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CPR > Chapter 20: The Kidney - Glomerular Diseases > Flashcards

Chapter 20: The Kidney - Glomerular Diseases Flashcards

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?

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
Q

In the Heymann mode of glomerulonephritis, Abs reacts to what Ag?

This Ag is normally found where?

A

Megalin, normally present in epithelial cell (podocyte) foot processes

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26
Q

Which Ag has been found to be the one underlying most cases of primary human membranous nephropathy?

A

M-type phospholipase A2 receptor (PLA2R)

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27
Q

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?

A

- SUBepithelial aspect of BM

- THICKENED BM appearance on light microscopy

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28
Q

In viewing membranous nephropathy (in-situ immune complex deposition) with immunofluorescence microscopy what is the pattern of immune deposition seen?

Reflects what?

A
  • Immune deposition in GRANULAR pattern (not linear)
  • Reflective of very localized and LARGE complexes of Ag-Ab interaction.
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29
Q

What is the antigen associated with anti-GBM nephritis?

A

NC1 domain of type IV collagen Ag

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30
Q

In situ immune complex deposition against “planted” Ags may occur, what are examples of exogenous sources of these Ags?

A
  • Infectious agents (viral, bacterial and parasitic products)
  • Drugs/toxins
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31
Q

In situ immune complex deposition against “planted” Ags may occur, what are examples of endogenous sources of these Ags?

A
  • DNA
  • Nuclear proteins
  • Immunoglobulins
  • Immune complexes themselves can serve as Ags!
  • IgA
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32
Q

Characteristic pattern seen with immunofluorescence in diseases caused by Abs directed against normal glomerular BM components (i.e., anti-GBM)?

A

Diffuse linear pattern as Abs bind intrinsic Ags along entire legnth of GBM

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33
Q

Often anti-GBM Abs cross react with other BM’s, especially where?

What syndrome does this occur in?

A
  • Lung alveoli, results in simultaneous lung and kidney lesions
  • Goodpasture syndrome
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34
Q

What kind of glomerular damage occurs due to anti-GBM Abs?

Leading to which clinical syndrome?

A
  • Causes severe necrotizing and crescentic glomerular damage
  • Leading to rapidly progressive glomerulonephritis (RPGN)
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35
Q

Microbial Ags from which bacteria/viruses may act as exogenous sources that trigger circulating immune complexes leading to glomerulonephritis?

A
  • Streptococcal proteins
  • Surface Ag of HBV and viral antigens of HCV
  • Ags of Treponema pallidum and Plasmodium falciparum
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36
Q

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?

A
  • Cationic–> cross the GBM and resultant complexes aresubepithelial
  • Anionic–> excluded from GBM and trappedsubendothelially
  • Neutral charge –> tend to accumulate in the mesangium
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37
Q

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?

A
  • Subendothelial portions of capillaries
  • Mesangial locations
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38
Q

Why are large circulating complexes usually NOT nephritogenic?

A

They are cleared by the mononuclear phagocyte system and do not enter the GBM in significant quantities

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39
Q

Lupus nephritis and membranoproliferative glomerulonephritis lead to immune-complex deposition in which part of the glomerulus?

A

Subendothelial deposits = membranoproliferative pattern

*#3 in the figure

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40
Q

Which coagulation factor may act as the stimulus for crescent formation associated w/ glomerular injury?

A

Thrombin

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41
Q

Which GF’s seem to be critical in the ECM deposition and hyalinization leading to glomerulosclerosis in chronic kidney injury?

A
  • TGF-β
  • Connective tissue GF
  • Fibroblast GF
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42
Q

In most forms of glomerular injury, loss of what is a key event in the development of proteinuria?

A

Loss of normal slit diaphragms

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43
Q

What is the principal glomerular manifestation of progressive glomerular injury?

A

Focal segmental glomerulosclerosis

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44
Q

Which mediator of chronic inflammation plays a particularly important role in the induction of scleroris seen in Focal Segmental Glomerulosclerosis?

A

TGF-β

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45
Q

What is the drug of choice for Focal Segmental Glomerulosclerosis?

A

RAAS inhibitors

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46
Q

What is the most frequent clinical presentation of Focal Segmental Glomerulosclerosis?

A
  • Nephrotic syndrome
  • Nonnephrotic proteinuria
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47
Q

The extent of damage to what renal structures is more correlated to decline in renal function?

A

Tubulointerstitial damage rather than the severity of glomerular injury

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48
Q

What plays a major role in the direct injury and activation of tubular cells seen in Tubulointerstitial Fibrosis?

What do activated tubular cells do?

A

- 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
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49
Q

Most common type of glomerular injury causing nephritic syndrome?

A

Immunologically mediated

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50
Q

How does Acute Proliferative (Poststreptococcal) Glomerulonephritis typically present (signs/sx’s and findings)?

What is seen in urine?

Typical age group?

A
  • Malaise + fever + nausea + oliguriaandhematuria –> 1-2 wksafter recovery fromsore throat or skin infection
  • Dysmorphic red cells or RBC casts, mild proteinuria, perioribital edema, and mild/moderate HTN
  • Children ages 6-10 yo
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51
Q

What has been discovered as the principal antigenic determinant in most cases of Poststreptococcal Glomerulonephritis?

This antigen can directly activate what?

A

Pyogenic exotoxin B (SpeB) –> directly activates complement

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52
Q

What class of streptococcus is the cause of Poststreptococcal Glomerulonephritis?

A

Group A, β-hemolytic Strep –> types 12, 4, or 1

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53
Q

Acute proliferative (postreptococcal) glomerulonephritis is characterized by what 2 findings histologically?

A
  1. Marked hypercellularity: ranging from simple mesangial to complex endocapillary cell infiltrate
  2. Leukocyte infiltration: both neutrophils and monocytes
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54
Q

The proliferation and leukocyte infiltration are seen in which parts of the glomeruli during acute proliferative (postreptococcal) glomerulonephritis?

A

Typically involving ALL lobules of ALL glomeruli

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55
Q

What is seen on immunofluorescence microscopy in acute proliferative (postreptococcal) glomerulonephritis?

A

Granular deposits of IgG and C3, and sometimes IgM in the mesangium and along the GBM

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56
Q

What is the characteristic findings on electron microscopy in acute proliferative (postreptococcal) glomerulonephritis?

A

Discrete, amorphous, electron-dense deposits = subepithelial “humps” = Ag-Ab complexes

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57
Q

What is the onset of acute proliferative (postreptococcal) glomerulonephritis like in an adult?

Clinical course?

A
  • 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
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58
Q

What is the typical clinical course of acute proliferative (postreptococcal) glomerulonephritis in a child?

A
  • >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
Q

How do the immune deposits found in postinfectious GN due to staphylococcal infection differ from that of strep?

A

Producing immune-deposits w/ IgA rather than IgG

60
Q

What are some of the bacterial, viral, and parasitic causes of Postinfectious GN?

A
  • Bacteria - Staph, pneumococcal, pneumonia, and meningococcemia
  • Viral - HBV, HCV, Mumps, HIV, VZV, and infectious mononucleosis (EBV)
  • Parasitic - malaria and toxoplasmosis
61
Q

What is the most common histological picture in Rapidly Progressive Glomerulonephritis (RPGN)?

A

Presence of crescents in most of the glomeruli (crescenteric GN)

62
Q

Type I RPGN (anti-GMB Ab) disease is characterized by what kind of deposits?

A

Linear deposits of IgG and often C3 in the GBM

63
Q

What is the antigen common to the alveoli and GBM, and is known as the Goodpasture Ag?

A

Noncollagenous portion of the α3 chain of collagen type IV

64
Q

Which HLA subtype is associated with RPGN (i.e., Goodpasture Syndrome)?

A

HLA-DRB1

65
Q

What is used in the treatment regimen for Type I RPGN (anti-GBM Ab disease)?

How effective?

A

- Plasmapheresis in conjunction w/ immunosuppressive therapy

  • Can reverse pulmonary hemorrhage and renal failure
66
Q

Major causes of Type II (immune complex) RPGN?

A
  • Idiopathic
  • Postinfection GN (aka acute proliferative GN)
  • Lupis nephritis
  • Henoch-Schonlein pupura
  • IgA nephropathy
67
Q

Type II RPGN frequently has what histological findings?

A

Granular pattern w/ cellular proliferation and influx of leukocytes within the glomerular tuft + crescent formation

68
Q

Can Type II RPGN benefit from plasmapheresis?

A
  • Generally do NOT respond
  • MUST TREAT UNDERLYING DISEASE!
69
Q

RPGN that is defined by a lack of detectable anti-GBM Abs or immune complexes is known as?

A

Type III (Pauci-Immune)

70
Q

Type III (Pauci-Immune) RPGN may be a component of what underlying disorders?

A
  • ANCA-associated
  • Idiopathic
  • Granulomatosis w/ polyangiitis (formerly Wegener granulomatosis)
  • Microscopic polyangiitis
71
Q

What is a hallmark finding of the GBM seen on electron micrscopy in RPGN?

What finding dominates the histological picture?

A

- Wrinkling of the GBM w/ ruptures = HALLMARK

  • Distinctive crescents dominate the histological picture
72
Q

In RPGN what is commonly seen in prominent amounts between the cellular layers in crescents?

A

Fibrin

73
Q

Ruptures in the GBM seen in RPGN allows what to enter?

A

Leukocytes, plasma proteins such as coagulation factors and complement + inflammatory mediators —> urinary space triggering crescent formation

74
Q

Hemoptysis and even life threatening pulmonary hemorrhage may be associated with what type of RPGN?

A

Goodpasture syndrome (Type I RPGN)

75
Q

Presence of what in the serum is virtually diagnostic of Type III (Pauci-Immune) RPGN?

A

ANCAs

76
Q

How does the cause of nephrotic syndrome in children <17 yo differ from adults?

A
  • Children = almost always caused by a lesion primary to the kidney
  • Adults = often associated with a systemic disease
77
Q

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?

A
  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
Q

What are the most frequent systemic causes of nephrotic syndrome?

A

- Diabetes

- Amyloidosis

- SLE

  • Drugs
  • Infections
  • Malignant dz (carcinoma, lymphoma)
79
Q

What does the term “nephrotic range proteinuria” refer to?

A

Loss of 3 grams or more/day in the urine

80
Q

Primary membranous glomerulopathy is now considered an autoimmune disease and linked to which HLA allele?

A

HLA-DQA1

81
Q

What is the autoantigen in most cases of primary membranous glomerulopathy?

A

Phospholipase A2 receptor (PLA2 receptor)

82
Q

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?

A
  • C5b-C9 (MAC)
  • IgG4 on SUBepithelial side of BM
83
Q

What are some of the secondary causes of Membranous Nephropathy?

A
  • Drugs
  • SLE
  • Underlying malignancy
  • Infections —> HBV, HCV, syphillis, schistosomiasis, malaria
  • Autoimmune disorders –> thyroiditis
84
Q

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?

A
  • 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
Q

What are the typical clinical features of membranous nephropathy?

A
  • 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
Q

How does glomerular nephropathy respond to corticosteroids?

A

Primary responds POORLY to steroid therapy

87
Q

Recurrence of Membranous Nephropathy is a common feature in which patients?

A
  • Pts who undergo transplant for end-stage renal disease
  • Spontaneous remissions and more benign outcome = more common in Women
88
Q

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

Peak incidence between what ages?

A
  • Minimal-change disease
  • Btw 2-6 y/o
89
Q

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?

A
  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
Q

A characteristic (even implicitly diagnostic) of minimal change disease is a dramatic response to what?

Prognosis of this disease?

A
  • Dramatic response to corticosteroid therapy
  • >90% of children w/ MCD respond to Tx w/ cure and no clinical recurrence = very good prognosis
91
Q

What is the proteinuria like in Minimal Change Disease vs. Membranous Nephropathy?

A
  • MCD = highly selective proteinuria, most of which is albumin
  • M.N. = the proteinuria is nonselective
92
Q

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?

A
  • Visceral epithelial cells (podocytes), show uniform and diffuse effacement of foot processes
  • But the effacement is associated w/ NORMAL glomeruli (unlike membranous nephropathy)
93
Q

Major clinical features of Minimal Change Disease?

A
  • Highly SELECTIVE massive proteinuria w/ good renal function
  • Commonly no HTN or hematuria
  • Dramatic response to corticosteroids
94
Q

What is the most common cause of nephrotic syndrome in adults in the US?

A

Focal Segmental Glomerulosclerosis (FSGS)

95
Q

Which populations have a higher incidence of Focal Segmental Glomerulosclerosis (FSGS)?

A
  • Hispanic
  • African American
96
Q

Focal Segmental Glomerulosclerosis (FSGS) is often an adaptive response to?

A

Loss of renal mass

97
Q

The clinical signs of FSGS differ from Minimal Change disease in what 4 ways?

A
  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
Q

What is the hallmark of FSGS that can be seen with electron microscopy?

A
  • Degeneration and focal disruption of visceral epithelial cells (podocytes)
  • DIFFUSE effacementoffoot processes
99
Q

What was the first relevant gene and protein to be identified related to a genetic basis for FSGS?

Which chromosome?

A
  • NPHS1 —> nephrin
  • Chromosome 19
100
Q

Mutations of NPH1 can give rise to what type of glomerulopathy?

A

Congenital nephrotic syndrome of the Finnish type

101
Q

A distinctive pattern of autosomal recessive FSGS results from mutations in which gene?

Chromosome?

A
  • NPHS2 —-> podocin
  • Chromosome 1q25-q31
  • Steroid-resistant nephrotic syndrome of childhood onset
102
Q

Mutation in the podocyte actin binding protein α-actinin 4 underlies some cases of what type of FSGS (i.e., inheritance pattern)?

A

Autosomal dominant FSGS

103
Q

Mutations in the gene encoding what protein have been linked to some inherited forms of adult-onset FSGS?

A

TRPC6

104
Q

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?

A
  • Apolipoprotein L1 gene (APOL1) on chromosome 22
  • Confers resistance to trypanosome infection (i.e., malaria)
105
Q

Which deposits may be seen in the sclerotic areas and mesangium of FSGS under immunofluorescence microscopy?

A

IgM and C3

106
Q

What is the most characteristic lesion (i.e, morphological variant of FSGS) seen in HIV-associated nephropathy?

A

Collapsing glomerulopathy = severe form of FSGS

107
Q

In FSGS, glomeruli that do not show segmental lesions usually appear normal on light microscopy, but may show increased what?

A

Increased mesangial matrix

108
Q

What is the prognosis of FSGS in chidren vs. adults?

A
  • Children generally have better prognosis than adults
109
Q

Which finding in a biopsy specimen has diagnostic value for the collapsing variant of FSGS seen in those w/ HIV?

A

Large # of tubuloreticular inclusions within endothelial cells

110
Q

What are the major histological findings in Membranoproliferative Glomerulonephritis (MPGN)?

Glomerular proliferation is predominantly of what type?

A
  • GBM = thickened –> “double-contour“or“tram-track” appearance
  • Prolieration of glomerular cells –> mainly the mesangiumbut may also involve the capillary loops =mesangiocapillary glomerulonephritis
  • Leukocyte infiltration
111
Q

Membranoproliferative Glomerulonephritis (MPGN) is best considered as what, rather than a specific disease?

A

Pattern of immune-mediated injury

112
Q

How does Type I vs. Type II MPGN differ when viewing under immunofluorescence and light microscopy?

A
  • Type I: will have SUBendothelial 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
Q

Which pathways are activated in MPGN Type I?

A

Both the classical and alternative complement pathways

114
Q

In the most basic sense how are the clinical findings of MPGN Type I different from Type II?

A
  • Type I = mixed nephrotic and nephritic findings = hematuria and mild proteinuria
  • Type II = hematuria with renal failure
115
Q

What is the characteristic findings seen with silver strain or PAS of the GBM in MPGN?

A
  • Thickened and shows a “double contour” or “tram-track” appearance
  • Due to “duplication” of the BM (also known as splitting)
116
Q

When do most cases of primary MPGN Type I present?

How do they present?

A
  • Presents in adolescence or young adulthood = normally
  • Nephrotic syndrome and a nephritic component manifested by hematuria, HTN, oliguria, some edema, and renal insufficiency
117
Q

About 50% of patients with MPGN Type I will develop what?

Response to immunosuppressant therapy?

A
  • Chronic renal failure within 10 years
  • Tx w/ steroids/immunosuppressive agents have not proven beneficial
118
Q

When does secondary MPGN Type I present?

Arises in which settings and with what associated disorders?

A
  • 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
Q

Most patients w/ dense deposit disease (aka type II MPGN) have abnormalities reulting in excessive activation of?

A

Alternative complement pathway

120
Q

Dense deposit dz (MPGN type II) primarily affects whom?

Only occurs as what kind of disease?

A
  • Children and young adults
  • Only occurs as a primary renal disease; no secondary form
121
Q

What is the dominant clinical finding in Dense Deposit disease vs. MPGN type I?

Prognosis of MPGN II vs. MPGN I?

A
  • 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
Q

Which antibody present in the seurm of pts with Dense Deposit dz (MPGN type II) plays a key role in its pathogenesis and how?

A
  • C3 nephritic factor (C3NeF) = IgG autoantibody
  • Binds C3 convertase leading to CONTINOUS activation of alternative pathway
123
Q

The defining feature of dense deposit dz (MPGN type II) seen on electron microscopy is what?

A

Permeation of the lamina densa of the GBM by ribbon-like, homogenous, extremely electron-dense material of unknown composition

124
Q

High incidence of recurrence of MPGN II in which patients?

A

Transplant patients

125
Q

What is the most common type of glomerulonephritis worldwide?

A

IgA nephropathy

126
Q

What are the 2 major characteristics of IgA nephropathy (Berger disease)?

A
  • IgA deposits in the mesangial regions
  • Recurrent gross or microscopic hematuria
127
Q

IgA nephropathy is primarily a disease seen in whom?

Which ethnicities more affected?

Which sex?

A
  • 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
Q

In IgA nephropathy, what is the predominant type of IgA seen in the glomerular deposits?

A

Polymeric IgA molecules w/ aberrant glycosylation (IgA1)

129
Q

Due to increased synthesis of abnormal IgA, there is an increased incidence of IgA nephropathy seen in which 2 conditions?

A
  1. Celiac disease (gluten enteropahty)
  2. Liver disease (defective hepatobiliary clearance of IgA) –> secondary IgA nephropathy
130
Q

Pts with IgA nephropathy commonly present with hematuria following what?

How long does it last?

A
  • Infection of the respiratory or, less commonly the GI/GU tracts
  • Hematuria lasts several days, then subsides, only to return every few months
131
Q

What are the clinical outcomes of IgA nephropathy?

Does it progress to chronic renal failure?

A
  • 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
Q

Renal IgA nephropathy WITHOUT systemic disease is known as?

A

Berger disease

133
Q

What is Henoch-Schonlein purpura (HSP)?

Typical clinical presentation?

A
  • IgA nephropathy associated w/ systemic disease –> onset following URI
  • Presents w/ cramping abd pain + hematuria and proteinuria + purpuric/echymottic manifestations
134
Q

Fully developed Alport Syndrome is manifested by what?

A
  • Hematuria w/ progression to chronic renal failure
  • Accompanied by nerve deafness + various eye disorders (i.e., lens dislocation, posterior cataracts, and corneal dystrophy)
135
Q

What is the major inheritance pattern of Alport Syndrome?

How does this effect the presentation in men and women?

A
  • 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
Q

Alport Disease is due to mutations in genes encoding subunits of which molecule?

A

Type IV Collagen

137
Q

Pts with the X-linked type of Alport Syndrome and what mutation often have ESRD at an earlier age?

A

Collagn IV α5 chain (COL4A5)deletion

138
Q

Which electron microscopy findings is characteristic of fully developed Alport Syndrome?

A
  • Irregular foci of thick/thin alternating areas of GBM w/ pronounced splitting and lamination of the lamina dense
  • Distinctive “basket-weave” appearance
139
Q

Symptoms of Alport Syndrome typically manifest btw what ages?

Frequent presentation?

A
  • Age 5-20 yo w/ onset of overt renal failure btw ages 20-50
  • Present w/ hematuria with red cell casts
140
Q

Thinned Basement Membrane Disease (aka Benign Familial Hematuria) is characterized by what?

What is renal function like and the prognosis?

A
  • Asymptomaatic (microscopic) hematuriadue tothinned GBM
  • Renal function = normal and prognosis = excellent
141
Q

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?

A
  • 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
Q

Homozygotes carriers with Thinned BM Disease resemble what other hereditary nephritis?

A

Autosomal recessive Alport Syndrome –> may progress to renal failure

143
Q

80% of patients w/ a family history of hematuria or recurrent hematuria dring childhood have what?

A
  • Hereditary nephritis
  • Alport Syndrome or Thin BM Disease

CPR (8 decks)

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