Approach to Nephrotic & Nephritic
Syndromes
Academic Half-Day
Aug 2, 2012
Nephrology
Olympics!
Name two NBA
athletes with
Nephrotic Syndrome
Proteinuria
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Some protein in urine is normal (< 4mg/m2/hr or < 100
mg/m2/24h)
Non-pathologic
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Postural (orthostatic)
Febrile
Exercise-induced
Pathologic
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Tubular
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Inherited (cystinosis, Wilson ds, Lowe syndrome)
Acquired (antibiotic, AIN, ATN, heavy metal poisoning)
Glomerular
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Gross
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Hematuria
Trauma - perform imaging and cystoscopy
Pain - rule out renal stones, mass, UTI
Painless - consider stones, mass, HSP, familial
(thin BM), hematologic, other glomerular disease,
systemic disease
Microscopic
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Symptomatic - symptoms direct investigation
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Asymptomatic hematuria and proteinuria - more
worrisome, requires thorough evaluation by
nephrology.
Isolated hematuria - rarely have significant renal
disease (benign familial hematuria or
hypercalciuria)
Edema
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Differential diagnosis
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Loss of oncotic pressure
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increased protein loss
Increased capillary permeability
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decreased protein synthesis
viral/bacterial
immune mediated
mechanical/thermal trauma
drugs
Increased hydrostatic pressure
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congestive heart failure
lymphatic blockage
What is the term for
extreme, generalized
edema?
ANASARCA
Golmerular Disease
• Presents in one of 4 ways:
• Acute Nephritic Syndrome
• Nephrotic Syndrome
• Rapidly Progressive
Glomeruloneprhitis
• Asymptomatic
Nephrotic Syndrome
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Nephrotic range proteinuria
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3+ or 4+
> 250 mg/mmol creatinine
> 40 mg/m^2/hr
Hypoalbuminemia
Hyperlipidemia
Hypercoagulable
Pathophysiology
Glomerular Filtration Barrier
NEPHROLOGY AND INFECTIOUS DISEASE!
What is this fictional doc’s
specialty?
Etiology
• Primary or idiopathic
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Minimal change disease
FSGS
MPGS
Membranous nephropathy
Minimal Change
Disease
85% of cases
FSGS
10-15% of cases
Membranous
Nephropathy
4% of cases
In what event did this athlete win
a bronze medal?
100m freestyle
Etiology
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Secondary causes
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Genetic
Metabolic
Infections
Drugs
Immunologic/Allergic
Malignancy
Glomerular hyperfiltration
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Idiopathic Nephrotic
Syndrome
90% of childhood nephrotic syndrome
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85% of all cases due to MCD
Consider diagnosis other than MCD in:
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Children < 1 year and > 10 years
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Extra-renal findings
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More than minimal hematuria
Family history nephrotic syndrome
Idiopathic Nephrotic
Syndrome
• Clinical manifestations:
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Most common between age 2 and 6.
Often follows minor infection.
Mild edema progressing to generalized.
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Ascites
Pleural effusions
Genital edema
Anorexia, abdo pain, diarrhea, irritability
common.
What food item is known
scientifically as Phaseolus
vulgaris?
Diagnosis
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Laboratory findings
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Low serum albumin
High cholesterol, triglycerides, lipoproteins
Low serum sodium
Nephrotic range proteinuria
Indications for biopsy:
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Age > 10, gross hematuria, hypertension
Renal insufficiency
Low C3 complement value
Persistent proteinuria following 4 week course of steroids
Treatment
• Prednisone drug of choice.
• Dose: 60 mg/m^2 per day divided TID
• Continue daily for 4 weeks, then
40mg/m^2 as single dose on alternate
days for 4 weeks.
• 90% of MCD is steroid responsive
• Of those, 60% relapse
• Frequent relapsers can be treated with
cyclophosphamide
Steroid-resistance
• Up to 10% of all children with NS
• Poor prognosis
• Eventually leads to dialysis and renal
transplant
Complications of Nephrotic
Syndrome
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Thromboembolic events
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Loss of antithrombin III and protein S
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Increase in fibrinogen concentration
Infection
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Loss of factor B, low IgG, impaired Tcell function
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Most common infection is peritonitis
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Most common organisms are Strep pneumo or gramnegatives
Steroid side effects
Where did this duo rank in
badminton at the 2012 Olympics?
DISQUALIFIED for CHEATING!
Nephritic Syndrome
• Results from inflammation within
glomerulus
• Characterized by
• Hematuria, RBC casts, dysmorphic
RBCs
• Mild to moderate proteinuria
• Azotemia, oliguria
• Hypertension
Etiology
Low complement
Normal complement
Primary
Postinfectious GN
Membranoproliferative
GN
IgA nephropathy
Anti-GBM disease
Secondar
y
SLE
Endocarditis
Abscess
Cryoglobulinemia
Polyarteritis nodosa
Wegener’s
HSP
Goodpasture’s
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Rapidly Progressive
Glomerulonephritis
Subset of nephritic syndrome
Medical emergency
Characterized by renal failure in days or weeks (months)
Classfication:
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Type I - anti-GBM (idiopathic, Goodpasture’s)
Type II - immune complex (PIAGN, SLE, HSP)
Type III - pauci-immune (idiopathic, Wegener’s, microscopic
polyangitis, drugs)
Treatment
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Induction of remission (pulse steroids, cyclophosphamide 3-6
months)
Maintenance therapy (azathioprine)
Newer agents - Rituximab, MMF
Crescent
BAD NEWS.
IgA Nephropathy
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Most common cause of GN
Idiopathic or secondary (HSP, rheumatic ds, HIV, Celiac ds,
chronic liver ds)
Variable presentation:
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Asymptomatic hematuria and mild proteinuria
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Recurrent episodes of gross hematuria
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Nephrotic range proteinuria or RPGN
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Hematuria coincident with URTI
Treatment depends on prognostic indicators
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Watch & wait vs. immunosuppressive agents
Poststreptococus
glomerulonephritis
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Prototypic acute nephritic syndrome
Occurs 2-3 weeks after pharyngitis or skin infection with GAS
(nephritogenic strain)
Typical history plus low C3, normal C4, and high ASOT, positive antiDNase B
Self-limited disease - three phases
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latent phase
acute phase
recovery phase
Supportive management of hypertension and edema
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Indications for biopsy include normal complement level, failure to
document strep infection, GFR < 30ml/min/1.73 m2
How much does the
average adult kidney
weigh?
120-140 grams!
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References
Gordillio, R. and Spitzer, A. The Nephrotic Syndrome. Pediatr Rev, 2009;30: 94-105.
Beck, L. and Salant, D. Glomerular and Interstitial Diseases. Prim Care Clin Office Pract
2008;35:265-296.
Bergstein, J. A Practical Approach to Proteinuria. Pediatr Nephrol 1999;13:697-700.
Massengill, S. Hematuria. Pedatr Rev 2008;29:342-348.
Pais, P. and Avner, E. Nephrotic Syndrome. Nelson’s Textbook of Pediatrics, Ch 52:18011806.
Eison, T., Ault, B., and Jones, D. Post-streptococcal cute glomerulonephritis in children:
clinical features and pathogenesis. Pedatr Nephrol 2011;16:165-180.