Nephrotic Syndrome in Children: Clinical Case and Viva QnA
Clinical Case of Nephrotic Syndrome in Children
Clinical Case: Nephrotic Syndrome in a 4-year-old Boy
A 4-year-old boy is brought to the pediatric clinic by his mother with complaints of generalized swelling of his body for the past week. The mother reports the following:
- Swelling started around the eyes and gradually progressed to involve the entire face, abdomen, and lower limbs
- Decreased urine output over the last 3 days
- No history of fever, joint pain, or skin rash
- No recent history of throat infection or any other illness
- No family history of kidney disease
On physical examination:
- Weight: 22 kg (increased from 18 kg at last well-child visit 2 months ago)
- Blood Pressure: 110/70 mmHg (slightly elevated for age)
- Generalized edema, most prominent in the periorbital region and lower extremities
- Distended abdomen with shifting dullness, suggestive of ascites
- No skin rash or joint swelling
Laboratory findings:
- Urinalysis: 4+ protein, no hematuria
- 24-hour urine protein: 2.8 g/m²/day (severe proteinuria)
- Serum albumin: 1.8 g/dL (hypoalbuminemia)
- Total cholesterol: 320 mg/dL (hypercholesterolemia)
- Serum creatinine: 0.4 mg/dL (normal)
- Complement C3 and C4 levels: Normal
Based on these findings, the child is diagnosed with Nephrotic Syndrome, likely Minimal Change Disease given his age and presentation. He is admitted for initiation of treatment with oral prednisolone and careful monitoring of fluid status and electrolytes.
5 Different Clinical Presentations of Nephrotic Syndrome in Children
Variety of Clinical Presentations in Pediatric Nephrotic Syndrome
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Classic Presentation
A 3-year-old girl presents with:
- Sudden onset of periorbital edema, progressing to generalized edema
- Weight gain
- Decreased urine output
- No hypertension or hematuria
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Atypical Age Presentation
A 14-year-old boy presents with:
- Gradual onset of leg swelling and abdominal distention
- Fatigue and loss of appetite
- Mild hypertension
- Microscopic hematuria on urinalysis
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Infection-Associated Presentation
A 5-year-old girl presents with:
- Edema developing a week after a streptococcal throat infection
- Low-grade fever
- Gross hematuria
- Hypertension
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Rapid Progressive Presentation
A 10-year-old boy presents with:
- Rapid onset of severe edema and ascites over 2-3 days
- Oliguria
- Severe hypertension
- Signs of fluid overload (tachypnea, crackles in lung bases)
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Steroid-Resistant Presentation
A 6-year-old girl presents with:
- Persistent edema and proteinuria despite 4 weeks of steroid therapy
- Progressive azotemia
- Hypertension
- Family history of kidney disease
25 Viva Questions and Answers on Nephrotic Syndrome in Children
Viva Questions and Answers: Nephrotic Syndrome in Children
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Q: What is the definition of Nephrotic Syndrome?
A: Nephrotic Syndrome is defined by the presence of:
- Heavy proteinuria (>40 mg/m²/hour or protein/creatinine ratio >2.0 mg/mg)
- Hypoalbuminemia (serum albumin <2.5 g/dL)
- Edema
- Hyperlipidemia (often present but not required for diagnosis)
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Q: What is the most common cause of Nephrotic Syndrome in children?
A: The most common cause of Nephrotic Syndrome in children is Minimal Change Disease (MCD), accounting for approximately 80-90% of cases in children under 10 years of age.
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Q: What are the other causes of Nephrotic Syndrome in children?
A: Other causes include:
- Focal Segmental Glomerulosclerosis (FSGS)
- Membranous Nephropathy
- Membranoproliferative Glomerulonephritis
- IgA Nephropathy
- Congenital Nephrotic Syndrome
- Secondary causes (e.g., lupus nephritis, Henoch-Schönlein purpura, infections)
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Q: What is the typical age of onset for idiopathic Nephrotic Syndrome in children?
A: The peak incidence of idiopathic Nephrotic Syndrome occurs between 2-8 years of age, with the median age of onset around 2.5 years.
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Q: How does the underlying pathophysiology of Nephrotic Syndrome lead to edema?
A: The pathophysiology involves:
- Increased glomerular permeability leading to proteinuria
- Hypoalbuminemia resulting in decreased oncotic pressure
- Fluid shift from intravascular to interstitial space causing edema
- Activation of the renin-angiotensin-aldosterone system, leading to sodium and water retention
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Q: What are the initial investigations for a child suspected of having Nephrotic Syndrome?
A: Initial investigations should include:
- Urinalysis and urine protein/creatinine ratio
- 24-hour urine protein (if possible)
- Serum albumin, total protein, and cholesterol
- Serum electrolytes, urea, and creatinine
- Complete blood count
- Complement C3 and C4 levels
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Q: What is the first-line treatment for a child with newly diagnosed Nephrotic Syndrome?
A: The first-line treatment is oral corticosteroids, typically prednisone or prednisolone. The standard initial regimen is:
- 60 mg/m²/day or 2 mg/kg/day (maximum 60 mg/day) for 4-6 weeks
- Followed by 40 mg/m²/48 hours or 1.5 mg/kg/48 hours for 4-6 weeks
- Then a gradual taper over 2-3 months
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Q: How is steroid responsiveness defined in Nephrotic Syndrome?
A: Steroid responsiveness is defined as:
- Complete remission: Urine protein negative or trace for 3 consecutive days
- Steroid sensitive: Remission achieved within 4 weeks of daily steroid therapy
- Steroid resistant: Failure to achieve remission after 8 weeks of daily steroid therapy
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Q: What are the criteria for relapse in Nephrotic Syndrome?
A: Relapse is defined as:
- Urine dipstick showing 3+ or 4+ protein for 3 consecutive days
- Often accompanied by recurrence of edema
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Q: What are the indications for renal biopsy in a child with Nephrotic Syndrome?
A: Indications for renal biopsy include:
- Steroid resistance (no remission after 8 weeks of daily steroids)
- Frequent relapses or steroid dependence
- Age of onset <1 year or >12 years
- Persistent hypertension, hematuria, or renal insufficiency
- Low complement levels
- Suspicion of secondary causes
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Q: What are the common complications of Nephrotic Syndrome in children?
A: Common complications include:
- Infections (particularly peritonitis and cellulitis)
- Thromboembolism
- Acute kidney injury
- Hypovolemic crisis
- Growth retardation (often due to prolonged steroid use)
- Hypothyroidism
- Vitamin D deficiency and bone disease
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Q: How is the risk of thromboembolism managed in Nephrotic Syndrome?
A: Management of thromboembolism risk includes:
- Early mobilization and avoiding dehydration
- Consider prophylactic anticoagulation in high-risk patients (e.g., serum albumin <2.0 g/dL, history of thrombosis)
- Low molecular weight heparin or warfarin may be used for prophylaxis
- Full anticoagulation for confirmed thrombosis
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Q: What are the second-line treatment options for frequently relapsing or steroid-dependent Nephrotic Syndrome?
A: Second-line treatment options include:
- Cyclophosphamide
- Mycophenolate mofetil
- Calcineurin inhibitors (cyclosporine, tacrolimus)
- Rituximab
- Levamisole
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Q: How is hypovolemic crisis recognized and managed in Nephrotic Syndrome?
A: Hypovolemic crisis:
- Recognition: Abdominal pain, tachycardia, hypotension, cold extremities, delayed capillary refill
- Management:
- Prompt IV fluid resuscitation (usually 20 mL/kg of normal saline)
- Careful monitoring of fluid status and electrolytes
- Consider albumin infusion (1 g/kg) if severe hypoalbuminemia
- Treat underlying trigger (e.g., diarrhea, vomiting)
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Q: What dietary modifications are recommended for children with Nephrotic Syndrome?
A: Dietary recommendations include:
- Normal protein intake (1-2 g/kg/day)
- Sodium restriction (especially during active disease)
- Adequate caloric intake to prevent catabolism
- Low saturated fat and cholesterol diet
- Calcium and Vitamin D supplementation
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Q: How is edema managed in Nephrotic Syndrome?
A: Edema management includes:
- Sodium restriction
- Judicious use of diuretics (usually loop diuretics like furosemide)
- Albumin infusion may be considered in severe cases, followed by diuretics
- Monitoring for electrolyte imbalances and hypovolemia
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Q: What is the role of ACE inhibitors or ARBs in pediatric Nephrotic Syndrome?
A: ACE inhibitors or ARBs may be used:
- To reduce proteinuria in steroid-resistant cases
- For management of hypertension
- As adjunctive therapy in frequently relapsing or steroid-dependent cases
- Caution: Monitor renal function and potassium levels closely
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Q: How is congenital Nephrotic Syndrome different from other forms of childhood Nephrotic Syndrome?
A: Congenital Nephrotic Syndrome:
- Presents within the first 3 months of life
- Often caused by genetic mutations (e.g., NPHS1, NPHS2)
- Usually resistant to steroid therapy
- May require early nephrectomy and renal replacement therapy
- Has a poorer prognosis compared to other forms
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Q: What are the long-term outcomes for children with Nephrotic Syndrome?
A: Long-term outcomes vary:
- Steroid-sensitive cases: Generally good prognosis, most achieve long-term remission by adulthood
- Steroid-resistant cases: Higher risk of progression to end-stage renal disease
- Frequent relapses: May have complications from prolonged steroid use
- FSGS: Variable prognosis, higher risk of renal failure
- Regular follow-up needed to monitor for long-term complications and renal function
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Q: How is the transition to adult care managed for adolescents with Nephrotic Syndrome?
A: Transition to adult care involves:
- Gradual process starting in early adolescence
- Education about the disease, medications, and self-management
- Joint clinics with pediatric and adult nephrologists
- Addressing psychosocial aspects and adherence issues
- Ensuring continuity of care and medical records transfer
- Discussing reproductive health and genetic counseling if applicable
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Q: What is the role of genetic testing in pediatric Nephrotic Syndrome?
A: Genetic testing in Nephrotic Syndrome:
- Useful in congenital and familial cases
- Can identify specific mutations (e.g., NPHS1, NPHS2, WT1)
- Helps in predicting steroid responsiveness and prognosis
- Guides management decisions and genetic counseling
- Particularly important in steroid-resistant cases
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Q: How does the management of Nephrotic Syndrome differ in developing countries?
A: Management in developing countries may involve:
- Limited access to specialty care and diagnostic facilities
- Use of shorter steroid regimens to improve adherence
- Higher incidence of infections as complications
- Limited availability of second-line immunosuppressive agents
- Greater emphasis on community-based follow-up and education
- Challenges in long-term monitoring and management of complications
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Q: What are the indications for hospitalization in a child with Nephrotic Syndrome?
A: Indications for hospitalization include:
- Severe edema or anasarca
- Suspected infection (especially peritonitis)
- Hypovolemic crisis
- Thromboembolism
- Severe hypertension
- Acute kidney injury
- Initial presentation for education and treatment initiation (in some centers)
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Q: How is the risk of infection managed in children with Nephrotic Syndrome?
A: Management of infection risk includes:
- Prompt treatment of infections
- Pneumococcal vaccination (and consideration of other encapsulated bacteria vaccines)
- Annual influenza vaccination
- Avoiding live vaccines during high-dose immunosuppression
- Prophylactic antibiotics in some high-risk cases
- Education about infection prevention and early recognition
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Q: What is the approach to managing hyperlipidemia in Nephrotic Syndrome?
A: Management of hyperlipidemia involves:
- Primary focus on treating the underlying Nephrotic Syndrome
- Dietary modifications (low saturated fat and cholesterol diet)
- Consider statins in persistent hyperlipidemia, especially in adolescents
- Monitor for potential side effects of lipid-lowering medications
- Assess cardiovascular risk factors in long-standing cases
