Definitions
Glomerular diseases are the pathological processes most often (but
not always) found on native renal biopsy (Ch. Jennette 2007).
Classification of glomerular disease
Non inflammatory glomerular diseases
•Inherited
•Acquired
• drug induced,
• metabolic diseases (Amyloidosis, DM, MIDD,)
• vascular – HT, pre eclampsia other
Inflammatory glomerular diseases (glomerulonephritis) classified
according to KB
Clinical
•Acute
•Rapid progressive
•Chronic
SIGNS & SYNDROMES
MINIMAL
NEPHROTIC NEPHRITIC URINARY
SYNDROME SYNDROME ANOMALIES
PRIMARY - GN - SECONDARY
MCD MPGN FSGS MGN MPGN
ACUTE
GLOMERULONEPHRITIS
DEFINITION
Acute glomerular inflammatory disease of several etiologies
Common clinical characteristics
• frequently associated to an infection
• clinical signs preceded by variable period free of symptoms
• sudden onset with nephritic syndrome ( hypertension, hematuria, proteinuria and
edema)
• frequently - diminished GFR
• frequently good outcome
ETIOLOGY
ACUTE PRIMARY GN
• Mez Prol GN,
• IgA GN,
• Mez Cap prol GN,
• RPGN
ACUTE SECONDARY GN
1. INFECTIOUS DISEASES
• Bacterial - streptococcus, staphylococcus, pneumococcus, meningococcus
– less frequently -brucellosis, leptospirosis
• Viral : Coxackie, ECHO, HBV, HCV, varicella, Epstein-Barr, etc
• Protozoa - toxoplasma, plasmodium falciparum, hystoplasma
• Parasitic infestations - trichinella
ETIOLOGY
2. SYSTEMIC DISEASES
• SLE, polyarteritis, Wegener granulomatosis, Goodpasture syndrome,
Henoch-Schonlein purpura, HUS, thrombotic trombocytopenic purpura,
mixed cryoglobulinemia,
3. IMMUNOTHERAPY AND SEROTHERAPY
• Corine bacterium, BCG
• different serotherapies
ETIOLOGY
• Group A, β hemolytic streptococcus
- the nephritogenic and mixed types
- most frequently - type 12
• Group C streptococci - rarely
Site of infection
• throat
• teeth
• skin
PATHOGENESIS
• IMMUNE
• Unknown antigen:
• endostreptosin – evidenced in the mesangium on KB- by
Lange
• cationic proteinase
• extra cellular streptococcal antigens – evidenced in
immune complexes
• Mechanisms :
• CIC - CIC elevated in most patients
- subendotelial IgG and C3 deposits
• In situ IC - cationic antigen captured in GBM
Crioglobuline – have been identified sometimes
PATHOGENESIS
GBM
Endo Epi
ATG
Autoimmune mechanisms: anti colagen,
IC anti-laminin, anti-HS, anti-reumathoid
factor
ATB
Immune effectors
• Chemotactism
Humps • PMNL • Phagocytes
Endo • Cytokines • GBM lesions
ATG • Inflammation
• Complement
• Proliferation
ATB
Humps
PATHOLOGY
Light microscopy
- Exudative lesions – PMNL, M, Eo
- Endocapillary proliferation (endothelial and mesangial)
- Sub epithelial eozinophile deposits
Immunofluorescence
- C3 +/- IgG deposits: finely granular (in the capillary walls),
lumpy ( in the mesangium), garland pattern (which outline the
capillary wall)
Electron microscopy
- Sub epithelial electron-dense deposits (humps)
PATHOLOGY
PATHOLOGY
C3 +/-IgG finely
granular deposits
“starry sky”
PATHOLOGY
Hump
Clinical signs in 3 periods:
CLINICAL SIGNS • Streptococci infection,
• No clin signs,
INCIDENCE • The acute nephritis
• Affects children more than adults
• Male/female ratio 4/1 – 10/1
• Seldom recorded after the age of 50
1 – THE STREPTOCOCCI INFECTION
a.) Sub-clinical or non-symptomatic infection
b.) Symptomatic infection
- site of infection - pharyngitis, intertrigo, dental abscesses
Clinical signs in 3
CLINICAL SIGNS periods:
• Streptococci infection,
• No clin signs,
• The acute nephritis
2. NO CLIN. SIGNS
- 7 – 21 days (after pharyngitis); 3 – 6 weeks (after intertrigo)
- free of symptoms
- seldom – mild proteinuria or microhematuria
The absence of the latent period or a latent period shorter
than 7 days suggests the idea that the AGN is not a post
streptococcal GN
Clinical signs in 3
CLINICAL SIGNS periods (steps):
3. THE ACUTE NEPHRITIS • Streptococci infection,
Nephritic Syndrome • Latent period,
•Hypertension • The acute nephritis
•Nephritic proteinuria - <3.5g/24h
•Hematuria microscopic or macroscopic
•Edema induced by salt and fluid overload
•(+/-)
• Oliguria – in the edema formation period
• Diffuse bilateral back pain
• Acute renal failure
LAB
• Inflammatory syndrome
- Increased ESR,
- Elevated levels of CRP and fibrinogen
- Elevated Fibrin Degradation Products in urine and serum
• Urinary syndrome
- proteinuria usually non-nephrotic (<3,5g/24h)
- casts – hematic and hyaline
- hematuria - microscopic or gross hematuria
> 80% dysmorphic erythrocytes
LAB
• Immune disorders
- Increased CIC levels
- Low C3 levels
- Decreased hemolytic activity of CH50
Sometimes – RF- present in the serum
- Urinary crioglobuline - present
LAB
• Streptococcal infection profile
- ASO titers - increase at 3 weeks time from the streptococcal
infection and normalizes in 6 months
– In cutaneous infection sites anti hyaluronidase, anti DNA
polymerase B ATB ( strains that do not synthesize SLO ? )
- anti streptozim ATB
- anti cationic proteinase ATB
- anti protein M ATB
LAB
Kidney function
• GFR (CKD Epi)
• RPF usually normal
• Concentrating ability preserved
IMAGISTICS
• Enlarged kidneys – Renal plain X ray, intravenous
pyelography, renal ultrasound
DIAGNOSIS
1. No history of glomerular disease
2. Recent streptococcal infection
3. Latent period > 7 days
4. Sudden onset with acute nephritic syndrome
LAB
1. Inflammatory syndrome
2. Immune disorders – elevated CIC , decreased C3 levels
3. Evidence for streptococci infection
4. Bilateral enlarged kidneys
5. Absence of a systemic disease
6. KB – proliferative endocapillary GN
KIDNEY BIOPSY only if:
1. Acute GN with oliguria or anuria
2. Elevated BUN and serum creatinine which persists >4 weeks
3. Persistent hypertension > 4 weeks
4. Proteinuria > 3,5g% persisting > 4 weeks
5. Decreased C3 levels persisting > 8 weeks
DIFFERENTIAL
DIAGNOSIS
Acute GN – Acute PN
- Signs and symptoms – NO EDEMA, NO HT
- leucocyturia > hematuria, hematuria with eumorphic erythrocytes
- NO SIGNS for streptococci infection
Acute GN – Chronic GN
- History for glomerular disease ( HT, Proteinuria, Edema, Hematuria )
- Latent period less than 7 days
- Bilateral small kidneys
DIFFERENTIAL
DIAGNOSIS
The etiology of acute GN
1. Secondary GN
- LES
- H-S purpura
- Bacterial endocarditis
- Vasculitis
1. Primary GN
- IgA GN
- RPGN
CLINICAL FORMS
1. The common type- acute nephritic syndrome
2. The type without renal signs (hematuria proteinuria)–
HT+ edema
3. Monosymptomatic forms –
4. The form with nephrotic syndrome
5. The form with AKI
COMPLICATIONS
1. Renal – AKI
2. Cardiac and vascular – APE, cerebral edema,
hypertensive encephalopathy and stroke, congestive
heart failure
3. Infectious – UTI, respiratory infections
OUTCOME
1. Overall prognosis – very good – healing - 1 year - 70 – 80%
of the children, 50 – 60% adults
2. Evolution to chronic GN – after 1 year from the onset
3. Rarely - RPGN
TREATMENT
1. Prophylactic treatment
- The prophylaxis of the streptococci infection
1. Cure of infection
- Penicillin G 400.000iu/6h IM - 14-21 days followed by
Slow release penicillin 1 200 000 iu/10 days IM – during
6-12 months
- Eritromicine, Roxitromicine, Clartitromicine
1. Diet
- bed rest until edema remission
- hyponatremic - 4g NaCl/day
- low protein intake 0,4 – 0.6g/kg/day – if AKI occurs
TREATMENT
1. Removal of infectious foci
- at least at 3 months after the onset of the disease
1. Treatment of the symptoms
- Edema – Loop diuretics – Furosemid, Torasemid , Bumetanide
- HT –
- ACEI – Perindopril 10mg/day (if no AKI) – eny other
- Ca Ch B – Amlodipine 10mg/day, Lecarnidipine 10mg/day
- Clonidin 3 x 0,15mg/day
- Treatment of the complications
DO NOT
- Vaccinate – first 2 years after healing of APGN
- Administer corticotherapy
- exception : RPGN, ARF
