella pneumoniae
Diplococcus pneumonia
Brucella suis
Meningococcus
Leptospira
Propionibacterium acnes
Mycobacterium leprae
Actinobacillus
 INFECTIONS PRECEDING ACUTE GN
VIRAL
§ Varicella-zantu - Coxsackie B
§ Rubella - Echovirus
§ Cytomegalovirus - Enterovirus
§ Epstein-Barr - Picornavirus
§ Hepatitis B - Onconavirus
§ Measles - Influenza
§ Mumps - HIV

PARASITIC
§ Plasmodium falsiparum - leishmanias
§ Plasmodium malariae - tripanosomes
§ Toxoplasma gondii - trichinosis
§ Schistosoma mansoni - filaria

FUNGAL RICKETSIAL
§ Coccidiodes immitus - Scrub typhus
ASSOCIATION BETWEEN
AGN – STREPTOCOCCI INFECTION

1. Following scarlet fever

2. Group A, -streptococcus hemolytic has been
isolated
3. ASTO 
• Latent period
# pharyngitis associated : 10 d
# impetigo associated : 21 d
 PATHOGENESIS

HYPOTHESIS:
• CIRCULATING IMMUNE COMPLEX
FORMATION
• IN SITU IMMUNE COMPLEX FORMATION
• AUTOIMMUNE PROCESS
Neuraminidase produced by streptococci alters
endogenous IgG and makes it autoantigenic  altered
IgG form circulating complexes  deposited in kidney
CLINICAL MANIFESTATIONS

A. ACUTE
B. SUB ACUTE (RAPIDLY
PROGRESSIVE)
C. CHRONIC
 CLINICAL MANIFESTATIONS

- Various (subclinical – mild - severe)

- Sudden onset of painless gross hematuria
(coke- or tea-colored urine)
- Oedema (puffy eyes - generalized)
- Oliguria / anuria
- Acute renal failure
- Hipertension
hypertensive encephalopathy :
headache,vomiting, lethargy, confusion,
seizures
- Congestive heart failure or pulmonary edema
- Anaemia
FREQUENCY OF CLINICAL MANIFESTATIONS IN APSGN

Gross hematuria 25 – 33 %
Volume overload
oedema 85 %
hipertension 60 – 80 %
circulatory congestion 20 %
CNS symptoms 10 %
LABORATORY FEATURES
URINALYSIS :
proteinuria 1 - 4+
hematuria
abnormal sediment:
dysmorphic RBCs, WBCs, cellular casts,
granular casts, RBC casts
SERUM :
- BUN/ureum  , creatinine 
- K , acidosis, hyperphosphatemia, Ca 
- Hypocomplementemia
in first week, normal in 8 –10 wks
- Properdin level 
- Evidence of a recent streptococcal infection
antistreptozyme, ASO, antihyaluronidase,
anti-DNase B 
 PATHOLOGY ANATOMY

 Light microscopy
DIFFUSE ENDOCAPILLARY PROLIFERATIVE
GLOMERULONEPHRITIS
- diffuse mesangial cell and matrix proliferation
- endothelial cell proliferation
- infiltration polymorphonuclear cells and monocytes
- occlusion capillary lumens

 Immunofluorescence microscopy
irregular fine – coarse granular staining in mesangium
and along capillary loop for IgG, C3, IgM, IgA,

 Electron microscopy
- electron-dense deposits in mesangium
- HUMPS (large deposits in subepithelial location)
 pathognomonic
 DIAGNOSIS
 Sudden onset of gross hematuria, oedema, hypertension
and acute renal failure following a recent streptococcal infection

 Urinalysis findings characteristic of GN

 Laboratory evidence of a recent streptococcal infection

 Low serum complement

DIFFERENTIAL DIAGNOSIS
 IgA Nephropathy  synpharyngetic hematuria
 Associated with systemic disease
 Chronic glomerulonephritis
TREATMENT (1)

1. Bed rest
2. Antibiotic for eradicating streptococci
- Procain Penicillin 10 days
- Erythromicyn
3. Dietetic (fluid & salt restriction)
- low protein 1 g/kgBW/day
- low salt 1 g/day
- IVFD as necesarry
4. Prolonged anuria  dialysis
- peritoneal dialysis
- haemodialysis
TREATMENT (2)

5. Diuretics
Furosemide 1 mg/kgBW/dose 2x/ day

6. Symptomatic treatment
hypertension
hypertensive encephalopathy
congestive heart failure
acute renal failure
TREATMENT (3)
Treatment of hypertension associated with APSGN

Mild Severe

Diuretics furosemide furosemide i.v.

i.v. or p.o.

Vasodilators hydralazine diazoxide i.v.

Na-nitroprusside i.v.

Ca-channel blocker nifedipine p.o. Nifedipin sublingual

ACE inhibitor captopril p.o.

Evaluation to Document Likelihood of Typical
APSGN (1)
1 . Typical of presentation with no findings suggestive
of other systemic disease

2. Evidence of prior streptococcal infection

a. Throat or skin lession culture positive for streptococci
b. Elevated antibody titers

3. Complement abnormalities typical

a. Decreased CH50 and C3 during acute phase
b. C4 usually normal
c. Levels rise toward normal by 6-8 wks
Evaluation to Document Likelihood of Typical
APSGN (2)

4. Beginning recovery in 1 week

a. Diuresis
b. Blood pressure normalize
c. BUN, creatinine begin to fall

5. Normalization of urine sediment

a. Resolution of gross hematuria by 2-3 weeks
b. Resolution of proteinuria by 3-6 months
c. Resolution of microscopic hematuria by 1 year
TREATMENT STRATEGY FOR ACUTE GLOMERULONEPHRITIS

1. Bed rest as necessary

2. Fluid and salt restriction
3. Specific intervention for
a. Hypertension and other sign of volume overload
b. Hyperkalemia
c. Acidemia
d. Hyperphosphatemia

4. Confirm likelihood of poststreptococcal disease

5. Watch for onset of recovery within 7 days
6. Keep high index of suspicion for diseases other
than APSGN
 NEPHRITIC OEDEMA NEPHROTIC OEDEMA

Renal and water retention Alteration of Starling forces

(capillary osmotic pressure )

Expansion of circulatory volume Oedema formation

Alteration of Starling forces Volume contraction

(capillary hydraulic pressure )

Oedema formation Renal and water retention

 EFFECTIVE CIRCULATORY VOLUME 

Renal perfusion  Volume receptors

Internal Sympathetic AVP  ANP  ?

PRA 
factors activity 

Angiotensin II 

Aldosterone  Alterations of Renal nerve activity 

peritubular Starling
forces

Distal Na Proximal Na Water

reabsorption  reabsorption  reabsorption

Sodium and water retention

PRA =plasma renin activity; AVP = arginine vasopressin; ANP=atrial natriuretic peptide
Clinical and laboratory evaluation in acute GN

History (sore throat, impetigo)

Physical examination (blood pressure, fluid overload)
Urinalysis, 24-h urine for protein and creatinine
Throat culture, skin lesion culture
Blood chemistry : serum electrolytes, ureum, creatinine,
Ca, P, total proteins, albumin, cholesterol
Serum complement (CH50, C3, C4)
Serum for anti streptococcal antibodies

 Antinuclear antibody test

Antiglomerular basement membrane and antineutrophil
cytoplasmic antibodies in patient presenting with
rapidly progressive GN
Renal biopsy (if unresolved)
RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS

A clinicopathologic entity

 Rapidly deteriorating renal function

 PA : diffuse glomerular epithelial crescent formation
(crescentic glomerulonephritis)

Clinical manifestations:
similar to APSGN  severe
rapidly deteriorating

Management:
steroid / immunosupressive agents : controversial
CHRONIC GLOMERULONEPHRITIS (1)

 Haematological abnormalities
persist
Proteinuria

 Acute exacerbation of chronic glomerulonephritis

 Evidence of chronicity of disease

anaemia,
abnormal growth pattern,
exacerbation of acute nephritic syndrome
CHRONIC GLOMERULONEPHRITIS (2)

Mightbe asymptomatic  renal failure

Mild oedema , subfebrile temperature

NEPHROTIC STAGE OF GLOMERULONEPHRITIS

a predominant picture of nephrotic syndrome

- clear oedema
- reverse ratio of albumin/globulin
- hypercholesterolemia

Renal function  progressively

CHRONIC GLOMERULONEPHRITIS (3)

Laboratory findings
Urine : isostenuria
proteinuria
hematuria
leukocyturia

Serum: ureum , creatinine 

K, Ca , P

anaemia : normochrom normocytic

CHRONIC GLOMERULONEPHRITIS (4)

PATHOLOGY ANATOMY
MACROSCOPICALLY
- SHRINKED KIDNEY
- CONTRACTED KIDNEY

MICROSCOPICALLY
- HYALINE DEGENERATION
- TUBULUS ATROPHY
- NEPHRON REPLACED WITH FIBROID TISSUE
+ LYMPHOCYTE INFILTRATION
TREATMENT STRATEGY FOR ACUTE GLOMERULONEPHRITIS

1. Bed rest as necessary

2. Fluid and salt restriction
3. Specific intervention for
a. Hypertension and other sign of volume overload
b. Hyperkalemia
c. Acidemia
d. Hyperphosphatemia

4. Confirm likelihood of poststreptococcal disease

5. Watch for onset of recovery within 7 days
6. Keep high index of suspicion for diseases other
than APSGN
 NEPHRITIC OEDEMA NEPHROTIC OEDEMA

Renal and water retention Alteration of Starling forces

(capillary osmotic pressure )

Expansion of circulatory volume Oedema formation

Alteration of Starling forces Volume contraction

(capillary hydraulic pressure )

Oedema formation Renal and water retention

 EFFECTIVE CIRCULATORY VOLUME 

Renal perfusion  Volume receptors

Internal Sympathetic AVP  ANP  ?

PRA 
factors activity 

Angiotensin II 

Aldosterone  Alterations of Renal nerve activity 

peritubular Starling
forces

Distal Na Proximal Na Water

reabsorption  reabsorption  reabsorption

Sodium and water retention

PRA =plasma renin activity; AVP = arginine vasopressin; ANP=atrial natriuretic peptide
Clinical and laboratory evaluation in acute GN

History (sore throat, impetigo)

Physical examination (blood pressure, fluid overload)
Urinalysis, 24-h urine for protein and creatinine
Throat culture, skin lesion culture
Blood chemistry : serum electrolytes, ureum, creatinine,
Ca, P, total proteins, albumin, cholesterol
Serum complement (CH50, C3, C4)
Serum for anti streptococcal antibodies

 Antinuclear antibody test

Antiglomerular basement membrane and antineutrophil
cytoplasmic antibodies in patient presenting with
rapidly progressive GN
Renal biopsy (if unresolved)