Dr. H.

Novadian, SpPD K-GH

FINASIM
Div. Nephrology and Hypertension. Dept. of Medicine
Medical Faculty, University of Sriwijaya
Dr. Moh Hosein Hospital, Palembang

Cap. loops

J.G.App.
DCT
Afferent.A

DCT

Efferent.A

1. Fenestrated Endothelium
2. Lamina Rara Interna
3. Lamina Rara Densa
4. Lamina Rara Externa
5. Podocytes + Slit membrane

Capillary Lumen

BLOOD

Glomerular Capillary Lumen

Proteins
3.6nm/70,000M
W

L.R.I
L.D.
L.R.E

GBM

Foot Process

Plasma Proteins

Podocyte
(Visceral epithelium)

FILTRATE

Bowmans Capsule Space

glomerulonephritis
- etiology primary (idiopathic)
- pathology is confined to the kidney
- any systemic features as direct
consequence of glomerular dysfunction
secondary
- kidney abnormality as a part of multisystem disorder

Glomerular diseases:
Primary GN:
Acute Diffuse Prol.
Poststrept & other Inf.
Crescentic (Rapidly
Progressive)
Membranous GN.
Lipoid / Minimal Change .
Focal segmental G.sclerosis.
Membranoproliferative GN.
IgA nephropathy.
Chronic Idiopathic GN.

Associated with Systemic

Diseases:
SLE, DiabetesMellitus.
Goodpasture's Syndrome.
Polyarteritis Nodosa.
Wegener's Granulomatosis.
Henoch-Schonlein Purpura.
Bacterial Endocarditis.
Amyloidosis
Hereditary Disorders:
Alport's Syndrome.
Fabry's Disease

Primary renal
disease

Systemic
disease

Nephritis
Post Infectious
IgA nephropathy
RPGN
-- Anti GBM
-- Idiopathic

Nephrotic Syndrome
Minimal Change
Focal Sclerosis
Membranous nephropathy
Membranoproliferative GN

Vasculitis
-- SLE
-- HSP
-- PAN
-- EMC
-- Wageners

Diabetes
Amyloid

glomerulonephritis
- chronology acute:

days to weeks

subacute/rapidly progressive:
over weeks to few months
chronic: many months to years

glomerulonephritis
- location focal:
<50% of all glomeruli
diffuse: 50% of all glomeurli
segmental:
global:

part of individual glomerulus

entire glomerulus

Glomerular damage patterns:

glomerulonephritis
pathology
membranous:
- expansion of glomerular basement membrane as a
dominant feature
sclerosis:
- increased amount of homogenous non-fibrillar
extracellular material (similar to GBM and
mesangeal
matrix)
fibrosis
- deposition of type I and III collagen
- commonly as a consequence of healing of crescents
or
tubulointerstitial inflammation

Pathogenesis
Primary insult
major insult to glomerulus
a. immune attack
b. metabolic stress
c. mechanical stress

1. Immune
Glomerulonephritis
In-Situ immune complex formation:
Tissue antigens - Goodpasture anti GBM Ag
Planted antigens - infections, toxins, drugs.
Circulating immune complex deposition.
Endogenous - DNA as in SLE
Exogenous - infections.
Cell mediated Immune injury

Immune
Glomerulonephritis:
C.Immune Complex ANTI-GBM
HEYMANN

Pathogenesis of Immune
1. Ab, Ag/Ab or Immune complex deposition.
GN:
2. Immune reaction
3. Inflammation Activation of complement
4. destruction of glomerular structure
5. Renal dysfunction, Proteinuria, Hematuria

Immune
Glomerulonephritis:

2. Metabolic stress (metabolic

injury)
Hyperglycemia ( Diabetes Melitus)
(1) advanced glycosylation end-products (AGEs)
(2)
reactive oxygen species
cell sorbitol accumulation
mitogen-activated protein kinase activation (3)
high glucose-triggered glomerular hypertension
(i)
(ii)
(iii)
(iv)

mesangial cell hypertrophy

increased mesangial cell matrix production
reduced matrix catabolism
glomerulosclerosis

3. Mechanical stress
(hemodynamic glomerular injury)
i.

systemic hypertension
malignant hypertension
massive fibrinoid necrosis of afferent arteriole and
glomeruli
thrombotic microangiopathy
nephritic urinary sediment
acute renal failure

chronic sustained hypertension

arteriolar vasoconstriction and sclerosis
secondary glomerular and tubulointerstitial
atrophy and sclerosis

mechanical stress
(hemodynamic glomerular injury)
ii.

glomerular hypertension
glomerular hypertension as an adaptive
response to increased workload 2 to loss of
other nephrons
sustained glomerular hypertension
increased mesangial matrix production
glomerulosclerosis

Phatophysiology of Diabetic Nephropathy

Diabetes Melitus Tipe 2

Metabolik

Genetik
HSPG, TGF, dll

Hemodinamik

ACE, ANP

Aliran/ Tekanan >

Glukosa
Protein
kinase C II

AGEs

Hormon Vasoaktif
Angiotensin II, ANP

Sitokin (TGF , VEGF)

Matriks ekstrasel
(ECM) Cross linking

ECM >

>>
Akumulasi ECM

Permeabilitas vaskuler
>

Proteinuria

Glomeruloskelerosis

Gagal ginjal

Glomerular pressure injury

Oxidative stress

Inflammation
Angiotensin II
Cell and tissue
growth

Glomerular capillary
hypertension

Chronic kidney
disease
Brewster, Perazella. Am J Med 2004;116:263272.

Reduction in
nephron mass

Glomerulosclerosis

Nephritic Syndromes :
Diffuse Proliferative GN
Post Streptococcal.

Rapidly Progressive GN (or Crescentic)

Post Streptococcal, Goodpastures,

Focal Glomerulonephritis
Primary: Bergers disease (IgA Nephritis)
Secondary IgA nephritis, Henoch Schonlein

purpura, SBE, Coeliac Disease etc.

acute nephritic syndrome

Oliguria
Abnormal

of
Urinalysis
(proteinuria
<2gr/day), hematuria, cylinder erythrocite)
azotemia
Hypertension
Acute lung edema
JVP >>, hepatomegali)
edema.

The Ethiology of ANS

1.

2.

3.
4.

5.

Glomerulopathy (GP) idiopatik

1.
2.
3.

GP acute proliferative
GP mesangioproliferatif nefritis Ig A or Berger disease
GP membrnoproliferative

1.
2.
3.
4.
5.

Post streptococcus beta hemoliticus

Bacterialis Endocarditis
Staphylococcus albus (shut nefritis)
Viseral Absces
Hepatitis B antigenemia

1.
2.
3.

Poliarteritis nodosa
Granulomatosis Wagener
Henoch-Schonlein Purpura (HSP)

Glomerulopathy postinfection

Disseminated Lupus Erythematosus (DLE)

Vasculitis

Nefritis herediter

Poststreptococcal GN
Usually occurs 10 days

after pharyngitis and 14

days after skin infection
(not synpharyngitic)
Fallen incidence in US,
but common in some
rural areas, poor
hygiene places, and
tropical countries
Occurs more often in
males and children

Post Streptococcal GN
(Prol.GN):

1-4 weeks following streptococcal infection

(nephritogenic strains)
Immune mediated (time for Ab formation)
Granular deposits of IgG,IgM & C3 in GBM,
(subepithelial location common)
Humps in GBM on EM or IF Microscopy

Poststreptoccal GN (nephritic
strains)
Known nephritic strains

include M types 1, 2, 4,
12, 18, 25, 49, 55, 57, 60
Many proposed
mechanisms: Molecular
mimickry vs. autoimmune
vs. polyclonal activation
of B lymphocytes
Repeat infections are not
common as immunity is
type specific and not
usually transient

Clinical Presentation
Most patients have milder disease
Classically, presents with overt nephritic

syndrome and oliguric ARF

Symptoms can include gross hematuria
(100% microscopic), HA, htn (60-80%),
hypervolemia, and edema (80-90%)

Clinical Presentation
Nephritic urinary

sediment
dysmorphic RBCs, red
cell casts, leukocytes,
subnephrotic
proteinuria
Nephrotic-range
proteinuria not
common

Clinical Features:
G.Nephritis

Hypertension
Skin Infections
Congestive Cardiac Failure

Labs
Serum Cr can be commonly elevated at presentation,

though mild
C3 and CH50 decreased w/in 2 weeks
C4 usually normal (complement level usually normal
within 6-8 weeks)
Most patients have directed Ab, such as ASO, antiDNAse B, etc
Serum IgG and IgM increased in 80% and returns to
normal in 1-2 months
Polyclonal cryoglobulinemia in 75%

Laboratory Features:
G.Nephritis

Inflammation
Decreased filtration
Damage to filtration unit

poststreptococcal glomerulonephritis
Tx: (1) antibiotics to eliminate streptococcal infection
(2) supportive therapy until spontaneous
resolution
(3) diuretics
(4) antihypertensive agent(s)
(5) dialysis rarely needed
(to control hypervolemia or uremic
syndrome)

prognosis:
excellent
spontaneous resolution in children
some degree of persistent proteinuria in 20% of adults

Pengobatan
Simptomatis mencegah penyulit fatal:
1. Istirahat: fase akut tak lebih 3 bulan
2. Diet selama fase oliguria/anuria:
protein dibatasi 0,5-0,75 gram/kgbb
protein hewani nilai biologis tinggi
KH: 35 cal/kgbb, Lemak tidak jenuh
Elektrolit: Na dibatasi, K( 70-90meq/hari)
3.Antibiotika
PP 2x 600.000 IU 7 hari
oral 2x 200.000iu fase konvalesen

Post Streptococcal GN Course

Sign

Resolution

Diuresis
Hypertension
Cr to Normal
Em Humps
Hematuria
Proteinuria

1 week
2 week
3-4 week
6-7 week
3-6 week
3 year
Acute Renal failure

: 5%

Chronic Renal Failure

: 2.5 %

Prognosis
GNA pasca streptokok anak : baik
Dewasa:
penyembuhan
(80-90%),

meninggal fase akut (0,5 %), RPGN (5-10%),

kronis (5-10%)
Tanda prognosis buruk : oliguri/anuri
beberapa
minggu,
penurunan
LFG,
hipokomplemenemia menetap, kenaikan
kosentrasi
circulating
fibrinogen
fibrin
complexes dan kenaikan FDP dalam urin

acute nephritic syndrome and

RPGN
- etiology immune-complex glomerulonephritis
in situ formation
glomerular trapping of circulating
complex

1.

idiopathic
ii. with known antigenic stimulus
(infection-associated GN)
iii. part of multisystem disorder
i.

acute nephritic syndrome and

RPGN
- etiology 2. anti-GBM diseases
autoantibody directed at 28 kDa Ag on 3 chain
of type VI collagen

3. pauci-immune glomerulonephritis

(ANCA-associated small vessel vasculitis)

idiopathic renal-limited crescentic
glomerulonephritis
ii. microscopic polyangiitis nodosa
iii. Wegeners granulomatosis
i.

Definisi: sindroma klinik dgn sejumlah kelainan

renal & ekstra renal.
Terdiri dari:
1. Proteinuria (>3,0-3,5gr/hr)
2. Hipoalbuminemia
3. Edema
4. Hiperlipidemia
5. Hiperkoagulasi

1. Primer (idiopatik) 75-80%

2. Sekunder : penyakit sistemik (DM,SLE),

keganasan,toksin spesifik

Causes of Idiopathic Nephrotic Syndrome

Disease

Children Adults

Minimal Change
Focal Sclerosis
Membranous nephropathy
Mrmbranoproliferative GN

70
10
15
10

Haas, et al. AJKD 30:621, 1997

Korbet, Et al. AJKD 27:647,1996

15
35
33
10

Minimal Change Disease

Focal Segmental
Membranous glomerulonephritis

Causes of the Nephrotic Syndrome

PRIMARY GLOMERULAR DISEASE

- Minimal change disease

- Focal segmental glomerulosclerosis
- Membranous glomerulonephritis
- Membranoproliferative glomerulonephritis
SECONDARY DISORDERS

- Systemic diseases (DM,SLE)

- Medications
- Infections
- Malignancy

Taken from the Clinical Nephrology on CD-ROM (Copyrights 1997, OUP) - Chapter 3.5, Figure 4: A diagram
of the events pictured in the 'classical' or 'underfill' hypothesis of neph.
-------------------------------Figure 4. A diagram of the events pictured in the classical or underfill hypothesis of nephrotic oedema. It is
possible that this sequence is dominant in childhood patients developing oedema with sudden onset of severe
proteinuria in a setting of minimal change disease, but this is an inadequate explanation for the continued

1.
2.
3.
4.

Minimal change disease (MCD)

Focal segmental glomerulosklerosis (FSGS)
Membranous glomerulopathy
Membranoproliferatif glomerulosklerosis
(MPGN)

Perlu biopsi untuk :

Diagnosis defenitif
Penatalaksanaan
prognosis

- Ditemukan pd 80% NS umur < 16 thn

& 20 % pd dewasa
- Ukuran & arsitektur glomerulus relatif
baik
- Respon terhadap steroid : baik
- Prognosis : baik

Minimal Change/Lipoid :

Loss of Foot processes

 Terjadi pada 1/3 NS dewasa

50% glomerulus sklerosis &

hyalinosis
Respon steroid : 20-40 % kasus
Remisi spontan : jarang
Prognosis : buruk

Terjadi pada 30-40 % NS dewasa

Patologi :penebalan diffuse basal membran
glomerulus tanpa adanya
inflamasi
atau proliferasi selluler
Tidak ada perbaikan dgn steroid

Patologi : Penebalan dan proliferasi memban

basalis glomerulus
Ada 3 tipe:
Tipe I : immune deposit pd sub endotel &
mesangium
Tipe II : Autoimmune
Tipe III : kombinasi Tipe I & membranous
glomerulopathy
Untuk MPGN tidak ada terapi spesifik

Bila edema : rawat di RS

Diet
: protein 0,8gr/kgBB/hr
garam dibatasi
Diuretik
: furosemid, spironolakton
Prednison : 1-1,5mg/kgBB/hr selama 4 mgg
diteruskan
1 mg/kgBB/hr alternate day 4 mgg
90% remisi pd terapi 20-24 mgg

Sitostatika
Cyclofosfamid 2-3 mg/kgBB/hr atau
Clorambusil 0,1-0,3mg/kgBB/hr selama 8-12 mgg
Dipertimbangkan jk terjadi relaps > 3 kali/thn atau
Sindroma nefrotik yang steroid dependent