Glomerular Diseases

Question 1

Characteristics of Nephrotic Syndrome

Answer 1

• >3.5 g/day proteinuria
• Hypoalbuminemia
• Edema
• Hyperlipidemia
• Lipiduria
• Increased infection risk (decreased Ig’s)
• Thromboembolism risk

Question 2

Characteristics of Nephritic Syndrome

Answer 2

• inflammation of the glomeruli
• Hematuria
• HT
• Edema
• Oliguria
• Elevated BUN/creatinine
• Proteinuria <3.5 g/day

Question 3

Mixed nephrotic and nephritic syndrome

Answer 3

• Proteinuria > 3.5 g/day and edema in the context of hematuria, renal failure, and HT

Casues:
• Lupus nephritis
• Membranoproliferative glomerulonephritis (MPGN)

Question 4

Identify laboratory studies used in the diagnosis of glomerulopathies.

Answer 4

Antibody/ Associated glomerular disease/ Antigen:

Antineutrophil cytoplasmic antibodies (ANCA) = Systemic vasculitis –> PR3 (C-ANCA); MPO (P-ANCA)

Antinuclear antibody = SLE –> Variety of antigens (ex: DNA, histones)

Anti-glomerular BM = Anti-glomerular BM diseases, Goodpasture syndrome –> Alpha3- type IV collagen

IgA = IgA nephropathy –> Unknown

IgG = Membranous nephropathy –> Unknown

IgG = Post-streptococcal glomerulonephritis –> NAPIr or zSpeB/SpeB

Question 5

Describe non-immunologic mechanisms of glomerular injury

Answer 5

Ischemia

Endothelial cell injury
• Fibrin deposition
• RBC trapping
• Smooth muscle proliferation

Deposition of proteins
• Light chain deposition disease (abnormal amount of light chains produced due to cancer)
• Amyloidosis

Question 6

Describe immunologic mechanisms of glomerular injury

Answer 6

Antibody- mediated:

Intrinsic antigens
Ex 1: alpha3 chain of Type IV collagen = component of GBM
o Autoantibodies bind to GBM → severe crescentic glomerulonephritis
Ex 2: M-type phospholipase A2 receptor (PLA2R) = protein on podocyte surfaces
o Autoantibodies bind → immune complexes
o Leads to idiopathic membranous glomerulopathy

“Planted” antigens
• Ex: drug (NSAID) or virus
• Binds to GBM
• Antibodies bind to antigen → immune complexes
• Leads to secondary membranous glomerulopathy

Circulating immune complexes
• Ex: bacterial proteins (nephritis-associated streptococcal plasmin receptor) = antigen
• Antibodies form → bind to circulating antigen
• Ab-antigen complexes get trapped in glomerular capillary wall
• Activates complement cascade = attracts neutrophils and other inflammatory cells
• Leads to diffuse proliferative, post-infectious GN

Cell-mediated
o Alternative pathway of complement activation
• Dense deposit disease/ C3 Glomerulonephritis
• C3 deposited in glomeruli

Question 7

Describe clinical disease entities presenting with the nephrotic syndrome.

Answer 7

• Minimal change disease
• Focal segmental GS
• Membranous glomerulopathy
• Diabetic nephropathy
• Amyloidosis

Question 8

Describe clinical disease entities presenting with the nephritic syndrome.

Answer 8

• IgA Nephropathy
• Anti-GBM Disease
• Thin BM nephropathy (Alport Syndrome)
• Lupus Nephritis (SLE)
• Membranoproliferative GN
• Post-Strep GN