Renal 04: Glomerular Disease

Front 1

What are the mechanisms that cause glomerular disease?

Back 1

- Immunocomplex deposition in glomerulus (activates complement resulting in neutrophil chemotaxis)
- Antibodies against GBM or glomerular Ags
- Cytokine production by inflammatory cells

Front 2

How do immunocomplexes injure the kidney?

Back 2

- Immunocomplexes can circulate in blood
- Then they get deposited in glomerulus
- Activates complement resulting in neutrophil chemotaxis

Front 3

What is an example of immunocomplexes that injure the glomerulus?

Back 3

DNA-anti-DNA complexes in Lupus

Front 4

How do antibodies injure the kidney?

Back 4

Antibodies that target the GBM or glomerular antigens

Front 5

How can glomerular disease be categorized?

Back 5

- Diffuse (all glomeruli) vs Focal (some glomeruli) injury to glomeruli
- Global (entire glomerulus) vs Segmental (fraction of glomerulus) injury to glomeruli

Front 6

How does glomerular disease present?

Back 6

- Loss of GFR (temporal change)
- Hematuria (quality)
- Proteinuria (quantity)

Front 7

What are the types of glomerular disease based on symptoms?

Back 7

- Nephrotic syndrome
- Nephritis

Front 8

What are the features of Nephrotic Syndrome?

Back 8

- Proteinuria >3.5 g/day
- Hypoalbuminemia
- Edema
- Hyperlipidemia
- Lipiduria
- Hypercoagulability

Front 9

What are the features of Nephritis?

Back 9

- Mild proteinuria
- Hematuria (RBCs, RBC casts, dysmorphic RBCs)
- HTN
- Edema

Front 10

What is similar between Nephrotic Syndrome and Nephritis?

Back 10

- Both have proteinuria (although >3.5g/day in nephrotic syndrome)
- Both have edema

Front 11

What factors distinguish Nephrotic Syndrome and Nephritis?

Back 11

Nephrotic Syndrome:
- More proteinuria (>3.5 g/day)
- Hypoalbuminemia
- Hyperlipidemia
- Lipiduria
- Hypercoagulability

Nephritis:
- Mild proteinuria
- Hematuria
- Hypertension

Front 12

What causes edema in Nephrotic Syndrome?

Back 12

- Loss of plasma oncotic pressure
- Na/H2O retention

Front 13

What causes hyperlipidemia in Nephrotic Syndrome?

Back 13

Increased hepatic protein production

Front 14

What causes hypercoagulability in Nephrotic Syndrome?

Back 14

Loss of proteins C & S

Front 15

What are the features of hematuria in Nephritis?

Back 15

In urine: RBCs, RBC casts, dysmorphic RBCs

Front 16

What glomerular diseases have "nephrotic syndromes" clinical manifestations?

Back 16

- Minimal change disease
- Focal segmental glomerulosclerosis
- Membranous nephropathy

Front 17

What glomerular diseases have "nephritis" clinical manifestations?

Back 17

- Crescentic (ANCA) Glomerulonephritis
- Acute Post-Infectious GN
- Membranoproliferative GN
- IgA Nephropathy

Front 18

What are the causes of Acute Glomerulonephritis (GN)?

Back 18

- IgA nephropathy
- Post-infectious GN
- Anti-GBM disease (Goodpasture's)
- Small vessel vasculitis (ANCA)
- Lupus nephritis
- Membranoproliferative GN

Front 19

What is the most common cause of Glomerulonephritis worldwide?

Back 19

IgA Nephropathy

Front 20

What kind of kidney injury/disease is caused by IgA nephropathy? Who is affected by it?

Back 20

- Glomerulonephritis
- Most between age 10-50

Front 21

What are the most prominent features of IgA Nephropathy?

Back 21

* 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

Front 22

What does hematuria in IgA nephropathy occur in conjunction with?

Back 22

*Upper respiratory infection ("synpharyngitic hematuria")

Front 23

What is Synpharyngitic hematuria? What is it a feature of?

Back 23

- Hematuria in conjunction with an upper respiratory infection
- Frequently in IgA nephropathy

Front 24

How do you diagnose IgA nephropathy?

Back 24

** 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)

Front 25

What determines the prognosis of IgA Nephropathy?

Back 25

- Serum creatinine
- BP
- Degree of proteinuria

Front 26

What is the systemic disorder characterized by IgA deposition in multiple organs?

Back 26

Henoch-Schönlein Purpura

Front 27

What are the symptoms of Henoch-Schönlein Purpura? Cause?

Back 27

- 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

Front 28

What is the classic cause of post-infectious GN?

Back 28

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

Front 29

What kind of streptococcal infections can cause post-infectious GN? How long does each take to cause GN?

Back 29

- Pharyngitis: 7-14 days later
- Skin infection: 14-28 days later

Front 30

What are the most prominent features of Post-Strep GN?

Back 30

- Sudden onset HTN
- Azotemia
- Oliguria
- Edema
- Cola or tea colored urine

Front 31

How do you diagnose Post-Strep GN?

Back 31

** 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)

Front 32

What does this EM signify?

Back 32

Post-Strep GN

Front 33

What is the prognosis for Post-Strep GN depending on age?

Back 33

- Children: 95% recover w/ conservative management, 1% progress to renal failure
- Adults: 60% recover promptly

Front 34

What kind of syndrome is Rapidly Progressive GN? How long does it take to "rapidly progress"? AKA?

Back 34

- Classic nephritic syndrome
- Rapid progression (days to weeks) to renal failure
- AKA: Crescentic GN

Front 35

What are the types of Rapidly Progressive GN? Causes?

Back 35

* Anti-GBM / Goodpasture's
* ANCA associated GN (Pauci immune)

- Immune complex GN (lupus nephritis, post-infectious, cryoglomulinemia)

Front 36

Who is more commonly affected by Anti-GBM / Goodpasture's Syndrome? Cause?

Back 36

- Males > Females
- Due to circulating anti-GBM antibody to α3-chain of type IV collagen

Front 37

What are the symptoms of Anti-GBM / Goodpasture's Syndrome?

Back 37

May present as a pulmonary-renal syndrome:
- Hemoptysis (coughing blood)
- Pulmonary infiltrates
- Glomerulonephritis

Front 38

How do you diagnose Anti-GBM / Goodpasture's Syndrome?

Back 38

** IF: LINEAR IgG and C3 on kidney biopsy
- + anti-GBM antibody in blood

Front 39

How do you treat Anti-GBM / Goodpasture's Syndrome?

Back 39

- Plasmapheresis (remove anti-GBM)
- Prednisone
- Cytoxan

Front 40

What signifies Pauci-immune GN?

Back 40

- Crescenteric GN w/ little deposition of immune reactants
- Idiopathic OR associated w/ anti-neutrophil cytoplasmic antibody (ANCA) vasculitis

Front 41

If there is little deposition of immune reactants, what is the cause of the GN?

Back 41

Pauci-immune GN:
- Idiopathic OR
- ANCA vasculitis (anti-neutrophil cytoplasmic antibody)

Front 42

What small vessel vasculitis are associated with Pauci Immune GN?

Back 42

- Microscopic Polyangitis (no granulomatous inflammation and no asthma)

- Wegener's Granulomatosis (necrotizing granulomatous inflammation, no asthma)

- Churg-Strauss Syndrome (necrotizing granulomatous inflammation, asthma, eosinophilia)

Front 43

Which vasculitis causes no granulomatous inflammation and no asthma?

Back 43

Microscopic polyangitis (small vessel vasculitis)

Front 44

Which vasculitis causes necrotizing granulomatous inflammation and no asthma?

Back 44

Wegener's Granulomatosis (small vessel vasculitis)

Front 45

Which vasculitis causes necrotizing granulomatous inflammation, asthma, and eosinophilia?

Back 45

Chrug-Strauss Syndrome (small vessel vasculitis)

Front 46

What are the features of Wegener's Granulomatosis?

Back 46

- Granulomatous vasculitis of medium to small arterioles
- c-ANCA + in 80%

- URI (sinusitis, nasal lesions, hemoptysis)
- Mononeuritis multiplex
- Purpura
- Nephritis

Front 47

What would you find on a renal biopsy with Wegener's Granulomatosis?

Back 47

Crescenteric GN w/o immune deposits (pauci-immune)
(c-ANCA+ in 80%)

Front 48

What are the types of Rapidly Progressive GN?

Back 48

- Anti-GBM
- Immune-complex
- Pauci-immune

Front 49

What are the clinical, LM, IF microscopy features of Anti-GBM Rapidly Progressive GN?

Back 49

- Clinical: + anti-GBM Ab in blood
- LM: crescenteric GN
- IF: LINEAR IgG and C3

Front 50

What are the clinical, LM, IF microscopy features of Immune-Complex Rapidly Progressive GN?

Back 50

- Clinical: Lupus, Post-strep
- LM: Crescenteric GN
- IF: Variable deposition of IC and complement

Front 51

What are the clinical, LM, IF microscopy features of Pauci-Immune Rapidly Progressive GN?

Back 51

- Clinical: ANCA+
- LM: Crescenteric GN
- IF: Negative

Front 52

What are the primary renal disease causes of Nephrotic Syndrome?

Back 52

- Membranous nephropathy
- Focal segmental glomerulosclerosis (FSGS)
- Minimal Change Disease (80% of children)

Front 53

What are the secondary causes of Nephrotic Syndrome?

Back 53

- Systemic disease: *DM*, SLE, amyloidosis
- Infection: HIV, HepB, HepC, syphilis
- Drugs: NSAIDs, gold, penicillamine

Front 54

What lab studies are helpful for diagnosing secondary causes of Nephrotic Syndrome?

Back 54

- ANA, anti-dsDNA, complement levels
- Serum and urine protein electrophoreses
- HBV and HCV serologies
- Cryoglobulins
- Syphilis serology

- Renal biopsy usually indicated

Front 55

How is Nephrotic Syndrome treated?

Back 55

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

Front 56

What is the most common cause of nephrotic syndrome in children?

Back 56

Minimal Change Disease

Front 57

When is Minimal Change Disease peak in occurrence? What kind of disease?

Back 57

- Peak: ages 2-6
- Nephrotic syndrome

Front 58

What are the potential outcomes of Minimal Change Disease?

Back 58

- 5% progress to ESRD
- Spontaneous remissions can occur
- Tx w/ steroids can induce remission, relapses in 75%
- Fewer relapses after puberty

Front 59

What can cause Minimal Change Disease in adults?

Back 59

Idiopathic or associated with:
- Drugs: *NSAIDs*
- Neoplasms: *Hodgkin's Lymphoma*, pancreatic, prostate, lung, colon, and renal cell carcinomas, mesothelioma, oncocytoma
- Infections: syphilis, HIV

Front 60

How do you diagnose Minimal Change Disease?

Back 60

* LM: Glomeruli, interstitium, and tubules are NORMAL (hence minimal change)

* EM: Podocyte foot process effacement (FUSION)

- IF: negative or mesangial IgM

Front 61

How do you treat Minimal Change Disease?

Back 61

- Children: corticosteroids
- Adults: steroids (but takes longer to respond than children, partial remissions may occur)

Front 62

What is the most common cause of Nephrotic Syndrome in Caucasian adults?

Back 62

Membranous Nephropathy

Front 63

What are the secondary causes of Membranous Nephropathy? How common are secondary causes?

Back 63

- 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

Front 64

What infection can cause Membranous Nephropathy?

Back 64

Hepatitis B Virus

Front 65

What disease can cause Membranous Nephropathy?

Back 65

CT disease: Systemic Lupus Erythematous

Front 66

What neoplasms can cause Membranous Nephropathy?

Back 66

- Carcinomas: lung, colon, stomach, breast
- Non-Hodgkin's Lymphoma

**consider age-appropriate cancer screening

Front 67

What are the features of Membranous Nephropathy?

Back 67

Nephrotic syndrome
- Insidious onset (gradual)
- Heavy proteinuria
- HTN and Azotemia
- Occult malignancies and infections
- Renal vein thrombosis (~20%)

Front 68

How do you diagnose Membranous Nephropathy?

Back 68

** LM: diffuse thickening of GBM, GBM "spikes" on silver stain

- IF: granular GBM deposits of IgG
- EM: SUB-EPITHELIAL deposits

Front 69

What disease is characterized by "sub-epithelial spikes"?

Back 69

Membranous Nephropathy

Front 70

What are the possible outcomes of Membranous Nephropathy?

Back 70

Rule of thirds:
- 1/3 spontaneous remission
- 1/3 partial remissions w/ stable function
- 1/3 slowly progressive loss of renal function

Front 71

How should a patient with Membranous Nephropathy be treated?

Back 71

- Without poor prognostic factors: manage conservatively w/ ACE-I and/or ARB (and closely follow)
- Others, steroids +/i other immunosuppressive drugs

Front 72

What is the most common cause of idiopathic nephrotic syndrome in African-Americans?

Back 72

Focal Segmental Glomerulosclerosis (FSGS)

Front 73

What are the symptoms of Focal Segmental Glomerulosclerosis (FSGS)?

Back 73

- 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

Front 74

What is the prognosis for patients with Focal Segmental Glomerulosclerosis (FSGS)?

Back 74

- ESRD 5-20 years after presentation
- 50% progression to ESRD in 10 years

Front 75

What are the types of Focal Segmental Glomerulosclerosis (FSGS)?

Back 75

- 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

Front 76

What can be caused by mutations in proteins that make up glomerular slit diaphragm?

Back 76

Focal Segmental Glomerulosclerosis (FSGS)

Front 77

What are the causes of secondary Focal Segmental Glomerulosclerosis (FSGS)?

Back 77

* Infections: HIV *
- Drugs (NSAIDs, Heroin)
- Massive obesity
- Healed previous glomerular injury
- Loss of functioning renal mass (unilateral agenesis, reflux nephropathy, etc)

Front 78

How do you diagnose Focal Segmental Glomerulosclerosis (FSGS)?

Back 78

* 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

Front 79

What does this image show? What is it diagnostic of?

Back 79

- Segmental glomerular sclerosis
- Focal Segmental Glomerulosclerosis (FSGS)

Front 80

What determines the prognosis of Focal Segmental Glomerulosclerosis (FSGS)?

Back 80

Degree of proteinuria (ACE-I ↓ proteinuria)

Front 81

What are the treatment options for Focal Segmental Glomerulosclerosis (FSGS)?

Back 81

- ACE-I - decrease proteinuria (better for prognosis)
- Corticosteroids can induce remission in some patients
- Immunosuppressives for steroid-resistant patients and patients who relapse

Front 82

What glomerular diseases have nephrotic and nephritis features?

Back 82

- Membranoproliferative Glomerulo-nephritis (MPGN)
- Lupus Nephritis (Systemic Lupus Erythematous)

Front 83

What are the features of Membranoproliferative Glomerulo-nephritis (MPGN)?

Back 83

- Proteinuria and hematuria
- Hypertension (1/3)
- Low C3 complement

- 50% nephrotic syndrome
- 30% asymptomatic proteinuria ± hematuria
- 20% acute glomerulonephritis

Front 84

What are the potential causes of secondary Membranoproliferative Glomerulo-nephritis (MPGN)?

Back 84

* Infections: Hepatitis C virus *, HBV, endocarditis, abscesses
- CT disease: SLE
- Cryoglobulinemia
- Neoplasms

Front 85

How do you diagnose Membranoproliferative Glomerulo-nephritis (MPGN)?

Back 85

- LM: hypercellular glomeruli, endocapillary cell proliferation, lobular appearing glomeruli

- IF: granular C3 deposition

- EM: subendothelial deposits

Front 86

What is Systemic Lupus Erythematosus (SLE)?

Back 86

Multi-system auto-immune disorder:
- Abnormal auto-Ab production
- Immune complex deposition
- Inflammatory cell infiltration

Front 87

What is a common cause of diffuse proliferative glomerulonephritis?

Back 87

Lupus Nephritis

Front 88

What percentage of patients with SLE develop overt nephritis?

Back 88

40%

Front 89

How many types of Lupus Nephritis are there?

Back 89

6 classes (I-VI)

Front 90

How do you treat Lupus Nephritis?

Back 90

- Aggressive BP control
- Control lipids
- Treatment of extra-renal involvement

- Classes III-V usually treated w/ corticosteroids + cytotoxic therapy

Front 91

How common is renal failure in Lupus Nephritis?

Back 91

Class IV: renal failure rate 25% by 5-10 years

Front 92

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?

Back 92

1. IgA Nephropathy
2. Minimal Change Disease
3. Membranous Nephropathy
4. Focal Segmental Glomerulosclerosis (FSGS)

Front 93

What disease is characterized by hematuria frequently occurring in conjunction w/ an upper respiratory infection ("synpharyngitis hematuria")?

Back 93

IgA Nephropathy

Front 94

What disease is diagnosed by mesangial IgA deposition on IF?

Back 94

IgA Nephropathy

Front 95

What disease is diagnosed by mesangial and large sub-epithelial "hump-like" deposits on EM?

Back 95

Post-Strep Glomerulonephritis

Front 96

What classic nephritic syndrome progresses rapidly (days to weeks) to renal failure?

Back 96

Rapidly Progressive GN

Front 97

What diseases are caused by anti-GBM antibodies or anti-neutrophil cytoplasmic antibodies (ANCA)?

Back 97

Rapidly Progressing GN
- Anti-GBM - Goodpasture's
- ANCA associated GN (Pauci Immune)

Front 98

What disease is diagnosed by linear IgG and C3 in kidney biopsy on IF?

Back 98

Anti-GBM / Goodpasture's Syndrome

Front 99

What disease is classically caused by NSAIDs or Hodgkin's Lymphoma?

Back 99

Minimal Change Disease

Front 100

What disease is diagnosed by podocyte foot process effacement (fusion) on EM and normal appearing glomeruli, interstitium, and tubules on LM?

Back 100

Minimal Change Disease

Front 101

What disease is classically caused either by Hepatitis B Virus, SLE, carcinoma of lung, colon, stomach, or breast, or non-Hodgkin's Lymphoma?

Back 101

Membranous Nephropathy

Front 102

What disease is diagnosed by diffuse thickening of GBM and GBM "spikes" on silver stain in LM?

Back 102

Membranous Nephropathy

Front 103

What disease is classically caused by HIV infection?

Back 103

Focal Segmental Glomerulosclerosis (FSGS)

Front 104

What disease is diagnosed by focal and segmental glomerular sclerosis on LM?

Back 104

Focal Segmental Glomerulosclerosis (FSGS)

Front 105

What disease is classically caused by Hepatitis C virus?

Back 105

Membranoproliferative Glomerulo-nephritis (MPGN)