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105 Cards in this Set
- Front
- Back
What are the mechanisms that cause glomerular disease?
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- Immunocomplex deposition in glomerulus (activates complement resulting in neutrophil chemotaxis)
- Antibodies against GBM or glomerular Ags - Cytokine production by inflammatory cells |
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How do immunocomplexes injure the kidney?
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- Immunocomplexes can circulate in blood
- Then they get deposited in glomerulus - Activates complement resulting in neutrophil chemotaxis |
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What is an example of immunocomplexes that injure the glomerulus?
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DNA-anti-DNA complexes in Lupus
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How do antibodies injure the kidney?
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Antibodies that target the GBM or glomerular antigens
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How can glomerular disease be categorized?
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- Diffuse (all glomeruli) vs Focal (some glomeruli) injury to glomeruli
- Global (entire glomerulus) vs Segmental (fraction of glomerulus) injury to glomeruli |
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How does glomerular disease present?
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- Loss of GFR (temporal change)
- Hematuria (quality) - Proteinuria (quantity) |
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What are the types of glomerular disease based on symptoms?
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- Nephrotic syndrome
- Nephritis |
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What are the features of Nephrotic Syndrome?
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- Proteinuria >3.5 g/day
- Hypoalbuminemia - Edema - Hyperlipidemia - Lipiduria - Hypercoagulability |
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What are the features of Nephritis?
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- Mild proteinuria
- Hematuria (RBCs, RBC casts, dysmorphic RBCs) - HTN - Edema |
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What is similar between Nephrotic Syndrome and Nephritis?
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- Both have proteinuria (although >3.5g/day in nephrotic syndrome)
- Both have edema |
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What factors distinguish Nephrotic Syndrome and Nephritis?
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Nephrotic Syndrome:
- More proteinuria (>3.5 g/day) - Hypoalbuminemia - Hyperlipidemia - Lipiduria - Hypercoagulability Nephritis: - Mild proteinuria - Hematuria - Hypertension |
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What causes edema in Nephrotic Syndrome?
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- Loss of plasma oncotic pressure
- Na/H2O retention |
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What causes hyperlipidemia in Nephrotic Syndrome?
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Increased hepatic protein production
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What causes hypercoagulability in Nephrotic Syndrome?
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Loss of proteins C & S
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What are the features of hematuria in Nephritis?
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In urine: RBCs, RBC casts, dysmorphic RBCs
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What glomerular diseases have "nephrotic syndromes" clinical manifestations?
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- Minimal change disease
- Focal segmental glomerulosclerosis - Membranous nephropathy |
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What glomerular diseases have "nephritis" clinical manifestations?
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- Crescentic (ANCA) Glomerulonephritis
- Acute Post-Infectious GN - Membranoproliferative GN - IgA Nephropathy |
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What are the causes of Acute Glomerulonephritis (GN)?
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- IgA nephropathy
- Post-infectious GN - Anti-GBM disease (Goodpasture's) - Small vessel vasculitis (ANCA) - Lupus nephritis - Membranoproliferative GN |
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What is the most common cause of Glomerulonephritis worldwide?
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IgA Nephropathy
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What kind of kidney injury/disease is caused by IgA nephropathy? Who is affected by it?
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- Glomerulonephritis
- Most between age 10-50 |
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What are the most prominent features of IgA Nephropathy?
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* Hematuria (50-60% have episodic gross hematuria, 30% persistent microhematuria, 10% acute GN or nephrotic syndrome)
- Mild proteinuria - Many sub-clinical - Dysuria and loin pain may accompany hematuria - HTN in advanced dz |
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What does hematuria in IgA nephropathy occur in conjunction with?
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*Upper respiratory infection ("synpharyngitic hematuria")
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What is Synpharyngitic hematuria? What is it a feature of?
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- Hematuria in conjunction with an upper respiratory infection
- Frequently in IgA nephropathy |
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How do you diagnose IgA nephropathy?
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** Immunofluorescence: Mesangial IgA deposition
- LM: variable mesangial hyper-cellularity (may see segmental proliferation, segmental sclerosis, and necrosis w/ crescents) - EM: mesangial e- dense deposits (paramesangial) |
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What determines the prognosis of IgA Nephropathy?
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- Serum creatinine
- BP - Degree of proteinuria |
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What is the systemic disorder characterized by IgA deposition in multiple organs?
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Henoch-Schönlein Purpura
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What are the symptoms of Henoch-Schönlein Purpura? Cause?
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- Skin: non-blanching purpura (legs / buttocks)
- Joints: transient arthralgias - GI: abdominal pain, vomiting, melena (dark smelly stool w/ blood), hematochezia (fresh blood in stool) - Kidney: hematuria, proteinuria, rarely progressive renal failure Cause: IgA deposition in multiple organs |
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What is the classic cause of post-infectious GN?
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Post-streptococcal GN
- Follows infection in nephritogenic strain of Group A β-hemolytic streptococcus - 7-14 days after pharyngitis - 14-28 days after skin infection |
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What kind of streptococcal infections can cause post-infectious GN? How long does each take to cause GN?
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- Pharyngitis: 7-14 days later
- Skin infection: 14-28 days later |
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What are the most prominent features of Post-Strep GN?
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- Sudden onset HTN
- Azotemia - Oliguria - Edema - Cola or tea colored urine |
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How do you diagnose Post-Strep GN?
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** EM: mesangial and large sub-epithelial "hump-like" deposits
- LM: enlarged, hypercellular glomeruli; diffuse mesangial and endocapillary proliferation w/ neutrophils (may see crescents) - IF: granular capillary wall and mesangial IgG and C3 - Low C3 complement level - Anti-streptolysin O (ASO) can be elevated - Urinalysis: RBC casts and mild proteinuria (nephritis) |
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What does this EM signify?
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Post-Strep GN
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What is the prognosis for Post-Strep GN depending on age?
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- Children: 95% recover w/ conservative management, 1% progress to renal failure
- Adults: 60% recover promptly |
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What kind of syndrome is Rapidly Progressive GN? How long does it take to "rapidly progress"? AKA?
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- Classic nephritic syndrome
- Rapid progression (days to weeks) to renal failure - AKA: Crescentic GN |
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What are the types of Rapidly Progressive GN? Causes?
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* Anti-GBM / Goodpasture's
* ANCA associated GN (Pauci immune) - Immune complex GN (lupus nephritis, post-infectious, cryoglomulinemia) |
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Who is more commonly affected by Anti-GBM / Goodpasture's Syndrome? Cause?
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- Males > Females
- Due to circulating anti-GBM antibody to α3-chain of type IV collagen |
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What are the symptoms of Anti-GBM / Goodpasture's Syndrome?
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May present as a pulmonary-renal syndrome:
- Hemoptysis (coughing blood) - Pulmonary infiltrates - Glomerulonephritis |
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How do you diagnose Anti-GBM / Goodpasture's Syndrome?
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** IF: LINEAR IgG and C3 on kidney biopsy
- + anti-GBM antibody in blood |
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How do you treat Anti-GBM / Goodpasture's Syndrome?
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- Plasmapheresis (remove anti-GBM)
- Prednisone - Cytoxan |
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What signifies Pauci-immune GN?
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- Crescenteric GN w/ little deposition of immune reactants
- Idiopathic OR associated w/ anti-neutrophil cytoplasmic antibody (ANCA) vasculitis |
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If there is little deposition of immune reactants, what is the cause of the GN?
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Pauci-immune GN:
- Idiopathic OR - ANCA vasculitis (anti-neutrophil cytoplasmic antibody) |
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What small vessel vasculitis are associated with Pauci Immune GN?
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- Microscopic Polyangitis (no granulomatous inflammation and no asthma)
- Wegener's Granulomatosis (necrotizing granulomatous inflammation, no asthma) - Churg-Strauss Syndrome (necrotizing granulomatous inflammation, asthma, eosinophilia) |
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Which vasculitis causes no granulomatous inflammation and no asthma?
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Microscopic polyangitis (small vessel vasculitis)
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Which vasculitis causes necrotizing granulomatous inflammation and no asthma?
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Wegener's Granulomatosis (small vessel vasculitis)
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Which vasculitis causes necrotizing granulomatous inflammation, asthma, and eosinophilia?
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Chrug-Strauss Syndrome (small vessel vasculitis)
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What are the features of Wegener's Granulomatosis?
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- Granulomatous vasculitis of medium to small arterioles
- c-ANCA + in 80% - URI (sinusitis, nasal lesions, hemoptysis) - Mononeuritis multiplex - Purpura - Nephritis |
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What would you find on a renal biopsy with Wegener's Granulomatosis?
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Crescenteric GN w/o immune deposits (pauci-immune)
(c-ANCA+ in 80%) |
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What are the types of Rapidly Progressive GN?
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- Anti-GBM
- Immune-complex - Pauci-immune |
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What are the clinical, LM, IF microscopy features of Anti-GBM Rapidly Progressive GN?
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- Clinical: + anti-GBM Ab in blood
- LM: crescenteric GN - IF: LINEAR IgG and C3 |
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What are the clinical, LM, IF microscopy features of Immune-Complex Rapidly Progressive GN?
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- Clinical: Lupus, Post-strep
- LM: Crescenteric GN - IF: Variable deposition of IC and complement |
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What are the clinical, LM, IF microscopy features of Pauci-Immune Rapidly Progressive GN?
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- Clinical: ANCA+
- LM: Crescenteric GN - IF: Negative |
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What are the primary renal disease causes of Nephrotic Syndrome?
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- Membranous nephropathy
- Focal segmental glomerulosclerosis (FSGS) - Minimal Change Disease (80% of children) |
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What are the secondary causes of Nephrotic Syndrome?
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- Systemic disease: *DM*, SLE, amyloidosis
- Infection: HIV, HepB, HepC, syphilis - Drugs: NSAIDs, gold, penicillamine |
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What lab studies are helpful for diagnosing secondary causes of Nephrotic Syndrome?
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- ANA, anti-dsDNA, complement levels
- Serum and urine protein electrophoreses - HBV and HCV serologies - Cryoglobulins - Syphilis serology - Renal biopsy usually indicated |
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How is Nephrotic Syndrome treated?
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All causes of nephrotic syndrome:
- ACE-I or ARBs - lower intraglomerular pressure and reduce proteinuria - Statins - lipid-lowering therapy - Diuretics or salt restriction - improve edema |
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What is the most common cause of nephrotic syndrome in children?
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Minimal Change Disease
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When is Minimal Change Disease peak in occurrence? What kind of disease?
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- Peak: ages 2-6
- Nephrotic syndrome |
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What are the potential outcomes of Minimal Change Disease?
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- 5% progress to ESRD
- Spontaneous remissions can occur - Tx w/ steroids can induce remission, relapses in 75% - Fewer relapses after puberty |
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What can cause Minimal Change Disease in adults?
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Idiopathic or associated with:
- Drugs: *NSAIDs* - Neoplasms: *Hodgkin's Lymphoma*, pancreatic, prostate, lung, colon, and renal cell carcinomas, mesothelioma, oncocytoma - Infections: syphilis, HIV |
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How do you diagnose Minimal Change Disease?
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* LM: Glomeruli, interstitium, and tubules are NORMAL (hence minimal change)
* EM: Podocyte foot process effacement (FUSION) - IF: negative or mesangial IgM |
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How do you treat Minimal Change Disease?
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- Children: corticosteroids
- Adults: steroids (but takes longer to respond than children, partial remissions may occur) |
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What is the most common cause of Nephrotic Syndrome in Caucasian adults?
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Membranous Nephropathy
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What are the secondary causes of Membranous Nephropathy? How common are secondary causes?
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- Infection: *HBV*
- CT Disease: *SLE* - Neoplasms: *Carcinoma of lung, colon, stomach, breast; non-Hodgkin's lymphoma* - Drugs: gold, penicillamine, mercury, NSAIDs, captopril - 15-20% of cases of membranous neuropathy have secondary causes |
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What infection can cause Membranous Nephropathy?
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Hepatitis B Virus
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What disease can cause Membranous Nephropathy?
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CT disease: Systemic Lupus Erythematous
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What neoplasms can cause Membranous Nephropathy?
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- Carcinomas: lung, colon, stomach, breast
- Non-Hodgkin's Lymphoma **consider age-appropriate cancer screening |
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What are the features of Membranous Nephropathy?
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Nephrotic syndrome
- Insidious onset (gradual) - Heavy proteinuria - HTN and Azotemia - Occult malignancies and infections - Renal vein thrombosis (~20%) |
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How do you diagnose Membranous Nephropathy?
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** LM: diffuse thickening of GBM, GBM "spikes" on silver stain
- IF: granular GBM deposits of IgG - EM: SUB-EPITHELIAL deposits |
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What disease is characterized by "sub-epithelial spikes"?
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Membranous Nephropathy
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What are the possible outcomes of Membranous Nephropathy?
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Rule of thirds:
- 1/3 spontaneous remission - 1/3 partial remissions w/ stable function - 1/3 slowly progressive loss of renal function |
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How should a patient with Membranous Nephropathy be treated?
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- Without poor prognostic factors: manage conservatively w/ ACE-I and/or ARB (and closely follow)
- Others, steroids +/i other immunosuppressive drugs |
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What is the most common cause of idiopathic nephrotic syndrome in African-Americans?
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Focal Segmental Glomerulosclerosis (FSGS)
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What are the symptoms of Focal Segmental Glomerulosclerosis (FSGS)?
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- Most common idiopathic nephrotic syndrome in African Americans
- More aggressive than minimal change disease - HTN, hematuria more common - Renal dysfunction commonly progressive - ESRD 5-20 years after presentation |
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What is the prognosis for patients with Focal Segmental Glomerulosclerosis (FSGS)?
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- ESRD 5-20 years after presentation
- 50% progression to ESRD in 10 years |
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What are the types of Focal Segmental Glomerulosclerosis (FSGS)?
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- Primary FSGS: acute onset of nephrotic syndrome
- Secondary FSGS: slowly increasing renal insufficiency and proteinuria - Hereditary FSGS: mutations in proteins that make up glomerular slit diaphragm |
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What can be caused by mutations in proteins that make up glomerular slit diaphragm?
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Focal Segmental Glomerulosclerosis (FSGS)
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What are the causes of secondary Focal Segmental Glomerulosclerosis (FSGS)?
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* Infections: HIV *
- Drugs (NSAIDs, Heroin) - Massive obesity - Healed previous glomerular injury - Loss of functioning renal mass (unilateral agenesis, reflux nephropathy, etc) |
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How do you diagnose Focal Segmental Glomerulosclerosis (FSGS)?
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* LM: Focal and segmental glomerular sclerosis* w/ capillary collapse, hyaline and lipid deposition, and adhesion to Bowman's capsule
- IF: Negative of IgM and C3 in mesangium or in segmental scars - EM: podocyte foot process effacement, may see segmental sclerosis |
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What does this image show? What is it diagnostic of?
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- Segmental glomerular sclerosis
- Focal Segmental Glomerulosclerosis (FSGS) |
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What determines the prognosis of Focal Segmental Glomerulosclerosis (FSGS)?
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Degree of proteinuria (ACE-I ↓ proteinuria)
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What are the treatment options for Focal Segmental Glomerulosclerosis (FSGS)?
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- ACE-I - decrease proteinuria (better for prognosis)
- Corticosteroids can induce remission in some patients - Immunosuppressives for steroid-resistant patients and patients who relapse |
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What glomerular diseases have nephrotic and nephritis features?
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- Membranoproliferative Glomerulo-nephritis (MPGN)
- Lupus Nephritis (Systemic Lupus Erythematous) |
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What are the features of Membranoproliferative Glomerulo-nephritis (MPGN)?
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- Proteinuria and hematuria
- Hypertension (1/3) - Low C3 complement - 50% nephrotic syndrome - 30% asymptomatic proteinuria ± hematuria - 20% acute glomerulonephritis |
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What are the potential causes of secondary Membranoproliferative Glomerulo-nephritis (MPGN)?
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* Infections: Hepatitis C virus *, HBV, endocarditis, abscesses
- CT disease: SLE - Cryoglobulinemia - Neoplasms |
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How do you diagnose Membranoproliferative Glomerulo-nephritis (MPGN)?
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- LM: hypercellular glomeruli, endocapillary cell proliferation, lobular appearing glomeruli
- IF: granular C3 deposition - EM: subendothelial deposits |
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What is Systemic Lupus Erythematosus (SLE)?
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Multi-system auto-immune disorder:
- Abnormal auto-Ab production - Immune complex deposition - Inflammatory cell infiltration |
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What is a common cause of diffuse proliferative glomerulonephritis?
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Lupus Nephritis
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What percentage of patients with SLE develop overt nephritis?
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40%
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How many types of Lupus Nephritis are there?
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6 classes (I-VI)
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How do you treat Lupus Nephritis?
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- Aggressive BP control
- Control lipids - Treatment of extra-renal involvement - Classes III-V usually treated w/ corticosteroids + cytotoxic therapy |
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How common is renal failure in Lupus Nephritis?
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Class IV: renal failure rate 25% by 5-10 years
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1. Most common Glomerulonephritis?
2. Most common nephrotic syndrome in children? 3. Most common cause of Nephrotic Syndrome in Caucasian adults? 4. Most common cause of idiopathic nephrotic syndrome in African-Americans? |
1. IgA Nephropathy
2. Minimal Change Disease 3. Membranous Nephropathy 4. Focal Segmental Glomerulosclerosis (FSGS) |
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What disease is characterized by hematuria frequently occurring in conjunction w/ an upper respiratory infection ("synpharyngitis hematuria")?
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IgA Nephropathy
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What disease is diagnosed by mesangial IgA deposition on IF?
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IgA Nephropathy
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What disease is diagnosed by mesangial and large sub-epithelial "hump-like" deposits on EM?
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Post-Strep Glomerulonephritis
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What classic nephritic syndrome progresses rapidly (days to weeks) to renal failure?
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Rapidly Progressive GN
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What diseases are caused by anti-GBM antibodies or anti-neutrophil cytoplasmic antibodies (ANCA)?
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Rapidly Progressing GN
- Anti-GBM - Goodpasture's - ANCA associated GN (Pauci Immune) |
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What disease is diagnosed by linear IgG and C3 in kidney biopsy on IF?
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Anti-GBM / Goodpasture's Syndrome
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What disease is classically caused by NSAIDs or Hodgkin's Lymphoma?
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Minimal Change Disease
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What disease is diagnosed by podocyte foot process effacement (fusion) on EM and normal appearing glomeruli, interstitium, and tubules on LM?
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Minimal Change Disease
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What disease is classically caused either by Hepatitis B Virus, SLE, carcinoma of lung, colon, stomach, or breast, or non-Hodgkin's Lymphoma?
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Membranous Nephropathy
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What disease is diagnosed by diffuse thickening of GBM and GBM "spikes" on silver stain in LM?
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Membranous Nephropathy
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What disease is classically caused by HIV infection?
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Focal Segmental Glomerulosclerosis (FSGS)
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What disease is diagnosed by focal and segmental glomerular sclerosis on LM?
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Focal Segmental Glomerulosclerosis (FSGS)
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What disease is classically caused by Hepatitis C virus?
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Membranoproliferative Glomerulo-nephritis (MPGN)
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