Nephrotic Syndrome

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

See also BSA & Steroid Dose Calculator

Background

Nephrotic syndrome is a clinical disorder characterised by heavy proteinuria,

hypoalbuminaemia and oedema
90% of children will have Idiopathic Nephrotic Syndrome, either minimal change disease
(85%), or Focal Segmental Glomerulosclerosis (10-15%)
Idiopathic Nephrotic Syndrome (INS) 90% of children(for which this guideline

applies)

Minimal change disease (MCD)

Focal segmental glomerulosclerosis (FSGS)

Non-idiopathic Nephrotic Syndrome - rare (discuss with nephrology if

features)

Secondary

Systemic Lupus Erythematosis (SLE), Henoch Schonlein

Purpura (HSP), Membranoproliferative Glomerulonephritis (MPGN)

Membranous nephropathy

Congenital nephrotic syndrome

The key acute complications of nephrotic syndrome are hypovolemia, infection and
thrombosis

Although in 80-90% of cases INS will respond to initial steroid therapy (hence called
steroid-sensitive nephrotic syndrome, SSNS), children with SSNS have an 80% chance of
having one or more relapses and approximately 50% of these children will have frequent
relapses.

Thus, the first admission is an important opportunity to educate families about

home monitoring and management (see Family Education, below), knowing that they
will be likely to have one or more relapses

Assessment

Oedema is the primary presenting feature. History can also include weight gain, poor
urine output, dizziness, or discomfort as a result of the oedema (including abdominal pain).
Degree of oedema ranges from:

Mild (subtle peri-orbital region, scrotum or labia)

Moderate with peripheral pitting oedema of the limbs and sacrum.

Severe with gross limb oedema, ascites and pleural effusions.

In the child with oedema, confirm the diagnosis of nephrotic syndrome with

Heavy proteinuria (dipstick 3-4+ or urine protein/creatinine ratio >0.2g/mmol)

Hypoalbuminaemia (<25g/L).

Other causes of generalised oedema include liver disease or protein losing

enteropathy (leading to hypoalbuminaemia) or congestive cardiac failure.
Assess for features suggesting not INS

Age <1y or >12y

Systemic symptoms of fever, rash, joint pains (SLE).

Persistent hypertension (can have mild hypertension first 1-2 days)

Rule out any nephritic features (requiring entirely different management)

Macroscopic haematuria (INS may have microscopic haematuria)

Hypertension

Raised serum creatinine (INS may have mild elevation with mod-severe volume
depletion)
Assess for severity and complications of INS

Intravascular volume depletion

Although patients are invariably oedematous, they can be concurrently

intravascular volume deplete

Clinically

Dizziness, abdominal cramps

Peripheral hypoperfusion (cold hands or feet, mottling, capillary

refill time > 2 seconds), tachycardia, oligoanuria, low urinary sodium,
hypotension (late sign)

Severe/symptomatic oedema potential skin breakdown/cellulitis, gross

scrotal/vulval oedema, increased work of breathing from pleural effusion

Infection (at increased risk in nephrotic state)

Cellulitis from gross oedema with skin compromise

Spontaneous bacterial peritonitis abdominal pain, fever,
nausea/vomiting, rebound tenderness
Thrombosis (at increased risk in nephrotic state)

Deep vein thrombosis, pulmonary embolus

Renal vein thrombosis macroscopic haematuria, palpable kidney, loin

tenderness, raised creatinine, hypertension

Cerebral vein thrombosis - headache, vomiting, impaired conscious

state or focal neurology

Investigations:

Urine

Dipstick (proteinuria)

Microscopy (quantify any haematuria)

Spot protein: creatinine ratio

For quantification of proteinuria with correction for urinary concentration

Also useful if lack of response to steroids (compare initial result to later
results for trend)

Sodium if required (to confirm intravascular volume depletion if clinically unclear.

Less than 10mmol/L consistent with volume depletion)
Blood

FBC

UECr, LFT (albumin)

Immunology

C3 and 4 (low in SLE and MPGN)

ANA (SLE)

Hep B if risk factors on history (secondary cause of membranous nephropathy)

Varicella serology (so serostatus known while immunosuppressed in case of contact)

Management
Admitting unit based on hospital policy. Paediatric nephrology consultation recommended if:

Age <12 months or >12 years

Persistent hypertension +/- persistent microscopic hematuria

Elevated creatinine despite correction of any hypovolemia

C3 or 4 below normal range

Unclear if nephrotic versus mixed nephritic-nephrotic (e.g. macroscopic haematuria,

intravascular fluid overload with hypertension, renal impairment)

Steroid resistance (Failure to achieve remission despite 4 weeks of prednisolone)

Treatment for INS

1.
2.

Admit to hospital on first presentation.

Manage the oedematous state
a.

No added salt diet

b.

Daily weights, daily urine dipstick

c.

Strict fluid balance with close attention to volume status

d.

Discuss with nephrology if severe, difficult to control oedema

Intravenous 20% albumin (with Frusemide)

There are 2 indications (see above for details)

a.

Intravascular volume depletion

b.

Severe or symptomatic oedema

It should only be given in consultation with the treating consultant, and ideally in
daytime hours (risk of hypertension and pulmonary oedema), unless severe
oedema or depletion very rarely indicated.

20% albumin 5ml/kg (1g/kg) over 4-6hrs IV.

1.

Give frusemide 1mg/kg (max 40mg) mid infusion

2. If giving for severe/symptomatic oedema, repeat frusemide 1mg/kg (max
40mg) at end of infusion, unless already has had brisk diuresis or signs
of peripheral hypoperfusion
3. Larger doses of frusemide are sometimes given if poor response

3.

Prophylaxis against complications

Oral penicillin V (phenoxymethylpenicillin) at a prophylactic dose 125mg/dose 12

hrly if under 5 years, or 250mg/dose 12hrly if over 5 years. Phenoxymethylpenicillin is to
continue until oedema subsides.

i. If the child is profoundly ill or appears to have sepsis use IV

Ceftriaxone 50 mg/kg/dose 24 hrly (max 2g)

Ranitidine 2-4mg/kg/dose 12 hrly (max 150mg per dose) or a proton pump

inhibitor as prophylaxis for prednisolone induced gastritis

Prednisolone: to induce remission, followed by a slow wean to reduce risk of

relapse. Consult with paediatric nephrology if remission not achieved after 4 weeks of
prednisolone.
BSA & Steroid Dose Calculator

60 mg/m2 per day as a single dose (max 60 mg/day) for 4 weeks. Then:

40 mg/m2 alternate day (max 40mg) for 4 weeks.

20 mg/m2 per alternate day for 4 weeks.

15 mg/m2 per alternate day for 4 weeks.

10 mg/m2 per alternate day for 4 weeks.

5 mg/ m2 per alternate day for 4 weeks.

Family Education
a.

The family should be taught to test urine protein each morning

a.

These can be documented in the booklets produced by the nephrology

department, which also contain information on INS. Printable forms for
documentation are available here:
NEPH DEPT BOOKLET (PDF)
DIARY FOR ENTERING PROTEIN LEVEL

b.

After remission, the urine protein should still be checked and documented daily
(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
a.

This allows for re-institution of prednisolone prior to the onset of

oedema, thus avoiding the associated consequences (admission, risk of sepsis,
thrombosis).

b.

Weight should also be checked daily while nephrotic (as a sign of fluid
accumulation).

b.

It is important to convey that, though their child will likely respond to therapy,
they will likely have relapses (80% chance)

c.

The most common relapse trigger is intercurrent infection. In patients 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.

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 per day until urine protein is 0, trace or + for 3

consecutive days.
Then weaning regimen:

40 mg/m2 alternate day for 2 weeks.

20 mg/m2 alternate day for 2 weeks.

15 mg/m2 alternate day for 2 weeks.

10 mg/m2 alternate day for 2 weeks.

5 mg/m2 alternate day for 2 weeks.

The total time of weaning regimen can be shortened if the patient relapses infrequently (2
3 relapses in any 12 month period) and responds to treatment quickly
If oedema recurs, penicillin prophylaxis should also be restarted.

Additional issues with relapsing or steroid dependant disease

Increased infection

Children with relapsing or persistent nephrotic syndrome qualify for the additional
booster Prevenar (pneumococcal conjugate vaccine), and the Pneumovax (23-valent
pneumococcal polysaccharide vaccine), timing as per schedule.

Vitamin D deficiency (loss in urine)

Hyperlipidaemia

Hypothyroidism (loss in urine)

Bone density and eye examination for cataracts should be monitored in patients on
prolonged maintenance steroid therapy.

Consider if >12m continuous therapy

Ongoing reasons for referral to nephrology

Frequent relapses (2 or more in first 6 months or 4 or more in any 12 month period)

Steroid dependant (relapses while taking steroids or within 2 weeks of cessation)

Steroid toxicity prompting consideration of alternative agent