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Glomerular Syndrome
1. Acute nephritic syndrome
2. Rapidly progressive glomerulonephritis
3. Chronic renal falure
4. Asymptomatic hematuria/proteinuria
Nephrotic Syndrome
• Manifestations
– Massive proteinuria
– Hypoalbuminemia
– Generalized edema
– Hyperlipidemia and lipiduria
Minimal Change Disease
• Lipoid nephrosis, Nil disease, Idiopathic
nephrotic syndrome
• Most common cause of NS in children
• Dramatic response to steroids
• Of unknown cause – NSAID, allergic
• May present with acute renal failure
• Differentiate from focal segmental
Minimal Change Disease
• LM: few, if any changes
• IF: usually negative; may have mesangial
• EM: widespread effacement of podocyte
foot processes
– Villous hypertrophy of podocytes
– Absence of deposits
Focal Segmental
• Classifications
– In association with other known conditions
• HIV, heroin, sickle cell disease, massive obesity
– As a secondary event reflecting glomerular
– As an adaptive response
– In certain inherited, congenital forms of NS
– As a primary disease --- idiopathic
•Failure to respond to steroids
•May have microscopic hematuria,

hypertension or renal insufficiency

•Some develop ESRD

•Recurrence after transplantation

•Differ from minimal change disease
–They have a higher incidence of hematuria,
reduced GFR and HPN
–Their proteinuria is more often nonselective
–They respond poorly to steroids
–Many progress to CGN
–IMF shows deposition of IgM and C3 in
sclerotic segment
•LM: some glomeruli with segmental sclerosis
(mesangial matrix material, collapse, BM-like
material) +/- hyalinosis
•Focal segmental consolidation of the tuft
with obliteration of the capillary, often with
adhesions to Bowman’s capsule
•+/- podocyte hypertrophy
•IF: usually negative except IgM +/- C3 in
sclerotic segment
•EM: widespread podocyte foot process

• accumulation in collapsed loop of matrix-like

• Can be primary or secondary
• Secondary causes
– Drugs
– Underlying malignant tumors
– Infections
– Metabolic disorders
•Some have asymptomatic proteinuria
•Nephrotic syndrome

•Some --- remission

•Others --- ESRD

•Deposits may be formed by the

interaction of autoantibodies with

podocyte surface antigens
•LM: normal to extreme diffuse thickening of
the cap wall, foam cells in the interstitium
•IF: finely granular diffuse cap wall staining
--- IgG +/- C3 and others
•EM: numerous subepithelial deposits +/-
spikes of GBM between
•Course: 1/3 progress, 1/3 remit, 1/3
proteinuria only
Membranoproliferative GN
• Can be primary or secondary
• Secondary causes
– Chronic immune-complex disorders
• SLE, hepatitis B, hepatitis C, endocarditis, HIV,
– Partial lipoid dystrophy associated with C3NeF
– Alpha-1 antitrypsin deficiency
– Malignant diseases
• CLL, lymphoma, melanoma
– Hereditary complement deficiency states
•MPGN types I, II and III
•LM: proliferative, mesangial matrix increase,
lobulation, tram-tracking, capillary wall thickening
•IF: broad cap wall deposits and less often in the
mesangium --- C3 +/- others
–Type I – massive subendothelial deposits +/- mesangial
–Type II – large electron-dense deposits in
intramembranous portion
–Type III – subepithelial deposits, segmental GBM
•Course: progressive (many to renal failure)
•DX: low complement, nephrotic/nephritic
IgA Nephropathy (Berger’s

• Frequent cause of recurrent gross or

microscopic hematuria
• +/- NS or RPGN
• Initially considered to be benign
• May lead to ESRD
• Reversible ARF from numerous tubular
casts and tubular injury
•LM: any glomerular pattern
•IF: intense mesangial granular IgA

•EM: dense deposits in mesangial

paramesangial areas

Pathogenesis: deposition in glomeruli of

abnormal forms of circulating IgA

resulting from abnormal glycosylation
• IgA binds to mesangial cells
• Role of alternative complement pathway
No diagnostic serologic test for IgA

• 1-4 weeks after a streptococcal infection
of the pharynx or skin
• 6-10 yo but may affect any age
• Group A beta- hemolytic streptococci
types 12, 4 and 1
• Acute nephritis syndrome: gross
hematuria, edema and hypertension
•A minority --- severe renal insufficiency
•Low C3

•Glomerular immune deposits represent

Ag-Ab complexes
•LM: proliferative, exudative (PMNs), +/-
•IF: granular GBM --- IgG +/- C3
•EM: subepithelial humps +/- small
subendothelial/mesangial deposits
•Course: resolves in vast majority of cases
•Dx: ASO up, complement down, nephritic
syndrome, HPN
•Nonstreptococcal acute GN
–Bacterial, viral and parasitic infections
Rapidly Progressive GN
• Crescentic GN
– Rapid and progressive loss of renal function
associated with severe oliguria and (if
untreated) death from renal failure within
weeks to months
–LM: over 50% of glomeruli with crescents
•1/3 granular (immune complex GN, e.g. SLE, post-
infectious GN)
•1/3 linear (anti-GBM, e.g. Goodpasture’s disease)
•1/3 no deposits (e.g. PAN, Wegener’s, vasculitis)
–EM: glomerular deposits anywhere
–Course: terrible (progression to ESRD except
Anti-GBM Disease
• Autoantibodies against the NC1 domain of
the alpha 3 chain of type IV collagen
(Goodpasture Ag)
• Associated with pulmonary hemorrhage
• LM: crescentic
• IF: strong linear staining along the GBM
Hereditary Nephritis
• Alport syndrome
– Nephritis accompanied by nerve deafness
and various eye disorders (lens dislocation,
post. Cataracts and corneal dystrophy)
– Males > females, hematuria
– Defective form of BM due to mutations in
genes that encode components of type IV
•In 80% x-linked inherritance
•In 15% autosomal recessive

•Rarely autosomal dominant

•Skin biopsy (alpha 5)

•Anti-GBM disease after transplantation

•LM: segmental proliferation or sclerosis,
fetal-like glomeruli, mesangial matrix
•EM: irregular foci of thickening or thinning

with splitting and lamination of lamina

• - mainly thinning in female carriers
Thin Basement Membrane
• Benign familial hematuria
• Diffuse thinning of the GBM to between
150 and 225 nm (normal = 300 to 400 nm)
Chronic GN
• End-stage pool of glomerular diseases
• A number of cases arise mysteriously
without antecedent history of any of the
well-recognized forms of early GN