What is minimal change disease?

What is Minimal Change Disease?

Minimal change disease (MCD) is a primary glomerular disease characterized by nephrotic syndrome with massive proteinuria (≥3.5 g/day in adults, ≥40 mg/m²/h in children), hypoalbuminemia, edema, and hyperlipidemia, where light microscopy shows no visible glomerular alterations but electron microscopy reveals diffuse podocyte foot process effacement. 1, 2

Epidemiology and Clinical Significance

• MCD is the most common cause of idiopathic nephrotic syndrome in children, accounting for >75% of pediatric cases and up to 90% in children under 5 years of age 1
• In adults, MCD accounts for approximately 10-25% of idiopathic nephrotic syndrome cases, with higher percentages in younger adults 1, 3, 2
• The risk of progression to end-stage renal disease (ESRD) is extremely low in MCD (<5% of patients), making it a relatively benign glomerulopathy compared to other causes of nephrotic syndrome 1, 3

Pathophysiology

• The exact cause remains unknown, but evidence suggests a primary T-cell disorder producing a circulating "glomerular permeability factor" that increases glomerular basement membrane permeability 1
• Immunologic dysregulation and podocyte modifications synergize to alter the integrity of the glomerular basement membrane, resulting in proteinuria 2
• The pathologic hallmark is absence of visible alterations by light microscopy with diffuse foot process effacement on electron microscopy 2

Clinical Presentation

Typical Features

• Sudden onset of nephrotic syndrome with heavy proteinuria, hypoalbuminemia (<3.0 g/dL in adults, <2.5 g/dL in children), edema, and hypercholesterolemia 1
• Absence of significant hematuria is characteristic—the presence of hematuria should prompt consideration of alternative diagnoses 4

Atypical Features in Adults

• Unlike children, adults with MCD may present with microscopic hematuria (seen in up to 58.5% of cases), hypertension, and renal insufficiency, making it clinically indistinguishable from focal segmental glomerulosclerosis (FSGS) 3, 5
• Acute kidney injury (AKI) occurs in approximately 24-25% of adult MCD patients, particularly in older, hypertensive patients with severe hypoalbuminemia and massive proteinuria 5, 6
• Patients with AKI tend to have residual renal dysfunction at follow-up 6

Diagnostic Approach

Children

• Renal biopsy is usually not performed in children if presentation is typical (age >1 year, no hematuria, normal blood pressure, normal complement levels) and the patient responds to oral prednisone at conventional doses 2
• In this setting, steroid-sensitive nephrotic syndrome can be considered synonymous with MCD 2

Adults

• Renal biopsy is mandatory in adults to distinguish MCD from FSGS and other glomerular diseases, as clinical features overlap significantly 1, 3
• Secondary causes of MCD must be excluded, as they occur in approximately 13% of adult cases and require different therapeutic approaches 3

Key Diagnostic Pitfall

• If hematuria is present, perform a complete hematuria workup including assessment for dysmorphic red blood cells and red cell casts, as these findings suggest glomerular bleeding and may indicate a different glomerular disease process 4

Prognosis

• Long-term kidney survival is excellent in MCD patients who respond to glucocorticoids, with patient survival of 83-98% at 15 years 1, 3
• Complete remission of proteinuria occurs in up to 97% of adults with appropriate treatment, though adults require more prolonged therapy (16-28 weeks) compared to children (8 weeks) 3
• Relapses are extremely common, occurring in 71% of children and up to 85% of adult patients 3
• Younger age at onset is an independent risk factor for relapse in adult-onset MCD 5
• Forms of MCD that respond to steroids usually do not lead to chronic renal damage, whereas steroid-resistant forms may subsequently reveal themselves as FSGS on repeat biopsy 2, 6