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Approach to Nephrotic & Nephritic Syndromes
Academic Half-DayAug 2, 2012
Nephrology Olympics!
Name two NBA athletes with
Nephrotic Syndrome
Proteinuria• Some protein in urine is normal (< 4mg/m2/hr or < 100
mg/m2/24h)
• Non-pathologic
• Postural (orthostatic)
• Febrile
• Exercise-induced
• Pathologic
• Tubular
• Inherited (cystinosis, Wilson ds, Lowe syndrome)
• Acquired (antibiotic, AIN, ATN, heavy metal poisoning)
• Glomerular
Hematuria• Gross
• 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
• Symptomatic - symptoms direct investigation
• Isolated hematuria - rarely have significant renal disease (benign familial hematuria or hypercalciuria)
• Asymptomatic hematuria and proteinuria - more worrisome, requires thorough evaluation by nephrology.
Edema• Differential diagnosis
• Loss of oncotic pressure
• decreased protein synthesis
• increased protein loss
• Increased capillary permeability
• viral/bacterial
• immune mediated
• mechanical/thermal trauma
• drugs
• Increased hydrostatic pressure
• 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
•Nephrotic range proteinuria
• 3+ or 4+
• > 250 mg/mmol creatinine
• > 40 mg/m^2/hr
•Hypoalbuminemia
•Hyperlipidemia
•Hypercoagulable
Pathophysiology
Glomerular Filtration Barrier
What is this fictional doc’s specialty?
NEPHROLOGY AND INFECTIOUS DISEASE!
Etiology
•Primary or idiopathic
• 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• Secondary causes
• Genetic
• Metabolic
• Infections
• Drugs
• Immunologic/Allergic
• Malignancy
• Glomerular hyperfiltration
Idiopathic Nephrotic Syndrome
•90% of childhood nephrotic syndrome
• 85% of all cases due to MCD
•Consider diagnosis other than MCD in:
• Children < 1 year and > 10 years
• Family history nephrotic syndrome
• Extra-renal findings
• More than minimal hematuria
Idiopathic Nephrotic Syndrome
• Clinical manifestations:
• Most common between age 2 and 6.
• Often follows minor infection.
• Mild edema progressing to generalized.
• Ascites
• Pleural effusions
• Genital edema
• Anorexia, abdo pain, diarrhea, irritability common.
What food item is known scientifically as Phaseolus
vulgaris?
Diagnosis• Laboratory findings
• Low serum albumin
• High cholesterol, triglycerides, lipoproteins
• Low serum sodium
• Nephrotic range proteinuria
• Indications for biopsy:
• 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
• Thromboembolic events
• Loss of antithrombin III and protein S
• Increase in fibrinogen concentration
• Infection
• Loss of factor B, low IgG, impaired Tcell function
• Most common infection is peritonitis
• Most common organisms are Strep pneumo or gram-negatives
• 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
EtiologyLow complement
Normal complement
PrimaryPostinfectious GN
Membranoproliferative GN
IgA nephropathyAnti-GBM disease
Secondary
SLEEndocarditis
AbscessCryoglobulinemia
Polyarteritis nodosa
Wegener’sHSP
Goodpasture’s
Rapidly Progressive Glomerulonephritis• Subset of nephritic syndrome
• Medical emergency
• Characterized by renal failure in days or weeks (months)
• Classfication:
• 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
• Induction of remission (pulse steroids, cyclophosphamide 3-6 months)
• Maintenance therapy (azathioprine)
• Newer agents - Rituximab, MMF
Crescent
BAD NEWS.
IgA Nephropathy• Most common cause of GN
• Idiopathic or secondary (HSP, rheumatic ds, HIV, Celiac ds, chronic liver ds)
• Variable presentation:
• Asymptomatic hematuria and mild proteinuria
• Recurrent episodes of gross hematuria
• Nephrotic range proteinuria or RPGN
• Hematuria coincident with URTI
• Treatment depends on prognostic indicators
• Watch & wait vs. immunosuppressive agents
Poststreptococus glomerulonephritis
• 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 anti-DNase B
• Self-limited disease - three phases
• latent phase
• acute phase
• recovery phase
• Supportive management of hypertension and edema
• 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!
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 52:1801-1806.
• Eison, T., Ault, B., and Jones, D. Post-streptococcal cute glomerulonephritis in children: clinical features and pathogenesis. Pedatr Nephrol 2011;16:165-180.