Glomerular Nephritis Flashcards
What are the most common causes of Secondary Nephrotic Syndrome
Diabetic Nephropathy Renal Amyloidosis Multiple Myeloma HIV associated Nephropathy Hepatitis B associated kidney disease
What are clinical features of Diabetic Nephropathy
Decline in kidney fxn
HTN
retinopathy
peripheral neuropathy
What is the pathophysiology of Renal Amyloidosis
Deposition of abnormal fibrillary structures of proteins
What is the epidemiology of Renal Amyloidosis
Dx in 60s
slight predominance in males
describe AL Amyloidosis
Most common systemic amyloidosis in USA
deposition of Ig LIGHT CHAIN
describe AA Amyloid
- more common in developed countries
- deposition of AMYLOID A PROTEIN
- develops secondary to chronic inflammatory states (RA, TB, IBD, FMF, Lymphoma)
- multiorgan failure
Describe AF Amyloid
- Autosomal dominant disorder (deformities of TRANSTHYRETIN)
- Disorders of fibrinogen A alpha chain
AB2m
Hemodialysis associated amyloidosis
What are the most common features of Renal Amyloidosis
Fatigue Weight loss purpura Hepatosplenomegaly Lymphadenopathy Macroglossia Urine LIGHT CHAIN Increased Plasma cells
What is Dx of Renal Amyloidosis
SERUM & URINE FREE LIGHT CHAINS
What is the Light microscopy appearance of Renal Amyloidosis
CONGO RED positivity
crystal violet stains amyloid deposits in glomeruli and vessels
What is the Immunostaining difference between amyloid AL and AA?
Amyloid AL: Anti-Ig Light chains (kappa, lambda)
What is the electronmicroscopy of Renal amyloidosis
nonbranching irregular fibrils deposited in glomeruli, vessel walls, and extracellular spaces
What is the treatment for AL Amyloid?
Chemo: high dose MELPHALAN, peripheral stem cell transplantation
What is the treatment for AA Amyloid?
control chronic infections
Colchicine
Liver transplant
What is the pathophysiology of Multiple Myeloma?
proliferation of plasma cells:
- Coppt of IG LIGHT CHAINS + TAMM-HORSFALL Proteins = cast formation in DCT
- tubularreabsorption of light chaings = INFLAMMATION + FIBROSIS
How does MM cause renal injury?
Nephrotic syndrome (Cast, Ig, FSGS nephropathy) ATN
What are the clinical manifestation of MM?
Pain in lower back, Generalized malaise, Bruising
-minimal proteinuria
What is the Dx of MM?
(need 1 major and 1 minor or 3 minor)
major:
Bx: plasmacytoma; Bone marrow: 30% PLASMA CELLS; elevated monoclonal Ig in blood/urine
minor:
marrow - 10%-30%, minor Ig, Osteopenia/lytic lesions, Abnormally low Ab levels
What is the most important determinant of survival in MM?
kidney fxn
What are the clinical manifestions of HIV associated nephropathy?
Nephrotic Syndrome
Kidney failure (ESRD)
No HTN - Sodium wasting in PCT
Severity of HIVAN correlates with CD4 cell count
What is the Bx of HIVAN?
Collapsing glomerulopathy (prominent visceral epithelial cells/podocytes)
Microscystic dilation of tubules (PATHOGNOMONIC)
Tubulo-reticular bodies on EM
What are 4 common causes for Nephritis
- Lupus nephritis
- MembranoProliferative GN
- IgA Nephropathy/HSP
- Pulmonary-Renal Syndromes
What are some Sx for SLE?
- Constitutional
- Arthralgia, arthropathy
- Dermatologic (malar rash)
- AKI, CKD, Nephritic disease, Nephrotic syndrome
- Seizure, psychosis
What happens to the glomerulus in Membranoproliferative GN?
- Mesangial hypercellularity
2. Endocapillary proliferation
What are the clinical features of Membranoproliferative?
- Nephrotic Syndrome
- Acute Nephritic syndrome
- Asymptomatic proteinuria
- Hematuria
- ESRD in 10 years
What is the histological difference between Type I, II, III MPGN?
Type I: Immunocomplexes in subendothelial space, mesangium
Type II: Dense Deposit Disease, deposits ain the mesangium, GBM, TBM and Bowman’s capsule
Type III: marked disruption of GBM w/ subendothelial and subepithelial electro-dense deposits
What are the two categories of MPGN based on etiology/pathogenesis?
- Immune Complex-associated MPGN (ICM-MPGN)
- Complement mediated MPGN-C3N, DDD
- –2 = complement dysregulation
What are characteristics of CM-MPGN?
- LOW C3, Normal C4
- Acquired cause: circulating Auto-antibodies
- Genetic cause: abnormalities in activating/regulating factors in CM
What are the autobodies directed against in CM-MPGN?
complement regulating factors:
Factor H, Factor I, Factor B, convertase
auto-Ab: C3NeF
What auto-Ab is predominantly found in patients affected by DDD (80%)
C3NeF (less frequently in C3GN, absent in CFHR5)
What is the activity of C3NeF
binds to C3 convertase prolonging its survival
C3NeF can stabilize C5 convertase
What does renal Bx look like in MPGN patients?
clear C3 staining with few/no immunoglobulin deposition
what cause C3 GN?
dysregulation and excessive activation of the ALT complement (low C3 and positive serum C3NeF)
What is the main cause of MPGN in the Middle East, South America, and Africa?
Chronic bacterial, viral, parasitic infections
What are are serum characteristics of ICM-MPGN?
circulating immune complexes
seen in chronic infections (Hep B, C, parasites)
Automimmune disease (SLE, RA)
What enzyme activity is decreased in patients with IgAN?
Leukocyte-b-1,3-galactosyl transferase
What is the clinical triad of Goodpasture’s syndrome
(ANCA-negative vasculitis)
- Pulmonary hemorrhage
- glomerulonephritis
- circulating Anti-GBM Abs
