Glomerular Disease 1 Flashcards
1
Q
what are the possible mechanisms of glomerular disease? (three)
A
• Immunocomplex deposition
– Circulate then deposit in glomerulus
• eg DNA-anti-DNA complexes in Lupus
– activates complement resulting in neutrophil chemotaxis
- Antibodies against GBM or glomerular antigens
- Cytokine production by inflammatory cells
2
Q
circulating cause of glomerular disease
A
immune complex deposition
3
Q
in situ cause of glomerular disease
A
anti-gbm, membranous: antibody against glomerular antigen
4
Q
nomenclature of glomerular disease: possible types
A
diffuse, focal, global, segmental
5
Q
how does glomerular disease present?
A
- loss of time (temporal change)
- hematuria (quality)
- proteinuria (quantity)
6
Q
nephrotic syndrome characteristics
A
• Proteinuria > 3.5 g/day
• Hypoalbuminemia
• Edema
– Loss of plasma oncotic pressure vs Na/H20 retention
• Hyperlipidemia
– increased hepatic protein
production
• Lipiduria
• Hypercoagulability
– loss of Proteins C & S
7
Q
characteristics of nephritic syndrome
A
• Mild proteinuria
• Hematuria
– RBCs, RBC casts, dysmorphic
RBCs
• Hypertension
• Edema
8
Q
common characteristic for both nephrotic and nephritic syndromes
A
both may have varying degrees of renal dysfunction
9
Q
causes of acute glomerularnephritis
A
– IgA nephropathy – Post-infectious GN – Anti-GBM disease/Goodpasture’s – Small vessel vasculitis – Lupus nephritis – Membranoproliferative GN
10
Q
IgA nephropathy prevelance and age of onset
A
- Most common GN worldwide
* Most patients between age 10-50
11
Q
features of IgA nephropathy
A
• Hematuria is most prominent feature
– 50-60% episodic gross hematuria
– 30% persistent microhematuria
– 10% acute GN or nephrotic syndrome
• Proteinuria, if present, is generally mild
• Many cases are subclinical
12
Q
symptoms of IgA nephropathy
A
- Dysuria and loin pain may accompany hematuria
- Hematuria frequently occurs in conjunction with an upper respiratory infection (“synpharyngitic hematuria”)
- HTN may be present in patients with more advanced disease
13
Q
IgA nephropathy histology features on LM
A
• LM: Variable mesangial hypercellularity (mesangial proliferation)
– May see segmental proliferation, segmental sclerosis and necrosis with crescents
14
Q
IgA nephropathy histology features on IF
A
• IF: Mesangial IgA deposition (KEY/bolded)
15
Q
IgA nephropathy histology features on EM
A
• EM: Mesangial electron dense deposits (“paramesangial”)
16
Q
IgA nephropathy prognosis
A
• Prognosis based on serum creatinine, BP, and degree of proteinuria
– 40% of patients will slowly develop chronic kidney disease
17
Q
IgA nephropathy treatment
A
- Fish oil may slow progression of disease
- ACE-inhibitors used to control blood pressure
- Corticosteroids, other immunosuppressants also may be used in progressive disease
18
Q
Henoch-Schönlein Purpura cause
A
• Systemic disorder characterized by IgA deposition in multiple organs
19
Q
Henoch-Schönlein Purpura manifestations
A
– skin–characteristic non-blanching purpura on legs and buttocks
– joints–transient arthralgias
– GI tract–abdominal pain, vomiting, melena, hematochezia
– kidney–hematuria, proteinuria; rarely progressive renal failure
20
Q
post-infectious GN classic example and characteristics
A
- Post-streptococcal GN– classic example
- Follows infection in nephritogenic strain of group A beta-hemolytic streptococcus
- Occurs 7-14 days after pharyngitis; 14-28 days after skin infection
21
Q
post-strep GN clinical features
A
• Sudden onset hypertension, azotemia, oliguria, edema (periorbital) and cola- or tea-colored urine
22
Q
post-strep lab findings
A
– low C3 complement level
– Anti-streptolysin O (ASO) can be elevated (high anti-DNase B titers)
– Urinalysis: red blood cell casts, mild proteinuria
23
Q
post-strep histology features on LM
A
• LM: Enlarged, hypercellular glomeruli. Diffuse mesangial and endocapillary proliferation with neutrophils. May see crescents.
24
Q
post-strep histology features on IF
A
• IF: Granular capillary wall and mesangial IgG and C3
25
post-strep histology features on EM
• EM: Mesangial and large subepithelial “hump-like” deposits (KEY/bolded)
26
post-strep GN prognosis
• 95% of children will recover with conservative management
~1% progress to renal failure
• 60% of adults will recover promptly
27
rapidly progressive GN features
* Classic nephritic syndrome with rapid progression (days to weeks) to renal failure
* Sometimes referred to as “crescentic GN”
28
causes of rapidly progressive GN
```
– Anti-GBM/Goodpasture’s
– Immune complex GN
• Lupus nephritis
• Post-infectious
• Cryoglobulinemia
– ANCA associated GN (Pauci immune)
```
29
rapidly progressive GN histology findings
- segmental necrosis (early)
| - segmental necrosis and cellular crescent
30
Anti-GBM/Goodpasture’s Syndrome clinical findings
```
• Males > Females
• May present as a pulmonary-renal syndrome:
– Hemoptysis
– Pulmonary infiltrates
– Glomerulonephritis
• GN alone in anti-GBM disease
```
31
Anti-GBM/Goodpasture’s Syndrome cause
• Due to circulating anti-GBM antibody
| – Antigen is α3-chain of type IV collagen
32
Anti-GBM/Goodpasture’s Syndrome diagnosis
– + anti-GBM antibody in blood
| – Linear IgG and C3 on kidney biopsy IF
33
Anti-GBM/Goodpasture’s Syndrome treatment
– Plasmapheresis
– Prednisone
– Cytoxan
34
Pauci-immune GN characteristics
• Crescenteric GN with little deposition of immune reactants
– “Pauci-immune”
– As opposed to:
• Anti-GBM disease
• IgA nephropathy
• Lupus nephritis
35
Pauci-immune GN causes
• Idiopathic or associated with antineutrophil cytoplasmic antibody (ANCA) vasculitis
36
Small vessel vasculitis diseases (3)
• Microscopic polyangiitits (MPO-ANCA/p-ANCA)
– No granulomatous inflammation and no asthma
• Wegener’s granulomatosis (PR3-ANCA/c-ANCA)
– Necrotizing granulomatous inflammation; no asthma
• Churg-Strauss syndrome
– Necrotizing granulomatous inflammation, asthma, eosinophilia
37
vasculitis focal necrotizing lesion locations
- glomerular capillaries
- alveolar capillaries
- epineural
- dermal venules
38
Wegener’s Granulomatosis characteristics
• Granulomatous vasculitis of medium to small arterioles
39
Wegener’s Granulomatosis findings
• c-ANCA + in 80%
40
Wegener’s Granulomatosis presentation
```
• Presentation:
– Upper resp tract symptoms (sinusitis, nasal lesions, hemoptysis)
– Mononeuritis multiplex
– Pupura
– Nephritis
```
41
Wegener’s Granulomatosis finding on renal biopsy
cresenteric GN without immune deposits
42
RPGN Summary for Anti-GBM disease (clinical, light microscopy, and IF microscopy)
- clinical: + anti-GBM antibody in blood
- light microscopy: Crescenteric GN
- IF microscopy: Linear IgG an C3
43
RPGN Summary for Immune-complex (clinical, light microscopy, and IF microscopy)
- clinical- Lupus Post-strep
- light microscopy-Crescenteric GN
- IF microscopy- Variable deposition of IC and complement
44
RPGN Summary for Pauci-immune (clinical, light microscopy, and IF microscopy)
- clinical-ANCA+
- light microscopy-Crescenteric GN
- IF microscopy-Negative
45
nephrotic syndrome-primary renal diseases
• Primary renal disease
– membranous nephropathy
– focal segmental glomerulosclerosis (FSGS)
– minimal change disease*
– *In children ~80% will have minimal change disease
46
secondary causes of nephrotic syndrome
– systemic diseases: Diabetes mellitus, SLE, amyloidosis
– infections: HIV, Hepatitis B, Hepatitis C, syphilis
– drugs: classical examples include NSAIDs, gold, penicillamine
47
nephrotic syndrome lab studies/tests to help with a diagnosis
• Helpful laboratory studies for secondary causes:
– ANA, anti-dsDNA, complement levels (lupus)
– serum & urine protein electrophoreses (amylodosis)
– HBV & HCV serologies
– cryoglobulins
– syphilis serology
• Renal biopsy generally indicated
48
nephrotic syndrome treatments
– ACE-inhibitor or angiotensin-II receptor blocker to lower intraglomerular pressure and reduce proteinuria
– lipid-lowering therapy (“statins”)
– diuretics, salt restriction to improve edema
49
minimal change disease characteristics
• Most common cause of nephrotic syndrome in children
- peak incidence ages 2-6
- 5% progress to end-stage renal disease
50
minimal change disease treatment and prognosis
- spontaneous remissions can occur
- treatment with steroids often induces remission although relapses occur in about 75%
- fewer relapses after puberty
51
minimal change disease causes
• In adults, can be idiopathic or associated with:
– drugs: NSAIDs (bolded)
– neoplasms: Hodgkin’s lymphoma (bolded), pancreatic, prostate, lung, colon, & renal cell carcinomas, mesothelioma, oncocytoma
– infections: syphilis, HIV
52
minimal change disease histologic features on LM
* LM: Glomeruli, interstitium and tubules appear normal (KEY/bolded)
* (lipid may been seen in PCT cells-Pathoma/First Aid)
53
minimal change disease histologic features on IF
• IF: Negative or mesangial IgM
54
minimal change disease histologic features on EM
• EM: Podocyte foot process effacement (fusion) (KEY/bolded)
55
minimal change disease treatment
• Children respond well to corticosteroids
• The majority of adults with minimal change disease respond to steroids
– usually takes longer than in children
– partial remissions may occur
56
membranous nephropathy prevalence
* Most common cause of nephrotic syndrome in Caucasian adults
* Secondary causes account for ~15- 20% of cases
57
secondary causes of membranous nephropathy
– Infections: HBV (bolded)
– Connective tissue diseases: SLE (bolded)
– Neoplasms: carcinoma of lung, colon, stomach, breast; non-Hodgkin’s lymphoma (bolded)
• Consider age appropriate cancer screening
– Drugs: gold, penicillamine, mercury, NSAIDs, captopril
58
membranous nephropathy clinical findings
• Onset is generally insidious
• Patients usually present with heavy proteinuria & nephrotic syndrome
– HTN & azotemia occur later
– Occult malignancies and infections may become evident later
– Renal vein thrombosis occurs in ~ 20%
59
membranous nephropathy histologic findings on LM
• LM: diffuse thickening of GBM, GBM “spikes” on silver stain (KEY/bolded)
60
membranous nephropathy histologic findings on IF
• IF: granular GBM deposits of IgG
61
membranous nephropathy histologic findings on EM
• EM: Subepithelial deposits (with "spike and dome" appearance)
62
key membranous nephropathy finding
immune deposits form on sub epithelial aspect of glomerular basement membrane; podocyte with effaced foot processes
63
membranous nephropathy outcomes
“Rule of thirds”:
– 1/3 spontaneous remission
– 1/3 partial remissions with stable function
– 1/3 slowly progressive loss of renal function
64
membranous mephropathy treatment
* Patients without poor prognostic factors might be managed conservatively with ACE-I and/or ARB and followed closely
* Otherwise, steroids +/- other immunosuppressive drugs are used
65
Focal segmental glomerulosclerosis (FSGS) characteristics/who it effects
• Most common cause of idiopathic nephrotic syndrome in African-Americans
66
Focal segmental glomerulosclerosis (FSGS) clinical features
• More aggressive than minimal change disease:
– Hypertension, hematuria more common
– renal dysfunction is commonly progressive – ESRD occurs 5-20 years after presentation
67
primary FSGS
• Primary FSGS--usually presents with acute onset of nephrotic syndrome
68
secondary FSGS
• Secondary FSGS--usually manifests with slowly increasing renal insufficiency and proteinuria
69
hereditary FSGS
• Hereditary FSGS--mutations in proteins that make up the glomerular slit diaphragm
70
Causes of secondary FSGS
```
– Drugs: NSAIDs, heroin
– Infections: HIV (bolded)
– Massive obesity
– Healed previous glomerular injury
– Loss of functioning renal mass: unilateral agenesis, reflux nephropathy, etc.
```
71
FSGS histologic findings on LM
* LM: Focal and segmental glomerular sclerosis with capillary collapse, hyaline and lipid deposition and adhesion to Bowman’s capsule (KEY/bolded)
* (hyalinosis-Pathoma/First Aid)
72
FSGS histologic findings on IF
• IF: Negative or IgM and C3 in mesangium or in segmental scars
73
FSGS histologic findings on EM
• EM: Podocyte foot process effacement; may see segmental sclerosis
74
FSGS prognosis
* Prognosis correlates with degree of proteinuria--ACE inhibitors decrease proteinuria
* Corticosteroids can induce remission in some patients
75
FSGS treatment
• Treatment for steroid-resistant patients and patients who relapse is problematic
– Immunosuppressives
• Progression to ESRD in 50% at 10 years
76
glomerular diseases with nephrotic and nephritic features
- Membranoproliferative Glomerulo-nephritis (MPGN)
| - Systemic Lupus Erythematosus (SLE); Lupus Nephritis
77
Membranoproliferative Glomerulo-nephritis (MPGN) characteristics
* Proteinuria & hematuria commonly coexist • Hypertension occurs in 1/3
* Low C3 complement is a prominent feature
78
Membranoproliferative Glomerulo-nephritis (MPGN) clinical features
• Variable clinical presentation
– 50% nephrotic syndrome
– 30% asymptomatic proteinuria ± hematuria
– 20% acute GN
79
causes of secondary MPGN
– Connective tissue diseases: SLE
– Cryoglobulinemia
– Infections: Hepatitis C virus (bolded), HBV, endocarditis, abscesses
– Neoplasms
80
MPGN histologic features of LM
• LM: hypercellular glomeruli, endocapillary cell proliferation, lobular appearing glomeruli
81
MPGN histologic features of IF
• IF: granular C3 deposition
82
MPGN histologic features of EM
• EM: Subendothelial deposits
83
Type I MPGN causes
HBV, HCV, may also be idiopathic
84
Type II MPGN causes
associated with C3 nephritic factor (stabilizes C3 convertase --> decreased serum C3 levels)
85
Systemic Lupus Erythematosus (SLE) characterization
• A multi-system auto-immune disorder
– abnormal autoantibody production
– immune complex deposition
– inflammatory cell infiltration
86
Lupus Nephritis causes what?
* Common cause of diffuse proliferative GN
| * Many of the different clinical syndromes of renal disease can be occur in the setting of SLE
87
lupus nephritis clinical findings
• 40% of patients develop overt nephritis
– follow U/A in SLE patients
– HTN suggests the presence of renal disease
88
lupus nephritis diagnostic tests
• Renal biopsy is important in order to classify the lesion in SLE
89
lupus nephritis classifications
Class I-VI
90
lupus nephritis treatment
• General principles of management of any class of lupus nephritis:
– aggressive BP control
– control of lipid levels
– appropriate treatment of extrarenal involvement
• Classes III-V: usually treated with corticosteroids + cytotoxic therapy
– Class IV: renal failure rate 25% by 5-10 years
91
key points to know from this lecture:
You should know:
• the difference between nephrotic and nephritic (GN) syndromes
• which glomerular diseases cause nephrotic syndrome vs glomerulonephritis
• the clinical and histopathologic features of IgA nephropathy, post-infectious GN, and the RPGNs (these are GNs)
• the clinical and histopathologic features of minimal change disease, membranous nephropathy, and FSGS (these are nephrotic diseases)
• that SLE can cause a number of different glomerular diseases
