Clinical Management Of Nephrotic And nephritic Syndromes Flashcards
Nephritic vs nephrotic syndrome
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
What does the term “active urinary sediment” mean?
Urine contains
- proteinuria of <2gm/dL
- RBCs >10/HPF
- WBCs
Can contain casts also
is seen in nephritic syndrome only
Types of casts and associated pathology
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)
What does the term “bland urinary sediment mean”
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
3 broad catagories of glomerulonephritis
1) ANCA is present
2) anti-GBM antibodies are present
3) immune complexes are present
What are possible causes of glomerulonephritis with ANCA bodies present
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
What are possible causes of glomerulonephritis if anti-GBM antibodies are present?
Goodpasture syndrome
- if lung hemorrhages are present
Anti-GBM specific GN
- if no lung hemorrhage is present
What are possible causes of glomerulonephritis with immune complex markers present?
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
Post infectious Glomerulonephritis (PIGN)
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)
Membranoproliferative glomerulonephritis (MPGN)
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
How do you treat type one MPGN?
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
IgA nephropathy (Berger disease)
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
How to treat IgA nephropathy
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
Alport syndrome (hereditary nephritis)
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*
ANCA+ w/ renal-limited glomerulonephritis
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
SLE
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
Cryoglobulinemia glomerulonephritis (MPGN)
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
Presentation and treatment of cryoglobulinemia glomerulonephritis
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
What CANT you use for HCV-associated renal disease?
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
Goodpasture syndrome and anti-GBM glomerulonephritis
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
What is the presentation of goodpasture disease and anti-GBM disease
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
Henoch-Schonlein purpura (HSP)
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
What are the 3 major pathogenic causes of RPGN
1) anti-GBM disease/ good pasture disease
2) immune complex deposition
3) pauci-immune disorder
Nephrotic syndrome symptoms
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
Why is proteinuria so high in nephrotic syndrome?
Serious effacement of podocytes and alteration of all 3 layers negative charges in the GBM
What do oval fat bodies look like under microscopy?
Light microscopy = cluster of grapes
Polarized light = “Maltese cross”
Why does hyperlidemia occur in nephrotic syndrome?
Low oncotic pressure triggers lipid production of cholesterol and apolipoprotein B
Low oncotic pressure also decreases clearance of VLDL proteins
What are the relative contraindications for ACE-Is and ARBs?
Hyperkalemia
Serum creatinine rise of greater than 30%
if either of these occurs stop use.
why shouldnt you use a statin and gemfibrozil together?
Causes rhabdomyolysis
Minimal change disease
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
Treatment of minimal change disease
Children = high dose steroids AFTER vaccination to pneumococcus and influenzas
Adults = steroids first, then cyclosporine as needed
Focal segmental glomerulosclerosis (FSGS)
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
Treatment of FSGS
Diuretics = edema
ACE-I/ARBs = proteinuria and HTN
Niacin and statin = hyperlipidemia
Steroids = inflammation
if resistant = mycophenolate mofetil or calcineurin inhibitors
Membranous nephropathy
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
Treatment of membranous nephropathy
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
What signs often signify a renal vein thrombosis?
Flank pain that is out of proportion
Hematuria
High LDH levels
What are the multifactorial risks of diabetic nephropathy?
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
What is the visual hallmark in renal biopsy for diabetic nephropathy?
Kimmelstiel-Wilson lesion
- expansion of mesamngium with thickening of GBM and nodular sclerosis
Treatment and presentation of the two stages of diabetic nephropathy
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
Multiple myeloma (MM)
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
Primary vs secondary amyloidosis
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.
What nephrotic syndromes should you NOT use steroids for?
Diabetes induced nephrotic
Amyloidosis induced nephrotic
