Disease of Kidneys I - Nephrotic & Others

Question 1

What’s the main difference between nephritic and nephrotic syndromes?

Answer 1

nephritic = cellular proliferations

nephrotic = GBM damages (thickened with immune-complex infiltrates

Question 2

What’s another name for minimal change disease?

Answer 2

liponephrosis or Mill disease

Question 3

What population is at risk for minimal change disease?

Answer 3

pediatrics! (#1 cause of nephrotic disease in these patients)

minimal change for the mini people

Question 4

What can effectively stop proteinuria in minimal change disease? (what’s treatment?)

Answer 4

steroids extremely effective - stops within 24hours

can use this as a test and avoid invasive biopsy (tapering off the steroids will not have recurrent proteinuria)

Question 5

What is minimal change disease associated with?

Answer 5

atopic disorders (eczema, rhinitis) and respiratory infections and immunization

Question 6

Is minimal change disease immune-complex mediated?

Answer 6

NO!

Question 7

What is seen on EM of minimal change disease?

Answer 7

effacement of foot processes (looks like the epithelial cell cytoplasm is flattened out)

BM continuous

Question 8

What is seen in H&E of minimal change disease?

Answer 8

looks normal!

Question 9

What is seen in fluorescence in minimal change disease?

Answer 9

NORMAL bc no immune complexes

Question 10

Why is it called minimal change disease?

Answer 10

bc minimal changes! (duh) - only change at ultrastructural level - no immune complexes; no hypercellularity

Question 11

What’s prognosis for minimal change disease?

Answer 11

good

Question 12

What are some unique characteristics of focal segmental glomerusclerosis?

Answer 12

only SOME glomeruli affected - of this, only PARTS/SEGMENTS (patchy)

involves sclerotic/hyalinized lesion (NOT proliferation/cellularity)

Question 13

Who is normally affected with focal segmental glomerusclerosis?

Answer 13

older children, young adults

Question 14

What disease was focal segmental glomerusclerosis mistakenly subtyped as?

Answer 14

minimal change disease

shared characteristic: foot process fusion

differential: it posses focal, sclerotic lesions; recurs when taken off steroids (steroid-dependent); non-selective proteinuria (minimal change is selective - no immunoglobinemia)

Question 15

What are some other characteristics of focal segmental glomerusclerosis?

Answer 15

idiopathic or associated with HIV or other forms of focal glomerulonephritis

may have some nephritic features

Question 16

What’s seen in H&E of focal segmental glomerulosclerosis?

Answer 16

looks okay but have patchy foamy looking sclerosis - sclerotic/hyalinized lesions (not cellular)

Question 17

What is shown here?

Answer 17

FSGS

have adhesions called synechiae- focal lesions on top (in purple) but the rest looks okay

Question 18

What is seen in fluorescences of focal segmental glomerulosclerosis?

Answer 18

NOT immune mediated

but you do see entrapped proteins in sclerotic lesions - LOCALIZED

Question 19

What is seen in EM of FSGS?

Answer 19

similar to minimal change in non-sclerotic segments!

effaced foot process of epithelial cells

Question 20

What’s the treatmet for FSGS?

Answer 20

steroids, supportive

Question 21

What’s the prognosis for FSGS?

Answer 21

poor - recurrence in transplants

tend to progress to global (lesions being fusing together) and chronic

Question 22

What are the characteristics od mebranous nephrotic disease?

Answer 22

most common nephrotic syndrome in adults

idiopathic or secondary (drugs, malignancy, SLE, chronic infections [TB, HBV, HCV, parasites], metabolic disorders [thyroiditis], tumors)

secondary causes chronic antigenmia (Abs form immune complexes that deposits in microvasculature)

subepithelial immune complex deposits

Question 23

What is seen in H&E of membranous nephrotic disease?

Answer 23

no hypercelluarity/prolferation (not nephritic)

looks like normal

Question 24

What’s seen in FM of membranous nephrotic disease?

Answer 24

“lighting up like Christmas trees”

diffuse - every glomerulus have granular pattern

Question 25

What's seen in EM of membranous nephoritic disease?

Answer 25

**numerous subepithelial immune complex deposits**

Question 26

What's the treatment for membranous nephrotic disease?

Answer 26

**if secondary, treat underlying disease** (try to get Ag complexes cleared); **otherwise, supportive** ## Footnote **try steroids if idiopathic**

Question 27

What's the prognosis for membranous nephrotic disease?

Answer 27

**very variable** - can be progressive or stabilize - need patient follow-up

Question 28

What's characteristic of Membranoproliferative GN?

Answer 28

have **both nephritic and nephrotic features** (**proliferation and GBM changes**) UA have both RBC and proteins can be **idiopathic or secondary** (SLE)

Question 29

What is Type I membranoproliferative GN?

Answer 29

66% of the cases - **subendothelial deposits on capillary lumen side of BM**

Question 30

What is Type II membranoproliferative GN?

Answer 30

33% of cases - **intramembranous deposits on lamina densa** (not really epithelial or endothelial)

Question 31

What is shared between the two types of membranoproliferative GN?

Answer 31

**clinically indistinguishable -** patients present the same, are managed the same and have same prognosis **low complement** - both are complement consuming entities (can be consumed in the formation of immune complexes - just like post infectious)

Question 32

What is seen in H&E of MPGN?

Answer 32

**hypercellularity** (lots of black dots) **basket weave BM** (split, splintered, duplicated) **membrane damages and proliferation!** endothelial crescents and mesangial cell proliferation

Question 33

What is particularly distinct about MPGN H&E stain?

Answer 33

**BM duplication! "train track"**

Question 34

What is seen in FM of MGPN?

Answer 34

**lights up everywhere** bc there are immune complexes (**highly positive immune complex**) **can be confused with "pure membranous"​** - so have to look at other diagnostic tests

Question 35

What's seen on EM for MPGN?

Answer 35

**expansion of mesangial matrix, duplication of BM** **grossly distorted ultrastructure** - can't see foot processes

Question 36

What's the treatment for MPGN?

Answer 36

steroids, immunosuppression, not effective

Question 37

What's the prognosis for MPGN?

Answer 37

poor; progressive (may progress to RPGN clinical pattern); can recur in transplants

Question 38

What's a major cause of renal morbidity and mortality?

Answer 38

diabetes mellitus

Question 39

What is seen secondarily in Diabetes Mellitus?

Answer 39

1) **nodular glomerulosclerosis** (hallmark) 2) arteriolosclerosis 3) papillary necrosis 4) uniformly thickened GBM 5) no immune deposits

Question 40

What is seen in H&E for DM Nephropathy?

Answer 40

**"basketballs" nodular, rounded hyalinized balls-** nodular glomerular necrosis - aka **K****immelstiel-Wilson syndrome** (key diagnostic feature of diabetes)

Question 41

What is shown here?

Answer 41

**diffuse thickening of BM** and **beginning mesangial expansion** before nodules develop (loops around the periphery of hyalinized lesions)

Question 42

What's seen on EM of DM Nephropathy?

Answer 42

**thickened BM** (about 5-8x thicker than foot) - no dense deposits

Question 43

What is seen in FM of DM Nephropathy?

Answer 43

**no immune complexes** (may have faint staining from passive absorption of Ig in nodules/BM - don't be mislead!)

Question 44

What are the characteristics of Amyloidosis?

Answer 44

**deposition of extracellular protein** in glomeruli, vessel walls, interstitium **heterogenous composition** (non-uniform consistency - there are multiple subtypes) **can be systemic** **idiopathic and secondary** **nephrotic syndrome**

Question 45

What stain is used to visualize amyloidosis?

Answer 45

congo red stain

Question 46

What is seen histologically that's unique to amyloidosis?

Answer 46

unique EM structure - **nonbranching fibrils**

Question 47

What is seen in H&E stain for amyloidosis?

Answer 47

**diffuse and irregular pink sclerotic/hyaline deposits** (not basketball like diabetes) ## Footnote **deposits not confined to glomeruli**

Question 48

What's seen in FM of amyloidosis?

Answer 48

light changes may give + immunofluorescence

Question 49

What are the key characteristics of SLE?

Answer 49

**can mimic ANY form of GN** **immune-complex mediated** **progressive** **significant morbidity and mortality** **"the wandering one"** - patients manifest differeny symptoms at different times bc different organs are infected at a time

Question 50

How is SLE diagnosed?

Answer 50

**clinical features** NOT renal biopsy

Question 51

What's the hallmark of SLE?

Answer 51

**anti-nuclear antibodies (ANA)**- explains why disease is multi-systemic (bc it can influenceANY cell that has a nucleus - chromosomal fragments bind to ANA forming complexes that get settled in the various organs)

Question 52

What is seen in H&E of SLE?

Answer 52

**membranoproliferative pattern** (proliferative nephritic) - NON DIAGNOSTIC sometimes can have crescents (\<50%)

Question 53

What's seen in FM of SLE?

Answer 53

membranoproliferative - NON DIAGNOSTIC

Question 54

What is shown here?

Answer 54

SLE - indicating that the deposits occur EVERYWHERE **subepithelial and subendothelial** - nondiagnostic

Question 55

What is shown here?

Answer 55

EM of SLE - showing that complexes can be **subepithelial**

Question 56

What is shown here?

Answer 56

EM of SLE - here showing it can be **sub-endothelial**

Question 57

What is seen in chronic glomerular disease?

Answer 57

**end stage disease!** **diffuse global GN** **diffuse tubular atrophy and interstitial fibrosis** etiology may be hard to determine (must look carefully for residual clues)