Nephrotic Syndrome 2 Flashcards
What are the 2 podoctyopathies?
minimal change disease and focal segmental glomerulosclerosis
Who usually gets minimal change disease?
very young and very old - bimodal distribution
What is the most common cause of nephrotic syndrome in kids?
minimal change disease
What other clinical findings are common in minimal change disease?
- insidious onset of edema
- normal blood pressure
- usually normal renal function
- highly selective proteinuria - albumin
What is thought to be the pathogenesis for minimal change disease?
not clear but thought to be mediated by a T cell that secretes a circulating permeability factor that causes podocyte damage
What is seen w/ minimal change disease for pathology?
effacement and detachment of foot processes
What is the treatment for minimal change disease?
oral glucocorticoids
Who responds well to steriods in minimal change disease?
kids
If there is a poor response to steroids what should be done?
- look for other cause (especially in children)
2. unsampled focal segmental glomerulosclerosis
What are some clinical findings for focal segmental glomerulosclerosis?
- high BP
2. low albumin –> proteinuria
How many of the pts w/ focal segmental glomerulosclerosis develop end stage kidney disease?
50%
What is Supar?
the circulating factor that binds to beta2 integrin and causes effacement of podocytes
What are some secondary causes of focal segmental glomerulosclerosis?
- familial – mutation in genes alpha-actinin-4, podosin, TRCP6, and APOL1
- infection - HIV or Parvo virus
- drugs - pamidronate, heroin, Li
- Loss of nephron mass
Why are people of African descent susceptible to getting focal segmental glomerulosclerosis?
b/c 40% of them have mutations in APOL1 making them susceptible to African sleeping sickness
Why does hyalinosis occur in FSG?
accumulation of leaked plasma proteins and lipids
T or F. Adhesion of involved segment to Bowman Capsule does occur in FSG?
T
What are subtypes of FSG?
- collapsing
- cellular
- tip
- Perhiliar
- not otherwise specified (42%)
Which of the subtypes of FSG will most likely obtain remission?
Tip
What is found in the collapsing type of FSG?
collapsed BM and adhesions common
What shows up on immunofluoresence for FSG?
nothing really
What is the treatment for FSG?
sterois and immunosuppressive
what immunosuppressive drugs are used for FSG?
calcinuerin inhibitors – cyclosporine and tacrolimus
What is steroid sensitivity for FSG?
- Steroid Sensitive - proteinuria remits w/ treatment and means good prognosis
- Sterois resistant - proteinuria persists and means bad prognosis
What happens to repeated relapses of Minimal change disease in children w/ steroid responsive nephrotic syndrome?
may develops into FSG secondar to repreated renal injury
What is the filtered cationic Ag formation of membranous nephropathy?
deposits from circulation cross endothelium and GBM and localize in the subepithelial spaces, then Abs localize and cause nephritis
What is the Autoimmunity model of in-situ formation of membranous nephropathy (MN)?
locally generated Ag and filtered AutoAb
What are examples of autoimmunity model?
- M-type Phospholipase A2 Recepto (PLA2R) – Primary MN
2. Neutral endopeptidase (NEP) - target Ag in congentical MN
How is PLA2R involved in primary MN?
- expressed by podocytes in normal human glomeruli
- found to be co-localized w/ IgG4 in immune deposits in glomeruli of patients w/ idiopathic MN
What are some secondary diseases taht MN is associated w/?
- infection - Hep B, syphilis, Malaria
- Autoimmune - SLE
- Drugs - Gold, penicillamine, captopril, NSAID
- Malignancy - lung cancer, colon cancer, melanoma
What is the most common cause of nephrotic syndrome in Caucasian adults?
Membranous nephropathy
What is the epidemiology of MN?
- peaks in 4th to 6th decades
- males commonly affected
What happens to pts w/ MN?
- spontaneous resolution in 30%
- progressive renal failure in 40%
- presistent proteinuria w/ variable renal dysfuntion in 30%
What are risk factors for loss of renal function in MN?
- male
- > 10g/24 hrs of proteinuria
- HTN
- Azotemia
- Tubulointerstitial fibrosis
- glomerulosclerosis
What do you see on light microscopy for MN?
thickened BM w/out increased cellularity
What do you see w/ immunofluorescence in MN?
granular deposits of IgG and complement
What would you see on electron microscopy for MN?
diffusely thickened BM w/ subepithelial deposits separated by spikes of new GBM –> spike and dome pattern
Is there inflammation found in MN?
no – remember it’s nephrotic! complement that you see is activated at a site that is not in contact w/ circulating inflammatory cells
What happens if MN is secondary to another disease?
resolution of subepithelial depotis is slow w/ concomitant slow resolution of proteinuria – up to 2 yrs
What is the likely mechanism for the retraction and effacement of podocyte foot processes in subepithelial deposits?
-complement dependent process mediated by MAC and intermediary chemotactic fragments are washed away into urinary space
What are the clinical findings w/ post-infectious glomerulonephritis? (PIGN)
- usually associated w/ recent infection
- gross hematuria
- HTN common
- signs of fluid retention –peripheral edema, ascites
- proteinuria
- impaired renal function
What are the lab result findings for PIGN?
- low C3 and C4
- elevated anti-streptolysin O titers if preceded by throat infection
- elevated anti-DNAse B titers if preceded by skin infection
- positive blood culture in sepsis
What is seen on light microscopy for PIGN?
- diffuse endocapillary proliferation and infiltration by numerous PMNS
What is seen on immunofluorescence for PIGN?
diffuse grandular deposits in capillary walls and mesangium (IgG and C3)
What is seen on EM for PIGN?
subepithelial humps
What are supportive measures for PIGN?
- control HTN w/ antihypertensives and diuretics
- renal replacement therapy if sever kidney dysfunction
- treat infection
How long does it take to resolve the HTN?
a few weeks
How long to get normal C3 levels
6 wks
how long to resolve hematuria
w/in 12 months
Summary – What is seen w/ the different kidney biopsies for minimal change disease?
LM- normal
Immuno - normal
EM - podocyte foot process fusion
Summary – What is seen w/ the different kidney biopsies for focal segmental glomerulosclerosis?
- LM - scarring and adhesion to Bowman’s Capsule
- Immuno - normal
- EM - podocyte foot process fusion
Summary – What is seen w/ the different kidney biopsies for MN?
LM - diffuse thickening of glomerular BM w/ normal cellularity
Immuno - fine granular w/ IgG and complement
EM - subepithelial deposits
Summary – What is seen w/ the different kidney biopsies for PIGN?
LM- proliferation , inflammation
Immuno- granular deposition of C3 and IgG
EM - subepithelial humps
