Idiopathic Nephrotic Syndrome in Children
NHS Scotland GGC Clinical guidelines 201 Idiopathic Nephrotic Syndrome Management in Children. Last revised: Sep 2022.
KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases
Background Information
Definition
Idiopathic nephrotic syndrome is a clinical diagnosis describing nephrotic syndrome of unknown cause, before biopsy
Causes of idiopathic nephrotic syndrome:
- Minimal change disease (>90%)
- Focal segment glomerulosclerosis (FSGS)
Note that a renal biopsy is required to reveal the underlying cause of idiopathic nephrotic syndrome. However, this is not necessary if the patient responds to treatment.
Clinical Manifestation
Key manifestations / complications of nephrotic syndrome: [Ref]
| Component | Mechanism | Clinical manifestation |
|---|---|---|
| Proteinuria | ↑ Glomerular permeability to proteins (esp. albumin) | Proteinuria itself can cause frothy / foamy urine |
| Oedema | Oedema occurs due to hypoalbuminaemia → ↓ intravascular oncotic pressure |
|
| ↑ Risk of thrombotic events | ↑ Urinary loss of anti-thrombin III, protein C&S, etc.
↑ Hepatic production of clotting factors and fibrinogen (stimulated by hypoalbuminaemia) |
Venous thrombosis (more common):
Arterial thrombosis (uncommon):
|
| ↑ Risk of infection | ↑ Urinary loss of immunoglobulins and immune-mediators |
|
| Hyperlipidaemia | Hypoalbuminaemia → compensatory hepatic upregulation (synthesis of proteins and lipoproteins) |
|
Other:
- Anaemia (from urinary loss of transferrin)
- Vitamin D deficiency (from urinary loss of vitamin D-binding protein)
Prognosis
Excellent prognosis overall
- Very rare risk of progression to CKD / ESRD (esp. in steroid-sensitive cases)
- Hypertension is uncommon or mild
- Typically a relapsing-remitting course that often resolves spontaneously after puberty
- Relapse is very common (occurs in the 1st year in up to 80-90% of patients) – can be triggered by URTI, allergies, vaccinations
- 15-25% cases persist into adulthood
Diagnosis
Diagnostic Criteria
Triad of:
- Heavy proteinuria
- Defined by 3+/4+ on urine dipstick or urine PCR >200 mg/mmol
- NB that the ≥3.5 g per 24 hours cut-off for nephrotic-range proteinuria only applies to adults
- Hypoalbuminaemia (<25 g/L)
- Oedema (peri-orbital oedema, lower limb pitting oedema, ascites, scrotal / vulval oedema)
Other features:
- 1-10 y/o
- Normal BP (hypertension is atypical)
- Hyperlipidaemia (due to hepatic compensation)
- ↓ Vitamin D (from urinary loss)
- Normal creatinine (i.e. normal renal function)
- Microscopic haematuria (macroscopic is atypical)
Assessment and Tests
Clinical assessment
- Height and weight
- Oedema assessment
- Fluid status assessment
1st Line Investigations (All Children)
Blood tests:
- FBC, U&E, LFT, bone profile (including serum albumin)
- Vitamin D
- Varicella IgG
Urine testing:
- Urinalysis
- Urinary PCR
- Urine sodium concentration
Quantifying nephrotic-range proteinuria in children is different from adults:
- In adults: gold standard is a 24-hour urine collection (≥3.5 g per 24 hours), or 2nd line: first morning void urine for PCR (≥300 mg/mmol)
- In children, the ≥3.5 g per 24 hours definition does NOT apply, and nephrotic-range proteinuria can be defined with ANY of the following:
- 24-hour urine collection: ≥40 mg/m²/h (often inaccurate in children)
- Urine PCR ≥200 mg/mmol from a first morning void or 24-hour sample
- Urine dipstick: protein 3+ or greater
- Urine protein concentration 300 mg/dl
Further Testing
The following tests should only be performed in those with atypical features to exclude alternative diagnoses:
| Test | Description |
|---|---|
| ASOT | ↑ Suggests Streptococcal throat infection and possible PSGN |
| Anti-DNase | ↑ Suggests Streptococcal throat infection and possible PSGN |
| Completion level (C3/C4) | ↓ C3 level may suggest:
|
| Hepatitis B serology | Perform if high risk:
|
Management
Definitive Management
First Presentation
Offer the following to ALL patients:
| Lifestyle advice (but not necessary once in remission) |
|
| Corticosteroid therapy | Offer a high-dose oral prednisolone for 8-12 weeks + PPI
|
Monitor BP and urine PCR.
> 80-90% of children are steroid-responsive, therefore the current practice is to treat empirically first without renal biopsy. Renal biopsy should only be considered if refractory to steroid therapy.
Note that there is an increased risk of adrenal suppression after 4 weeks of high-dose steroids. See this article for more information on adrenal insufficiency.
Prophylactic trimethoprim–sulfamethoxazole should be considered in patients receiving high-dose prednisone for PCP prophylaxis.
Relapse Management
1st line: restart high-dose prednisolone
- 60 mg/m2/day until in remission (-ve / trace only for protein for 3 consecutive days)
- Then, the weaning regimen
2nd line options (by specialist):
- Levamisole
- Cyclophosphamide
- Calcineurin inhibitor (ciclosporin, tacrolimus)
- Mycophenolate mofetil
- Rituximab – last resort
Complications Management
| Complication | Management |
|---|---|
| ↑ Infection risk | Antibiotic prophylaxis is NOT routinely recommended
Vaccinations
|
| Persistent oedema | Diuretics:
20% albumin infusion
|
| Vitamin D deficiency | Measure 25-hydroxyvitamin D levels and treat any deficiency accordingly |