Glomerular Syndrome
1. 2. 3. 4. Acute nephritic syndrome Rapidly progressive glomerulonephritis Chronic renal falure 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 reactions • May present with acute renal failure • Differentiate from focal segmental glomerulosclerosis

Minimal Change Disease
• LM: few, if any changes • IF: usually negative; may have mesangial IgM • EM: widespread effacement of podocyte foot processes
– Villous hypertrophy of podocytes – Absence of deposits

Focal Segmental Glomerulosclerosis
• Classifications
– In association with other known conditions
• HIV, heroin, sickle cell disease, massive obesity

– As a secondary event reflecting glomerular scarring – 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 •Hyalinosis •+/- podocyte hypertrophy

IF: usually negative except IgM +/- C3 in sclerotic segment •EM: widespread podocyte foot process effacement

accumulation in collapsed loop of matrix-like material

Membranous Glomerulonephritis
• Can be primary or secondary • Secondary causes
– Drugs – Underlying malignant tumors – SLE – 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 •Spikes •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, schistosomiasis

– 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 •EM:
–Type I – massive subendothelial deposits +/- mesangial deposits –Type II – large electron-dense deposits in intramembranous portion –Type III – subepithelial deposits, segmental GBM fragmentation

•Course: progressive (many to renal failure) •DX: low complement, nephrotic/nephritic

IgA Nephropathy (Berger’s Disease)
• 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 nephropathy

Poststreptococcal Glomerulonephritis
• 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), +/crescents •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 –IF:
•1/3 granular (immune complex GN, e.g. SLE, postinfectious 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 post-infectious)

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 collagen

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 increase •EM: irregular foci of thickening or thinning with splitting and lamination of lamina densa • - mainly thinning in female carriers

Thin Basement Membrane Disease
• 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

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