Nephrotic syndrome


  • Statewide logo

    This guideline has been adapted for statewide use with the support of the Victorian Paediatric Clinical Network

  • Key Points

    1. Nephrotic syndrome is a clinical disorder characterised by heavy proteinuria, hypoalbuminaemia and oedema
    2. Idiopathic Nephrotic Syndrome 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 e.g. periorbital. Consider other causes of generalised oedema e.g. 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 >0.2g/mmol = >200mg/mmol)
    • Hypoalbuminaemia (<25g/L)

    Urine

    • Dipstick: proteinuria 3-4+
    • Microscopy: quantify any haematuria – INS may have microscopic haematuria
    • Consider:
      • Spot protein : creatinine ratio >0.2g/mmol  
      • Sodium <10mmol/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 Guideline)

    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)
      Monitor for hypertension and pulmonary oedema

      Albumin: 20% Albumin 5mL/kg (1g/kg) over 4 hours IV 

      Furosemide: 1mg/kg max 40mg 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 (e.g. gross or symptomatic oedema, unimmunised) 
      • If indicated, manage with oral Penicillin V (phenoxymethylpenicillin) 125mg/dose 12 hourly if under 5 years, or 250mg/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 60mg) 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 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:

    Children 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 

  • Reference List

    1. Cyriac, J. Childhood Nephrotic Syndrome. Retrieved from http://www.meht.nhs.uk/EasysiteWeb/getresource.axd?AssetID=19263&type=full&servicetype=Attachment (viewed 25 February 2019)
    2. Lombel, R et al. Treatment of steroid-resistant nephrotic syndrome in children: new guidelines from KDIGO. Pediatric Nephrology. 2012. 28 (3) [Available from https://www.researchgate.net/publication/232229355_Treatment_of_steroid-resistant_nephrotic_syndrome_in_children_New_guidelines_from_KDIGO]
    3. Lombel, R et al. Treatment of steroid-sensitive nephrotic syndrome in children: new guidelines from KDIGO. Pediatric Nephrology. 2012. 28 (3) [Available from https://www.researchgate.net/publication/232229358_Treatment_of_steroid-sensitive_nephrotic_syndrome_New_guidelines_from_KDIGO
    4. Niaduet, P. Complications of nephrotic syndrome in children. Retrieved from https://www.uptodate.com/contents/complications-of-nephrotic-syndrome-in-children?search=nephrotic%20syndrome&source=search_result&selectedTitle=3~150&usage_type=default&display_rank=3 (viewed 27 February 2019)
    5. Niaduet, P. Etiology, clinical manifestations, and diagnosis of nephrotic syndrome in children. Retrieved from https://www.uptodate.com/contents/etiology-clinical-manifestations-and-diagnosis-of-nephrotic-syndrome-in-children?search=nephrotic%20syndrome&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1 (viewed 27 February 2019)
    6. Niaduet, P. Treatment of idiopathic nephrotic syndrome in children. Retrieved from https://www.uptodate.com/contents/treatment-of-idiopathic-nephrotic-syndrome-in-children?search=nephrotic%20syndrome&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2 (viewed 27 February 2019)
    7. Nishi, S et al. Evidence-based clinical practice guidelines for nephrotic syndrome 2014. Clinical and Experimental Nephrology. 2016. 20 (3), 342 – 370. [available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4891386/]
    8. Sydney Children’s Hospital Network. Nephrotic Syndrome: Management in Childhood. Retrieved from http://www.schn.health.nsw.gov.au/_policies/pdf/2016-9008.pdf (viewed 25 February 2019)