Renal Pathology Pt. 2 Flashcards
what are the causes of nephritic syndrome?
post-streptococcal/post-infectious glomerulonephritis (acute proliferative)
rapidly progressive (crescentic) glomerulonephritis
what is acute proliferative glomerulonephritis?
diffuse proliferation of glomerular cells associated with influx of leukocytes caused by immune complexes
*most common is post-strep
what are the pathologic characterizations of acute proliferative glomerulonephritis?
hypercellularity
leukocyte infiltration
granular deposits of IgG, IgM and C3
subepithelial “humps” of immune complexes
what is the clinical presentation of post-strep glomerulonephritis in children?
malaise, fever, nausea, oliguria and hematuria 1-2 weeks after recovery from a sore throat
dysmorphic RBC or RBC casts with mild proteinuria
what is rapidly progressive glomerulonephritis?
syndrome associated with severe glomerular injury - typically immunologically mediated
what are the classifications of RPGN?
Type 1 - anti-GBM antibody
Type 2 - immune complex
Type 3 - ANCA +/Pauci immune
what is Goodpasture syndrome?
Type 1 RPGN
anti-basement membrane antibody (IgG) deposition in kidneys and lungs
manifests as pulmonary and renal hemorrhage
what HLA subtype is associated with Goodpasture?
HLA-DRB1
How is Goodpasture treated?
plasmaphoresis
what diseases are associated with Type 2 RPGN?
acute proliferative glomerulonephritis
SLE
IgA nephropathy
Henoch-Schonlein purpura
what is the definition of Type 3/Pauci immune RPGN?
lack of detectable anti-GBM antibodies or immune complexes by immunofluorescence or electron microscopy
what is typically found on serology with Type 3 RPGN?
p-ANCA or c-ANCA
what disorders are associated with type 3 RPGN?
vasculitides such as Wegeners or polyangiitis
what are the causes of nephrotic syndrome?
Membranous nephropathy Minimal change disease Focal segmental glomerulosclerosis Membranoproliferative glomerulonephritis IgA nephropathy
what is membranous nephropathy?
diffuse thickening of the glomerular capillary wall due to the accumulation of IgG deposits along the basement membrane
can be primary (idiopathic) or secondary
what is the pathogenesis of primary membranous nephropathy?
autoimmune disease linked to PLA-2 Ab
what are common causes of secondary membranous nephropathy?
drugs (NSAIDs) malignancy SLE infections other autoimmune disorders (thyroiditis)
what are the histological hallmarks of membranous nephropathy?
effaced foot processes (podocytes)
thick basement membrane
subepithelial IgG deposits
what is minimal change disease?
podocytopathy
relatively benign disorder characterized by effacement of podocytes detectable only by electron microscopy
most frequent cause of nephrotic syndrome in children
what is the peak incidence of minimal change disease?
2-6 y/o
what features of minimal change disease indicate its immunologic basis?
- immune dysfunction often following respiratory infection or routine prophylactic immunization
- responsive to steroids/immunosuppressives
- association with other atopic disorders
- increased incidence with certain HLA haplotypes
- increased incidence in patients with Hodgkin lymphoma
what is focal segmental glomerulosclerosis?
podocytopathy
sclerosis of some but not all glomeruli with only a portion of the capillary tuft involved
most common cause of nephrotic syndrome in adults
what are the classifications of FSGS?
primary/idiopathic *most common* in association with other conditions secondary event due to antecedent glomerular injury adaptive response to loss of renal mass hereditary
how does FSGS differ from MCD?
- higher incidence of hematuria, reduced GFR and HTN
- proteinuria tends to be non-selective
- poor response to steroids
- significant progression to CKD
what is termed the “collapsing variant” FSGS?
HIV associated FSGS
what gene variation is associated with FSGS and renal failure in patients of African descent?
APOL1 on Chr. 22
what is membranoproliferative glomerulonephritis?
considered a pattern of immune-mediated injury to the mesangial cells or capillary loops
what are the classes of MPGN?
Type 1 - IgG and complement deposition
Type 2 - complement deposition and activation
what are the histologic findings of MPGN?
alterations in the glomerular basement membrane
proliferation of glomerular cells
leukocyte infiltration
what is the clinical presentation of primary MPGN Type 1?
typically occurs in children or young adults
nephrotic syndrome with nephritic features
mild HTN
50% of patients develop CKD
what is the clinical presentation of secondary MPGN Type 1?
occurs exclusively in adults
chronic antigenemia causing immune complex deposition
associated with other disease or malignancy
50% of patients develop CKD
what is the clinical presentation of MPGN Type 2/Dense Deposit Disease?
generally occurs in adults
hematuria
50% have nephritic syndrome
poorer prognosis than MGPN Type 1
what is the pathogenesis of MPGN type 2?
C3NeF or “nephritic factor” IgG autoantibody binds C3 convertase leading to continuous activation of the alternative complement pathway
what two diseases often manifest with IgA nephropathy?
Berger disease
Henoch-Scholein purpura
what are the clinical characteristics of IgA nephropathy?
older children and young adults most common
Caucasian and Asian
male > female
genetic susceptibility
hematuria with the presence of significant infection (URI/respiratory/GI/abscess)
association with gluten enteropathy and liver disease
what is chronic glomerulonephritis?
end-stage glomerular disease may occur with or without an antecedent history of acute glomerulonephritis
what primary glomerular diseases are most likely to progress to chronic glomerulonephritis?
crescentic GN (90%) focal segmental GS (50-80%) membranoproliferative GN (50%) membranous nephropathy (30-50%) IgA nephropathy (30-50%)
