Nephrotic Syndrome

SIMON, Romnick M.
Nephrotic Syndrome
• Clinical manifestation of glomerular diseases
associated with heavy (nephrotic-range) proteinuria
• Nephrotic range proteinuria
• proteinuria >3.5 g/24 hr or a urine protein: creatinine ratio >2
• Triad of clinical
• hypoalbuminemia (≤2.5 g/dL)
• edema
• hyperlipidemia (cholesterol >200 mg/dL)
• 2-3/100,000 children/year
• 10% have secondary NS
• Most (90%) have idiopathic form
1. Minimal change disease (85%)
2. Focal segmental glomerulosclerosis (10%)
3. Mesangial proliferation (5%)
Histological types of Idiopathic
NS:
1. Minimal change disease (85%)
 more than 95% of children respond to steroids
2. Focal segmental glomerulosclerosis (10%)
 mesangial cell proliferation segmental scarring:
(+ IgM and C3; only 20% respond to steroids)
3. Mesangial proliferation (5%)
 diffuse increase in mesangial cell and matrix and
50% respond to steroids
4. Membranous nephropathy
5. Membranoproliferative GN
Pathophysiology
• Increase in permeability of the glomerular capillary
wall  massive proteinuria and hypoalbuminemia
• Minimal change disease-T-cell dysfunction leads to
alteration of cytokines which causes a loss of
negatively charged glycoproteins within the
glomerular capillary wall
Reason for Protein Leakage
Figure 12-2. Underfill
hypothesis of edema
formation in nephrotic
syndrome. Proposed
sequence of
pathophysiologic events
leading to the formation
of edema in nephrotic
syndrome.
Pathophysiology of
Hyperlipidemia
• Hypoalbuminemia stimulates generalized hepatic
protein synthesis
• Increased urinary loss of lipoprotein lipase 
decreased lipid catabolism  elevated serum lipid
levels
CLINICAL MANIFESTATION
• Proteinuria
• Hypoalbuminemia
• Secondary to proteinuria
• Generalized edema
• Follows massive albumin urinary losses
• Begins in areas with low resistance (eyelid swelling, or
“puffy eyes”)
• Can also lead to scrotal or vulvar edema
• Hyperlipidemia
DIAGNOSIS
• Urinalysis reveals 3+ to 4+ proteinuria
• Urinary protein excretion >40 mg/m2/hr
• Serum creatinine usually normal
• Serum albumin < 2.5 g/dL
• Elevated serum cholesterol & TGs
• C3 & C4 levels are normal
DIAGNOSIS
• Histology
• Glomeruli appear normal on light microscopy, hence the
name "minimal change"
• E/M: flattening or effacement of epithelial cell foot
processes
TREATMENT
• First episode with mild to moderate edema  can be
treated as outpatient
• Low sodium diet
• Severe symptomatic edema (pleural effusions, ascites) 
confine; fluid restriction
• Diuretics (furosemide 1 mg/kg/dose IV)
• Intravenous 25% human albumin (0.5 g/kg/12 hours)
• Monitor volume status, serum electrolytes, renal function
• Onset at 1-8 years old: steroid-responsive minimal
change form  Steroids may be initiated without renal
biopsy
Steroids
• Prednisone 60mg/m2/day (max dose 80mg) 2-3 doses
for at least 4 weeks
• How can you say that the patient is steroid responsive?
• Urine trace or negative protein for 3 consecutive days (80-
90% of children respond to steroids)
• Taper prednisone after 4 wks to 40 mg/m2/day every
other day as a single morning dose  tapered and
discontinued over the next 2-3 months
• When do you say that a child is steroid & resistant?
• Children who continue to have proteinuria 2+ or greater after
8 wks of steroids are considered steroid resistant  renal
biopsy
Steroids
• Methylprednisolone 30 mg/kg bolus (max, 1 g) with
the 1st 6 doses given very other day then tapered
up to 18 months
• Cyclophosphamide for relapsers (prolong the
remission and reduce the number of relapses) at 2-3
mg/kg day single dose, for. 8-12 wks; monitor WBC
weekly and withhold drug if <5,000/mm3
COMPLICATIONS
• Infection is the major complication of NS.
• Increased susceptibility to bacterial infections due to urinary
losses of lg and properdin factor B, defective cell-mediated
immunity, immunosuppressive therapy, malnutrition edema
acting as potential "culture medium"
• What are the usual causes of spontaneous bacterial
peritonitis?
• Streptococcus pneumoniae (most common in children) and E. coli
• What vaccines are given to patients with NS?
• All children with NS should receive polyvalent pneumococcal vaccine,
ideally given when the child is in remission and off of daily steroids
• If (-) varicella titer, give vaccine when in remission Influenza vaccine
should be given yearly
PROGNOSIS
• If steroid-resistant, focal segmental
glomerulosclerosis is the usual form and has a much
poorer prognosis  ESRD requiring dialysis or
renal transplantation
• If in remission, they are considered normal and may
have unrestricted diet and activity.
Thank you!