SUPERStudy: Minimal Change Disease (MCD) 

By usmlevideoss

Introduction

Minimal Change Disease (MCD) is the most common cause of nephrotic syndrome in children and is characterized by podocyte foot process effacement on electron microscopy without significant findings on light microscopy. It is often steroid-responsive and has a good prognosis.

Etiology

  • Idiopathic (most common)
  • Secondary causes:
  • Medications (NSAIDs, lithium)
  • Malignancies (Hodgkin’s lymphoma)
  • Infections (EBV, Mycoplasma)
  • Allergies (e.g., atopy, food allergies)

Epidemiology

  • Most common cause of nephrotic syndrome in children (80–90%)
  • Less common in adults (~10–15% of nephrotic cases)
  • Slight male predominance in childhood cases

Pathophysiology

Minimal Change Disease (MCD) is primarily a podocyte disorder leading to nephrotic syndrome. The exact cause is not fully understood, but it is believed to involve immune system dysfunction, possibly due to T-cell dysregulation, leading to the release of circulating permeability factors (e.g., IL-13 or hemopexin). These factors cause podocyte injury, resulting in effacement (flattening) of podocyte foot processes on electron microscopy.

Podocyte dysfunction leads to loss of the negative charge on the glomerular basement membrane (GBM), increasing permeability to albumin and causing selective proteinuria (mainly albumin loss). Since albumin helps maintain oncotic pressure, its loss leads to hypoalbuminemia, which causes fluid to shift from the intravascular space to the interstitial space, resulting in generalized edema. In response, the liver increases lipid synthesis, leading to hyperlipidemia, a hallmark of nephrotic syndrome. Importantly, there is no immune complex deposition or complement activation, distinguishing MCD from immune-mediated glomerular diseases.

 

Clinical Manifestations

  • Nephrotic syndrome features:
  • Generalized edema (periorbital in the morning, peripheral later)
  • Proteinuria >3.5 g/day (or >40 mg/m²/hr in children)
  • Hypoalbuminemia
  • Hyperlipidemia (due to compensatory hepatic lipid synthesis)
  • Frothy urine (due to proteinuria)
  • No hematuria, hypertension, or azotemia (unlike other glomerular diseases)

Diagnosis

  • Urinalysis: Heavy proteinuria (>3.5 g/day) with no significant hematuria
  • Serum findings: Hypoalbuminemia, hyperlipidemia, normal creatinine
  • Renal biopsy:
  • Light Microscopy: Normal (hence “minimal change”)
  • Electron Microscopy: Podocyte foot process effacement
  • No immune deposits on immunofluorescence

Treatment

  • First-line: Corticosteroids (Prednisone) – most cases respond within 4–8 weeks
  • If steroid-resistant or frequently relapsing:
  • Calcineurin inhibitors (Cyclosporine, Tacrolimus)
  • Rituximab (anti-CD20 therapy)
  • Supportive care:
  • ACE inhibitors/ARBs to reduce proteinuria
  • Salt and fluid restriction to manage edema
  • Diuretics (cautiously in severe edema)

Prognosis

  • Excellent prognosis in children: 90% respond to steroids
  • Frequent relapses (steroid-dependent cases) occur in ~40%
  • Rare progression to end-stage renal disease (ESRD)

Memory Aid / Mnemonic

“CHANGE”

  • Children (most common cause of nephrotic syndrome in kids)  
  • Heavy proteinuria (nephrotic-range, selective proteinuria)  
  • Albumin low (hypoalbuminemia)  
  • No hematuria or hypertension (distinguishes from other glomerular diseases)  
  • Glucocorticoids work (first-line treatment, high-dose corticosteroids)  
  • Electron microscopy shows podocyte effacement (diagnostic hallmark)  

SUPERPoint

Minimal Change Disease is the leading cause of nephrotic syndrome in children, characterized by podocyte foot process effacement on electron microscopy, massive proteinuria, edema, and steroid responsiveness.

SUPERFormula

Child presents with periorbital swelling + pitting edema in lower limbs + Nephrotic syndrome + Selective proteinuria (albumin loss) + hyperlipidemia + Normal light microscopy + Podocyte foot process effacement on EM + Steroid responsiveness = Minimal Change Disease

Reference

Kamil ES. Minimal Change Disease. In: Lerma EV, Rosner MH, Perazella MA. eds. CURRENT Diagnosis & Treatment: Nephrology & Hypertension, 2e. McGraw-Hill Education; 2017