L4. Glomerular diseases II: Glomerulonephritis

Question 1

IgA NEPHROPATHY

Highest incidence:

Age range

Presentation:

Pathology

Pathogenesis

Prognosis

Answer 1

Highest incidence: Pacific rim, SE Asia Spe Japan, Singapore and China

Age range: all

Presentation: gross hematuria or microscopic hematuria. Dysmorphic RBCs in urine.

Henoch Schonlein syndrome: small vessel vasculitis w/ purpuric skin rash, GI symptoms, arthralgia and renal IgA disease

Pathology: Mesangial hypercellularity on LM, IF –> Mesangial IgA deposition. EM –> mesangial deposits

Pathogenesis: Defective galactosylation of polymeric IgA –> deposits in mesangium

Prognosis: 15-4-% –> CRF

Question 2

ACUTE POSTINFECTION GLOMERULONEPHRITIS (PIGN)

Classic agent:

Age grp:

Presentation:

Pathology:

Pathogenesis:

Prognosis:

Answer 2

Classic agent: Most commonly post streptococcal

Age grp: 2-10 yrs, Adults –> diabetes, HIV, IV drug abuse

Presentation: renal disease 1-2 wks post pharyngitis OR 2-6 wks after skin infection

Pathology: LM –> endocapillary hypercellularity, IF –> granular IgG and C3 in capillary walls, EM –> subepithelial hump + subendothelial and mesangial deposits

Pathogenesis: Immune complex formation w/ GADPH and SpeB Ag

Prognosis: Good in children, not good in adults

Question 3

PSGN: Possibe pathogenic mechanism

Answer 3

Nephritogenic antigens
(GADPH or SpeB) are normally repelled (a) in both their free and
antibody-bound form by the GBM. These antigens can interact with
plasmin or plasminogen (b) to activate procollagenase and latent MMPs,
which degrade the GBM negative charges (c). The antigens or complexes can then pass thru the GBM forming the subepithelial hump deposits (d).

Question 4

MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS (MPGN)
 Age grp:

Presentation:

Pathology:

Pathogenesis:

Prognosis:

Answer 4

Age grp: Children and youn adults (8-30) –> idiopthic, older adults –> secondary to infection = HepC

Presentation: Low serum complement levels (C3, C1, C2, C4, properdin, factor B)

Pathology: LM –> severe glomerular endocapillary hypercellularity w/ doible contouring of capillary walls, IF –> Granular capillary wall C3 and some IgG and IgM, EM–> new inner basal lamina and subendothelial deposits.

Pathogenesis: immune complex disease of unknown etilogy –> infectious agents contribute in some cases. Alternate complememtn path is ofeten activated w/ C3 depletion. Ab agains C3 convertase might be present

Prognosis: Progressive disease. 50% renal failure after 10 yrs

Question 5

In MPGN associated with HepC what particular deposit component is characteristic?

Answer 5

Cryoglobulins

Question 6

Explain the alternative complememtn pathway in MPGN

Answer 6

Normally, C3bBb is stabilized by properdin and degraded by factors I and H.

Some patients have a circulating auto- antibody C3 nephritic factor (C3NeF) that binds to and stabilizes C3bBb.

Some patients have mutations in factors I and H. Thus, there is enhanced C3 activation and consumption, causing hypocomplementemia.

Question 7

CRESCENTIC GLOMERULONEPHRITIS

Injury or disease?

Presentation:

Pathology:

Treatment:

Answer 7

Injury or disease? –> Pattern of injury of many diseases

Presentation: Rapid and progressive decline in renal fct w/severe nephritic syndrome. Prominent proteinuria is uncommon

Pathology: 3 cathegories –> anti-GBM nephritis, immune complex and pauci-immune glomerulonephritis

Treatment: Intensive plasmapheresis combined w/ steroids and cyclophosphamide

85% survival 40% ESRD

Question 8

Common Anti-GBM diseases

Answer 8

• Goodpasture’s syndrome
• Isolated anti-GBM disease

Question 9

How do we differentiate anti-GBM diseases?

Answer 9

• Goodpasture’s syndrome –> Lung and kidney involvement
• Isolated anti-GBM D –> w/o lung OR lung only

Question 10

Pathogenesis of anti-GBM disease

Answer 10

Circulating auto-GBM Ab against carboxyterminal non collagenous domain of alpha3 chain of collagen IV