What is minimal change kidney disease?

What is Minimal Change Disease?

Minimal change disease (MCD) is a primary glomerular disorder characterized by massive proteinuria and nephrotic syndrome, with the pathologic hallmark being normal-appearing glomeruli on light microscopy but diffuse effacement of podocyte foot processes on electron microscopy. 1, 2

Epidemiology and Clinical Significance

• MCD accounts for 70-90% of nephrotic syndrome cases in children over 1 year of age, making it the most common cause of childhood nephrotic syndrome 3, 2, 4
• In adults, MCD represents approximately 15-30% of idiopathic nephrotic syndrome cases, with the percentage decreasing with increasing age 3, 2
• Secondary causes of MCD occur in approximately 13% of adult cases and must be excluded, as treatment targets the underlying etiology 3

Pathophysiology

• The disease results from immunologic dysregulation combined with podocyte modifications that alter glomerular basement membrane integrity, leading to massive proteinuria 2
• The specific etiology remains unknown, though oxidative stress-mediated mechanisms and immune dysregulation have been proposed 5
• Genetic mutations affecting podocyte structures (WT1, NPHS2, CD2AP, ACTN4, TRPC6) can produce similar histologic patterns, though their incidence is significantly higher in children than adults 1

Clinical Presentation

MCD presents with the full nephrotic syndrome: 1, 6

• Massive proteinuria ≥3.5 g/day in adults (≥40 mg/m²/hour or spot urine protein-to-creatinine ratio ≥2 g/g in children) 6
• Hypoalbuminemia <3.0 g/dL in adults (<2.5 g/dL in children) 1, 6
• Edema 1, 6
• Hypercholesterolemia is commonly present 1

Atypical Features in Adults

Unlike the classic pediatric presentation, adult MCD can present with features that make it clinically indistinguishable from focal segmental glomerulosclerosis: 3

• Microscopic hematuria may be present 3
• Hypertension can occur 3, 7
• Renal insufficiency may be present at diagnosis 3

Acute Kidney Injury Complication

Acute kidney injury (AKI) complicates approximately 20-33% of adult MCD cases, a phenomenon rarely seen in children except with intercurrent complications 4, 7

Risk factors for AKI in MCD include: 4, 7

• Male sex and age >50 years 4
• Massive proteinuria and severe hypoalbuminemia 4
• Background hypertension and vascular lesions on kidney biopsy 4
• Diuretic-induced hypovolemia and nephrotoxic agents 4

The mechanism involves endothelin-1-induced vasoconstriction causing ischemic tubular necrosis, and AKI may require dialysis for weeks to months until proteinuria remission allows resolution 4

Diagnostic Approach

In children with typical presentation (age >1 year, no hematuria, normal blood pressure, normal complement), renal biopsy is not required, and steroid-sensitive nephrotic syndrome is considered synonymous with MCD 2

In adults, renal biopsy is mandatory because clinical features cannot reliably distinguish MCD from other causes of nephrotic syndrome, particularly FSGS 1, 3

Histopathologic Features

• Light microscopy shows normal-appearing glomeruli (hence "minimal change") 2
• Electron microscopy reveals diffuse effacement of podocyte foot processes, the pathologic hallmark 2
• Immunofluorescence is typically negative 2

Important Diagnostic Caveat

The presence of significant hematuria in suspected MCD warrants complete hematuria workup, including assessment for dysmorphic red blood cells and red cell casts, as this suggests an alternative glomerular disease process 8

Prognosis and Natural History

Long-term kidney survival is excellent in MCD patients who respond to glucocorticoids, with fewer than 5% progressing to end-stage renal disease and patient survival of 83-98% at 15 years 1, 3

However, relapse rates are extremely high: 9, 3

• 34-85% of adults experience relapses 9
• Up to 71% of children relapse 9
• Relapses occur more frequently in younger adults (<45 years) and typically within the first 6-12 months after remission 3

Steroid-resistant forms may subsequently reveal themselves as FSGS, indicating worse prognosis 2

Special Considerations

Patients with mesangial IgA deposition and histologic features otherwise consistent with MCD should be treated according to MCD guidelines, not as IgA nephropathy 1

Spontaneous remission is extremely rare, emphasizing the critical importance of initiating appropriate immunosuppressive therapy 1