Nephrotic Syndrome

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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