Treatment in children

Seek expert advice.

Provided there are no features to suggest otherwise children are assumed to have minimal change disease. Treatment measures include:

• all children presenting with their first episode of nephrotic syndrome (NS) should be admitted to hospital for diagnostic assessment, nursing and medical management, and parental education (1,2)
  
  
• fluid balance, hypovolaemia and blood pressure
  • oedematous nephrotic child is at significant risk of hypovolaemia. If hypovolaemia is present it should be promptly corrected with administration of 10-20 ml/kg of 4.5% albumin. Those with only mild oedema do not need to have fluid restriction
    • diuretics are used in some cases to help control the oedema until remission begins
      • use of diuretics should be reviewed on a daily basis
        • check U+Es regularly
        • child who is fluid restricted and/or who is on diuretics should be kept under close review to avoid inducing hypovolaemia
    • hypotension is a sign of severe hypovolaemia and must be promptly addressed
    • hypertension may also occur in the acute phase - if there is persistent hypertension in the absence of hypovolaemia then this requires referral to a paediatric nephrologist
• infection
  • Streptococcus pneumoniae and Gram-negative organisms are the commonest pathogens causing possible peritonitis, septicaemia and cellulitis
  • prophylactic oral phenoxymethylpenicillin (12.5 mg/kg twice daily) administration is recommended while the child is oedematous and any suspected infection should be promptly treated with broad-spectrum antibiotics while awaiting culture
• mobilization
  • children should be encouraged to mobilize as normal.
• diet
  • a 'no added salt' diet is advisable in view of the salt and water overload
  • children should be encouraged to have a normal healthy diet
• immunization
  • live vaccines should not be given to immunosuppressed children
  • children with steroid-sensitive nephrotic syndrome are considered immunosuppressed if they have received daily steroids for greater than 1 week in the previous 3 months
    • a live vaccine can however be given if the child is on a low dose alternate day regimen
• steroid therapy - first presentation
  • large majority of children are given an empirical course of corticosteroids as greater than 90% of those with MCD and 20% of those with FSGS will respond to corticosteroid therapy
    • the International Study of Kidney Disease (ISKD) regimen, which is still largely in use, consists of prednisolone 60 mg/m2 (maximum dose 80 mg) for 28 days, followed by prednisolone 40 mg/m2 (maximum 40 mg) on alternate days for 28 days
      • steroids are given in a once-daily dose. Some centres use a H2 antagonist for gastric protection, though acute or chronic gastric ulceration is extremely uncommon in children on steroid treatment
• relapsing steroid-sensitive nephrotic syndrome
  • more than 70% of children with steroid-sensitive NS will relapse
    • a relapse is characterized by 3 consecutive days of 2+ or more proteinuria and is usually detected on routine daily urinalysis at home
    • current ISKD relapse regimen is prednisolone 60 mg/m2/ day (maximum 80 mg) until urinary remission, followed by prednisolone 40 mg/m2/day (maximum 60 mg) on alternate days for 28 days (14 doses)
      • infrequently relapsing children can be managed with repeated courses of this regimen
        • however, 50% of children will follow a frequently relapsing course or will become steroid dependent (two consecutive relapses during corticosteroid treatment or within 14 days of stopping corticosteroid treatment)
          • these children should be referred to a paediatric nephrologist for further management
        • a longer course of alternate-day maintenance therapy can be considered for those children with a frequently relapsing course
    • growth and blood pressure of a child on long-term steroids should be reviewed every 3 months, they should have an annual ophthalmology assessment to check for cataracts, and pubertal status should be monitored and bone age checked if there is any delay (2)

A review stated (4)

• oral corticosteroids are the first-line treatment for a child presenting with idiopathic nephrotic syndrome
  • for children who present with their first episode of nephrotic syndrome, about 90% will achieve remission with corticosteroid therapy
• children who fail to respond to corticosteroids are treated with immunosuppressive agents such as calcineurin inhibitors (CNI) (cyclosporin, tacrolimus), cyclophosphamide (CPA), chlorambucil, mycophenolate mofetil (MMF), and the anti CD 20 monoclonal antibody, rituximab
• rates of complete and partial remission with CNI based on observational studies and individual groups in randomised controlled trials (RCTs) vary between 30% and 80%
• remission rates of up to 60% with combinations of intravenous (IV) methylprednisolone and CPA are reported in observational studies and of around 50% in individual treatment groups in RCTs
• concluded that calcineurin inhibitors may increase the likelihood of complete or partial remission compared with placebo/no treatment or cyclophosphamide

Reference:

• (1) Lancet (1995); 346 (8969):148-52.
• (2) Dolon MN, Gill D. Management of nephrotic syndrome. Paediatrics and Child Health 2002:369-374
• (3) Hodson EM et al. Corticosteroid therapy in nephrotic syndrome: a meta-analysis of randomised controlled trials. Arch Dis Child 2000;83:45-51.
• (4) Liu DL et al. Interventions for idiopathic steroid-resistant nephrotic syndrome in children. Cochrane Database Syst Reviews 21 November 2019