Paediatric Clinical Guidelines

Renal 6.1

November 2002

THE Investigation and MANAGEMENT OF NEWLY PRESENTING Childhood Nephrotic Syndrome

RevisedNovember 2002

Patient GroupChildren with Nephrotic Syndrome

AuthorDr JHC Evans, Consultant Paediatric Nephrologist, Nottingham City Hospital NHST, Ext 47428

Background

Nephrotic syndrome is characterised by heavy proteinuria (protein or albumin:creatinine ratio > 200mg/mmol), hypoalbuminaemia (serum albumin <25g/l) and oedema. It is an uncommon childhood condition with an annual incidence in the UK of only 2 per 100,000 children1.

There are many different causes of nephrotic syndrome, but the majority of cases (over 90%) are primary and due to minimal change disease (MCD)2. Approximately 80% of children will respond to prednisolone and this is the most important factor in terms of management and prognosis.

Nephrotic syndrome is thought of as a relatively benign condition, however the mortality rate remains around 1%. There is significant acute and long term morbidity also, therefore it is appropriate to consider early referral of all patients to the Paediatric Renal Team at City hospital.

  1. Clinical history

To include history of…

Atopy

Immunisation

Natural childhood infections (particularly Varicella Zoster)

Family history (particularly renal disease and thrombophilia)

  1. Clinical examination

To include…

Height, Weight, Surface area

Blood pressure

Cardiovascular status and perfusion

  1. Investigations

In all new patients

Urine for…

Dipstick urinalysis

Urine culture

Urine microscopy for casts if gross haematuria

Urine protein/albumin:creatinine ratio (early morning specimen) - correlates with overnight protein loss and replaces the need for 24hr urine collection. Do not delay starting treatment in order to obtain.

Blood for…

Urea, electrolytes, creatinine and albumin

Full blood count

"Varicella Zoster immunity status"

(Plan tests, single venepuncture is ideal in children who may be difficult to bleed because of oedema. Femoral stabs should never be performed as thrombosis is a described complication)

If mixed nephrotic/nephritic picture with macroscopic haematuria and hypertension, cases should be discussed with a Consultant Nephrologist where other investigations may be appropriate (C3, C4 complement, C3d, ANF, ASOT, ANCA and immunoglobulins).

  1. Management

Nephrotic syndrome treatment aims to induce remission with steroids (most patients respond within 5-14 days), and therefore promote diuresis. All other therapies are symptomatic and aimed at preventing complications. Children who do not respond to prednisolone within 28 days will require a renal biopsy.

4..1.Cortico-steroids

There is considerable debate as to the optimal regimen of prednisolone. Prolonged courses (3-6 months) reduce the likelihood of relapse in the subsequent 2 years, but this may be at the expense of greater steroid induced adverse effects3,4. Two regimens are therefore used. A standard regimen and an intensified regimen. The intensified regimen is used in children considered at high risk of relapse taking into account factors such as young age, ethnicity (south asian) severe illness on initial presentation and delay in achieving initial remission. The choice between the two regimens is an elective decision that should be made after discussion with the consultant paediatric nephrologist.

Standard Regimen

Initial therapy - Prednisolone 60mg/m2/day in a single morning dose (maximum dose 80mg) for 28 days even if proteinuria remits. Methyl prednisolone 60mg/m2/day can be used intra-venously in the vomiting child. After 28 days, the dose of steroid is reduced to 40mg/m2 alternate days for the next 28 days and then stopped

Week / Prednisolone dosage
1-4 (first 28 days) / 60 mg/m2/day (maximum dose 80 mg)
5-8 (next 28 days) / 40 mg/m2/alternate day (maximum 40mg)
Intensified Regimen

The first 8 weeks are as in the standard regimen, followed by a further 8 weeks of tapering dosage.

Week / Prednisolone dosage
1-4 (first 28 days) / 60 mg/m2/day (maximum dose 80 mg)
5-8 (next 28 days) / 40 mg/m2/alternate day (maximum 40mg)
9-12 / 25 mg/m2/alternate day (maximum 25mg)
13-17 / 10mg/m2/alt day (maximum 10mg)

A "steroid warning card" should be provided for the patient to carry.

4..2.Oedema and ascites

A balanced no added salt diet is recommended.

Suggested fluid intake <5yrs = 750mls, >5yrs = 1 litre

Diuretics

(use only if severe and worsening oedema/ascites, in the absence of hypovolaemia,)

Spirinolactone 2mg/kg/day in two divided doses

Frusemide 1-2mg/kg/day in two divided doses

Albumin infusions

Albumin infusion is only indicated in symptomatic hypovolaemia or severe diuretic resistant oedema. It should be administered with great caution with frequent monitoring of vital signs until at least two hours after the infusion is completed.

Doses;

Severe circulatory failure = 4.5% albumin 20ml/kg over 30-60 mins repeated if necessary until volume status restored.

Mild hypovolaemia + oedema = 20% albumin 5ml/kg (1g/kg) over 2-4 hrs with IV frusemide 1mg/kg halfway through the infusion provided signs of hypovolaemia have resolved.

Severe diuretic resistant oedema = 20% albumin 5ml/kg (1g/kg) over 2-4 hrs with IV frusemide 1mg/kg half way through infusion

4..3.Risk of thrombosis

Thrombosis either arterial or venous is rare (5%5) in nephrotic syndrome. The consequences however can be devastating.

To decrease the risk of thrombosis;

Avoid hypovolaemia

Prevent sepsis

Encourage mobilisation and avoid bedrest

Low dose Aspirin*

*Nb: There is no definite evidence (even in adults) that prophylactic anti-platelet or anticoagulation treatment is of benefit. However, it seems reasonable that patients with a family history of thrombophilia or raised platelet count (>800) should receive low dose Aspirin as prophylaxis three times per week (if <30kg 37.5mg, >30kg 75mg).

4..4.Hypertension

Check volume status, if satisfactory…

Anti-hypertensives

Atenolol 0.5-1mg/kg/day in single daily dose

or Nifedipine SR 0.25-2mg/kg/day in two divided doses

4..5.Infection prophylaxis

4..5.1.Antibiotics

Oral Penicillin V (125mg BD if < 5yrs or 250mg BD <12yrs) should be prescribed to oedematous/ascitic patients to protect against pneumococcal infection.

Nb: If peritonitis is suspected then cover for Gram negative organisms is recommended until cultures are available.

4..5.2.Immunisation

Pneumococcal (23 valent) polysaccharide vaccine (Pneumovax II 0.5ml intramuscular) is recommended for all children with nephrotic syndrome over 2 years whether on steroids or overtly nephrotic. It should be given during initial admission.

Pneumococcal polysaccharide (7 valent) conjugate vaccine (Prevenar 0.5 ml) is recommended for children under 2 years. The first dose should be given during the initial admission, subsequent doses should be administered as outlined in the BNF.

Routine vaccinations should be given as outlined in the DoH handbook unless the child is "immunosuppressed"(as defined below). "Immunosupressed" children should not receive live vaccines (ie. oral polio, measles, mumps, rubella, BCG).

"Immunosuppression" in the context of immunisation is defined as any child who is receiving or has received in the last 3 months; (a) Prednisolone 2mg/kg/day for > 1 week, (b) Prednisolone 1mg/kg/day or equivalent for 1 month (ie 40mg/ m2 alternate days) (c) lower doses of prednisolone combined with cytotoxic drugs, (d) long term lower dose immunosuppression.

In some instances where the risk of relapse is high, immunisation may be deferred. This requires discussion with the consultant.

4..5.3.Varicella Zoster

Chicken pox whilst immunosuppressed can be a very serious illness.

"Varicella zoster immunity status" should be known (and documented) in each nephrotic patient.

ZIG or Aciclovir may be required please refer to renal protocol 6.3 "Chickenpox and immunosuppression therapy in renal children."

4..6.Dietary advice

A dietician should see the child and family. A balanced no added salt diet is recommended

4..7.Psychosocial support

Making adequate information available for the family is essential. Childhood Nephrotic Syndrome booklets and a video are available from the Renal unit at City hospital. Carers should be instructed on how to dipstick the child's early morning urine and record this in a daily diary.

Referral to the paediatric community renal nurse and social worker is routine.

A family support group exists; "Childhood Nephrotic Support" (contact Mrs Sandra Warhurst, 7 Bonnymead, Cotgrave. NG12 3QH. Tel. 0115 9892975).

  1. Relapse

Relapse within the first year is common (86%3) and can occur years after the initial presentation. Relapse can follow immunisation or viral infection. A relapse is defined as proteinuria of ++ or more for three consecutive days. Prednisolone treatment usually delayed for at least 5 days unless the child is becoming oedematous.

Duration / Prednisolone dosage
Daily until urinary protein negative
or trace for 3 days / 60 mg/m2/day (maximum dose 80 mg)
Next 28 days / 40 mg/m2/alternate day (maximum 40mg)
Subsequent therapy / Individualised (may / may not taper steroids)

Frequent relapsers are defined as having 2 or more relapses in 6 months and should receive second line treatments (not covered by this guideline).

Contact Numbers

Consultant Paediatric Nephrologists
Dr Jonathan Evans / 47428 or bleep via City Hospital switchboard
Dr Alan Watson / 46169 or bleep via City Hospital switchboard
Paediatric Renal Nurse – Liz Moore / 46488
Paediatric Nephrology SpR / 46458 )(Lambley Ward) or bleep via City Hospital switchboard

Audit Points

As patient numbers per year are very low, a retrospective audit of case notes could be undertaken as there are only minor changes in the new version of the guidelines compared with the3 previous version.

  1. Do patients receive Pneumovac?
  2. Are patients managed according to the guidelines

References

1Kherr KK, Sweet M, Makker SP,: Nephrotic syndrome in children. Curr Prob Pediatr; 18: 197-251.

2The International Study of Kidney disease in Children: The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisolone. J Pediatr. 1981; 98: 561-564.

3Evans J :National Audit of Childhood Nephrotic Syndrome. The Royal College of Paediatrics and Child Health/The British Association for Paediatric Nephrology. 1999

4Hodson EM, Knight JF, Willis NS, Craig JC. Corticosteroid Therapy for nephrotic syndrome in children (Cochrane Review). The Cochrane Library, Issue 3, 2002. Oxford Update

5Mehls O, Andrassy K, Koderisch J, Herzog U, Ritz E,: Hemostasis and thromboemblism in children with nephrotic syndrome: Differences from adults. J Pediatr 1987:110:862-867

PAEDIATRIC CLINICAL GUIDELINES

ISSUE:VERSION: FINAL

Title: THE INVESTIGATION AND MANAGEMENT OF NEWLY PRESENTING

CHILDHOOD NEPHROTIC SYNDROME

Author: Dr JHC Evans,

Job Title:Consultant Paediatric Nephrologist,

Nottingham City Hospital NHST, Ext 47428

First Issued:Date Revised:November 2002 Review Date: October 2004

Document Derivation:Consultation Process: PaediatricNephrologists

i.e. References:Cross town Paediatric Clinical Guidelines Group

Included in documentPharmacist

Ratified By:Paediatric Clinical Guidelines Committee

Chaired By:

Consultant with Responsibility: Dr Stephanie Smith

Distribution:All wards QMC and CHN

Training issues: Included in Induction Programme

Audit: included in document

This guideline has been registered with Nottingham City Hospital NHS Trust and QMC Clinical Guidelines Committee. However, clinical guidelines are ’guidelines’ only. The interpretation and application of clinical guidelines will remain the responsibility of the individual clinician. If in doubt contact a senior colleague or expert. Caution is advised when using guidelines after the review date.

MANUAL AMENDMENTS RECORD
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