Overview
Definition:
Minimal change nephrotic syndrome (MCNS) is the most common cause of nephrotic syndrome in children, characterized by heavy proteinuria, hypoalbuminemia, edema, and hyperlipidemia, with normal appearing glomeruli on light microscopy and effacement of podocyte foot processes on electron microscopy.
Epidemiology:
MCNS accounts for approximately 75-80% of nephrotic syndrome cases in children under 10 years of age, with a bimodal peak incidence between ages 2-5 years
It is more common in boys than girls (2:1 ratio).
Clinical Significance:
MCNS is a clinically significant condition in pediatrics due to its potential for recurrent relapses, complications from nephrotic state, and side effects of long-term immunosuppressive therapy
Early and appropriate management is crucial for favorable outcomes and minimizing morbidity.
Clinical Presentation
Symptoms:
Significant edema, often starting in the face (periorbital) and progressing to the extremities and abdomen
Ascites
Respiratory distress due to pleural effusions
Lethargy
Reduced urine output (oliguria) in severe cases
Vomiting or diarrhea
Abdominal pain.
Signs:
Generalized edema (pitting edema)
Ascites
Pleural effusions
Pulmonary edema
Hypertension (can occur, especially with volume overload or steroid use)
Normal blood pressure is common in untreated MCNS
Pale, swollen appearance.
Diagnostic Criteria:
Nephrotic syndrome is defined by the presence of: 1
Heavy proteinuria (urine protein-to-creatinine ratio > 2 mg/mg or 24-hour urine protein > 40 mg/m²/day)
2
Hypoalbuminemia (serum albumin < 2.5 g/dL)
3
Edema
4
Hyperlipidemia (serum cholesterol > 200 mg/dL)
MCNS is diagnosed by exclusion of other causes of nephrotic syndrome, particularly in the absence of hematuria, hypertension, and significant renal impairment at presentation, and confirmed by renal biopsy showing normal glomeruli on light microscopy.
Diagnostic Approach
History Taking:
Detailed history of onset and progression of edema
Recent infections (e.g., upper respiratory tract infection, viral illness) as potential triggers
Family history of kidney disease
Previous episodes of edema or proteinuria
Medications
Allergies
Diet and fluid intake.
Physical Examination:
Thorough assessment of edema distribution and severity
Measurement of abdominal girth for ascites
Auscultation for pleural effusions and signs of pulmonary edema
Evaluation of vital signs including blood pressure
Examination for any signs of underlying systemic disease.
Investigations:
Urine analysis: protein, specific gravity, absence of red blood cells and casts
Urine protein-to-creatinine ratio
Serum biochemistry: albumin, total protein, electrolytes, renal function tests (urea, creatinine), lipid profile (cholesterol, triglycerides)
Complete blood count
Serological tests if infection is suspected (e.g., ASO, viral titers)
Renal ultrasound to rule out structural abnormalities
Renal biopsy is the gold standard for diagnosis, revealing normal glomeruli on light microscopy, absence of significant immune deposits on immunofluorescence, and podocyte foot process effacement on electron microscopy.
Differential Diagnosis:
Other causes of nephrotic syndrome in children: Focal segmental glomerulosclerosis (FSGS), Membranous nephropathy, Membranoproliferative glomerulonephritis (MPGN), Systemic lupus erythematosus (SLE), Henoch-Schönlein purpura (HSP) nephritis, Diabetic nephropathy (rare in children), Drug-induced nephrotic syndrome
Distinguishing features include hematuria, hypertension, renal insufficiency, and specific biopsy findings.
Management
Initial Management:
Supportive care: Fluid and salt restriction
Diuretics (e.g., furosemide, spironolactone) to manage edema and ascites
Close monitoring of fluid balance, electrolytes, and renal function
Treatment of infection if present
Careful attention to nutritional status.
Medical Management:
Corticosteroid therapy is the cornerstone of MCNS treatment
Initial treatment typically involves prednisone 60 mg/m²/day (maximum 80 mg/day) orally in 3 divided doses for 4-6 weeks, followed by a tapering regimen
A common tapering schedule includes alternate-day prednisone 40 mg/m² (maximum 60 mg) every other day for 6-8 weeks, gradually reducing the dose
For frequent relapsers or steroid-dependent cases, other immunosuppressants like cyclophosphamide, cyclosporine, or mycophenolate mofetil may be considered.
Steroid Regimen For Relapse:
Upon relapse (return of heavy proteinuria), re-initiate daily prednisone 60 mg/m²/day for 1 week or until proteinuria resolves, then switch to alternate-day therapy and taper
The duration of alternate-day therapy depends on the frequency of relapses and steroid response.
Prevention Of Relapses:
Strategies include: 1
Steroid tapering to the lowest effective dose
2
Use of steroid-sparing agents (e.g., cyclophosphamide, levamisole, mycophenolate mofetil, cyclosporine) in frequent relapsers or steroid-dependent patients
3
Identifying and managing triggers for relapse, such as infections
4
Patient and family education on early recognition of relapse symptoms.
Supportive Care:
Monitoring for complications: infection (especially during immunosuppression), thromboembolism (prophylaxis may be considered in patients with severe hypoalbuminemia < 1.5 g/dL and significant edema), growth retardation (due to steroids), osteoporosis, cataracts, and hypertension
Nutritional support to ensure adequate protein intake
Vaccination, especially against pneumococcus, is important.
Complications
Early Complications:
Infections (bacterial peritonitis, pneumonia, sepsis) due to impaired immunity and fluid accumulation
Thromboembolic events (renal vein thrombosis, DVT, PE)
Acute kidney injury (AKI) from intravascular volume depletion or hemodynamic instability
Electrolyte imbalances.
Late Complications:
Growth retardation from prolonged steroid use
Osteoporosis
Cataracts
Hyperlipidemia and increased cardiovascular risk
Steroid-induced diabetes mellitus
Hypertension
Steroid resistance (rare in MCNS, suggesting alternative diagnosis).
Prevention Strategies:
Prophylactic antibiotics (e.g., penicillin) may be considered in high-risk patients with frequent relapses
Careful monitoring for signs of infection and prompt treatment
Judicious use of steroids, using the lowest effective dose and duration
Thromboembolism prophylaxis in selected high-risk patients
Close monitoring of growth and bone health
Annual eye examinations for cataracts.
Prognosis
Factors Affecting Prognosis:
Response to steroids is a key prognostic factor
Children who respond to steroids generally have a good prognosis with minimal long-term renal damage
Steroid resistance, frequent relapses, and development of complications can impact prognosis.
Outcomes:
The majority of children with MCNS achieve remission with corticosteroid therapy
About 60% achieve initial remission within 4 weeks
About 20-30% experience infrequent relapses, and about 10-20% develop frequent relapses or become steroid-dependent
Steroid-resistant nephrotic syndrome or progression to FSGS are uncommon in true MCNS.
Follow Up:
Regular follow-up is essential
Initial follow-up includes monitoring for remission, side effects of steroids, and prevention of complications
As children enter remission and steroid dose is reduced, follow-up frequency can decrease
Long-term monitoring is needed for those with frequent relapses or on long-term immunosuppression
Education on recognizing early signs of relapse is crucial.
Key Points
Exam Focus:
MCNS is the most common cause of nephrotic syndrome in children
Diagnosis is often clinical and based on exclusion, with renal biopsy confirming normal glomeruli on light microscopy
Steroids (prednisone) are the mainstay of treatment
Relapse is defined by return of heavy proteinuria.
Clinical Pearls:
Always consider infection as a trigger for relapse or a cause of complications like peritonitis
Differentiate between infrequent relapse, frequent relapse, and steroid dependence to guide long-term management
Consider steroid-sparing agents for frequent relapsers or steroid-dependent patients
Monitor for steroid side effects diligently.
Common Mistakes:
Delayed diagnosis due to overlooking edema or mild proteinuria
Inadequate steroid dosing or duration
Overuse of diuretics without addressing the underlying proteinuria
Failure to monitor for and manage complications like infections and thromboembolism
Incorrectly diagnosing MCNS in the presence of significant hematuria or hypertension, which warrants a biopsy.