Minimal Change Disease

Minimal change disease (MCD), also known as lipoid nephrosis, is the most common cause of nephrotic syndrome in children Nephrotic Syndrome in Children Nephrotic syndrome is a renal disorder caused by conditions that increase the permeability of the glomerular filtration barriers. Nephrotic syndrome affects all age groups but has a higher pediatric prevalence. This disorder can be due to both primary (renal) and secondary (systemic) causes. 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 Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). 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.

Last update:

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Table of Contents

Share this concept:

Share on facebook
Share on twitter
Share on linkedin
Share on reddit
Share on email
Share on whatsapp

Overview

Definition

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.

Epidemiology

  • MCD is the most common cause of nephrotic syndrome in children Nephrotic Syndrome in Children Nephrotic syndrome is a renal disorder caused by conditions that increase the permeability of the glomerular filtration barriers. Nephrotic syndrome affects all age groups but has a higher pediatric prevalence. This disorder can be due to both primary (renal) and secondary (systemic) causes. Nephrotic Syndrome in Children.
    • Accounts for 90% of cases of nephrotic syndrome in children Nephrotic Syndrome in Children Nephrotic syndrome is a renal disorder caused by conditions that increase the permeability of the glomerular filtration barriers. Nephrotic syndrome affects all age groups but has a higher pediatric prevalence. This disorder can be due to both primary (renal) and secondary (systemic) causes. Nephrotic Syndrome in Children < 6 years old
    • Accounts for 50% of cases of nephrotic syndrome in children Nephrotic Syndrome in Children Nephrotic syndrome is a renal disorder caused by conditions that increase the permeability of the glomerular filtration barriers. Nephrotic syndrome affects all age groups but has a higher pediatric prevalence. This disorder can be due to both primary (renal) and secondary (systemic) causes. 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

Etiology

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

Pathophysiology

  • 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 Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
    • ↓ Serum albumin → ↑ liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver production of lipoproteins → ↑ cholesterol and triglycerides
    • Urinary loss of immunoglobulins Immunoglobulins Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins → ↑ risk of infection with encapsulated bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview
    • Urinary loss of antithrombin III, protein C, and protein S → hypercoagulable Hypercoagulable Hypercoagulable states (also referred to as thrombophilias) are a group of hematologic diseases defined by an increased risk of clot formation (i.e., thrombosis) due to either an increase in procoagulants, a decrease in anticoagulants, or a decrease in fibrinolysis. Hypercoagulable States state
Effacement of the foot processes of podocytes

Electron microscope (left) and diagram (right) showing effacement of the foot Foot The foot is the terminal portion of the lower limb, whose primary function is to bear weight and facilitate locomotion. The foot comprises 26 bones, including the tarsal bones, metatarsal bones, and phalanges. The bones of the foot form longitudinal and transverse arches and are supported by various muscles, ligaments, and tendons. 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 Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema:
    • Periorbital
    • Peripheral
    • Scrotal
    • Labial
    • Ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites
    • Pleural effusion Pleural Effusion Pleural effusion refers to the accumulation of fluid between the layers of the parietal and visceral pleura. Common causes of this condition include infection, malignancy, autoimmune disorders, or volume overload. Clinical manifestations include chest pain, cough, and dyspnea. Pleural Effusion
    • Pericardial effusion Pericardial effusion Pericardial effusion is the accumulation of excess fluid in the pericardial space around the heart. The pericardium does not easily expand; thus, rapid fluid accumulation leads to increased pressure around the heart. The increase in pressure restricts cardiac filling, resulting in decreased cardiac output and cardiac tamponade. Pericardial Effusion and Cardiac Tamponade
  • 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 Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema. The degree to which edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema occurs can vary. There may be slight edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). 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

Diagnosis

  • 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 Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. 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 Mesothelioma Malignant mesothelioma (usually referred to as simply "mesothelioma") is the malignant growth of mesothelial cells, most commonly affecting the pleura. The majority of cases are associated with occupational exposure to asbestos that occurred > 20 years before clinical onset, which includes dyspnea, chest pain, coughing, fatigue, and weight loss. Malignant Mesothelioma” by BMC Cancer. License: CC BY 4.0

Management

Management

  • 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 Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). 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

Complications

  • Renal:
    • AKI AKI Acute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury
    • Chronic renal failure (CRF)
  • Thromboembolic events:
    • Pulmonary embolism Pulmonary Embolism Pulmonary embolism (PE) is a potentially fatal condition that occurs as a result of intraluminal obstruction of the main pulmonary artery or its branches. The causative factors include thrombi, air, amniotic fluid, and fat. In PE, gas exchange is impaired due to the decreased return of deoxygenated blood to the lungs. Pulmonary Embolism (PE)
    • Renal vein thrombosis
    • Prevention with ambulation and anticoagulants Anticoagulants Anticoagulants are drugs that retard or interrupt the coagulation cascade. The primary classes of available anticoagulants include heparins, vitamin K-dependent antagonists (e.g., warfarin), direct thrombin inhibitors, and factor Xa inhibitors. Anticoagulants
  • Infections:
    • Spontaneous bacterial peritonitis
    • Bacteremia
    • Cellulitis Cellulitis Cellulitis is a common infection caused by bacteria that affects the dermis and subcutaneous tissue of the skin. It is frequently caused by Staphylococcus aureus and Streptococcus pyogenes. The skin infection presents as an erythematous and edematous area with warmth and tenderness. Cellulitis
    • Pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
    • Protect with immunizations:
      • Pneumococcal 23 valent
      • Influenza Influenza Influenza viruses are members of the Orthomyxoviridae family and the causative organisms of influenza, a highly contagious febrile respiratory disease. There are 3 primary influenza viruses (A, B, and C) and various subtypes, which are classified based on their virulent surface antigens, hemagglutinin (HA) and neuraminidase (NA). Influenza typically presents with a fever, myalgia, headache, and symptoms of an upper respiratory infection. Influenza Viruses/Influenza
  • Medication related:
    • Effects of prolonged corticosteroid administration
    • Progression to steroid dependency
    • Requires transition to other immunosuppressants Immunosuppressants Immunosuppressants are a class of drugs widely used in the management of autoimmune conditions and organ transplant rejection. The general effect is dampening of the immune response. Immunosuppressants:
      • Levamisole
      • Mycophenolate
      • Cyclosporine

Differential Diagnosis

  • Nephritic syndrome Nephritic syndrome Nephritic syndrome is a broad category of glomerular diseases characterized by glomerular hematuria, variable loss of renal function, and hypertension. These features are in contrast to those of nephrotic syndrome, which includes glomerular diseases characterized by severe proteinuria, although there is sometimes overlap of > 1 glomerular disease in the same individual. Nephritic Syndrome: a form of kidney disease caused by immune-mediated inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation and injury of the glomeruli. Clinical presentation is characterized by the combination of hematuria, proteinuria, hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. 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 Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver function by various causes. Hypoalbuminemia and edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema are common clinical findings. A lack of increased urinary protein excretion differentiates liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. 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 Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea, differentiate heart failure from MCD as a cause of nephrotic syndrome. 
  • Protein malnutrition Malnutrition Malnutrition is a clinical state caused by an imbalance or deficiency of calories and/or micronutrients and macronutrients. The 2 main manifestations of acute severe malnutrition are marasmus (total caloric insufficiency) and kwashiorkor (protein malnutrition with characteristic edema). Malnutrition in children in resource-limited countries: 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.

References

  1. Kamil, ES. (2019). Minimal change disease. In Lerma, E., et al. (Eds.). Nephrology secrets. pp. 179–185. http://dx.doi.org/10.1016/B978-0-323-47871-7.00035-6
  2. Erkan, E. (2020). Nephrotic syndrome. In Kliegman, RM., et al. (Eds.) Nelson textbook of pediatrics. pp. 2752–2760.e3 http://dx.doi.org/10.1016/B978-0-323-52950-1.00545-9
  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. http://dx.doi.org/10.1016/B978-0-323-47909-7.00016-0
  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. https://pubmed.ncbi.nlm.nih.gov/713276/
  5. McKinney, PA, et al. (2001). Time trends and ethnic patterns of childhood nephrotic syndrome in Yorkshire, UK. Pediatr Nephrol. 16(12),1040–1044. https://pubmed.ncbi.nlm.nih.gov/11793096/ 
  6. Gipson, DS, et al. (2009). Management of childhood-onset nephrotic syndrome. Pediatrics. 124(2),747–757. https://pubmed.ncbi.nlm.nih.gov/19651590/ 
  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. https://doi.org/10.2215/CJN.05000516

USMLE™ is a joint program of the Federation of State Medical Boards (FSMB®) and National Board of Medical Examiners (NBME®). MCAT is a registered trademark of the Association of American Medical Colleges (AAMC). NCLEX®, NCLEX-RN®, and NCLEX-PN® are registered trademarks of the National Council of State Boards of Nursing, Inc (NCSBN®). None of the trademark holders are endorsed by nor affiliated with Lecturio.

Study on the Go

Lecturio Medical complements your studies with evidence-based learning strategies, video lectures, quiz questions, and more – all combined in one easy-to-use resource.

Learn even more with Lecturio:

Complement your med school studies with Lecturio’s all-in-one study companion, delivered with evidence-based learning strategies.

User Reviews

0.0

()

¡Hola!

Esta página está disponible en Español.

🍪 Lecturio is using cookies to improve your user experience. By continuing use of our service you agree upon our Data Privacy Statement.

Details