Nephritic Syndromes

Question 1

What are the General Features of Nephritic Syndromes?

Answer 1

1- red blood cells and/or red blood cell casts

2- granular casts

3- variable proteinuria

4- possibly WBC

Question 2

what are the 4 Nephritic disorders with normal complement leves?

Answer 2

• IgA nephropathy/ Henoch-Schönlein Purpura
• Alport’s syndrome (hereditary nephritis)
• SLE ( class I, II, V)
• Benign hematuria

Question 3

what are the 5 Nephritic disorders with low complement leves?

Answer 3

*Post-streptococcal glomerulonephritis

*Membranoproliferative glomerulonephritis

*SLE ( class III, IV)

*Bacterial endocarditis/ infected ventriculoatrial shunt

*Cryoglobulinemia

Question 4

What is the 1 nephritic disorder with variable complement level?

Answer 4

**Rapidly progressive glomerulonephritis

Question 5

IgA nephropathy Clinical:

Answer 5

• Greatest incidence in Asians & Caucasians
• Rare in blacks
• Episodes of gross hematuria (associated with viral respiratory illness or GI illness)
• Persistent microscopic hematuria between these episodes
• Usually non-nephrotic range proteinuria (<3.5gm/day)
• Normal C3/C4
• Most cases of IgA nephropathy are clinically restricted to kidney

Question 6

What is the IgA Nephropathy Pathogenesis?

Answer 6

• Most likely due to deposition of circulating IgA ICs with subsequent activation of complement { supported by finding of granular deposits of IgA and complement (C3) in the glomerular mesangium on IF

Question 7

What is seen in the LM, IF, and EM of IgA nephropathy

Answer 7

• LM: Segmental areas of increased mesangial matrix & hypercellularity
• IF: Mesangial and subendothelial deposits of IgA & C3 (+/- IgG, IgM)
• EM: Mesangial and Subendothelial deposits

Question 9

what are the Post-streptococcal GN clinical presentations?

Answer 9

• GN manifests usually 10 days following pharyngitis & 3 weeks following impetigo {late period of antibody formation}
• More common in children (6-10year age)
• Usually abrupt onset of nephritic syndrome with:
• Proteinuria >2gm/day
• Complement levels always low
• elevated titers of anti-streptolysin O Ab or anti-DNAase B in association with low complement

Question 10

what are the Post-streptococcal GN clinical/outcome:

Answer 10

• Some glomeruli irreversibly damaged during acute episode of PSGN.
• Results in compensatory hyperfiltration in remaining glomeruli to maintain normal GFR
• Long-standing increased glomerular capillary pressure eventually results in hemodynamic mediated injury & glomerulosclerosis

Question 11

What is seen initally vs later in Post-Streptococcal glomerulonephritis
pathogenesis?

Answer 11

• Initially : subendothelial IC deposits (activation ofcomplement, influx of inflammatory cells with resultant proliferative GN…decline in GFR
• Deposits are rapidly cleared accounting for resolution of hematuria & renal failure
• Later: characteristic subepithelial “HUMPS”…responsible for epithelial cell damage & proteinuria.
• IC deposits cleared slowly (separated from circulation by GBM) limiting their clearance

Question 12

What is seen in the LM, IF, and EM of Post-streptococcal GN

Answer 12

• LM: * Hypercellular glomeruli (neutrophils + monocytes) * Proliferation of mesangial, endothelial, epithelial cells. * Process is diffuse (entire lobules of all glomeruli) • Closure of capillary loops due to:
proliferation & swelling of endothelial cells & leukocytes infiltration

• IF: granular deposits of IgG & C3 in the mesangium & along capillary walls
• EM: electron dense deposits in subepithelial space “ humps”.

Question 13

what are the LM,IF, and EM of Membranoproliferative glomerulonephritis

Answer 13

LM: mesangial expansion & hypercellularity “Thickening of the peripheral capillary loops due to double contour formation “ tram track” = duplication of GBM”

Electron microscopic (EM):

Type I: subendothelial deposits

Type II: deposition of dense material along GBM (unknown composition)

Type III: subendothelial, mesangial, subepithelial deposits

Question 14

Membranoproliferative
glomerulonephritis- Pathogenegis for type 1:

Answer 14

• Complement activation via the classical pathway
in Type I disease

Question 15

Membranoproliferative
glomerulonephritis- Pathogenegis for type 2:

Answer 15

Complement activation Via alternate pathway in Type II disease

Question 16

What is the clinical presentation for Membranoproliferative glomerulonephritis?

Answer 16

1-Hematuria or proteinuria discovered on urinalysis

2-Acute nephritic syndrome with hematuria HTN and edema

3-Recurrent episodes of gross hematuria

4-Insidious onset of edema and nephrotic syndrome

• Most progress to ESRD within 10-15 years

Question 17

what is the main concern for someone with Rapidly progressive glomerulonephritis (RPGN)/ crescentic glomerulonephritis:

Answer 17

A group of disorders associated with rapid decline in renal function with associated severe oliguria & if untreated death from renal failure within weeks to months

Question 18

RPGN LM finding?

Answer 18

• Histologically (LM): characterized by a proliferative GN with prominent “crescent” formation in 30-70% of glomeruli and +/- segmental necrosis
• The crescents evolve from cellular to fibrocellular to fibrous crescents

Question 19

What is the Pathogenesis of someone with RPGN?

Answer 19

Question 20

What are the clinical Presentation with someone with RPGN?

Answer 20

• Proteinuria (non-nephrotic), hematuria, red blood cell casts, hypertension, edema, variable degree of oliguria
• Overall 75% die or are placed on dialysis within 2 years of diagnosis

Question 21

What is SLE?

Answer 21

• SLE is an autoimmune disorder of unknown etiology characterized by
production of autoantibody and subsequent immune-complex formation
that may lead to chronic inflammation & tissue destruction in a variety of organ systems

• Abnormal excess production of antibodies against “endogenous” nuclear antigens {dsDNA, ANA, Sm., RNA, Ro, La}
• Immune complex (anti-DNA) deposited in the kidney, with subsequent complement activation, recruitment of inflammatory cells and tissue destruction