Introduction
Nephrotic syndrome (NS) is a common renal disorder in childhood characterised by massive proteinuria, hypoalbuminemia, generalised oedema, and hyperlipidemia. It results from increased permeability of the glomerular basement membrane, allowing abnormal leakage of plasma proteins into urine.
It is a major cause of morbidity among Ghanaian children, particularly between the ages of 2 and 8 years, and is a frequent reason for referral to paediatric renal clinics. Early recognition and appropriate management are critical to prevent complications such as infection, thrombosis, and renal failure.
Incidence and Epidemiology
Nephrotic syndrome is one of the most common glomerular diseases in children worldwide, but its pattern varies by geography and race.
- Age: Most cases occur between 2 and 8 years, with a peak around 4 years.
- Sex: There is a male predominance (M:F ≈ 2:1).
- Geographical variation:
- In Europe and North America, minimal change disease (MCD) accounts for 70–90% of idiopathic cases.
- In West Africa, including Ghana, focal segmental glomerulosclerosis (FSGS) is more common, and steroid resistance rates are higher.
- Secondary nephrotic syndrome may be seen with infections such as hepatitis B, malaria, HIV, or systemic diseases such as lupus nephritis.
Aetiology and Classification
Nephrotic syndrome can be classified into primary (idiopathic) and secondary forms.
Primary (Idiopathic) Nephrotic Syndrome
No identifiable systemic cause. Includes:
- Minimal Change Disease (MCD) – the most common cause in younger children; characterised by normal light microscopy but podocyte effacement on electron microscopy.
- Focal Segmental Glomerulosclerosis (FSGS) – affects older children; may follow MCD or occur de novo; associated with steroid resistance.
- Membranoproliferative Glomerulonephritis (MPGN) – uncommon but causes persistent proteinuria and reduced complement levels.
Secondary Nephrotic Syndrome
Occurs due to identifiable systemic or renal disorders:
- Infections: Hepatitis B, HIV, malaria, syphilis, tuberculosis.
- Systemic diseases: Systemic lupus erythematosus (SLE), Henoch-Schönlein purpura.
- Drugs: NSAIDs, gold salts, penicillamine.
- Metabolic and inherited conditions: Diabetes mellitus, amyloidosis, Alport syndrome.
Pathophysiology
The glomerular filtration barrier, comprising the endothelium, basement membrane, and podocyte layer, normally prevents large proteins, such as albumin, from passing into the urine.
In nephrotic syndrome:
- Podocyte injury or loss of charge selectivity leads to massive proteinuria (>40 mg/m²/hr or >3.5 g/day).
- Loss of plasma proteins, especially albumin, reduces plasma oncotic pressure, resulting in fluid movement into interstitial spaces → oedema.
- Hypovolemia triggers activation of the renin–angiotensin–aldosterone system and antidiuretic hormone, worsening sodium and water retention.
- The liver’s compensatory response increases lipoprotein synthesis → hyperlipidemia and lipiduria.
Thus, the four hallmark features are:
- Proteinuria
- Hypoalbuminemia
- Oedema
- Hyperlipidemia
Clinical Features
General Presentation
Onset is usually insidious over days to weeks.
Main features:
- Oedema: Initially periorbital (especially in the morning), then generalized (anasarca).
- Ascites and pleural effusion: From fluid transudation.
- Weight gain: Due to fluid retention.
- Reduced urine output (oliguria): Often dark and frothy.
- Fatigue and anorexia.
Examination Findings
- Puffy face, periorbital and pedal oedema
- Distended abdomen with ascites
- Pleural effusion causing respiratory distress.
- In advanced cases, scrotal or labial swelling
- Pulse may be small due to hypovolemia.
- Blood pressure is usually normal or slightly raised (if renal impairment develops)
Differential Diagnosis
Other causes of oedema in children must be considered:
| Acute glomerulonephritis |
Haematuria, hypertension, mild proteinuria, elevated ASO titre |
| Congestive heart failure |
Cardiomegaly, hepatomegaly, pulmonary congestion |
| Liver disease |
Jaundice, hepatomegaly, abnormal LFTs |
| Protein-losing enteropathy |
Diarrhoea, malabsorption features |
| Severe malnutrition (Kwashiorkor) |
Wasting, dermatosis, low total protein and albumin |
Investigations
Urine Studies
- Dipstick: Heavy proteinuria (≥3+).
- 24-hour urinary protein: >40 mg/m²/hr or spot protein/creatinine ratio >200 mg/mmol.
- Microscopy: Few red cells and casts (in MCD, urine is bland).
- Lipiduria: Fat droplets or “Maltese crosses” under polarised light.
Blood Tests
- Serum albumin: <25 g/L.
- Serum cholesterol: Often >6.5 mmol/L.
- Electrolytes, urea, creatinine: Assess renal function.
- Complement levels (C3, C4): Reduced in lupus and MPGN.
- ASO titre, Hepatitis B, HIV screening as indicated.
Imaging
- Renal ultrasound: Usually normal in MCD; may show increased echogenicity in chronic or secondary disease.
- Chest X-ray: May reveal pleural effusion.
Kidney Biopsy
Indicated when:
- Age <1 year or >10 years
- Gross haematuria
- Persistent hypertension or renal failure
- Low complement levels
- Steroid resistance or frequent relapses
Diagnosis
The diagnosis of nephrotic syndrome is made clinically and supported by laboratory findings:
Diagnostic criteria:
- Proteinuria >3+ on dipstick
- Serum albumin <25 g/L
- Oedema
- Hyperlipidemia
The child is classified based on steroid responsiveness as:
- Steroid-sensitive nephrotic syndrome (SSNS)
- Steroid-resistant nephrotic syndrome (SRNS)
- Frequent relapser or steroid-dependent
Management
The approach to treatment depends on the underlying cause and the child’s response to steroids.
Emergency and Supportive Care
Hospital admission is warranted for the first presentation or severe relapse with anasarca.
Fluid and salt management
- Restrict sodium intake.
- Maintain appropriate fluid balance, usually restricted to insensible loss plus urine output.
- Daily weight and urine monitoring.
Management of hypovolemia
- Suspect if tachycardia, abdominal pain, or cold extremities occur.
- Give 10–20 mL/kg of 4.5% albumin or normal saline cautiously, followed by furosemide.
Infection prevention
- High risk for peritonitis (commonly Streptococcus pneumoniae), cellulitis, and sepsis.
- Start broad-spectrum antibiotics if infection suspected.
- Pneumococcal and varicella vaccination recommended.
Nutritional support
- Adequate calories and protein (1–2 g/kg/day).
- Avoid high-fat diets to prevent exacerbation of hyperlipidemia.
Specific Treatment
Corticosteroid Therapy
Prednisolone remains the cornerstone of therapy for idiopathic nephrotic syndrome.
Initial episode (ISPN guidelines):
- Prednisolone 60 mg/m²/day (max 60 mg) for 4 weeks, followed by
- 40 mg/m² on alternate days for another 4 weeks, then taper gradually.
Response monitoring:
- Daily urine dipstick for protein.
- Complete remission: 3 consecutive days of negative or trace proteinuria.
Relapse
Reappearance of proteinuria (≥3+) for ≥3 days after remission. Treat with prednisolone 60 mg/m²/day until remission, then taper.
Steroid-Resistant Nephrotic Syndrome (SRNS)
No remission after 4 weeks of adequate steroid therapy. - Evaluate for secondary causes or FSGS (via biopsy).
- Consider calcineurin inhibitors (cyclosporine or tacrolimus), mycophenolate mofetil, or cyclophosphamide.
- Manage under paediatric nephrology care.
Management of Complications
| Infection |
Prompt antibiotic therapy; pneumococcal prophylaxis |
| Hypovolemia |
Albumin infusion + diuretics |
| Thrombosis (DVT, renal vein) |
Anticoagulation (heparin → warfarin) |
| Acute renal failure |
Supportive care, treat underlying cause |
| Dyslipidemia |
Dietary modification; statins if persistent |
| Hypertension |
ACE inhibitors (enalapril) beneficial for proteinuria |
Preparation for Discharge
Before discharge: - Ensure oedema resolution and stable renal function.
- Teach caregivers how to check urine protein at home.
- Educate on signs of relapse and infection prevention.
- Arrange follow-up schedule (weekly initially, then monthly).
- Encourage vaccination where indicated.
Long-Term Management and Follow-Up
- Monitor relapses: Up to 70% of idiopathic cases relapse within 6 months.
- Minimise steroid toxicity: Screen for growth retardation, obesity, cataracts, and hypertension.
- Address psychosocial impact: School attendance and family anxiety.
- Nephrology referral: For steroid dependence or resistance.
Complications
Acute
- Infection (spontaneous bacterial peritonitis, cellulitis)
- Hypovolemia and shock
- Thrombosis (renal vein, cerebral venous sinus)
- Acute renal failure
Chronic
- Persistent proteinuria leading to chronic kidney disease
- Growth retardation and delayed puberty
- Steroid toxicity (hypertension, osteoporosis, Cushingoid features)
Prevention
While idiopathic cases cannot be prevented, complications can be minimized by: - Early diagnosis and appropriate steroid therapy
- Routine immunization, especially pneumococcal and varicella vaccines
- Avoiding nephrotoxic drugs (e.g., NSAIDs)
- Educating families on prompt infection treatment
- Regular follow-up at renal clinics
Prognosis
- Minimal Change Disease: Excellent prognosis; over 90% achieve remission with steroids.
- FSGS or secondary causes: Higher risk of chronic renal failure.
- Steroid-dependent or frequent relapsers: Often require second-line therapy but may maintain long-term renal function.
Relapses often decrease with age, and most children achieve permanent remission by adolescence.
Conclusion
Nephrotic syndrome remains a significant paediatric renal disorder in Ghana, accounting for substantial hospital admissions and morbidity. The majority of cases respond well to corticosteroids, though steroid-resistant forms, particularly FSGS, are increasingly recognized. A sound understanding of its clinical features, complications, and management principles is essential for medical students and practitioners.
Timely diagnosis, infection control, family education, and close follow-up remain the pillars of good outcomes in paediatric nephrotic syndrome.