Nephrotic Syndromes Flashcards
MCD presentaiton and etiology
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
Patho of MCD
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
MCD on microscopy
LM - normal histology
IF- negative…just pdocotye injury
EM - widespread foot process effacement due to pdocyte injury and swelling
Tx of MCD
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
FSGS
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
Types of FSGS
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
FSGS genetic/familai
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
FSGS microscopy
LM - segmetal areas of slcerosis
IF - negative
EM - foot process effacement
FSGS collapsing variant
Retraction of glomerlar tuft and narrowing of cap limens
Hypertrophy and hyperplasia of visceral epithelial cells
May be idiopathic of HIV infection associated
Primary FSGS tx
Take care of HTN, etc with ACEI and ARBs
In idiopathic - LT CSs
Second line - cyclosporine A or cyclophosphamide…maybe MM
MN on microscopy
Thick GMB covered with a thin layer like a “membrane”
Produced by immune complex deposition
DEf of MN
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
COnditions associated with MN (seocndaery MN)
IMmune dz
INfections
Drugs/toxins (gold, penicillamine, NSAID)
Malignancy
MN microscopy
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
Diff between MN and MPGN
MN - non-smooth peripheral
MPGN - smooth peripheral
MN tx
ID possible cause - malignancy over 50
Spontaneous remission in 30%
Use cyclophosphamide or cyclosporine A
Can use ACTH or rituxmiab in refractory
Most common in ages
MCD - most comm in pediatrics
Young and middle age - just about all
MN - highest in old and middle age
FSGS - think african amercians
Hemodynamic and metabolic pathways of DN
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
Risk factors for DN
Genetics (AA, Mexican, native americans)
Poor glucose control
HTN, obesity, smoking
DN microscopy
Nodular mesnagial expansion +/- thick cap walls and arteriolar hyalinosis
IF - neg
EM - thick GBM with diffuse or nodular mesangial expansion
Why is the GBM so thick in DN
Because higher pressure leadsto higher collagen depositon
DN managmenet
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
Amyloidosis
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
AL-amyloidosis
More lambda than kappa…plasma cell
MM associated
Cardiomyopahty (L loves heart) Macroglossia Peripheral neuropahy Proteinuria Elevated creatinine with enlarged kindey
AA
Seoncdary to chornic inflammation
Proteinuria, GI sx and no heart involvement
Tissue dx of amyoidisis
Faint, eosinophilic granules in the glomerulus
Apple greeen - congo red staining under polarized light
Fibirls on EM
Tx of amyloidosiss
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
