Nephrotic Syndrome

Heavy proteinuria, Hypoalbuminemia, Edema (often frank anasarca), Hyperlipidemia

Primary idiopathic renal disorder or result from underlying systemic disease

Laboratory

Urine: Routine
Urine protein : creatinine ratio - First morning sample
Blood urea nitrogen and creatinine
Serum total protein and Albumin
Serum Cholesterol
Serum Electrolytes
Total calcium: ionized calcium levels.
Complement C3
24-hour urinary protein

Laboratory Interpretation

Urine: Proteinuria >3+, Hematuria ± (Microscopic/Gross), First morning urine protein : creatinine ratio >2
Blood urea nitrogen and creatinine: Normal/slight increase
Serum total protein and Albumin: Low (Alb: <2.5g/dL)
Serum Cholesterol: Increased
Serum Na: Mild hyponatremia ±
Total calcium: low; ionized calcium levels: usually normal.
Complement C3: Generally normal (low level suggests MPGN, poststreptococcal glomerulonephritis, or lupus nephritis.)
24-hour urinary protein losses:
Nephrotic range urinary protein excretion > 40 mg/m2 per hour or 1 g/m2 per day in children
In incontinent children, urine protein-to-creatinine ratio > 2:1 on a random urine sample
Urinary protein quantification is helpful for monitoring the response to treatment of children with resistant forms NS.

A renal biopsy is not routinely performed if the patient fits the standard clinical picture of MCNS.

Specific Treatments

Corticosteroids (Start 4 to 6 --- Maintain 4 to 6 --- Taper 4 wk)

Prednisone, 2 mg/kg daily or 60 mg/m2 daily (maximum, 60–80 mg/day) for 4–6 weeks

Usually in divided doses - Can be given as a single morning dose

Followed by single dose of 1.3 mg/kg or 40 mg/m2 for an additional 4–6 weeks given in the morning on alternate days

Tapered off over an additional 4 weeks

Treatment of relapse (Start till Protein Negative - Maintain 4 - Taper 4 wk)

Prednisone, 2 mg/kg daily or 60 mg/m2 daily until urine is free of protein for 3 consecutive days

Dose then changed to 1.3 mg/kg or 40 mg/m2 on alternate days for 4 weeks

Tapered off over an additional 4 weeks

Treatment Approach

Long-term outcome depends upon Clinical response to corticosteroids - 85% respond to a trial of prednisone -75% within 2 weeks - 94% by 4 weeks.
Biopsy findings do not predict corticosteroid resistant or responsive NS.
Who achieve remission on steroids and remain responsive to corticosteroid do not progress to renal failure.
Age 1–6 years (most likely to have MCNS) with new onset of typical, pure nephrotic syndrome should be given a trial of corticosteroids.

Relapse:

Urine Protein ≥ 2+ on 3 consecutive days
Usually triggered by intercurrent illnesses or allergies.
Parents can be taught to use albumin test sticks or sulfosalicylic acid at home to monitor urinary protein excretion.

Children who have relapse while corticosteroids are being tapered or within 2 weeks of completing a course of corticosteroids are considered corticosteroid dependent and may develop toxicity.

When to Refer

Complicated nephrotic syndrome
Outside the expected age range (< 1 year or > 10 years of age)
Accompanied by signs of glomerulonephritis (renal insufficiency, hypertension, hematuria, hypocomplementemia)
Refractory edema
Frequently relapsing nephrotic syndrome
Corticosteroid-dependent nephrotic syndrome
Corticosteroid-resistant nephrotic syndrome

When to Admit

Initial episode for teaching of parents, especially if complications +
Anasarca interfering with ambulation or compromising ventilation
Pleural effusions or ascites interfering with ventilation
Signs of volume overload (congestive heart failure)
Infection (eg, severe cellulitis, peritonitis)
Significant hypertension
Significant electrolyte abnormalities
Compromised renal function - May require dialysis to manage edema, electrolyte disturbances, and uremia

Epidemiology

Incidence: 2–7 cases per 100,000 children annually
Sex: Male : Female Children (2:1); adolescents and adults (1:1)
Children 3 months to 16 years: 76% Minimal Change Nephrotic syndrome (MCNS).
Peaks between 2 and 5 years of age.
7–25% - focal segmental glomerulosclerosis (FSGS).
2–5% - diffuse mesangial hypercellularity or mesangial proliferation.
7% - membranoproliferative glomerulonephritis (MPGN).
1% - membranous nephropathy.

Adolescents are more likely than younger children to have a more aggressive cause, such as FSGS, MPGN, or membranous nephropathy.

Major causes include:

Membranous glomerulonephritis (MGN, also called membranous nephropathy)
Minimal change disease (MCD)
Focal and segmental glomerulosclerosis (FSGS)
Diabetic nephropathy
Glomerular deposition diseases
Amyloidosis
Light chain deposition disease
Fibrillary glomerulonephritis and immunotactoid glomerulonephritis
Fabry disease

Complications of corticosteroid therapy

Development of cushingoid features
Cataract formation
Glaucoma
Gastritis
Peptic ulcer disease
Pancreatitis
Hypokalemia
Hypertension
Increased risk of infection
Behavioral changes
Growth delay if treatment is prolonged

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