Glomerulonephritis B&B

Question 1

which proteins cause the basement membrane of the glomerular filtration barrier to be negatively charged?

Answer 1

1. Type IV collagen
2. heparan sulfate

repels (-) molecules like albumin

Question 2

How does glomerular bleeding usually appear in the urine?

Answer 2

red cells casts (generally not clots - too big), acanthocytes (dysmorphic RBC), red/smoky brown/“coca cola” color

Question 3

What systemic effects are caused by nephrotic syndrome?

Answer 3

nephrotic syndrome: filtration barrier to proteins lost, but RBC filtration barrier is intact

proteinurea triggers cascade is pathology:
—> low immunoglobins cause infection
—> low albumin increases liver activity, causing hyperlipidemia
—> low albumin decreases oncotic pressure, causing edema
—> low ATIII causes thrombosis

Question 4

what occurs in nephrotic syndrome?

Answer 4

nephrotic syndrome: filtration barrier to proteins lost, but RBC filtration barrier is intact

proteinurea triggers cascade is pathology:
—> low immunoglobins cause infection
—> low albumin increases liver activity, causing hyperlipidemia
—> low albumin decreases oncotic pressure, causing edema
—> low ATIII causes thrombosis

Question 5

how does urine in nephrotic syndrome appear?

Answer 5

nephrotic syndrome: filtration barrier to proteins lost, but RBC filtration barrier is intact

—> massive proteinuria
—> hyperlipidemia (low albumin triggers liver activity) - fatty casts or oval fat bodies

Question 6

how do urine samples appear in nephrotic vs nephritic syndrome?

Answer 6

nephrotic syndrome (protein barrier lost): massive proteinuria, hyperlipidemia (increased liver activity)

nephritic syndrome (protein and RBC barrier lost - renal failure): RBC casts, mild proteinuria

Question 7

Pt is a 31yo F presenting to their GP for complaints of a suspected allergic reaction. PE notes swollen ankles and periorbital swelling. Labs reveal high serum cholesterol (>300mg/dL), frothy urine, and proteinuria (>3.5g/day). What is likely going on?

Answer 7

nephrotic syndrome: filtration barrier to proteins lost, but RBC filtration barrier is intact

—> massive proteinuria
—> hyperlipidemia (low albumin triggers liver activity) - fatty casts or oval fat bodies

nephrotic syndrome often mistaken for allergic rxn

Question 8

what occurs in nephritic syndrome?

Answer 8

nephritic syndrome: inflammatory process damages entire glomeruli, filtration barrier to RBCs and protein is lost —> decreased GFR

—> dysmorphic RBC in urine, RBC casts
—> proteinuria (less than nephrotic syndrome due to lower GFR)

Question 9

What are the systemic effects of nephritic syndrome?

Answer 9

nephritic syndrome: inflammatory process damages entire glomeruli, filtration barrier to RBCs and protein is lost —> decreased GFR —>

—> increased BUN/Cr
—> increased hydrostatic pressure causes HTN and edema
—> oliguria

Question 10

On rounds, you encounter a patient with generalized swelling and fatigue complaining of dark urine. Lab workup reveals mild proteinuria. What is the likely diagnosis?

Answer 10

nephritic syndrome: inflammatory process damages entire glomeruli, filtration barrier to RBCs and protein is lost —> decreased GFR —>

—> increased BUN/Cr
—> increased hydrostatic pressure causes HTN and edema
—> oliguria
—> dysmorphic RBC + casts in urine (dark urine)

Question 11

where is the site of glomerular injury in nephritic vs nephrotic syndrome and why does this make sense?

Answer 11

nephrotic: podocyte injury (filtration barrier) —> protein loss only (separated from blood by GBM)

nephritic: endothelial and mesangial cell injury (exposed to blood) —> inflammation (nephritis) —> loss of RBC and protein in urine

Question 12

describe how post-streptococcal glomerular injury occurs? is it nephritic or nephrotic?

Answer 12

post-streptococcal nephritic syndrome: 2-3 weeks following group A beta-hemolytic strep infection (impetigo, pharyngitis) with nephritogenic strain (specific M protein virulence factor subtype)

—> immune complexes deposit in kidney, fix complement, attract PMNs
—> hypocomplementemia, enlarged/hypercellular glomeruli, sub-epithelial humps (IgG, C3) on electron microscopy

Question 13

Pt is a 4yo M presenting 3 weeks post strep throat infection. Parent notes the child’s urine has been dark. Labs are done which show RBC and protein in the urine. A kidney biopsy is taken for electron microscopy, which shows enlarged, hypercellular glomeruli with subepithelial humps. What is going on, and what is the prognosis for this patient?

Answer 13

post-streptococcal nephritic syndrome: 2-3 weeks following group A beta-hemolytic strep infection (impetigo, pharyngitis) with nephritogenic strain (specific M protein virulence factor subtype)

—> immune complexes deposit in kidney, fix complement, attract PMNs
—> hypocomplementemia, enlarged/hypercellular glomeruli, sub-epithelial humps (IgG, C3) on electron microscopy

Question 14

which class of antibodies deposit in the kidneys in post-streptococcal nephritis, and where do they deposit?

Answer 14

subepithelial humps see on electron microscopy

due to IgG, C3 seen on immunofluorescence

Question 15

which patients are classically affected by post-streptococcal nephritis? what is the prognosis for adults vs children and how is it treated?

Answer 15

more common in children - classically child 2-3 weeks after strep throat infection (due to group A, beta-hemolytic strep of nephritogenic strain)

good prognosis in children (95% recover)

worse prognosis in adults - many develop renal insufficiency, even 10-40 years later

supportive therapy with spontaneous resolution

Question 16

describe how Berger’s disease occurs? is it nephritic or nephrotic?

Answer 16

Berger’s disease, aka IgA nephropathy: nephritic syndrome with repeated episodes of hematuria over time leading to end-stage renal disease

due to overactive immune system with high IgA synthesis which deposit in mesangium and activate complement (alternative and lectin pathways)

Question 17

which class of antibodies deposit in the glomerulus in Berger’s disease? where do they deposit?

Answer 17

Berger’s disease, aka IgA nephropathy: nephritic syndrome with repeated episodes of hematuria over time leading to end-stage renal disease

due to overactive immune system with high IgA synthesis which deposit in mesangium and activate complement (alternative and lectin pathways)

Question 18

which antibodies deposit and where in post-streptococcal nephritis vs Berger’s disease nephritis vs DPGN?

Answer 18

post-streptococcal nephritis: IgG, C3 deposit in subepithelial humps

Berger’s disease, aka IgA nephropathy (nephritis): IgA deposit in mesangium

DPGN (diffuse proliferative glomerulonephritis): “full house” immunofluorescence - IgG, IgA, IgM, C3, C1q, subendothelial deposits

Question 19

Pt is a 17yo M with PMH of recurrent episodes of hematuria since childhood, following respiratory (URI) or GI (diarrhea) infections. Renal function has been on a steady decline, as noted by increase BUN/Cr levels, and there is concern of ESRD in the next few years. What is likely going on?

Answer 19

Berger’s disease, aka IgA nephropathy: nephritic syndrome with repeated episodes of hematuria over time leading to end-stage renal disease, most common glomerulonephritis

due to overactive immune system with high IgA synthesis which deposit in mesangium and activate complement (alternative and lectin pathways)

triggered days after respiratory, GI infections

Question 20

how do the following glomerular disorders vary in the timing of their presentation?
a. post-streptococcal nephritis
b. IgA nephropathy
c. minimal change disease

Answer 20

a. post-streptococcal nephritis: weeks after infection (by Group A beta-hemolytic strep)
b. IgA nephropathy: nephritic syndrome days after infection (respiratory, GI)
c. minimal change disease: nephrotic syndrome after URI (respiratory)

Question 21

Henoch-Schonlein Purpura

Answer 21

IgA nephropathy with extra-renal involvement —> diffuse IgA deposition

—> palpable purpura on butt/legs, GI and joint pain

most common childhood systemic vasculitis

Question 22

describe how diffuse proliferative glomerulonephritis (DPGN) develops

Answer 22

DPGN: Type IV systemic lupus erythematous (SLE) nephritis, most common subtype of SLE renal disease (I-V types)

due to subendothelial immune complex deposition in glomeruli, triggering inflammatory response —> increased cellularity, PMN infiltration, thickened capillary loops (“wire looping”), “full house” immunofluorescence* (IgG, IgA, IgM, C3, C1q), hypocomplementemia

“diffuse” because 50%+ of glomeruli are affected

often presents with other SLE features (fever, rash, arthritis) and often leads to ESRD

Question 23

which subtype of SLE renal disease is DPGN? is it nephritic or nephrotic?

Answer 23

diffuse proliferative glomerulonephritis (DPGN): Type IV systemic lupus erythematous (SLE), most common subtype of SLE renal disease (I-V types)

due to subendothelial immune complex deposition in glomeruli (IgG, IgA, IgM, C3, C1q), triggering inflammatory response —> increased cellularity, PMN infiltration, thickened capillary loops (“wire looping”)

often presents with other SLE features (fever, rash, arthritis) and often leads to ESRD

usually nephritic (blood + protein in urine) but can be nephrotic (proteins only)

Question 24

what renal structural changes occur in diffuse proliferative glomerulonephritis (DPGN)?

Answer 24

DPGN: Type IV systemic lupus erythematous (SLE) nephritis

due to subendothelial immune complex deposition (IgG, IgA, IgM, C3, C1q) in glomeruli, triggering inflammatory response —> increased cellularity, PMN infiltration, thickened capillary loops (“wire looping”)

severe, often leads to ESRD

Question 25

which of these will NOT present with hypocomplementemia? a. post-streptococcal nephritis b. IgA nephropathy c. diffuse proliferative glomerulonephritis (DPGN)

Answer 25

b. IgA nephropathy (nephritis): IgA immune complexes in mesangium, complement activated but not depleted (only IgA deposits) a. post streptococcal nephritis and c. DPGN (type IV renal SLE) lead to hypocomplementemia following complement fixation (deposit with antibodies in glomerulus)

Question 26

how does rapidly progressive glomerulonephritis (RPGN) develop? is it nephrotic or nephritic?

Answer 26

RPGN: severe form of glomerulo*nephritis*, crescents form by inflammation (monocytes/macrophages/fibrin) rapid onset with progressive loss of renal function (often presents as acute renal failure) Type I (linear IF), II (granular IF), or III (negative IF)

Question 27

what is the cause and presentation of Type I RPGN (rapidly progressive glomerulonephritis)?

Answer 27

RPGN: severe form of glomerulo*nephritis*, crescents form by inflammation Type I (linear): antibodies against glomerular basement membrane (*Type II hypersensitivity*) cause linear pattern of *IgG* antibodies on immunofluorescence

Question 28

what type of hypersensitivity reaction is Type I RPGN?

Answer 28

RPGN (rapidly progressive glomerulonephritis): severe form of nephritis, crescents form by inflammation Type I (linear): antibodies against glomerular basement membrane (*Type II hypersensitivity*) cause linear pattern of *IgG* antibodies on immunofluorescence

Question 29

what type of rapidly progressive glomerulonephritis (RPGN) is Goodpasture’s Syndrome?

Answer 29

Goodpasture’s Syndrome: antibodies to *alpha-3 chain* of *type IV collagen* (found in GBM and alveoli) —> Type I RPGN (linear): antibodies against glomerular basement membrane (*Type II hypersensitivity*) cause linear pattern of *IgG* antibodies on immunofluorescence

Question 30

what is the cause and presentation of Type II RPGN (rapidly progressive glomerulonephritis)?

Answer 30

RPGN (rapidly progressive glomerulonephritis): severe form of nephritis, crescents form by inflammation Type II (granular): due to immune complex deposition (*Type III hypersensitivity*), most often progression of *post-streptococcal glomerulonephritis*, can also be progression of diffuse proliferative glomerulonephritis (SLE)

Question 31

what type of hypersensitivity reaction is Type II RPGN?

Answer 31

RPGN (rapidly progressive glomerulonephritis): severe form of nephritis, crescents form by inflammation Type II (granular): due to immune complex deposition (*Type III hypersensitivity*) most often progression of *post-streptococcal glomerulonephritis*, can also be progression of diffuse proliferative glomerulonephritis (SLE)

Question 32

post-streptococcal glomerulonephritis can progress to what type of RPGN (rapidly progressive glomerulonephritis)?

Answer 32

post-streptococcal *nephritic* syndrome: 2-3 weeks following group A beta-hemolytic strep infection can progress to —> Type II (granular) RPGN (rapidly progressive glomerulonephritis): immune complex deposition (*Type III hypersensitivity*) *most common cause of RPGN

Question 33

diffuse proliferative glomerulonephritis (DPGN, most common type of renal SLE disease) can progress to what type of RPGN (rapidly progressive glomerulonephritis)?

Answer 33

DPGN: *Type IV* systemic lupus erythematous (SLE), *subendothelial* immune complex deposition in glomeruli, thickened capillary loops can progress to —> Type II (granular) RPGN (rapidly progressive glomerulonephritis): immune complex deposition (*Type III hypersensitivity*)

Question 34

what is the cause and presentation of Type III RPGN (rapidly progressive glomerulonephritis)?

Answer 34

RPGN (rapidly progressive glomerulonephritis): severe form of nephritis, crescents form by inflammation Type III: “negative” due to lack of Ig staining (“pauci-immune”), most patients are *ANCA positive* (anti-neutrophil cytoplasmic antibodies) and have *vasculitis syndrome*

Question 35

in Type III (“negative”) RPGN, most patients are ____ positive and have _____ syndrome

Answer 35

RPGN (rapidly progressive glomerulonephritis): severe form of nephritis, crescents form by inflammation Type III: “negative” due to lack of Ig staining (“pauci-immune”), most patients are *ANCA positive* (anti-neutrophil cytoplasmic antibodies) and have *vasculitis syndrome*

Question 36

Type I vs Type II vs Type III RPGN

Answer 36

RPGN (rapidly progressive glomerulonephritis): severe form of nephritis, crescents form by inflammation Type I (linear): anti-glomerular basement membrane antibodies, Type II hypersensitivity Type II (granular): immune complex deposition, Type III hypersensitivity Type III (negative, “pauci-immune”): ANCA positive (anti-neutrophil cytoplasmic antibodies)

Question 37

Alport Syndrome

Answer 37

hereditary nephritis; X-linked *type IV collagen* defect (mutation in alpha-3/4/5 chains) triad - hematuria, hearing loss, ocular disturbances (chains found renal basement membrane, eye, ear)

Question 38

what syndrome does this describe? hereditary nephritis; X-linked *type IV collagen* defect triad - hematuria, hearing loss, ocular disturbances

Answer 38

Alport Syndrome

Question 39

describe the cause/triggers of minimal change disease. is this nephritic or nephrotic?

Answer 39

minimal change disease: effacement (flattening) of foot processes of glomerular podocytes —> loss of anion charge barrier to GBM —> *nephrotic syndrome* triggered by cytokines, usually idiopathic but associated with *Hodgkin Lymphoma* (lots of cytokines produced by RS cells) can also be triggered by prior *viral infection (URI)*, allergic rxn (bee sting), or recent immunization

Question 40

minimal change disease

Answer 40

minimal change disease: effacement (flattening) of foot processes of glomerular podocytes —> loss of anion charge barrier to GBM —> *nephrotic syndrome* triggered by cytokines

Question 41

what type of cancer is associated with minimal change disease and why does this make sense?

Answer 41

minimal change disease: effacement of foot processes of glomerular podocytes —> *nephrotic syndrome* triggered by cytokines, usually idiopathic but associated with *Hodgkin Lymphoma* - lots of cytokines produced by Reed Sternberg cells

Question 42

what is the typical immunological trigger for minimal change disease?

Answer 42

minimal change disease: effacement of foot processes of glomerular podocytes —> loss of anion charge barrier to GBM —> *nephrotic syndrome* triggered by cytokines, such as by prior *viral infection (URI)*

Question 43

what kind of proteinuria is caused by minimal change disease?

Answer 43

minimal change disease: effacement of foot processes of glomerular podocytes, triggered by cytokines —> *nephrotic syndrome* “selective” proteinuria - only albumin in urine (NOT immunoglobin)

Question 44

Pt is an 8yo presenting to their pediatrician after a bout of viral URI, feeling unwell. Urine analysis shows selective proteinuria (only albumin in urine, not immunoglobins). Biopsy is normal under light microscopy and immunofluorescence. The patient is prescribed steroids and responds well. What is likely going on?

Answer 44

minimal change disease: effacement of foot processes of glomerular podocytes —> *nephrotic syndrome* triggered by cytokines, such as by prior *viral infection (URI)*, allergic rxn (bee sting), or recent immunization favorable prognosis, *responds very well to steroids*

Question 45

describe the structural changes that occur in focal segmental glomerulosclerosis (FSGS)

Answer 45

FSGS: podocyte injury —> nephrotic syndrome (severe version of minimal change disease) —> segmental (only portion of glomeruli) / focal (only some glomeruli) —> pink/dense collagen deposition (hyalinosis) causes collapse of basement membranes —> effacement of foot processes

Question 46

is focal segmental glomerulosclerosis (FSGS) nephritic or nephrotic?

Answer 46

FSGS: podocyte injury —> nephrotic syndrome (severe version of minimal change disease) —> segmental (only portion of glomeruli) / focal (only some glomeruli) —> pink/dense collagen deposition (hyalinosis) causes collapse of basement membranes —> effacement of foot processes often progresses to chronic renal failure (within 10-20 years), does not respond well to steroids

Question 47

what conditions are associated with focal segmental glomerulosclerosis (FSGS)? (name a few)

Answer 47

FSGS: podocyte injury/hyalinosis —> nephrotic syndrome (severe version of minimal change disease) usually idiopathic, but secondary causes include: - HIV - sickle cell - heroin - obesity - interferon treatment - nephron loss (single kidney)

Question 48

describe what occurs in membranous nephropathy - is this condition nephritic or nephrotic?

Answer 48

membranous nephropathy: thick glomerular basement membrane due to *subepithelial* granular immune complex deposition (IgG, C3) —> *nephrotic* syndrome (proteinuria)

Question 49

what structural changes occur in membranous nephropathy?

Answer 49

membranous nephropathy: *subepithelial* granular immune complex deposition (IgG, C3) —> *nephrotic* syndrome (proteinuria) —> thick glomerular basement membrane (but absence of hypercellularity) —> “spike and dome” immune deposition on basement membrane

Question 50

what glomerular disease is the cause of Type V renal SLE disease?

Answer 50

nephrotic membranous nephropathy: type V renal SLE thick glomerular basement membrane due to *subepithelial* granular immune complex deposition (IgG, C3) —> *nephrotic* syndrome (proteinuria) [recall most lupus renal disease is nephritic]

Question 51

autoantibodies against which antigen are associated with nephrotic membranous nephropathy?

Answer 51

membranous nephropathy: thick glomerular basement membrane due to *subepithelial* immune complex deposition (IgG, C3) —> *nephrotic* syndrome associated with autoantibodies against *phospholipase A2 receptor (PLA2R)* expressed on podocytes

Question 52

what are the classic secondary causes of nephrotic membranous nephropathy?

Answer 52

membranous nephropathy: thick glomerular basement membrane due to *subepithelial* immune complex deposition (IgG, C3) secondary causes: tumor, hepatitis, rheumatoid arthritis [it rhymes] - solid tumors, Hep B/C, drugs used to treat RA

Question 53

does diabetic nephropathy caused nephritic or nephrotic syndrome?

Answer 53

diabetic nephropathy: non-enzymatic glycosylation causes leakage of proteins from glomerular basement membrane —> nephrotic syndrome long term - sclerosis of glomerulus

Question 54

does amyloidosis cause nephritic or nephrotic syndrome?

Answer 54

amyloidosis: extracellular buildup of amyloid *proteins*, kidney is most common involved organ —> *nephrotic* syndrome classic biopsy findings: apple-green birefringence and Congo red stain

Question 55

what occurs in membranoproliferative glomerulonephritis (MPGN)? is it nephritic or nephrotic?

Answer 55

MPGN: thick basement membrane + proliferation of mesangial cells/matrix can be nephritic or nephrotic! depends on whether proteinuria is in nephrotic range Type I (more common): subendothelial immune complex deposition Type II: basement membrane complement deposition

Question 56

what occurs in Type I membranoproliferative glomerulonephritis (MPGN)?

Answer 56

Type I MPGN: more common, due to *subendothelial* immune complex deposition IgG activates complement (C3), deposits trigger *mesangial ingrowth* - “tram track” appearance on light microscopy associated with *hep B and C*

Question 57

what occurs in Type II membranoproliferative glomerulonephritis (MPGN)?

Answer 57

Type II MPGN: “electron dense” deposits in the *basement membrane* mediated by *complement* C3 convertase nephritic factor (stabilizing antibody) found in most patients [recall C3 activates *alternative pathway*] —> over activation of complement, hypocomplementemia (low C3) mostly disease of children, half develop ESRD within 10 years

Question 58

what antibody is found present in most patients with Type II membranoproliferative glomerulonephritis (MPGN)?

Answer 58

Type II MPGN: “electron dense” deposits in the *basement membrane* mediated by *complement* C3 convertase nephritic factor (stabilizing antibody) found in most patients [recall C3 activates *alternative pathway*] —> over activation of complement, hypocomplementemia (low C3)

Question 59

which patients are most often affected by Type II membranoproliferative glomerulonephritis (MPGN)? what is the prognosis?

Answer 59

Type II MPGN: “electron dense” deposits in the *basement membrane* mediated by *complement* C3 convertase nephritic factor (stabilizing antibody) found in most patients mostly disease of children, half develop ESRD within 10 years

Question 60

Type I vs Type II membranoproliferative glomerulonephritis (MPGN)

Answer 60

MPGN: thick basement membrane + proliferation of mesangial cells/matrix Type I: subendothelial immune complex, “tram track” appearance, associated with hepatitis B/C Type II: complement (C3) deposition within basement membrane, mostly disease of children