Paediatric Nephrotic Syndrome - Complete Clinical Examination Guide

Definition & Diagnostic Criteria

• Proteinuria >40 mg/m²/hour OR urine protein:creatinine ratio >2.0 mg/mg (or >3.5 g/24h in older children)
• Hypoalbuminemia - serum albumin <2.5 g/dL
• Oedema - clinically apparent
• Hyperlipidaemia - elevated cholesterol/triglycerides

PART 1 - HISTORY TAKING

Chief Complaint & Onset

• Oedema is the presenting symptom in ~95% of children. Ask:
  • Where did the swelling start? (periorbital swelling is often the first sign - typically worse in the mornings and decreases by evening)
  • How long has it been present?
  • Is it intermittent or continuous?
  • Has it progressed (face → abdomen → limbs)?
• Common missed diagnosis: parents are often told periorbital puffiness is "allergies" - clarify this history

Character of Oedema

• Periorbital puffiness (especially on waking)
• Facial puffiness
• Scrotal/labial oedema
• Pedal and ankle oedema
• Ascites (abdominal distension)
• Generalised anasarca in severe cases

Associated Symptoms

• Oliguria / decreased urine output - ask parents about wet nappies or toilet frequency
• Frothy/foamy urine - sign of heavy proteinuria (important positive history)
• Haematuria - cola/tea-coloured urine suggests nephritic component
• Abdominal pain - bowel wall oedema, ascites, or spontaneous bacterial peritonitis
• Anorexia, irritability, fatigue - very common
• Diarrhoea - from bowel wall oedema or ascites
• Respiratory distress - tachypnoea from massive ascites compressing the diaphragm, or pleural effusions

Precipitating Factors

• Recent upper respiratory tract infection (URTI) - very common trigger for first episode and relapses
• Otitis media, other infections
• History of allergy/atopy - ~30% of children with INS have atopic history
• Bee sting or insect bite (rare hypersensitivity trigger)
• Recent vaccinations

Past Medical History

• Previous episodes of swelling (relapsing nephrotic syndrome?)
• Any chronic illness (diabetes, SLE, hepatitis - secondary causes)
• Medication use: NSAIDs, penicillamine, gold (secondary causes)
• Congenital anomalies

Family History

• Familial nephrotic syndrome (rare, but genetic mutations in 30+ genes identified)
• Renal disease in family members
• Autoimmune conditions (SLE)

Birth History & Development

• Age at onset is critical:
  • <3 months: congenital NS (Finnish type)
  • 3-12 months: infantile NS
  • 1-8 years: most likely MCNS (steroid-sensitive)

  • 8 years: increasing likelihood of FSGS, MN, or secondary cause

PART 2 - CLINICAL EXAMINATION

General Appearance

• Overall state: alert or lethargic, ill-looking
• Nutritional status: may appear well-nourished despite low albumin
• Pallor: anaemia from loss of transferrin (iron-binding protein)
• Moon face (if already on steroids)
• Cushingoid features if relapsing disease on long-term steroids

Vital Signs

Head & Neck Examination

• Periorbital oedema - the hallmark early sign; puffiness around eyes, typically worse in the morning (gravity-dependent, redistributes when the child lies flat overnight)
• Look for xanthelasma (rare, severe hyperlipidaemia)
• Fundoscopy: hypertensive changes if BP elevated

• Facial puffiness and fullness
• Pallor of conjunctivae (anaemia)

• Evidence of recent URTI (erythema, tonsillar enlargement)
• Candidiasis (if on steroids)

Chest Examination

• Respiratory distress signs: nasal flaring, intercostal/subcostal retractions
• Increased respiratory rate
• Barrel-shaped appearance if air trapping

• Stony dullness at lung bases - pleural effusion (transudative, from low oncotic pressure)
• Reduced breath sounds over dull area

• Reduced air entry at bases
• Crepitations if pulmonary oedema
• Added sounds if pneumonia (a common complication)

Why pleural effusion occurs: Low plasma oncotic pressure (from hypoalbuminaemia) causes fluid to leak across pleural membranes into the pleural space.

Cardiovascular Examination

• Raised JVP (rare in MCNS which is an "underfill" state; more common in secondary NS with overfill)
• Peripheral oedema

• Peripheral pulses - check volume
• Capillary refill time (prolonged in hypovolaemia)

• Pericardial friction rub (rare, pericardial effusion)
• Muffled heart sounds (pericardial effusion in severe hypoalbuminaemia)
• Tachycardia

Volume Status Assessment is critical: Children with MCNS tend to be volume-depleted (underfill) due to low oncotic pressure driving fluid into interstitium. Children with other causes may be volume-overloaded (overfill). This distinction governs management (whether to give albumin + diuretics vs diuretics alone).

Abdominal Examination

• Abdominal distension from ascites - measure abdominal girth (serial measurements track progress)
• Visible veins (from raised intra-abdominal pressure)
• Scrotal/labial oedema (from dependent oedema and ascites)
• Genital oedema can be massive and alarming for parents

• Shifting dullness - for ascites (fluid shifts to dependent area when patient rolls to one side)
• Fluid thrill - for massive ascites

• Fluid in the flanks
• Abdominal tenderness - important red flag for spontaneous bacterial peritonitis (SBP), which complicates 2-6% of cases (caused by Streptococcus pneumoniae or gram-negative organisms)
• Renal enlargement (palpate both kidneys - bilateral enlargement may occur)
• Hepatomegaly (from fatty change due to hyperlipidaemia)
• Bowel wall oedema (vague diffuse tenderness)
• Umbilical hernia (from raised intra-abdominal pressure)

Limb & Skin Examination

• Check for pitting oedema over:
  • Ankles and dorsum of foot
  • Pre-tibial region
  • Sacrum (examine the back while child lies down - fluid pools posteriorly)
  • Genitalia
• Grade the pitting oedema (1+ to 4+)
• Press firmly for 5 seconds, then assess depth and time to rebound

• Pallor - anaemia
• Xanthomata (skin deposits of cholesterol - rare in children, suggests severe longstanding hyperlipidaemia)
• Stretch marks / striae - from rapid weight gain or steroid use
• Cellulitis - a complication of nephrotic syndrome (immunoglobulin loss causes immune compromise)
• Petechiae/purpura - consider HSP (Henoch-Schonlein Purpura) as a secondary cause, especially if palpable purpura on buttocks/lower limbs
• Butterfly rash - consider SLE (secondary NS)
• Check for thrombosis signs: limb swelling, redness, warmth in one limb (deep vein thrombosis)
• Nail changes: white bands (Muehrcke's lines) in hypoalbuminaemia

Neurological Examination

• Assess conscious level and orientation
• Seizures - can result from cerebral venous thrombosis (a serious complication)
• Focal neurological deficits - cerebral thrombosis
• Hypertensive encephalopathy signs if severely hypertensive

PART 3 - EXAMINATION FOR COMPLICATIONS

1. Infections (most common cause of mortality)

Why susceptible: Loss of IgG and complement factors (factor B, factor D) in urine impairs opsonisation and immune defence.

2. Thromboembolism (up to 20% of nephrotic patients)

• Renal vein thrombosis - haematuria (macroscopic), flank pain, enlarged kidney
• Pulmonary embolism - tachypnoea, tachycardia, desaturation
• Cerebral venous thrombosis - seizures, headache, focal deficit
• Deep vein thrombosis - asymmetric limb swelling

Why hypercoagulable: Urinary loss of anticoagulants (protein C, protein S, antithrombin III, plasminogen) + increased clotting factors (fibrinogen) + platelet hyperaggregability + haemoconcentration.

3. Hypovolaemia / Circulatory Insufficiency

• Signs: tachycardia, cold extremities, prolonged capillary refill, hypotension, oliguria
• More common in MCNS ("underfill" state)
• Triggered by aggressive diuretic use

4. Acute Kidney Injury

• Signs: oliguria, rising creatinine, electrolyte imbalance

5. Malnutrition

• Muscle wasting (masked by oedema)
• Growth failure in chronic/relapsing disease

PART 4 - ATYPICAL FEATURES (REQUIRE BIOPSY BEFORE TREATMENT)

1. Age <1 year at presentation
2. Macroscopic haematuria (cola-coloured urine)
3. Persistent hypertension
4. Hypocomplementaemia (low C3 or C4)
5. Extrarenal features - rash, arthritis, oral ulcers (suggest SLE, HSP, vasculitis)
6. Steroid resistance (no remission within 4-8 weeks)
7. Positive family history of renal disease

PART 5 - INVESTIGATIONS TO CORRELATE WITH EXAMINATION

Summary: The Classic Paediatric NS Presentation

Sources: Campbell Walsh Wein Urology, p. 459; National Kidney Foundation Primer on Kidney Diseases, 8e; Brenner and Rector's The Kidney; Medscape Paediatric NS Clinical Presentation