What is the likely diagnosis and initial management for a 14-year-old girl presenting with periorbital edema, bilateral lower-extremity edema, a small right pleural effusion, and minimal ascites?

Nephrotic Syndrome: Diagnosis and Initial Management

Most Likely Diagnosis

This 14-year-old girl with periorbital edema, bilateral lower-extremity edema, minimal pleural effusion, and minimal ascites most likely has nephrotic syndrome, and you should immediately obtain a urinalysis with urine protein quantification and serum albumin level to confirm the diagnosis. 1, 2

The clinical presentation is classic for nephrotic syndrome, which is characterized by:

• Edema (periorbital and bilateral lower extremities)
• Third-space fluid accumulation (pleural effusion and ascites)
• Expected laboratory findings: proteinuria >3 g/day (or >50 mg/kg/day), hypoalbuminemia <30 g/L, and hypoproteinemia <60 g/L 3

Why This Is Nephrotic Syndrome and Not Infectious Pleural Disease

The provided guidelines on pleural infection in children 4 are not applicable to this case because:

• Infectious pleural effusions are typically unilateral, not bilateral with systemic edema 4
• Parapneumonic effusions present with fever, cough, dyspnea, and pneumonia symptoms, which are absent in this case 4
• The combination of periorbital edema, bilateral lower-extremity edema, pleural effusion, AND ascites indicates a systemic protein-losing state, not localized infection 1, 2

Immediate Diagnostic Workup

Order these tests immediately:

• Urinalysis with urine protein-to-creatinine ratio or 24-hour urine protein collection to quantify proteinuria 2, 5
• Serum albumin and total protein levels to confirm hypoalbuminemia and hypoproteinemia 1, 3
• Complete blood count to assess for anemia and thrombocytosis 4
• Serum electrolytes and creatinine to evaluate renal function and detect inappropriate ADH syndrome 4
• Lipid panel to document hyperlipidemia, which is characteristic of nephrotic syndrome 2, 5
• Blood pressure measurement to identify hypertension, which may suggest focal segmental glomerulosclerosis rather than minimal change disease 3

Age-Specific Diagnostic Considerations

In a 14-year-old, minimal change disease remains the most common cause of primary nephrotic syndrome, but focal segmental glomerulosclerosis becomes increasingly prevalent in adolescents. 2, 6

• If proteinuria >3.5 g/day, hypoalbuminemia <25 g/L, no hematuria, no hypertension, and normal renal function are present, this suggests minimal change disease and a corticosteroid trial can be initiated without renal biopsy 3
• If hematuria, hypertension, or renal dysfunction are present, renal biopsy is indicated to differentiate focal segmental glomerulosclerosis from other glomerular diseases 3

Initial Management Algorithm

Step 1: Confirm the diagnosis with laboratory testing as outlined above 2, 5

Step 2: Assess for life-threatening complications:

• Measure oxygen saturation; levels <92% indicate severe disease requiring urgent intervention 4
• Evaluate for signs of infection, particularly spontaneous bacterial peritonitis, which is a serious complication of nephrotic syndrome 2
• Assess for thrombotic risk: albumin <20 g/L significantly increases risk of venous thromboembolism, including pulmonary embolism 3

Step 3: Initiate supportive management:

• Sodium restriction (1-2 g/day) to reduce edema formation 1
• Loop diuretics (furosemide) for symptomatic edema relief, but use cautiously to avoid intravascular volume depletion 1
• Consider prophylactic anticoagulation if serum albumin <20 g/L, given the high thrombotic risk in nephrotic syndrome 3

Step 4: Determine need for renal biopsy versus empiric corticosteroid therapy:

• In adolescents with typical minimal change disease features (no hematuria, no hypertension, normal renal function), initiate prednisone 60 mg/m²/day (maximum 80 mg/day) for 4-6 weeks 2
• If atypical features are present (hematuria, hypertension, renal dysfunction, age >10 years with first presentation), perform renal biopsy before starting immunosuppression 2, 3

Critical Pitfalls to Avoid

Do not assume this is a primary pulmonary or infectious process based on the pleural effusion alone; the constellation of periorbital edema, bilateral lower-extremity edema, and ascites mandates evaluation for nephrotic syndrome 1, 2

Do not delay anticoagulation assessment; nephrotic syndrome with albumin <20 g/L carries significant risk of pulmonary embolism and deep vein thrombosis due to urinary loss of antithrombin III 3

Do not perform renal biopsy without first correcting coagulopathy if anticoagulation is required for thrombotic complications; in such cases, consider empiric corticosteroid therapy for presumed minimal change disease 3

Do not overlook secondary causes of nephrotic syndrome, including systemic lupus erythematosus, which should be considered in adolescent females 2, 6

Monitoring and Follow-Up

Monitor daily weights and urine output to assess response to diuretic therapy 1

Repeat serum albumin and urine protein measurements after 2-4 weeks of corticosteroid therapy to assess treatment response 2

If no response after 4-6 weeks of corticosteroids, the patient has steroid-resistant nephrotic syndrome and requires renal biopsy and alternative immunosuppression (calcineurin inhibitors, mycophenolate mofetil, or rituximab) 2, 5