Paediatric Clinical Guidelines
Renal 6.1
November 2002
THE INVESTIGATION AND MANAGEMENT OF NEWLY
PRESENTING CHILDHOOD NEPHROTIC SYNDROME
Revised
November 2002
Patient Group
Children with Nephrotic Syndrome
Author
Dr 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)
2. Clinical examination
To include…
 Height, Weight, Surface area
 Blood pressure
 Cardiovascular status and perfusion
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Paediatric Clinical Guidelines
Renal 6.1
November 2002
3. 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).
4. 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.
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Paediatric Clinical Guidelines
Renal 6.1
November 2002
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
1-4 (first 28 days)
5-8 (next 28 days)
Prednisolone dosage
60 mg/m2/day (maximum dose 80 mg)
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
1-4 (first 28 days)
5-8 (next 28 days)
9-12
13-17
Prednisolone dosage
60 mg/m2/day (maximum dose 80 mg)
40 mg/m2/alternate day (maximum 40mg)
25 mg/m2/alternate day (maximum 25mg)
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
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Paediatric Clinical Guidelines
Renal 6.1
November 2002
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).
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Paediatric Clinical Guidelines
Renal 6.1
November 2002

"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



4..6.



Dietary advice
A dietician should see the child and family. A balanced no added salt diet is
recommended
4..7.

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."
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).
5. 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
Daily until urinary protein negative
or trace for 3 days
Next 28 days
Subsequent therapy
Prednisolone dosage
60 mg/m2/day (maximum dose 80 mg)
40 mg/m2/alternate day (maximum 40mg)
Individualised (may / may not taper steroids)
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Paediatric Clinical Guidelines
Renal 6.1
November 2002
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
Dr Alan Watson
Paediatric Renal Nurse – Liz Moore
Paediatric Nephrology SpR
47428 or bleep via City Hospital switchboard
46169 or bleep via City Hospital switchboard
46488
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
1
2
3
4
5
Kherr KK, Sweet M, Makker SP,: Nephrotic syndrome in children. Curr Prob Pediatr;
18: 197-251.
The 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.
Evans J :National Audit of Childhood Nephrotic Syndrome. The Royal College of
Paediatrics and Child Health/The British Association for Paediatric Nephrology. 1999
Hodson EM, Knight JF, Willis NS, Craig JC. Corticosteroid Therapy for nephrotic
syndrome in children (Cochrane Review). The Cochrane Library, Issue 3, 2002.
Oxford Update
Mehls 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
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Paediatric Clinical Guidelines
Renal 6.1
November 2002
PAEDIATRIC CLINICAL GUIDELINES
ISSUE:
VERSION: FINAL
Title: THE INVESTIGATION AND MANAGEMENT OF NEWLY PRESENTING
CHILDHOOD NEPHROTIC SYNDROME
Author:
Job Title:
Dr JHC Evans,
Consultant Paediatric Nephrologist,
Nottingham City Hospital NHST, Ext 47428
First Issued:
Date Revised: November 2002
Review Date:
October 2004
Document Derivation:
i.e. References:
Group
Included in document
Consultation Process: Paediatric Nephrologists
Cross town Paediatric Clinical Guidelines
Pharmacist
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
(please complete when making any hand-written changes/ amendments to guideline and not processed
through guideline committee)
Date
Author
Description
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