Path - Nephrotic Syndrome II Flashcards by Abteen Moshref

Name 2 main podocyte disorders?

1) Minimal change disease,
2) Focal segmental glomerulosclerosis

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Another name for podocyte?

Visceral epithelial cell

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Most important prognostic indicator of nephrotic syndrome?

Degree of proteinuria

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Minimal Change Disease Facts.

age distribution?

Most common cause of nephrotic syndrome in?

Blacks or whites?

Bimodal age distribution

Most common cause of Nephrotic Syndrome in children

More common in da whites

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Minimal Change Disease facts

Describe edema, blood pressure, and renal function?

Insiduous onset of edema

Blood pressure usually normal

Renal function usually normal

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Minimal Change disease facts.

Describe type of proteinuria?

Highly selective for albumin

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Primary cause of minimal change disease? Secondary causes?

Primary: Idiopathic

Secondary:

Malignancy (Hodgkin’s lymphoma)
Drugs: NSAIDS, interferon alpha

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Minimal Change disease pathology

Describe light microscopy findings.

Describe electron microscopy findings

Describe immunofluoresence findings

Light microscopy = normal

Electron microscopy = effacement/fusion and detachment of foot processes

Immunofluoresence = normal (no immune complex deposition)

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What type of nephrotic syndrome is this? What does the blue arrow show? What does the red arrow show?

Minimal change disease. Blue = effacement/fusion, Red = detachment

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Supportive therapy for MCD?

Disease modifier for MCD? Describe the difference in treatment in children vs adults

Supportive = control HTN via ACEI/ARB

Disease modifier = Oral glucocorticoids, >90% excellent response in children. Response to steroids in adults is slow

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Is recurrence common in MCD?

Yes

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If patients have poor response to steroids in MCD, what should you suspect?

In children, look for another cause. However, poor response could also indicate that patient has progressed to FSGS(which has a poor response to steroids)

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Name the 2 main differences between minimal change disease and focal segmental glomerulosclerosis?

FSGS causes:

HTN, 2. impaired renal function

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FSGS facts.

More common in adults or children?

More common in what race(s)?

More common in adults

More common in blacks and hispanics

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FSGS facts

Describe proteinuria

Proteinuria = nonselective

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50% of patients with FSGS develop what worsening disorder? How long does this take?

50% develop end stage kidney disease within 10 years of diagnosis

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What is suPAR? What disease is it associated with? What does it do?

suPAR = soluble urokinase type plasminogen activity receptor. Associated with FSGS

Binds to and activates Beta3 Integrin, causing podocyte dysfunction and effacement, leading to proteinuria

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FSGS causes:

What 4 familial mutations?

What 2 infections?

What drugs?

Anything else cause it?

4 familial mutation are alpha-actinin 4, podocin, TRPC6, and Apolipoprotein L1 gene

2 infections are HIV, parvovirus

Drugs include pamidronate, heroin, lithium

Adaptive structural functional response: loss of nephron mass (as in a patient who had renal cancer)

Pathoma also mentions sickle cell disease

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Variant apolipoprotein L1 prevents against what?

Variant APOL1 increases resistance to african sleeping sickness (trypanosome).

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Variant APOL1 increases risk of developing what 3 disorders?

HIV nephropathy, hypertensive nephropathy, & FSGS

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I’m stupid. What does focal segmental glomulerosclerosis actually mean in terms of glomerular involvement? (focal? segmental?)

Focal = only some of the glomeruli (i.e 1 out of 3)

Segmental = only part of the 1 glomeruli (i.e. 2/3 of 1)

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Most common cause of nephrotic syndrome in children?

Minimal change disease

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What is hyalinosis? What disease process is it commonly associated with?

Hyalinosis = accumulation of leaked plasma proteins and lipids. Associated with FSGS

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What disease process is shown here? What does the green arrow indicate? What do the black arrows (hard to see) indicate?

FSGS, green arrow = large hyalinosis. Black arrows = small hyalinosis

Hyalinosis = accumulation of leaked plasma proteins and lipids

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What do the 2 arrows indicate? What glomerular disease?

FSGS, Top left black arrow indicates microscopic adhesions (of involved segment) to bowman's capsule Bottom arrow shows hyalinosis

Describe light microscopy of FSGS

"Scarring" obliterated capillary lumen areas of adhesion to bowman's capsule

Describe immunofluorescence pattern of FSGS.

No immune complex deposition = no immunofluorescence. Dont forget this rule

Describe electron microscopy of FSGS?

Foot processes effacement/fusion and detachement, just like MCD

What are the subtypes of FSGS (5)? Which one has the worst renal survival? Which has best prognosis?

1) Collapsing - 11%, heavier proteinuria, worst renal survival 2) Cellular - 3% 3) Tip - 17%, heavier proteinuria, more likely to obtain remission (best prognosis) 4) Perihilar - 26% 5) Not otherwise specificied = 42%

Collapsing FSGS. Describe rate of onset of nephrotic syndrome and rate of progression to renal failure.

Collapsing FSGS has a **rapid onset of nephrotic syndrome** and **rapid progression to renal failure** Buzzword: RAPID

HTN in FSGS, primary site of involvement (vascular or urinary pole)? is this common?

If primary site = vascular pole, think HTN (this type of involvement is not common)

If urinary pole is primary site affected in FSGS, what is the prognosis? What subtype is this referring to?

Good prognosis (increased chance of remission) = TIP subtype

Supportive measures of FSGS?

Control blood pressure via ACEI/ARB, treat the hyperlipidemia

Most common disease modifier in FSGS? Are they effective? Another option is?

Corticosteroids most commonly used, but response is poor. Other options included calcineurin inhibitors (cyclosporine or tacrolimus) Combo of both = best treatment option, but calcineurin inhibitor can cause nephrotoxicity

Steroid sensitive nephrotic syndrome. Is this minimal change disease or FSGS? Prognosis?

minimal change disease, prognosis is good

Steroid resistant nephrotic syndrome. Minimal change disease or FSGS? Prognosis?

FSGS, Bad prognosis

What 2 nephrotic syndromes are associated with subepithelial deposits?

Post infectious glomerulonephritis, membranous nephropathy

Most common cause of nephrotic syndrome in da whites?

membranous nephropathy

Name the 2 common fixed antigens in membranous nephropathy. Which is associated with primary MN? Which is associated with congenital MN

PLA2R= M-type phospholipase A2 receptor = (primary MN) NEP = Neutral endopeptidase = congenital MN

Main antigen in primary membranous nephropathy?

PLA2R (M-type phospholipase A2 receptor)

Main antigen in congenital membranous nephropathy?

NEP (neutral endopeptidase) antigen

NEP and PLA2R are recognized by what antibody? Describe this mechanism?

PLA2R and NEP (not shown in picture) are expressed in normal podocytes. However, in primary (PLA2R) and congenital (NEP) MN, IgG4 recognizes these antigens, causing immune complex deposition in the subepithelial space

Membranous nephropathy etiology. What infections can cause it?

Hep B or C, Syphilis, Malaria

Membranous nephropathy etiology. What autoimmune disease can cause it?

SLE (systemic Lupus erythematosus)

Membranous nephropathy etiology. What drugs can cause it?

Gold (yes gold), penicillamine, Captopril, NSAID

Membranous nephropathy etiology. What malignancies can cause it?

Lung cancer, colon cancer, melanoma

Clinical correlation. Patient over 50 diagnosed with membranous nephropathy. What should you check for?

Patient could possibly have a malignancy. Check for signs of lung cancer, colon cancer, melanoma, etc

Diagnosed with membranous nephropathy, what are the 3 main prognostic paths? Which is most likely?

Spontaneous resolution (30%) Progression to renal failure (40%) Persistant proteinuria with variable renal dysfunction (30%). This just means they dont get better or worse

What 6 risk factors indicate that patient is more likely to develop end stage renal disease as a result of membranous nephropathy? Does a patient need all of these factors?

1. Male gender 2. \> 10 grams proteinuria/24 hours 3. HTN 4. Azotemia 5-6 on renal biopsy you see tubulointerstitial fibrosis and glomerulosclerosis - Can have some or all to be at higher risk

What disease process is shown here? Key features of it?

Membranous nephropathy, Thickened basement membrane **without** increased cellularity. Also know subepithelial deposits (spike and dome seen on EM)

Treament of membranous nephropathy is based on what feature?

Degree of proteinuria (\< or \> 4 grams of proteinuria)

Treatment of MN. If \< 4 grams proteinuria, what is the treatment plan?

Supportive therapy for HTN (use ACEI/ARB)

Treatment of MN if proteinuria \> 4 gm?

Supportive therapy (ACEI/ARB) + cytoxic agents (steroids/calcineurin inhibitors)

Patient has upper respiratory tract infection and develops gross hematuria within the same week. Is this IgA nephropathy or post infectious glomerulonephritis? Distinguish the two

IgA nephropathy (a type of nephritic syndrome) will have URI and hematuria around the same time; however, in post infectious glomerulonephritis, patient will not develop hematuria until a couple weeks after their URI symptoms. KNOW THIS DIFFERENCE

Buzz word. "tea or cola colored urine" What disorder?

Post infectious glomerulonephritis

3 most common types of infection preceding post infectious glomerulonephritis? Which is now thought to be the most common?

Upper respiratory tract infection, skin infection, or sepsis. Sepsis is now thought to be more common than URI in patients that develop PIGN (post infectious glomerulonephritis)

Lab findings in PIGN (post infectious glomerulonephritis) Describe complement levels? Reason for these levels?

**Low C3 and normal C4 levels** (indicating alternative pathway activation in immune complex vs capillary walls).

Lab findings in PIGN (post infectious glomerulonephritis) Finding indicating preceding throat infection?

Elevated anti-streptolysin O (ASO) titers

Lab findings in PIGN (post infectious glomerulonephritis) Skin infection causes what lab finding?

Elevated Anti-DNAse B titers

Lab findings in PIGN (post infectious glomerulonephritis) Sepsis patient?

Positive blood cultures

Pathologic findings of post infectious glomerulonephritis Light microscopy shows?

Diffuse endocapillary proliferatiion and infiltration of numerous neutrophils

Pathologic findings of PIGN Immunofluorescence findings? What 2 immunologic markers are common

Diffuse granular deposits in capillary walls and mesangium (**especially IgG and C3)**

Pathologic findings in PIGN Electron microscopy shows?

**Buzzword: dome shaped subepithelial humps**

Supportive treatment for PIGN? Prognosis of infection treatment?

Supportive: Control HTN with anti-hypertensives and diuretics Good prognosis for treatment of infection