20. Glomerular diseases II. 1

20. Glomerular diseases II.
NEPHRITIC SY
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Acute onset of moderate proteinuria, hematuria, and renal hypertension
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Some degree of oliguria, azotemia (elevation of the BUN and creatinine levels), and periorbital edema
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Urinalysis: dysmorphic RBCs and red blood cell casts; gross hematuria – urine appears smoky brown
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GLOMERULONEPHRITIDES ASSOCIATED WITH THE NEPHRITIC SYNDROME
The glomeruli are hypercellular (proliferative glomerulonephritides)
Poststreptococcal GN
Membranoproliferative GN
Crescentic GN
POSTSTREPTOCOCCAL GN
Pathogenesis
1 to 4 weeks after ß-hemolytic streptococcal infection of the pharynx or skin, streptococcal-antigen containing ICs
deposit in the glomeruli and induce acute nephritis
Glomerular injury is caused by complement activation
hypocomplementemia in the serum
A similar GN can occur after pneumococcal or staphylococcal infection (postinfectious GN)
Morphology
LM: hypercellular glomeruli because of intracapillary accumulation of neutrophils and monocytes
IF: granular deposits of IgG and complement 3 component (C3) along glomerular capillary loops
EM: subepithelial, large deposits (humps)
Healing: the deposits are cleared over a period of 2 months
Clinical features
Mostly in children 6 to 10 ys of age; macrohematuria is common
Prognosis - excellent: 95% - complete recovery, 4% - slow progression towards ESRD, and 1% - crescentic GN
MEMBRANOPROLIFERATIVE GN (MPGN)
Pathogenesis
IC disease, with subsequent complement activation; hypocomplementemia in the serum
Morphology
LM: severe mesangial cell proliferation
“the proliferating cells interpose between the GBM and endothelial cells
duplication of the GBM
IF: granular IgG, C3 in the mesangium and along the loops
EM: mesangial and subendothelial deposits
Clinical features
Relatively rare; in older children and young adults
Common manifestations: nephritic sy or nephrosonephritic sy
50% of patients develop ESRD
Recurrence after Tx: in 30% of cases
Sec. MPGN
In chronic IC disorders, such as SLE
CRESCENTIC GN
Definition and classification
Crescents in at least 50% of the glomeruli
A rapid progressive decline in renal function: acute nephritic sy with 50% or greater loss of renal function within 3
months + oligoanuria
Renal biopsy evaluation explores the cause of rapidly progressive GN symptoms; IF identifies 3 subgroups
- Linear deposits: anti-GBM antibody-mediated crescentic GN
- Granular deposits: immune complex-mediated crescentic GN (poststreptococcal, lupus GN, etc.)
- Lack of significant immune deposits: pauci-immune crescentic GN, induced by ANCA-positive vasculitis (for details
see vasculitis chapter)
ANTI-GBM NEPHRITIS
Pathogenesis
The Goodpasture-antigen resides in the 3chain of type IV collagen of the GBM
Exposure of GP antigen (the cause is unknown)
circulating autoantibodies to GP antigen deposit in the GBM and
elicit necrotizing capillaritis
Morphology
LM: crescentic-necrotizing GN
IF: linear deposits of IgG and C3 along the GBM
EM: no diagnostic feature
Clinical features
Rare disease; in adults
Most aggressive form of GN
ESRD
Anti-GBM disease: the autoantibodies may crossreact with alveolar basement membranes: Goodpasture sy:
pulmonary hemorrhage + rapidly progressive GN sy; may be lethal
GLOMERULAR DISEASES ASSOCIATED WITH HEMATURIA + PROTEINURIA
IgA GN
Alport NP
Thin basement membrane NP
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20. Glomerular diseases II.
IGA GN
The most common GN
Pathogenesis
Genetic or acquired defects in immune regulation are implicated
Increased mucosal IgA secretion in response to ingested or inhaled antigens
Aberrantly glycosylated IgA1-containing ICs deposit in the mesangium, and activate the alternative complement
pathway
glomerular injury
Morphology
LM: mesangial proliferative GN, often with segmental sclerosis
progression: complete obliteration of the gl-i
IF: mesangial granular IgA and C3
EM: dense deposits in the mesangium
Clinical features
Macrohematuria with low-grade proteinuria, associated with upper resp. tract infection or acute gastroenteritis. Most
frequent in young males; heals mainly
Microhematuria with moderate or nephrotic-range proteinuria. Patients over 30 y, no sex preponderance, tendency to
progress ESRD.
Commonly recurs in transplants in 30%
ALPORT NP
Pathogenesis and morphology
Hereditary disease
Type IV collagen molecule in the GBM is composed of a trimeric complex of various α-chains
In the fetuses, type IV collagen displays 1. 1. 2 network; in adults, type IV collagen is composed of 3. 4. 5
network (developmental switch)
Mutation in the COL4A5 gene located on the X chromosome
lack of 5 chain
the adult-type 3. 4. 5 network
cannot assemble; the fetal network persists, but does not stand against hemodynamic stresses
ongoing, insidious
damage to capillary tufts
sec. FSGS
ESRD
Clinical features
Starts with hematuria in early childhood
Teenage period: hematuria + slowly increasing proteinuria
Around age 30: chronic renal insufficency + extrarenal symptoms: hearing loss and eye abnormalities (lens
dislocation, cataract, etc.)
Males are affected XmY); the carrier females (XmX) display only microhematuria
Since Alport patients ( 1. 1. 2) lack the Goodpasture antigen (it resides in the 3 chain!), if they receive a renal
allograft ( 3. 4. 5), anti-GBM nephritis develops
THIN BASEMENT MEMBRANE NP
Pathogenesis
Frequent cause of glomerular hematuria
May be sporadic or familial
Heterozygous mutations for COL4A3 or COL4A4 gene in familial cases
Morphology
LM: the majority of gl-i are normal; a few may display segmental or global sclerosis
IF: normal expression of 3- 5(IV) chains of GBM
EM: diffusely thin GBM
Clinical presentation
80%: microhematuria, otherwise normal renal function
15%: microhematuria; focal-global glomerulosclerosis
substantial proteinuria, and renal hypertension; usually
middle-aged persons
CHRONIC RENAL FAILURE; CHRONIC SCLEROSING GN
Pathogenesis
End-stage of all GN-es
Hyperfiltration injury contributes to its development
Central role of TGF-ß
Morphology
Gross: symmetric shrinkage (80-80 g); granular surface; on section, the cortex is thinned
LM: the majority of glomeruli are sclerotic; widespread interstitial fibrosis and tubular atrophy
Clinical features
Chronic renal insufficiency
renal failure: 40% to 10% of normal GFR
Azotemia, renal anemia, renal hypertension
LV hypertrophy; decreased concentrating ability can cause polyuria
Patients may display edema, metabolic acidosis, and hyperkalemia, often with overt uremia
Some patients are presented with chronic sclerosing GN without history of early GN
Hemodialysis within 0.5-2 ys
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