Harnavi Harun

Glomerulus
Glomerulus: “capillary tuft that performs the first step in
filtering blood to form urin
Filtration barrier
1. Endothelial cells : fenestrae 30-90 nm
2.Glomerular basement membran
- 250-350 nm
- collagen, heparin sulfat ,proteoglicans
- 3 layers
lamina rara externa
lmina densa , >>> elektron
lamina rara interna
3. Podocytes : visceral epithelial
- enzymatic and structural protein
- pedicle
- interdigitating foot processes
- filtration slit
- diaphragma
Mesangeal cell
 In the interstitium between endothelial cells
of the glomerulus
 They are not part of filtration barrier
 Specialized pericytes that participate
indirectly in filtration
Anatomy of the glomerulus

Marieb EN, dkk. Human Anatomy & Physiology. 7th ed.

Marieb EN, dkk. Human Anatomy & Physiology. 7th ed.
Primary Glomerular Diseases
Nephrotic presentation (nephrotic
syndrome)
 Minimal change disease (MCD)
 Focal segmental glomerulosclerosis
(FSGS)
 Membranous GN
 Membranoproliferative GN

Acute nephritis (nephritic syndrome)

 Acute proliferative GN
 Crescentic glomerulonephritis (RPGN)
 Anti-GBM Disease

Primary hematuria
 IgA Nephropathy
Immune
disorder
Kidney
involvement
Injury by
inflammation
and other
mediators
Glomerular
dysfunction
Immune
disorder

1. Circulating immune complex >>

2. Immune complex formation

3. Cell-mediated
Glomerular
dysfunction
Pathogenesis

1. Circulating Immuno complex

Pathogenesis
Circulating Immune complex nephritis (type III
hypersensitivity
Ag-Ab complex --- sirculation
Complement activation
Ag-Ab complex is trapped in glomerular
Injury
Antigen is not glomerular origin
Antigen : intrinsic and extrinsic
Intrinsic ( SLE )
Extrinsic ( Post streptococcal, Hep B, Malaria )
Pathogenesis
Circulating Immune complex nephritis (type III
hypersensitivity)
Morphology:
 IF:deposits (glomerular)
 EM: electron-dense deposits (mesangial,

subendothelial, subepithelial)
 Proliferative: leukocytes, endothelial, mesangial,

epithelial
Pathogenesis
Circulating Immune complex nephritis
(type III hypersensitivity)
What happen
Shortlived Ag-Ab complex---- Recovery
Repeated Ag-Ab complex------- chronic GN
Circulating Immune
In situ – Anti-GBM
Complex deposition
Mecanisms of
glomerular damage
Pathophysiology of Proteinuria
General clinical syndrome in
patients with glomerulonephritis

1. Asymptomatic/persistent hematuria and/or

proteinuria
2. Sindrom nefritik
3. Sindrom nefrotik
4. RPGN, acute renal failure
5. Chronic glomerulonephritis
Correlation between site of glomerular injury and
clinicopathology presentation
Target of Physiologic role Response to injury Representative glomerular
injury disease
Endothelial Maintain glomerular perfusion Vasoconstriction ARF
cell Prevents leukocyte adhesion Leukocyte infiltration Focal or diffuse proliferative GN
Prevents platelet agg. & cloting Intravasc. microthrombi Thrombotic microangiopathies

Mesangial Controls glomerular filtration Proliferation/ ￪ matrix Mesangioproliferative GN/

cell surface area Glomerulosclerosis

Basement Prevents filtration of plasma Proteinuria Membranous nephropathy

Membrane protein

Visceral Prevents filtration of plasma Proteinuria MCD and FSGS

Epithelial cell protein

Parietal Maintain Bowman’s space Crescent formation Crescentic GN

Epithelial cell
Selected serologic finding in patient with primary
glomerular disease
Treatment
 Cytotoxic drugs with corticosteroid:
(for steroid dependent or steroid resistant)
Cyclophosphamide (CTX): p.o. or intravenously
Side effects: liver injury, inhibition of bone marrow, etc.

Cyclosporine
(for those failed responsing to combination of steroid and
cytotoxic drugs)
Dose: 5mg/kg/d, bid, p.o.
Side effects: renal and liver toxic injury, expensive, etc.
 Treatment
Mycophenolate mofetil, MMF
(for steroid dependent or steroid resistant)
Dose:1.5-2g/d, bid, p.o. for 3-6 months, maintaining 0.5 year
Treatment
Minimal changes: sensitive to steroids; single drug;
reuse when relapse; combined with cytotoxic drugs
when resistant or dependent on steroids
Membranous GN: combine steroid with cytotoxic
drugs or cyclosporin; avoid using drugs when
Scr>354umol/L; for the patients with risks for
progressing, otherwise, investigate 6 months
(antihypertensive).
Immunosupresan dari golongan
antriproliferative

Zat aktif: Mycophenolate

mofetil 500 mg

Indikasi:
- Pasien pasca transplantasi
(ginjal, hati, jantung)
- Systemic Lupus Erythematosus
 UNIQUE SELLING POINT

Bioekivalen dengan Kualitas survival organ

originator lebih baik

Me too pertama MMF di

Indonesia Lebih Ekonomis
Kesimpulan
Pemberian imunosupresan dapat diberikan dalam
terapi sindrom nefrotik yang resisten steroid dan
dependen steroid

Pemberian imunosupresan juga dapat diberikan

pada pasien transplantasi organ
TERIMA KASIH