Key points

1. Nephrotic syndrome is a clinical disorder characterised by heavy proteinuria, hypoalbuminaemia and oedema
2. Idiopathic Nephrotic Syndrome (INS) is the commonest type; any child with atypical features should have an early referral to nephrology
3. The key acute complications are hypovolemia, infection and thrombosis
4. Discharge education is crucial with the first presentation due to the high risk of relapse 
   

Background

• 90% of nephrotic syndrome is idiopathic
• Secondary causes such as Systemic Lupus Erythematosus (SLE) or Henoch Schonlein Purpura (HSP) should be considered if there are atypical features
• 80-90% of cases of Idiopathic Nephrotic Syndrome (INS) are steroid sensitive and respond to initial therapy
• Of the children with steroid-sensitive Nephrotic Syndrome 80% will have one or more relapses
  

Assessment

Nephrotic Syndrome usually presents with the classic triad of oedema, proteinuria and hypoalbuminaemia.

Oedema can be non-dependant eg periorbital. Consider other causes of generalised oedema eg liver disease, congestive cardiac failure and protein losing enteropathy.  

Assessment of severity and complications:

• Intravascular volume depletion (although children are invariably oedematous, they can be concurrently intravascular volume deplete):                                     
  • dizziness, abdominal cramps 
  • peripheral hypoperfusion (cold hands or feet, mottling, capillary refill time >2 seconds)
  • tachycardia, reduced urine output, hypotension (late sign) 
• Severe or symptomatic oedema:
  • discomfort (genital, abdominal), gross scrotal / vulval oedema
  • gross limb oedema with potential for skin breakdown / cellulitis
  • increased work of breathing from pleural effusion 
  • ascites
• Infection (increased risk in nephrotic state):                                      
  • cellulitis
  • spontaneous bacterial peritonitis – abdominal pain, fever, nausea/vomiting, rebound tenderness 
• Thrombosis (increased risk in nephrotic state)  
  

Features suggesting diagnosis other than INS 

• Age <18 months or >12 years 
• Systemic symptoms of fever, rash, joint pains (SLE, HSP)
• Persistent hypertension (can have mild hypertension first 1–2 days) 
• Features of nephritic syndrome (macroscopic haematuria, hypertension and renal impairment) 
  

Management

Investigations

The diagnosis of nephrotic syndrome includes: 

• Heavy proteinuria (dipstick 3–4+ or urine protein/creatinine ratio >0.2 g/mmol = >200 mg/mmol)
• Hypoalbuminaemia (<25 g/L)
  

Urine

• Dipstick: proteinuria 3–4+
• Microscopy: quantify any haematuria – INS may have microscopic haematuria
• Consider:
  • spot protein : creatinine ratio >0.2 g/mmol  
  • sodium <10 mmol/L (consider if concerns about intravascular volume depletion) 
    

Blood

• FBE
• UEC: may have mild elevation of serum creatinine with mod-severe volume depletion. If creatinine very high, consider nephritic syndrome
• LFT including albumin
  

Treatment (for INS)

1. Admit to hospital on first presentation

2. If the child is profoundly ill or appears to have sepsis treat accordingly (see Sepsis)

3. Manage oedema

• No added salt diet
• Daily weights, daily urine dipstick
• Strict fluid balance with close attention to volume status 
  
  Albumin and Furosemide 
  Indications include: intravascular volume depletion, severe or symptomatic oedema (see assessment section above)
  Monitor for hypertension and pulmonary oedema
  
  Albumin: 20% Albumin 5 mL/kg (1 g/kg) over 4 hours IV 
  
  Furosemide: 1 mg/kg max 40 mg over 20 minutes IV

• Give mid albumin infusion provided adequate peripheral perfusion
• A second dose may be required at the end of albumin infusion if severe or symptomatic oedema (discuss with nephrology)   

4.Steroid therapy

• Prednisolone: to induce remission, followed by a slow wean to reduce risk of relapse
  • 60 mg/m²/day (max 60 mg) for 4 weeks
  • then 40 mg/m²/day (max 40 mg) on alternate days for 4 weeks
  • then 20 mg/m²/day on alternate days for 10 days
  • then 10 mg/m²/day on alternate days for 10 days
  • then 5 mg/m²/day on alternate days for 10 days
  • then cease  
    Body Surface Area (m²) calculator
    When calculating maximum doses use pre-morbid weight if known
    
• Defer live vaccines whilst on high dose steroids - see Australian Immunisation Handbook 

5. Prophylaxis against complications 

• Infection
  • Routine prophylaxis is not indicated unless there is risk of pneumococcal infection (eg gross or symptomatic oedema, unimmunised) 
  • If indicated, manage with oral penicillin V (phenoxymethylpenicillin) 125 mg/dose 12 hourly if under 5 years, or 250 mg/dose 12 hourly if over 5 years. Cease after oedema subsides
• Gastritis
  • Routine use of acid suppressing therapies is not indicated unless there are upper gastrointestinal symptoms while on steroid therapy
    
    

Treatment of relapses

A relapse is defined as proteinuria 3+ or 4+ for 3 consecutive days, and should prompt re-introduction of full dose prednisolone:  

• Prednisolone 60 mg/m²/day (max 60 mg) until urine protein is 0, trace or + for 3 consecutive days
• Then weaning regimen:  
  • 40 mg/m²/day on alternate days for 2 weeks
  • 20 mg/m²/day on alternate days for 2 weeks
  • 15 mg/m²/day on alternate days for 2 weeks
  • 10 mg/m²/day on alternate days for 2 weeks
  • 5 mg/m²/day on alternate days for 2 weeks
    Body Surface Area (m²) calculator
    When calculating maximum doses use pre-morbid weight if known
    

The total time of weaning regimen can be shortened if the child relapses infrequently (2–3 relapses in any 12-month period) and responds to treatment quickly

If oedema recurs, penicillin prophylaxis should also be restarted (see dosing above)

Consider consultation with local paediatric team when

Discuss with nephrology if:

• features suggesting diagnosis other than INS (see assessment section above)
• severe, difficult to control oedema
• elevated creatinine despite correction of any hypovolemia
• not in remission after 4 weeks of steroid therapy
• relapses (while taking steroids or within two weeks of cessation, >2 in first 6 months or >4 in 12 months)
• steroid toxicity prompting consideration of alternative agent
  

Consider transfer when:

Child requiring care beyond the comfort of the local health care facility

For emergency advice and paediatric or neonatal ICU transfers, see Retrieval Services.

Consider discharge when

• Diagnosis clear
• Management instituted
  

Discharge education

• The family should be taught to test urine protein each morning
• Printable forms for documentation are available below  
• After remission, the urine protein should still be checked and documented every day (for at least 1–2 years), in order to identify a relapse (defined as 3+ or 4+ protein for 3 consecutive days), at which point the family should contact their treating clinician
  • This allows for re-institution of prednisolone prior to the onset of oedema, thus avoiding the associated consequences (admission, risk of sepsis, thrombosis)
  • Weight should also be checked daily while nephrotic (as a sign of fluid accumulation)
  • It is important to convey that, though their child will likely respond to therapy, they will likely have relapses (80% chance) 
  • The most common relapse trigger is intercurrent infection. In children on weaning or maintenance alternate day prednisolone, the risk of relapse can be reduced by temporarily increasing the dose from alternate to every day for 3–5 days
    

Parent information sheet

Nephrotic Syndrome Parent Information
Diary for entering protein level

Last updated November 2019