Nephrotic Syndromes

Question 1

MCD presentaiton and etiology

Answer 1

Minimal change disease

Heavy proteinuria and severe edema

Usually normal BP and NO hematureia

Most in children under 10…idiopathic

Hx of allergic rxn

Drugs - NSAIDs and alpha IFN

Malignancy from lymphproliferative disorders

Question 2

Patho of MCD

Answer 2

Injury to podocyte

Loss of GBM neg charge

T cell involvement associated with too much IL-13 and sensitivitu to CSs

Presence of circulating factors

Question 3

MCD on microscopy

Answer 3

LM - normal histology

IF- negative…just pdocotye injury

EM - widespread foot process effacement due to pdocyte injury and swelling

Question 4

Tx of MCD

Answer 4

Steroid-responsive

If relapse during CS reudction - CS dependent

If 2 ralpses in 6 mos - frequently relapsiing

Some are steroid resistant

Long-term prognosis is excellent

Resistant tx with cyclosporine A or retuximab

Question 5

FSGS

Answer 5

Not all glomeruli and only a portion of the glomerulus…collagne accumulation with increased ECM…no cell proliferation

Patho - pdocytopathy

Often neprhotic range proteinuria but could be less

Microscopic hematuria and HTN may be present (unike MCD)

Most common in african americans

Question 6

Types of FSGS

Answer 6

Idiopathic - due ot circulating permeability factors…after transplant…positive suPAR

Familial - mutations in podocyte protens

Viral - HIV

Durg induced - pamidronate, heroin, IFN

Maladaption to reduced nephron number or hyperfiltration of nephrons - unilateral renal agenesis, reflux neprhopathy, morbid obesity/sleep apnea

Question 7

FSGS genetic/familai

Answer 7

Neprhin - NPHS 1 on chromosome 19…responsible for congenital of FInnihs type

Podocin - NPHS2…chromosome 1…auto rec from steroid resistant of childhood onset

Mutations in alpa-actin-4…auto dom FSGS with high rate of progression to renal insufficiency

Question 8

FSGS microscopy

Answer 8

LM - segmetal areas of slcerosis

IF - negative

EM - foot process effacement

Question 9

FSGS collapsing variant

Answer 9

Retraction of glomerlar tuft and narrowing of cap limens

Hypertrophy and hyperplasia of visceral epithelial cells

May be idiopathic of HIV infection associated

Question 10

Primary FSGS tx

Answer 10

Take care of HTN, etc with ACEI and ARBs

In idiopathic - LT CSs

Second line - cyclosporine A or cyclophosphamide…maybe MM

Question 11

MN on microscopy

Answer 11

Thick GMB covered with a thin layer like a “membrane”

Produced by immune complex deposition

Question 12

DEf of MN

Answer 12

Subepithelial immune deposits of IgG and C3

AI dz cause by autoantibodies to podcyte membrane

AB to PLAR have been ID’d

Most common cause of nephrotic in adults

Serum complemtn levels are usually NORMAL

Question 13

COnditions associated with MN (seocndaery MN)

Answer 13

IMmune dz
INfections
Drugs/toxins (gold, penicillamine, NSAID)
Malignancy

Question 14

MN microscopy

Answer 14

Thick glomerular cpaillary wall with spikes in BM which are areas of normal GMB between immune complexes

Granular capillary wall IgG and C3

Diffuse subepithelial electorn dense deposits

Question 15

Diff between MN and MPGN

Answer 15

MN - non-smooth peripheral

MPGN - smooth peripheral

Question 16

MN tx

Answer 16

ID possible cause - malignancy over 50

Spontaneous remission in 30%

Use cyclophosphamide or cyclosporine A

Can use ACTH or rituxmiab in refractory

Question 17

Most common in ages

Answer 17

MCD - most comm in pediatrics

Young and middle age - just about all

MN - highest in old and middle age

FSGS - think african amercians

Question 18

Hemodynamic and metabolic pathways of DN

Answer 18

Hemo - glomerular HTN and hyperinfiltration…glucose, IGF1, glucagon, NO, AII, TGF-beta, sorbitol, and AGE all implicated

Met - AGEs stimulate growth factors expressed by mesangial cells

Question 19

Risk factors for DN

Answer 19

Genetics (AA, Mexican, native americans)

Poor glucose control

HTN, obesity, smoking

Question 20

DN microscopy

Answer 20

Nodular mesnagial expansion +/- thick cap walls and arteriolar hyalinosis

IF - neg

EM - thick GBM with diffuse or nodular mesangial expansion

Question 21

Why is the GBM so thick in DN

Answer 21

Because higher pressure leadsto higher collagen depositon

Question 22

DN managmenet

Answer 22

Optimize glycemic control

Moderate protein restriction

ACEI/ARB - microalbuminuria

BP control

Aggressive managment of CV risks

Prepare for RRT as GFR appraoches 20 ml/min

Question 23

Amyloidosis

Answer 23

Beta - alzehimer
L - light chain in primary
A - secojndary (acute phase reactant protein)…think inflammatory dz that is not tx

Glumerulus is target for AL and AA despotion

Depositon leads to proteinuria and neprhotic syndrome

Question 24

AL-amyloidosis

Answer 24

More lambda than kappa…plasma cell

MM associated

Cardiomyopahty (L loves heart)
Macroglossia 
Peripheral neuropahy 
Proteinuria 
Elevated creatinine with enlarged kindey

Question 25

AA

Answer 25

Seoncdary to chornic inflammation

Proteinuria, GI sx and no heart involvement

Question 26

Tissue dx of amyoidisis

Answer 26

Faint, eosinophilic granules in the glomerulus

Apple greeen - congo red staining under polarized light

Fibirls on EM

Question 27

Tx of amyloidosiss

Answer 27

AL - survival about 10 mos…due to cardiac involvement

Chemo

Stem cell transplant

AA - 130 months…death due to infection…tx the underlying inflammatory condition