CPR II Exam 3 > Chapter 20: The Kidney - Glomerular Diseases > Flashcards

Chapter 20: The Kidney - Glomerular Diseases Flashcards

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1
Q

What is the most common and second most common causes of Chronic Renal Failure and End-Stage Renal Disease?

A
  • Diabetes = MOST common
  • High BP = second most common
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2
Q

What is the single most important question to ask a patient suspected of having renal disease?

Why?

A
  • “Have you had this before?”
  • Hx of disease can imply a significantly worse prognosis!
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3
Q

What is the major mediator of injury in Glomerular disease vs. Tubular/Interstitial?

A
  • Glomerular is typically immunologically mediated
  • Tubular/interstitial is frequently due to toxins or infectious agents
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4
Q

Elevated BUN and creatinine, largely realted to decreased GFR is known as?

A

Azotemia

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5
Q

Hypoperfusion of the kindeys (i.e., hypotension, shock, CHF, or cirrhosis of liver) in the absence of parenchymal damage is known as?

A

Pre-renal Azotemia

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6
Q

When azotemia becomes associated with a constellation of clinical signs and sx’s and biochemical abormalities resulting from renal damage, it is termed?

A

Uremia

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7
Q

Diabetes typically affects which morphological component of the kidney?

A

Primarily glomerular disease (microvasculature) manifestations

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8
Q

Systemic HTN, is primarily a disease affecting which morphological component of the kidney?

A

Primarily, vascular (arteriolar) disease –> Tubulointerstitial

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9
Q

Nephritic syndrome is characterized by what main findings?

A
  • Hematuria (micro/macroscopic) + variable proteinuria
  • Diminshed GFR —> Azotemia + Oliguria
  • Edema
  • HTN
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10
Q

Nephritic syndrome is the classic presentation of disease state?

Hint: What type of glomerulonephritis?

A

Acute poststreptococcal glomerulonephritis

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11
Q

What characterized rapidly progressive glomerulonephritis?

A

Nephritic syndrome w/ rapid decline in GFR (within hours to days)

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12
Q

Nephrotic syndrome is characterized by what main findings?

One major difference from Nephritic syndrome?

A
  • HEAVY proteinuria (>3.5 g/day) = major difference from Nephritic*
  • HYPOalbuminemia —-> SEVERE edema
  • HYPERlipidemia —> Lipiduria
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13
Q

Injury to what morphological structure of the kidney is the most common cause of Acute Kidney Injury?

A

Acute tubular injury (ATN)

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14
Q

Diminished GFR that is persistently <60 mL/min/1.73 m2 for at least 3 months and/or persistent albuminuria, defines what?

A

Chronic kindey disease

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15
Q

Glomerular disease is often associated with what 4 main systemic disorders?

A
  1. SLE
  2. Diabetes
  3. Amyloidosis
  4. Vasculitis
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16
Q

Which cells of the glomerulus are contractile, phagocytic, capable of proliferation, and laying down both matrix and collagen?

A

Mesangial cells

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17
Q

Which cells are important for maintenance of the glomerular barrier function?

Injury to these cells results in?

A
  • Visceral epithelial cells (podocytes)
  • Injury results in —> proteinuria
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18
Q

What is a diffuse vs. global glomeruopathy?

A
  • Diffuse = involves ALL of the glomeruli in kidney
  • Global = involves the entirety of individual glomeruli
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19
Q

What is focal vs. segmental glomerulopathy?

A
  • Focal = involving only a fraction of glomeruli in kidney
  • Segmental = affecting a part of each glomerulus
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20
Q

In diabetic glomerulosclerosis there is increased synthesis of which components of the glomerulus?

A

Protein components of the basement membrane

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21
Q

Chronic glomerular responses to injury include what 3 morphological changes?

A
  • Basement membrane thickening
  • Hyalinosis
  • Sclerosis
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22
Q

Glomerular basement membrane thickening is best seen with what stain?

A

PAS

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23
Q

What morphological change to the glomerulus is characterized by the accumulation of homogenous/eosinophilic material under light microscopy and is typically the end result of many forms of glomerular injury?

A

Hyalinosis

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24
Q

The major cause of glomerulonephritis resulting from formation of antigen-antibody complexes is the consquence of?

A

In situ immune complex formation

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25
In the Heymann mode of glomerulonephritis, Abs reacts to what Ag? This Ag is normally found where?
**Megalin**, normally present in **epithelial cell (podocyte) foot processes**
26
Which Ag has been found to be the one underlying most cases of primary human **membranous nephropath**y?
M-type phospholipase A2 receptor (**PLA2R**)
27
Ab binding to PLA2R in glomerular epithelial cell membranes, followed by complement activation, leads to immune complex formation where on the BM? Characteristic BM appearance on light microscopy?
**- SUB**epithelial aspect of BM **- THICKENED BM** appearance on light microscopy
28
In viewing **membranous nephropathy (in-situ immune complex deposition)** with immunofluorescence microscopy what is the pattern of immune deposition seen? Reflects what?
- Immune deposition in **GRANULAR pattern** (not linear) - Reflective of very **localized** and **LARGE complexes** of Ag-Ab interaction.
29
What is the antigen associated with anti-GBM nephritis?
NC1 domain of type IV collagen Ag
30
In situ immune complex deposition against "planted" Ags may occur, what are examples of **exogenous** sources of these Ags?
- Infectious agents (viral, bacterial and parasitic products) - Drugs/toxins
31
In situ immune complex deposition against "planted" Ags may occur, what are examples of **endogenous** sources of these Ags?
- DNA - Nuclear proteins - Immunoglobulins - Immune complexes themselves can serve as Ags! - IgA
32
Characteristic pattern seen with immunofluorescence in diseases caused by Abs directed against normal glomerular BM components (i.e., anti-GBM)?
**Diffuse linear** pattern as Abs bind intrinsic Ags along entire legnth of GBM
33
Often anti-GBM Abs cross react with other BM's, especially where? What syndrome does this occur in?
- **Lung alveoli,** results in simultaneous **lung** and **kidney lesions** - **Goodpasture syndrome**
34
What kind of glomerular damage occurs due to anti-GBM Abs? Leading to which clinical syndrome?
- Causes **severe necrotizing** and **crescentic** glomerular damage - Leading to **rapidly progressive glomerulonephritis (RPGN)**
35
Microbial Ags from which bacteria/viruses may act as exogenous sources that trigger circulating immune complexes leading to glomerulonephritis?
- Streptococcal proteins - Surface Ag of HBV and viral antigens of HCV - Ags of *Treponema pallidum* and *Plasmodium falciparum*
36
How do highly cationic Ags vs. highly anionic Ags vs. neutral Ags differ in where they get deposited and in turn where immune-complexes form within the glomerulus?
- **C****ationic**--\> cross the GBM and resultant complexes are**subepithelial** - **A****nionic**--\> excluded from GBM and trapped**subendothelially** - **Neutral** charge --\> tend to accumulate in the **mesangium**
37
Immune complexes deposited in which locations of the glomerulus are **more likely** to be involved in an **inflammatory response** due to be accessible to the circulation?
- **Subendothelial** portions of capillaries - **Mesangial** locations
38
Why are large circulating complexes usually NOT nephritogenic?
They are **cleared** by the **mononuclear phagocyte system** and do not enter the GBM in significant quantities
39
Lupus nephritis and membranoproliferative glomerulonephritis lead to immune-complex deposition in which part of the glomerulus?
Subendothelial deposits = membranoproliferative pattern \*#3 in the figure
40
Which coagulation factor may act as the stimulus for crescent formation associated w/ glomerular injury?
Thrombin
41
Which GF's seem to be critical in the ECM deposition and hyalinization leading to glomerulosclerosis in chronic kidney injury?
- TGF-β - Connective tissue GF - Fibroblast GF
42
In most forms of glomerular injury, loss of what is a key event in the development of proteinuria?
Loss of normal **slit diaphragms**
43
What is the principal glomerular manifestation of **progressive** glomerular injury?
Focal segmental glomerulosclerosis
44
Which mediator of chronic inflammation plays a particularly important role in the induction of scleroris seen in Focal Segmental Glomerulosclerosis?
TGF-β
45
What is the drug of choice for Focal Segmental Glomerulosclerosis?
RAAS inhibitors
46
What is the most frequent clinical presentation of Focal Segmental Glomerulosclerosis?
- Nephrotic syndrome - Nonnephrotic proteinuria
47
The **extent of damage to what renal structures** is **more correlated** to decline in renal function?
**Tubulointerstitial damage** rather than the severity of glomerular injury
48
What plays a major role in the direct injury and activation of tubular cells seen in Tubulointerstitial Fibrosis? What do activated tubular cells do?
**- Proteinuria** can cause **direct injury** and activation of tubular cells - Tubular cells then express adhesion molecules and elaborate pro-inflammatory cytokines, chemokines, and GF's --\> **interstitial fibrosis**
49
Most common type of glomerular injury causing nephritic syndrome?
**Immunologically** mediated
50
How does Acute Proliferative (Poststreptococcal) Glomerulonephritis typically present (signs/sx's and findings)? What is seen in urine? Typical age group?
- **M****alaise + fever + nausea + oliguria**and**hematuria --\> 1-2 wks**after recovery from**sore throat** or skin infection - Dysmorphic red cells or **RBC casts**, mild proteinuria, perioribital edema, and mild/moderate HTN - **Children** ages 6-10 yo
51
What has been discovered as the principal antigenic determinant in most cases of Poststreptococcal Glomerulonephritis? This antigen can directly activate what?
Pyogenic exotoxin B (**SpeB**) --\> directly **activates** complement
52
What class of streptococcus is the cause of Poststreptococcal Glomerulonephritis?
Group A, β-hemolytic Strep --\> types 12, 4, or 1
53
Acute proliferative (postreptococcal) glomerulonephritis is characterized by what 2 findings histologically?
1. Marked **hypercellularity**: ranging from simple mesangial to complex endocapillary cell infiltrate 2. **Leukocyte infiltration**: both neutrophils and monocytes
54
The proliferation and leukocyte infiltration are seen in which parts of the glomeruli during acute proliferative (postreptococcal) glomerulonephritis?
Typically involving **ALL lobules** of **ALL glomeruli**
55
What is seen on immunofluorescence microscopy in acute proliferative (postreptococcal) glomerulonephritis?
Granular deposits of **IgG** and **C3**, and sometimes **IgM** in the **mesangium** and along the **GBM**
56
What is the characteristic findings on electron microscopy in acute proliferative (postreptococcal) glomerulonephritis?
Discrete, amorphous, electron-dense deposits = **subepithelial** **"humps"** = Ag-Ab complexes
57
What is the onset of acute proliferative (postreptococcal) glomerulonephritis like in an **adult**? Clinical course?
- More **atypical** --\> sudden **HTN** or **edema**, frequently w/ elevated BUN - Only 60% recover completely, while many cases manifest as persistent proteinuria, hematuria, and HTN ---\> chronic glomerulonephritis or even rapidly progressiving glomerulonephritis
58
What is the typical clinical course of acute proliferative (postreptococcal) glomerulonephritis in a **child**?
- **\>95% recover** completely in **6-8 weeks** w/ conservative tx (maintain Na+ and H2O balance) - Around 1% do not improve and become severely oliguric, and develop a rapidly progressive GN or chronic GN
59
How do the immune deposits found in postinfectious GN due to **staphylococcal** infection differ from that of strep?
Producing immune-deposits w/ **IgA** rather than IgG
60
What are some of the bacterial, viral, and parasitic causes of Postinfectious GN?
- **Bacteria** - Staph, pneumococcal, pneumonia, and meningococcemia - **Viral** - HBV, HCV, Mumps, HIV, VZV, and infectious mononucleosis (EBV) - **Parasitic** - malaria and toxoplasmosis
61
What is the most common histological picture in Rapidly Progressive Glomerulonephritis (RPGN)?
Presence of **crescents** in most of the glomeruli (**crescenteric GN**)
62
Type I RPGN (anti-GMB Ab) disease is characterized by what kind of deposits?
**Linear** deposits of **IgG** and often **C3** in the GBM
63
What is the antigen common to the alveoli and GBM, and is known as the Goodpasture Ag?
**Noncollagenous** portion of the **α3 chain** of collagen **type IV**
64
Which HLA subtype is associated with RPGN (i.e., Goodpasture Syndrome)?
HLA-**DRB1**
65
What is used in the treatment regimen for Type I RPGN (anti-GBM Ab disease)? How effective?
**- Plasmapheresis** in conjunction w/ immunosuppressive therapy - Can reverse **pulmonary hemorrhage** and **renal failure**
66
Major causes of Type II (immune complex) RPGN?
- Idiopathic - Postinfection GN (aka acute proliferative GN) - Lupis nephritis - Henoch-Schonlein pupura - IgA nephropathy
67
Type II RPGN frequently has what histological findings?
**Granular** pattern w/ **cellular proliferation** and influx of leukocytes within the glomerular tuft + **crescent** formation
68
Can Type II RPGN benefit from plasmapheresis?
- Generally do **NOT** respond - MUST TREAT UNDERLYING DISEASE!
69
RPGN that is defined by a **lack of detectable anti-GBM Abs** or i**mmune complexes** is known as?
Type III (**Pauci-Immune**)
70
Type III (Pauci-Immune) RPGN may be a component of what underlying disorders?
- ANCA-associated - Idiopathic - Granulomatosis w/ polyangiitis (formerly Wegener granulomatosis) - Microscopic polyangiitis
71
What is a hallmark finding of the GBM seen on electron micrscopy in RPGN? What finding dominates the histological picture?
**- Wrinkling** of the GBM w/ **ruptures = HALLMARK** - Distinctive **crescents** dominate the histological picture
72
In RPGN what is commonly seen in prominent amounts between the cellular layers in crescents?
Fibrin
73
Ruptures in the GBM seen in RPGN allows what to enter?
Leukocytes, plasma proteins such as coagulation factors and complement + inflammatory mediators ---\> **urinary space** triggering **crescent** formation
74
**Hemoptysis** and even life threatening pulmonary hemorrhage may be associated with what type of RPGN?
Goodpasture syndrome (Type I RPGN)
75
Presence of what in the serum is virtually diagnostic of Type III (Pauci-Immune) RPGN?
ANCAs
76
How does the cause of nephrotic syndrome in children \<17 yo differ from adults?
- **Children** = almost always caused by a lesion **primary** to the kidney - **Adults** = often associated with a **systemic disease**
77
What are the 3 most common primary glomerular lesions responsible for the development of nephrotic syndrome? Which is most common in children and which in adults?
1. **Minimal change disease** = most common in **children** 2. **Membranous glomerulopathy** = most common in **older adults** 3. **Focal segmental glomerulosclerosis** = occurs at **all ages**
78
What are the most frequent systemic causes of nephrotic syndrome?
**- Diabetes** **- Amyloidosis** **- SLE** - Drugs - Infections - Malignant dz (carcinoma, lymphoma)
79
What does the term "nephrotic range proteinuria" refer to?
Loss of **3 grams** or more/day in the urine
80
Primary membranous glomerulopathy is now considered an autoimmune disease and linked to which HLA allele?
HLA-DQA1
81
What is the autoantigen in most cases of primary membranous glomerulopathy?
Phospholipase A2 receptor (PLA2 receptor)
82
What plays an important role in causing the glomerular capillary wall to become leaky in (primary) membranous glomerulopathy? What is the principal immunoglobulin seen deposited and on which side of the BM?
- C5b-C9 (**MAC**) - **IgG4** on **SUBepithelial side** of BM
83
What are some of the secondary causes of Membranous Nephropathy?
- Drugs - SLE - Underlying malignancy - Infections ---\> HBV, HCV, syphillis, schistosomiasis, malaria - Autoimmune disorders --\> **thyroiditis**
84
What is the **morphological characteristics** of the **glomerular capillary wall** and **podocyte foot processes** seen in Membranous Glomerulopathy? The BM will have what histological finding/pattern, and is best seen with what stain?
- **Uniform, diffuse thickening (5-20x increased)** w/o increasing cellularity - **Effacement** of **podocyte** foot processes - **"Spike and dome" pattern** of **SILVER-staining** **matrix** projecting from BM
85
What are the typical clinical features of membranous nephropathy?
- **85% of pts will have typical NS** manifestations (i.e., proteinuria, hypoalbuminemia, edema and hyperlipidemia) - 15-35% of pts may have **hematuria** and **mild HTN**
86
How does glomerular nephropathy respond to corticosteroids?
Primary responds **POORLY** to **steroid therapy**
87
Recurrence of Membranous Nephropathy is a common feature in which patients?
- Pts who undergo **transplant** for **end-stage renal disease** - Spontaneous remissions and more benign outcome = more common in **Women**
88
What is the most common cause of nephrotic syndrome in children? Peak incidence between what ages?
- **Minimal-change disease** - Btw **2-6 y/o**
89
What are 5 features of **minimal-change disease** which point to an immunologic basis for its development? Increased incidence in pts with what conditions and cancer?
1. Clinical assoc. w/ **respiratory infections** and **prophylactic immunizations** 2. Response to **corticosteroids** 3. Assoc. w/ **atopic disorders** (i.e., eczema, rhinitis) 4. Increased prevalence of certain **HLA** haplotypes 5. Increased incidence in pts w/ **Hodgkin lymphoma**
90
A characteristic (even implicitly diagnostic) of **minimal change disease** is a dramatic response to what? Prognosis of this disease?
- Dramatic response to **corticosteroid therapy** - \>90% of children w/ MCD respond to Tx w/ cure and no clinical recurrence = **very good prognosis**
91
What is the proteinuria like in Minimal Change Disease vs. Membranous Nephropathy?
- **MCD** = highly **selective** proteinuria, most of which is albumin - **M.N.** = the proteinuria is **nonselective**
92
How is the principal lesion associated with minimal change disease seen under electron microscopy? What are its characteristics and how is it different from membranous nephropathy?
- Visceral epithelial cells (podocytes), show **uniform** and **diffuse effacement of foot processes** - But the **effacement** is associated w/ **NORMAL glomeruli** (unlike membranous nephropathy)
93
Major clinical features of Minimal Change Disease?
- Highly **SELECTIVE** massive proteinuria w/ **good renal function** - Commonly **no HTN** or **hematuria** - Dramatic response to **corticosteroids**
94
What is the most common cause of nephrotic syndrome in adults in the US?
Focal Segmental Glomerulosclerosis (FSGS)
95
Which populations have a higher incidence of Focal Segmental Glomerulosclerosis (FSGS)?
- Hispanic - African American
96
Focal Segmental Glomerulosclerosis (FSGS) is often an adaptive response to?
Loss of renal mass
97
The clinical signs of FSGS differ from Minimal Change disease in what 4 ways?
1. **Higher incidence of hematuria**, reduced GFR and HTN 2. **Proteinuria** is often **nonselective** 3. **Poor** **response to corticosteroid therapy** 4. **Progression** to CKD w/ 50% developing **ESRD** within 10 years
98
What is the hallmark of FSGS that can be seen with electron microscopy?
- **Degeneration** and **focal disruption** of **visceral epithelial cells (podocytes)** - DIFFUSE **e****ffacement**of**foot processes**
99
What was the first relevant gene and protein to be identified related to a genetic basis for FSGS? Which chromosome?
- ***NPHS1*** ---\> ***nephrin*** - Chromosome **19**
100
Mutations of *NPH1* can give rise to what type of glomerulopathy?
Congenital nephrotic syndrome of the Finnish type
101
A distinctive pattern of autosomal **recessive** FSGS results from mutations in which gene? Chromosome?
- *NPHS2 ----\> **podocin*** - Chromosome **1q25-q31** - **Steroid-resistant** nephrotic syndrome of childhood onset
102
Mutation in the podocyte actin binding protein α-actinin 4 underlies some cases of what type of FSGS (i.e., inheritance pattern)?
Autosomal **dominant** FSGS
103
Mutations in the gene encoding what protein have been linked to some inherited forms of adult-onset FSGS?
TRPC6
104
There is a strong association with 2 sequence variants of which gene and on which chromosome with an increased risk of FSGS and renal failure in people of African descent? What is the importance of these sequence variants in this population?
- **Apolipoprotein L1 gene (APOL1)** on **chromosome 22** - Confers **resistance** to **trypanosome** infection (i.e., **malaria**)
105
Which deposits may be seen in the sclerotic areas and mesangium of FSGS under immunofluorescence microscopy?
**IgM** and **C3**
106
What is the most characteristic lesion (i.e, morphological variant of FSGS) seen in HIV-associated nephropathy?
**Collapsing glomerulopathy** = **severe form** of FSGS
107
In FSGS, glomeruli that do not show segmental lesions usually appear normal on light microscopy, but may show increased what?
Increased **mesangial matrix**
108
What is the prognosis of FSGS in chidren vs. adults?
- Children generally have **better** prognosis than adults
109
Which finding in a biopsy specimen has diagnostic value for the collapsing variant of FSGS seen in those w/ HIV?
**Large #** of **tubuloreticular inclusions** within endothelial cells
110
What are the major histological findings in Membranoproliferative Glomerulonephritis (MPGN)? Glomerular proliferation is predominantly of what type?
- GBM = **thickened** --\> **"double-contour****"**or**"tram-track" appearance** - Prolieration of glomerular cells --\> **mainly** the **m****esangium**but may also involve the capillary loops =**mesangiocapillary glomerulonephritis** - **Leukocyte infiltration**
111
Membranoproliferative Glomerulonephritis (MPGN) is best considered as what, rather than a specific disease?
**Pattern** of **immune-mediated injury**
112
How does Type I vs. Type II MPGN differ when viewing under immunofluorescence and light microscopy?
- **Type I**: will have **SUB**endothelial deposition of **IgG** + **C3**; **C1q + C4** in **granular** pattern - **Type II**: **INTRAmembranous DENSE deposits** --\> will have **C3** present (usually **no** IgG; C1q or C4) on GBM, but not in the **dense deposits**
113
Which pathways are activated in MPGN Type I?
Both the **classical** and **alternative complement** pathways
114
In the most basic sense how are the clinical findings of MPGN Type I different from Type II?
- **Type I** = mixed nephrotic and nephritic findings **= hematuria** and **mild proteinuria** - **Type II** = hematuria with renal failure
115
What is the characteristic findings seen with silver strain or PAS of the GBM in MPGN?
- **Thickened** and shows a **"double contour"** or **"tram-track" appearance** - Due to **"duplication" of the BM** (also known as **splitting**)
116
When do most cases of **primary** MPGN Type I present? How do they present?
- Presents in **adolescence** or **young adulthood** = normally - **Nephrotic** syndrome and a **nephritic** component manifested by **hematuria, HTN, oliguria, some edema,** and **renal insufficiency**
117
About 50% of patients with MPGN Type I will develop what? Response to immunosuppressant therapy?
- Chronic renal failure within 10 years - Tx w/ steroids/immunosuppressive agents have **not** proven beneficial
118
When does **secondary** MPGN Type I present? Arises in which settings and with what associated disorders?
- Almost exclusively in **adults** - Associated w/ **chronic antigenemia** (from infection, autoimmune dz or neoplasia) causing immune complex deposition - **SLE, HBV, HCV (w/ cryoglobulinemia)**, endocarditis, HIV, and schistosomiasis - α1- antitrypsin deficiency - Malignancies (CLL, lymphomas, melanomas)
119
Most patients w/ dense deposit disease (aka type II MPGN) have abnormalities reulting in excessive activation of?
**Alternative complement** pathway
120
Dense deposit dz (MPGN type II) primarily affects whom? Only occurs as what kind of disease?
- Children and young adults - Only occurs as a **primary renal disease**; no secondary form
121
What is the dominant clinical finding in Dense Deposit disease vs. MPGN type I? Prognosis of MPGN II vs. MPGN I?
- **Hematuria** is a **more dominant** finding (proteinuria is more characteristic of MPGN I) - 50% of patients will also have **nephritic syndrome** - Generally has a **poorer** prognosis than MGPN I due to most pts having **severe renal dz.**
122
Which antibody present in the seurm of pts with Dense Deposit dz (MPGN type II) plays a key role in its pathogenesis and how?
- **C3 nephritic factor (C3NeF)** = **IgG autoantibody** - Binds **C3 convertase** leading to CONTINOUS activation of **alternative pathway**
123
The defining feature of dense deposit dz (MPGN type II) seen on electron microscopy is what?
**Permeation** of the lamina densa of the GBM by **ribbon-like,** homogenous, **extremely electron-dense material** of unknown composition
124
High incidence of recurrence of MPGN II in which patients?
Transplant patients
125
What is the most common type of glomerulonephritis **worldwide**?
IgA nephropathy
126
What are the 2 major characteristics of IgA nephropathy (Berger disease)?
- **IgA deposits** in the **mesangial** regions - **Recurrent** gross or microscopic **hematuria**
127
IgA nephropathy is primarily a disease seen in whom? Which ethnicities more affected? Which sex?
- Older children and young adults, **most common** in 2nd and 3rd decades - Caucasians and Asians \> African Americans - Male predominance: **2:1** or **higher** (**N. America** and **Europe**)
128
In IgA nephropathy, what is the predominant type of IgA seen in the glomerular deposits?
Polymeric IgA molecules w/ **aberrant glycosylation** (**IgA1**)
129
Due to increased synthesis of abnormal IgA, there is an increased incidence of IgA nephropathy seen in which 2 conditions?
1. **Celiac disease** (gluten enteropahty) 2. **Liver disease** (defective hepatobiliary clearance of IgA) --\> **secondary IgA nephropathy**
130
Pts with IgA nephropathy commonly present with hematuria following what? How long does it last?
- **Infection of the respiratory** or, less commonly the GI/GU tracts - Hematuria lasts several days, then subsides, only to return every few months
131
What are the clinical outcomes of IgA nephropathy? Does it progress to chronic renal failure?
- Recurrent episodes of hematuria w/o progression of renal disease = **major outcome** - Acute nephritic syndrome w/ HTN in 5-10% pts - Chronic renal failure occurs in 15-40% as a slowly progressing dz over **20 year period**
132
Renal IgA nephropathy WITHOUT systemic disease is known as?
Berger disease
133
What is **Henoch-Schonlein purpura (HSP)**? Typical clinical presentation?
- **IgA nephropathy** associated **w/ systemic disease** --\> onset following **URI** - Presents w/ **cramping abd pain** + **hematuria** and **proteinuria** + **purpuric/echymottic** manifestations
134
Fully developed Alport Syndrome is manifested by what?
- **Hematuria** w/ progression to **chronic renal failure** - Accompanied by **nerve deafness** + **various eye disorders** (i.e., lens dislocation, posterior cataracts, and corneal dystrophy)
135
What is the major inheritance pattern of Alport Syndrome? How does this effect the presentation in men and women?
- **X-linked** (85%) also can be **AR** or **AD** - Affected **males** express the **full syndrome --\> ESRD** before age 40 - **Females** are heterozygotes and typically only have **hematuria**
136
Alport Disease is due to mutations in genes encoding subunits of which molecule?
Type IV Collagen
137
Pts with the X-linked type of Alport Syndrome and what mutation often have ESRD at an earlier age?
**Collagn IV α5 chain** **(C****OL4A5)****deletion**
138
Which electron microscopy findings is characteristic of fully developed Alport Syndrome?
- **Irregular foci of thick/thin alternating areas of GBM** w/ pronounced splitting and lamination of the lamina dense - Distinctive **"basket-weave" appearance**
139
Symptoms of Alport Syndrome typically manifest btw what ages? Frequent presentation?
- Age **5-20 yo** w/ onset of overt renal failure btw ages 20-50 - Present w/ **hematuria** with **red cell casts**
140
Thinned Basement Membrane Disease (aka Benign Familial Hematuria) is characterized by what? What is renal function like and the prognosis?
- Asymptomaatic (microscopic) **h****ematuria**due to**thinned** GBM - **Renal function** = normal and prognosis = **excellent**
141
The anomaly of thinned BM's in Thinned BM Disease is due to mutations in genes encoding what? Most patients are what type of carriers?
- Mutations in genes encoding α3 or α4 chains of type IV collagen - **Most pts are heterozygous** for the defective gene and thus are carriers
142
Homozygotes carriers with Thinned BM Disease resemble what other hereditary nephritis?
Autosomal **recessive** Alport Syndrome --\> may progress to **renal failure**
143
80% of patients w/ a family history of hematuria or recurrent hematuria dring childhood have what?
- Hereditary nephritis - Alport Syndrome or Thin BM Disease
CPR II Exam 3
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