Minimal Change Disease

Minimal change disease (MCD), also known as lipoid nephrosis, is the most common cause of nephrotic syndrome in children. The designation “minimal change” comes from the very little changes noticed in kidney biopsies under light microscopy. Hallmark clinical findings include edema, proteinuria, hypoalbuminemia, and hyperlipidemia. Diagnosis is based on clinical suspicion and supportive lab findings. Corticosteroid administration is the cornerstone of management, and the prognosis is largely favorable.

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Minimal change disease (MCD) is a primary glomerular disorder of unclear etiology that causes nephrotic syndrome. The term “minimal” refers to the minimal structural changes of the glomeruli when observed under light microscopy.


  • MCD is the most common cause of nephrotic syndrome in children.
    • Accounts for 90% of cases of nephrotic syndrome in children < 6 years old
    • Accounts for 50% of cases of nephrotic syndrome in children > 10 years old
  • Incidence: 2 per 100,000 children per year
  • The male-to-female ratio is 2:1 in younger children.
  • Equal incidence between genders in adolescents


  • Primary: 90% of cases idiopathic
  • Secondary causes: 
    • NSAIDs
    • Hematologic malignancies
    • Infection
    • Immunization
    • Allergic reactions
    • Autoimmune disorders


  • Nephrotic syndrome’s primary symptom:
    • Edema
    • Hyperproteinuria
    • Hypoalbuminemia
    • Hyperlipidemia
  • A series of pathologic processes lead to the signs and symptoms of MCD:
    • T cell cytokine secretion → glomerular podocyte damage → loss of anionic charge of the glomerular basement membrane → ↑ glomerular permeability → selective proteinuria → loss of albumin
    • ↓ Serum albumin → ↓ intravascular colloid pressure → intravascular fluid loss → edema
    • ↓ Serum albumin → ↑ liver production of lipoproteins → ↑ cholesterol and triglycerides
    • Urinary loss of immunoglobulins → ↑ risk of infection with encapsulated bacteria
    • Urinary loss of antithrombin III, protein C, and protein S → hypercoagulable state
Effacement of the foot processes of podocytes

Electron microscope (left) and diagram (right) showing effacement of the foot processes of podocytes

Image: “Managing a locally advanced malignant thymoma complicated by nephrotic syndrome: a case report” by Teoh DC, El-Modir A. License: CC BY 2.0, edited by Lecturio.

Clinical Presentation

  • History:
    • Sudden onset of symptoms 
    • Sometimes preceded by upper respiratory infection
    • Increased urination
    • Weight gain
  • Examination: soft, pitting edema:
    • Periorbital
    • Peripheral
    • Scrotal
    • Labial
    • Ascites
    • Pleural effusion
    • Pericardial effusion
  • Typically normotensive (90% of patients)
Edema due to nephrotic syndrome

Nephrotic syndrome:
The condition is accompanied by retention of water and sodium. The image shows facial swelling/edema. The degree to which edema occurs can vary. There may be slight edema in the eyelids that decreases during the day, swelling affecting the lower limbs, generalized swelling, or full-blown anasarca.

Image: “Nephrotic syndrome” by Charles Picavet. License: Public Domain


  • Urine:
    • First morning urine dip with 3+ or 4+ protein
    • Spot urine protein: creatinine ratio > 2
    • 24-hour urine protein > 40 mg/m2/hour
    • Negative microscopic blood
    • Microscopy with fatty casts
  • Serum:
    • Albumin < 2.5 g/dL
    • Total cholesterol and triglycerides > 200 mg/dL
    • Normal-to-elevated creatinine
    • Normal-to-low sodium
    • Hemoconcentration
    • Thrombocytopenia
    • Normal C3 and C4 complement levels
  • Kidney biopsy:
    • Performed if unresponsive to treatment or atypical MCD presentation
    • Light microscopy: normal to minimal mesangial proliferation
    • Immunofluorescence: negative for antibody complex deposition
    • Electron microscopy: shows podocyte fusion and effacement
Electron microscopy of a glomerulus seen in a patient with minimal change disease

Electron microscopy of a glomerulus seen in a patient with minimal change disease (MCD):
In minimal change disease, podocytes are fused, appearing as a single layer (white arrows).
Electron-dense deposits are not seen in MCD, and the glomerular basement membrane remains of normal thickness distinguish it from other glomerular diseases.

Image: “Pembrolizumab-associated minimal change disease in a patient with malignant pleural mesothelioma” by BMC Cancer. License: CC BY 4.0



  • Lifestyle changes:
    • Sodium restriction < 3 g/day
    • Fluid restriction
    • Adequate dietary protein intake
    • Low-cholesterol diet
  • Medication:
    • Corticosteroids:
      • Oral prednisone
      • IV methylprednisolone
      • The goal is remission of proteinuria.
    • Diuretics:
      • Commonly utilized in adults
      • Rarely used in children, only in cases of severe edema

Classification based on response to corticosteroids

  • Steroid responsive:
    • > 90% of cases
    • Best prognosis
    • Remission with corticosteroid course
    • Slow taper to discontinue steroids
    • Relapse possibility:
      • No relapse in approximately 30%
      • Infrequent relapse in approximately 30% → repeat corticosteroid course
      • Frequent relapse in approximately 40% → steroid dependent
  • Steroid dependent: initial remission with relapse during steroid course or within 2 weeks after course completion 
  • Steroid resistant:
    • Worse prognosis
    • Failure to achieve remission after 8-week corticosteroid course
    • Need to investigate other causes of nephrotic syndrome other than MCD:
      • Biopsy
      • Genetic testing


  • Renal:
    • AKI
    • Chronic renal failure (CRF)
  • Thromboembolic events:
    • Pulmonary embolism (PE)
    • Renal vein thrombosis
    • Prevention with ambulation and anticoagulants
  • Infections:
    • Spontaneous bacterial peritonitis
    • Bacteremia
    • Cellulitis
    • Pneumonia
    • Protect with immunizations:
      • Pneumococcal 23 valent
      • Influenza
  • Medication related:
    • Effects of prolonged corticosteroid administration
    • Progression to steroid dependency
    • Requires transition to other immunosuppressants:
      • Levamisole
      • Mycophenolate
      • Cyclosporine

Differential Diagnosis

  • Nephritic syndrome: a form of kidney disease caused by immune-mediated inflammation and injury of the glomeruli. Clinical presentation is characterized by the combination of hematuria, proteinuria, hypertension, and renal insufficiency. Examples include post-streptococcal glomerulonephritis and Henoch-Schonlein purpura. Management is dependent on the specific cause.
  • Liver failure: general term referring to impaired liver function by various causes. Hypoalbuminemia and edema are common clinical findings. A lack of increased urinary protein excretion differentiates liver failure from MCD as a cause of nephrotic syndrome. 
  • Heart failure: general term referring to impaired cardiac function by various causes. Edema is a common clinical feature. Other clinical findings, including murmurs, gallops, and dyspnea, differentiate heart failure from MCD as a cause of nephrotic syndrome. 
  • Protein malnutrition: kwashiorkor and reduced protein intake can be correlated with reduced protein synthesis, reduced serum albumin, and total protein levels.
  • Congenital and infantile nephrotic syndrome: early presentation of this form of nephrotic syndrome prior to 12 months of age differentiates it from MCD. Early onset is worrisome for genetic etiology.


  1. Kamil, ES. (2019). Minimal change disease. In Lerma, E., et al. (Eds.). Nephrology secrets. pp. 179–185.
  2. Erkan, E. (2020). Nephrotic syndrome. In Kliegman, RM., et al. (Eds.) Nelson textbook of pediatrics. pp. 2752–2760.e3
  3. Feehally, J, Floege, J. (2019). Introduction to glomerular disease: Histologic classification and pathogenesis. In Feehally, J., et al. (Eds.). Comprehensive clinical nephrology. pp. 199–208.e1.
  4. International Study of Kidney Disease in Children. (1978). Nephrotic syndrome in children: Prediction of histopathology from clinical and laboratory characteristics at time of diagnosis: A report of the international study of kidney disease in children. Kidney Int. 13(2),159–165.
  5. McKinney, PA, et al. (2001). Time trends and ethnic patterns of childhood nephrotic syndrome in Yorkshire, UK. Pediatr Nephrol. 16(12),1040–1044. 
  6. Gipson, DS, et al. (2009). Management of childhood-onset nephrotic syndrome. Pediatrics. 124(2),747–757. 
  7. Vivarelli, M, et al. (2017). Glomerular diseases: Update for the clinician, minimal change disease. Clinical Journal of the American Society of Nephrology. 12(2),332–335.

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