Clinical Management Of Nephrotic And nephritic Syndromes Flashcards

1
Q

Nephritic vs nephrotic syndrome

A

Nephritic

  • acute or chronic
  • reversible
  • inflammatory process with active urinary sediment
  • 3 primary symptoms:
    1) proteinuria of <2gm/dL
    2) WBCs (neutrouria)
    3) RBCs (hematuria)
    • may show RBC casts but must have glomerular disease present also
  • can show (+/-) HTN, edema, renal failure

Nephrotic

  • acute or chronic
  • noninflammatory proces
  • 3 primary symptoms:
    1) proteinuria of >3,5 bpm/dL
    2) mass edema
    3) Hypercholesterolemia with hypoalbuminemia
  • (+/-) show oval fat bodies and HTN
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2
Q

What does the term “active urinary sediment” mean?

A

Urine contains

  • proteinuria of <2gm/dL
  • RBCs >10/HPF
  • WBCs

Can contain casts also

is seen in nephritic syndrome only

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3
Q

Types of casts and associated pathology

A

Red cell casts : glomerulonephritis

White cell casts : pyelonephritis, interstitial nephritis

Waxy casts : advanced renal diseases

Hyaline casts : concentrated urine or use of diuretics only (may not be pathology)

Fatty casts = nephrotic syndrome

Granular Casts = renal failure (ATN if muddy brown)

Epithelial cell/renal tubular cell casts = ATN (acute tubular necrosis)

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4
Q

What does the term “bland urinary sediment mean”

A

Contains

  • heavy proteinuria (>3.5)
  • urine fat/oval fat bodies
  • fatty/waxy cats
  • renal tubular cells with lipid droplets
  • NO inflammation

seen in nephrotic syndrome

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5
Q

3 broad catagories of glomerulonephritis

A

1) ANCA is present
2) anti-GBM antibodies are present
3) immune complexes are present

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6
Q

What are possible causes of glomerulonephritis with ANCA bodies present

A

ANCA-associated crescentic GN:
- if there is no extra-renal symptoms

Microscopic polyangitis:
- if systemic necrotizing symptoms are present

Granulomatosis polyangitis
- if respiratory symptoms with granulomas are present

Eosinophilic granulomatosis w/ polyangitis
- if asthma and eosinophila are present

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7
Q

What are possible causes of glomerulonephritis if anti-GBM antibodies are present?

A

Goodpasture syndrome
- if lung hemorrhages are present

Anti-GBM specific GN
- if no lung hemorrhage is present

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8
Q

What are possible causes of glomerulonephritis with immune complex markers present?

A

Lupus GN
- if ANAs are present and lupus systemic symptoms

Postinfectious GN
- if recent strep/staph infection and antipathogenic antibodies are present

IgA nephropathy
- if IgA complexes are present

Cryoglobulinemic GN
- if cryoglobulins are present

MPGN
- if complement is active

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9
Q

Post infectious Glomerulonephritis (PIGN)

A

A cause of nephritic syndrome w/ low complement and primarily kidney presentation only

Almost ONLY seen in recent staph/strep infections (1-3 weeks after)
- presents with ASO antibodies if strep

Urine shows hematuria and sub nephrotic proteinuria (<3.5)

Imaging shows granular deposition of IgG and C3 in GBM
- EM will show large dense endothelial deposits (humps)

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10
Q

Membranoproliferative glomerulonephritis (MPGN)

A

Rare pattern of glomerular injury and can be seen across the entire nephritic spectrum

Can be idiopathic or associated with chronic HCV or autoimmune infections/disorders

Type 1: MOST COMMON

  • shows low C3/C4 levels in blood and urine
  • all over the spectrum (can be asymptomatic hematuria to gross hematuria to extreme proteinuria)
  • biopsy shows “tram-track” apperance with hypercellularity
  • shows C3 deposition and immunoglobulin staining on IF stains

Type 2: “dense deposit disease

  • shows low levels of C3 only in blood and urine
  • is an inherited disease
  • kidney EM biopsy shows ribbon-like electron dense deposits on the GBM
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11
Q

How do you treat type one MPGN?

A

Mild disease = ACE-I/ARB

Severe disease = cyclophosphamide or mycophenolate mofetil + steroids

even with treatment, end stage renal disease (ESRD) is very likely

type 2 treatment is novel therapies and experiment processes, no first line

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12
Q

IgA nephropathy (Berger disease)

A

Cause of nephritic syndrome with normal complement

most common primary glomerular disease worldwide

classic presentation: acute viral illness with gross hematuria/proteinuria with “coca-cola” urine

Commonly seen in females, children and Asians

Serum complement levels are NORMAL

Biopsy shows focal glomulonephritis w/ IgA and C3 depositions and proliferation

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13
Q

How to treat IgA nephropathy

A

Mild = just monitor
- NO HTN and within normal limits of GFR and minimal proteinuria

Severe: ACE-I/ARB to reduce HTN (125/75) and proteinuria (< 1g/d)

  • HTN, reduced GFR and >1g/d proteinuria
    • if this doesn’t solve it, add corticosteroids

IgA + RPGN (“crescent nephropathy”)
- treat with corticosteroids and cyclophosphamide

IgA + ESRD = renal transplant

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14
Q

Alport syndrome (hereditary nephritis)

A

X-linked nephritic syndrome with normal complement levels

Presents with chronic glomerulonephritis w/ hearing and eye issues

caused by defects in (a)-3/4 type 4 collagen subunits

Kidney biopsy shows split lamina densa of the GBM (hallmark finding)

Treatment = ACE-I/ARB
- * if ESRD is present = renal transplant, however need to be careful with risk of developing anit-GBM disease against the normal type 4 collagen seen in the transplant kidney*

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15
Q

ANCA+ w/ renal-limited glomerulonephritis

A

Cause of nephritic syndrome w/ normal compliment levels

Presents idiopathic crescentic GN and is essentially RPGN w/:

  • HTN
  • nephritic urine
  • ANCA antibodies present

Kidney biopsy shows NO immunoglobulin or compliment deposition

Treatment = cyclophosphamide and high dose corticosteroids

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16
Q

SLE

A

Is a cause of nephritic syndrome w/ low complement

Has 6 separate classes

  • 1 ) normal mesangial
  • 2) mesangial
  • 3) focal proliferative
  • 4) diffuse proliferative
  • 5) membranous
  • 6) ESRD w/ sclerosis

Treatment = aggressive high dose corticosteroids + cyclophosphamide or mycophenolate mofetil
- can also use rituximab in refractory cases

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17
Q

Cryoglobulinemia glomerulonephritis (MPGN)

A

Cause of nephritic syndrome w/ low complement and systemic presentations

Is a vasculitis with cold-precipitate immunoglobulins
- **most common underlying etiology = HCV infections

Can also be caused by underlying bacterial/viral/fungal pathogens, infective endocarditis, myeloma present

Shows high levels of rheumatoid factor, HCV antigens and polyclonal IgG complexes

18
Q

Presentation and treatment of cryoglobulinemia glomerulonephritis

A

Purpura rash with necrotizing skin lesions w/ fever, arthralgia and hepatosplenomegaly

Low complement levels with high RF present

Kidney biopsy = various patterns

Treatment = aggressive treatment of underlying cause, high dose corticosteroids, hemodialysis
- can also use rituximab, cyclosporine or mycophenolate mofetil

19
Q

What CANT you use for HCV-associated renal disease?

A

Ribavirin
- normally this can be used in HCV infections, however with renal disease, casues hemolysis and toxic effects so it is contraindicated if renal disease is also present

20
Q

Goodpasture syndrome and anti-GBM glomerulonephritis

A

Both of the above show nephrotic syndrome w/ normal complement and primary systemic presentations

  • Good pasture = has pulmonary hemorrhages
  • anti-GBM disease = NO pulmonary hemorrhages

Bimodal peak with males in ages of 20-30 yrs and 60-70yrs

**can also show HLA-DR2 and B7 antigens but always NORMAL compliment

21
Q

What is the presentation of goodpasture disease and anti-GBM disease

A

Shared:

  • sometimes starts with a URI
  • dyspnea
  • glomerular hematuria
  • proteinuria
  • minimal renal dysfunction

Goodpasture = hemoptysis and infiltrates in lungs on CXR

Treatment for both = plasmapheresis and corticosteroids and cyclophosphamide

monitor levels of anti-GBM to determine effectiveness

22
Q

Henoch-Schonlein purpura (HSP)

A

Presents mostly in children after a GAS infection
- affects skin/GI tract/joints and kidneys

Presentation:

  • GI disturbances
  • joint pains
  • erythema
  • purpura rash (especially on lower extremities)
  • hematuria

**kidney biopsy looks identical to IgA nephropathy

23
Q

What are the 3 major pathogenic causes of RPGN

A

1) anti-GBM disease/ good pasture disease
2) immune complex deposition
3) pauci-immune disorder

24
Q

Nephrotic syndrome symptoms

A

Bland urinary sediment (no casts or very few)

Heavy proteinuria >3.5g

Hypoalbuminemia <3g/dL
- causes vit D, zinc and copper deficiencies also as a side effect

Peripheral edema (usually lower extremity)
- can shows dyspnea and SOB because of this 

Hyperlipidemia (50% of patients)

Hypercoagulable state

Oval fat bodies in urine

most common cause in US is diabetes mellitus

25
Q

Why is proteinuria so high in nephrotic syndrome?

A

Serious effacement of podocytes and alteration of all 3 layers negative charges in the GBM

26
Q

What do oval fat bodies look like under microscopy?

A

Light microscopy = cluster of grapes

Polarized light = “Maltese cross”

27
Q

Why does hyperlidemia occur in nephrotic syndrome?

A

Low oncotic pressure triggers lipid production of cholesterol and apolipoprotein B

Low oncotic pressure also decreases clearance of VLDL proteins

28
Q

What are the relative contraindications for ACE-Is and ARBs?

A

Hyperkalemia

Serum creatinine rise of greater than 30%

if either of these occurs stop use.

29
Q

why shouldnt you use a statin and gemfibrozil together?

A

Causes rhabdomyolysis

30
Q

Minimal change disease

A

most common nephrotic syndrome in children and presents in 10-15% of adults

T-cell dysfunction leading to fusion in the podocytes of the glomerular capillary walls and a leaky GBM
- causes significant proteinuria

high rates seen in lithium, heavy NSAID use and lymphomas

Presentation:

  • anasarca/severe peripheral edema
  • NO HTN
  • shows fatty casts in urine
  • nephrotic proteinuria
31
Q

Treatment of minimal change disease

A

Children = high dose steroids AFTER vaccination to pneumococcus and influenzas

Adults = steroids first, then cyclosporine as needed

32
Q

Focal segmental glomerulosclerosis (FSGS)

A

Most common glomerular disease that causes ERSD
- very high rates in African Americans

Primary has 3 types:
1) heritable abnormalities in several podocyte proteins or type 4 collagen mutations

2) polymorphisms in the APOL 1 gene
3) increased levels of circulating permeable factor

Secondary can be caused by any of the following:
- HIV/AIDS, IV drug use, sickle cell disease, diabetes, HTN, bisphosphonate exposure

33
Q

Treatment of FSGS

A

Diuretics = edema

ACE-I/ARBs = proteinuria and HTN

Niacin and statin = hyperlipidemia

Steroids = inflammation

if resistant = mycophenolate mofetil or calcineurin inhibitors

34
Q

Membranous nephropathy

A

Primary MN:

  • is idiopathic and common in Caucasian males > 40yrs that are NON-diabetic
  • **70% of these patients have antiphospholipase A2 receptor (anti-PLA2R) and if so is automatically primary

Secondary MN:
- often caused by chronic infections, NSAIDS and penicillamine use, solid tumors being present and autoimmune diseases

Presentation =

  • gradually worsening nephrotic syndrome with 50% chance of having hematuria (NO RBC CASTS)
  • usually normal blood pressure
  • biopsy shows “spike and dome” pattern

**membranous nephropathy shows highest rates of renal vein thrombosis of all nephrotic syndromes

35
Q

Treatment of membranous nephropathy

A

Primary

  • may show spontaneously remission
  • treat with ACE-I/ARB if high proteinuria
  • use corticosteroids + cyclophosphamide if it doesn’t spontaneously remiss and ACEI/ARB is not enough

Secondary = treat cause

36
Q

What signs often signify a renal vein thrombosis?

A

Flank pain that is out of proportion

Hematuria

High LDH levels

37
Q

What are the multifactorial risks of diabetic nephropathy?

A

Age at diagnosis

Genetics

Race (increased in African Americans/Hispanics/natives)

Blood pressure

GFR (high GFR in first 5 yrs = higher risk)

Glycemic control

Being obese

Oral contraceptive use

38
Q

What is the visual hallmark in renal biopsy for diabetic nephropathy?

A

Kimmelstiel-Wilson lesion

- expansion of mesamngium with thickening of GBM and nodular sclerosis

39
Q

Treatment and presentation of the two stages of diabetic nephropathy

A

1) silent/preclinical phase
- microalbuminema (30mg albumin:1g creatinine in urine) is present w low to no change in renal function

Treatment = ACEI/ARB and stress strict glycemic control

2) clinical phase
- shows proteinuria, HTN and renal function loss as well as other diabetic systemic symptoms

Treatment = ACEI/ARB and possible renal transplant

40
Q

Multiple myeloma (MM)

A

Shows hence-jones proteins in urine and tubule casts in urine
- also shows negative on urine dipstick but positive proteinuria in the lab samples

Can cause nephrotic syndrome

41
Q

Primary vs secondary amyloidosis

A

Both can present with nephrotic syndrome

Primary:

  • nephrotic syndrome with renal failure
  • shows “apple green” birefringence crystals on biopsy
  • often occurs with multiple myeloma if MM is present (doesnt need it though)
  • 5 yr survival = <20%

Secondary:

  • seen in chronic inflammatory states (RA/MFM/reactive arthritis/scleroderma/etc.)
  • shows recurrent skin and ST infections with new onset carpel tunnel syndrome and heart failure.
42
Q

What nephrotic syndromes should you NOT use steroids for?

A

Diabetes induced nephrotic

Amyloidosis induced nephrotic