10/5/2018

GLOMERULAR DISEASES
GLOMERULAR DISEASES

Peter S. Aznar, MD, FPSP, MHPE

Clinical Syndromes in Glomerular Diseases

Diagnosis of Glomerular Diseases

a. Clinical Syndrome:

a1. Nephritic Syndrome

a2. Nephrotic Syndrome

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b. Renal biopsy
i. Light microscopy (LM)
ii. Immunoflurescence (IF)
PRIMARY GLOMERULOPATHIES (NEPHRITIC)
iii. Electron microscopy (EM)

1. Acute Poststreptococcal GN b. Clinical features

i. Decreasing in incidence in the United States
ii. Children affected more frequently than adults
a. Synonyms iii. Occurs 2-4 weeks after a streptococcal infection of
– acute proliferative GN the throat or skin
– postinfectious GN iv. Organism: Hemolytic group A streptococci
v. May be caused by other bacteria, viruses, and
parasites and systemic diseases (SLE and
polyarteritis nodosa [PAN])
vi. Nephritic syndrome
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d. Light microscopy
• Laboratory studies
i. Hypercellular glomeruli with neutrophils and
i. Elevated antistreptolysin O (ASO) titers monocytes
ii. Red cell casts in the renal tubules
ii. Low serum complement
c. Immunofluorescence

i. granular deposits of IgG, IgM and C3 subepithelial area

ii. this deposits are known as “humps”

Subepithelial Humps

e. Electron microscopy

i. subepithelial (humps) immune complex deposits

f. Treatment

i. conservative fluid management

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h. Prognosis
2. Goodpasture syndrome (anti-GBM disease)

i. Children a. Pathogenesis
– Complete recovery in >95% of cases
i. Production of antibodies directed against basement
– Rapidly Progressive Glomerulonephritis (RPGN) (1%)
membrane (anti-GBM ntibodies), which result in damage
– Chronic Glomerulonephritis (2%)
of the lungs and the kidney

ii. Adults
– Complete recovery (60%)
ii. The Goodpasture antigen is the noncollagenous
– RPGN/Chronic Renal Disease (40%)
component of type IV collagen

b. Clinical features c. Light microscopy: hypercellularity, crescents and fibrin

i. Males > Females
d. Electron microscopy: no deposits, but there is glomerular
ii. Peak incidence: ages 20-40 years basement membrane (GBM) disruption

iii. Pulmonary involvement typically precedes the renal e. Immunofluorescence: smooth and linear pattern of IgG and C3 in
disease the GBM

iv. Present with pulmonary hemorrhage and recurrent f. Treatment: plasma exchange, steroids and cytotoxic drugs
hemoptysis

v. Most develop Rapidly Progressive Glomerulonephritis

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3. Rapidly Progressive Glomerulonephritis

g. Prognosis (RPGN)
i. Poor
a. Synonym: Crescentic Glomerulonephritis
ii. Pulmonary hemorrhage may be severe and life threatening
b. Clinical feature: rapid progression to severe renal failure
iii. Rapidly progressive renal failure is common
in weeks or months
iv. Early aggressive treatment may prevent end-stage renal failure

Crescentic GN
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3. Rapidly Progressive Glomerulonephritis

(RPGN)
d. Light microscopy
c. Occurs in several clinical settings i. Hypercellular glomeruli
ii. Crescent formation in Bowman space
i. Following Goodpasture syndrome iii. Crescents originate from the parietal epithelial cells

ii. Following other forms of glomerulonephritis e. Immunofluorescence

i. Variable
iii. (post-streptococcal, SLE, Berger disease) ii. May show granular or linear deposits of immunoglobulin and
complement
iv. Associated with vasculitis (i.e., Wegener granulomatosis)

v. Idiopathic

Types of RPGNs
f. Electron microscopy
• Type I (25%)
i. Variable
– anti-GBM +
ii. May or may not have electron-dense deposits
– May have a pulmonary component
iii. GBM disruption and discontinuity is commonly seen
(Goodpasture syndrome)
– High prevalence of HLA subtypes
f. Prognosis
i. poor with rapid progression to acute renal failure and
end-stage renal disease
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• Type II (25%) • Type III (> 50%)

– Immune complex mediated – Pauci immune type
– Characteristic (lumpy bumpy) granular – Anti GBM (-)
patterns of staining – Anti Neutrophil Cytoplasmic Antibodies
(ANCA) +
– Associated with Wegener granulomatosis or
microscopic polyarthritis

4. IgA Nephropathy (Berger disease) 4. IgA Nephropathy (Berger disease)

a. Clinical features
a. Epidemiology
iv. Recurrent gross hematuria
i. Most common cause of glomerulonephritis in the world
v. Onset may follow a respiratory infection
ii. Common in France, Japan, Italy and Austria
vi. Predominantly nephritic
iii. Affects children and young adults (mostly males)
vii. Associated with Celiac Sprue and Henoch-Schonlein
purpura
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b. Pathogenesis
d. Immunofluorescence: mesangial deposits of IgA and C3
i. The mechanism is unknown. There is a possible
entrapment of circulating immune complexes with e. Electron microscopy: mesangial immune complex
activation of the alternate complement pathway. There is deposits
also a possible genetic predisposition.
f. Prognosis: many cases slowly progress to renal failure
c. Light microscopy over 25 years

i. Variable
ii. Normal or mesangial proliferation

5. Membranoproliferative glomerulonephritis b. Clinical features

(MPGN)
i. May be nephritic, nephrotic, or mixed!
a. Types of MPGN
ii. MPGN may be secondary to many systemic
i. Type I disorders (SLE, endocarditis), chronic
infections (HBV, HCV, HIV) and
malignancies (chronic lymphocytic leukemia)
ii. Type II (dense deposit disease)
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GBM Tram Tracking

c. Lab
i. Decreased serum C3
ii. C3 nephritic factor (MPGN type II)

d. Light microscopy
i. Lobulated appearance of the glomeruli
ii. Mesangial proliferation and basement-membrane
thickening
iii. Splitting of the basement membrane (“tram-tracking”) may be
seen with a silver or periodic acid-Schiff (PAS) stain

e. Immunofluorescence
i. Type I: granular pattern of C3 often with IgG, C1q and g. Prognosis
C4
ii. Type II: granular and linear pattern of C3
i. Slowly progressive course, resulting in chronic renal
failure over the course of 10 years
f. Electron microscopy
i. Type I: subendothelial and mesangial immune ii. High incidence of recurrence in transplants
complex deposits
ii. Type II: dense deposits within the GBM
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6. Alport Syndrome

a. Definition: a rare X-linked disorder caused by a c. Clinical features

defect in type 4 collagen that is i. Gross or microscopic hematuria begins in childhood
characterized by hereditary nephritis, ii. Hearing loss leading to sensorineural deafness
hearing loss and ocular abnormalities iii. Various ocular abnormalities of the lens and cornea can occur

d. Electron microscopy: alternating thickening and thinning of

b. Genetics basement membrane is seen with splitting of the lamina
i. X-linked densa
ii. The most common mutation causing Alport
syndrome is in the COL4A5 gene coding for e. Alport syndrome is a progressive disease that ultimately
the alpha-5 chain of type 4 collagen results in renal failure