Nephrotic Syndrome Type 2
Disease Details
Family Health Simplified
- Description
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Nephrotic syndrome type 2 is a chronic kidney disorder characterized by significant proteinuria, hypoalbuminemia, hyperlipidemia, and edema, typically caused by genetic mutations affecting podocyte function.
**One-sentence description:** Nephrotic syndrome type 2 is a genetic kidney disorder marked by severe protein loss in urine, leading to swelling and other systemic complications. - Type
- Nephrotic syndrome type 2 is transmitted in an autosomal recessive manner.
- Signs And Symptoms
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Nephrotic Syndrome Type 2 typically presents with the following signs and symptoms:
1. **Proteinuria**: Large amounts of protein in the urine.
2. **Hypoalbuminemia**: Low levels of albumin in the blood.
3. **Edema**: Swelling, often around the eyes, ankles, and feet.
4. **Hyperlipidemia**: Elevated levels of lipids in the blood.
5. **Foamy urine**: Due to high protein content in the urine.
6. **Fatigue**: General feeling of tiredness or lack of energy.
7. **Weight gain**: Due to fluid retention.
8. **Hypertension**: High blood pressure, although this may not always be present.
These symptoms result from the kidneys' inability to retain protein due to glomerular damage. - Prognosis
- Nephrotic syndrome type 2, also known as focal segmental glomerulosclerosis (FSGS), has a variable prognosis. The outlook depends on several factors, including the underlying cause, response to treatment, and severity of kidney damage. Some patients respond well to treatment and achieve remission, while others may progress to chronic kidney disease or end-stage renal disease, requiring dialysis or a kidney transplant. The prognosis is generally better for those who achieve and maintain remission. However, frequent relapses and resistance to therapy can result in a poorer outcome.
- Onset
- Nephrotic syndrome type 2, also known as idiopathic nephrotic syndrome or minimal change disease, typically has an onset in childhood, most commonly between 2 and 6 years of age. However, it can also occur in adults.
- Prevalence
- The prevalence of Nephrotic Syndrome Type 2 (also known as Steroid-Resistant Nephrotic Syndrome type 2) is not well-defined, but it is considered a rare condition. It affects a small percentage of children with nephrotic syndrome, particularly those who do not respond to steroid treatment. Precise prevalence rates are not widely available due to the rarity and variability of the condition.
- Epidemiology
- Nephrotic syndrome type 2, or focal segmental glomerulosclerosis (FSGS), affects individuals regardless of age, though it is more commonly diagnosed in adults. The incidence is estimated to be about 7 per million in adults and 2-3 per million in children annually. It is more prevalent in African Americans compared to Caucasians, with a higher frequency observed in males relative to females. This condition can be primary (idiopathic) or secondary to other diseases and factors such as infections, drugs, or genetic mutations.
- Intractability
- Nephrotic syndrome type 2 can be challenging to treat and may be considered intractable in some cases, particularly when it is resistant to standard therapies such as corticosteroids and immunosuppressive medications. The intractability depends on the underlying cause, response to treatment, and individual patient factors.
- Disease Severity
- Nephrotic syndrome type 2 is a kidney disorder characterized by significant proteinuria, hypoalbuminemia, hyperlipidemia, and edema. Disease severity can vary widely among individuals, ranging from mild to severe. In severe cases, it can lead to complications such as infections, thromboembolism, and progressive kidney damage. Early diagnosis and treatment are crucial for managing symptoms and preventing complications.
- Healthcare Professionals
- Disease Ontology ID - DOID:0080379
- Pathophysiology
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Nephrotic syndrome type 2, also known as steroid-resistant nephrotic syndrome (SRNS), is characterized by significant proteinuria, hypoalbuminemia, hyperlipidemia, and edema. The pathophysiology involves damage to the glomeruli in the kidneys, leading to a loss of the selective barrier function. Key aspects include:
1. **Genetic Mutations**: Mutations in genes such as NPHS2 (encoding podocin) and WT1 are common and lead to structural abnormalities in the podocytes, cells critical for the filtration barrier.
2. **Podocyte Dysfunction**: The integrity of the slit diaphragm is compromised due to these genetic anomalies, causing increased permeability of the glomerular capillary walls.
3. **Immune Mechanisms**: Though less understood, immune system dysregulation may contribute to podocyte injury and proteinuria in some cases.
The result is excessive leakage of proteins into the urine (proteinuria), reducing plasma oncotic pressure and causing fluid to accumulate in tissues (edema). - Carrier Status
- Nephrotic syndrome type 2 (NPHS2-related nephrotic syndrome) is typically caused by mutations in the NPHS2 gene. Carrier status for this condition follows an autosomal recessive inheritance pattern. This means that an individual must inherit two mutated copies of the NPHS2 gene (one from each parent) to manifest the disease. Carriers, who have only one mutated copy and one normal copy of the gene, typically do not show symptoms of nephrotic syndrome type 2.
- Mechanism
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Nephrotic syndrome type 2 is characterized by excessive protein loss in the urine due to glomerular damage. The molecular mechanisms involved typically include:
1. **Genetic Mutations**: Mutations in genes encoding proteins critical for the structure and function of the glomerular filtration barrier, such as NPHS2 (podocin), are commonly implicated.
2. **Podocyte Dysfunction**: Podocytes are specialized cells in the kidney that provide support to the glomerular capillaries. Mutations in podocyte proteins lead to dysfunction, causing the filtration barrier to become leaky to proteins.
3. **Structural Protein Alterations**: Podocin, a protein encoded by NPHS2, is crucial for maintaining slit diaphragm structure. Mutations result in altered or dysfunctional podocin, leading to compromised slit diaphragm integrity and increased protein permeability.
4. **Signaling Pathway Disruptions**: Abnormalities in signaling pathways that maintain podocyte health and function, including those involving nephrin and other slit diaphragm-associated proteins, contribute to the pathology.
5. **Cell-Cell Junction Impairment**: Impaired cell-cell junctions within the glomerulus, particularly at the slit diaphragms between podocyte foot processes, lead to defective filtration and proteinuria.
In summary, nephrotic syndrome type 2 primarily arises due to genetic mutations affecting podocyte structure and function, leading to compromised glomerular filtration and significant proteinuria. - Treatment
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Treatment for Nephrotic Syndrome Type 2 generally involves addressing the underlying causes and managing symptoms. Approaches may include:
1. **Medications**:
- Immunosuppressive drugs like corticosteroids (e.g., prednisone).
- Calcineurin inhibitors (e.g., cyclosporine or tacrolimus).
- ACE inhibitors or ARBs to manage high blood pressure and reduce proteinuria.
- Diuretics to reduce edema.
- Anticoagulants if there is a risk of blood clots.
2. **Dietary Changes**:
- Low-sodium diet to manage edema.
- Possible dietary protein adjustments based on kidney function.
3. **Monitoring and Regular Check-Ups**:
- Frequent monitoring of kidney function, electrolytes, and protein levels in urine.
Early diagnosis and treatment can help manage symptoms and slow the progression of the disease. Regular follow-up with a healthcare provider is critical for optimal care. - Compassionate Use Treatment
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Nephrotic syndrome type 2, also known as steroid-resistant nephrotic syndrome (SRNS), often requires treatments beyond standard therapies due to its resistance to steroids. Compassionate use treatments and off-label or experimental therapies may include:
1. **Calcineurin Inhibitors (CNIs)**: Medications such as cyclosporine and tacrolimus are used to reduce proteinuria and preserve kidney function.
2. **Rituximab**: This monoclonal antibody targets B-cells and has been used off-label in patients who do not respond to CNIs.
3. **ACTH (Adrenocorticotropic Hormone)**: Used experimentally to reduce proteinuria.
4. **ACE Inhibitors/ARBs**: While not experimental, these are commonly used to reduce proteinuria and protect kidney function.
5. **Plasmapheresis**: This treatment may be considered in severe cases to remove antibodies from the blood.
6. **Mycophenolate Mofetil (MMF)**: Used off-label to modulate the immune system and reduce proteinuria.
These treatments are typically considered when standard approaches fail and are based on individual patient needs and the potential for benefit versus risks. - Lifestyle Recommendations
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For nephrotic syndrome type 2, lifestyle recommendations focus on managing symptoms and reducing complications. Recommendations may include:
1. **Diet:**
- **Low-Sodium Diet:** Helps control swelling (edema) and blood pressure.
- **Fluid Restriction:** Particularly if swelling and fluid retention are severe.
- **Healthy Protein Consumption:** Though protein loss in urine is significant, intake should be balanced to avoid overloading the kidneys.
- **Low-Saturated Fat Diet:** Reduces the risk of cardiovascular disease, which is higher in nephrotic syndrome patients.
2. **Exercise:**
- **Moderate Activity:** Engage in regular, low-impact exercise such as walking or swimming to maintain overall health and manage weight.
3. **Medication Adherence:**
- Follow prescribed treatments, including corticosteroids or other immunosuppressive drugs, to manage the underlying condition and symptoms.
4. **Regular Monitoring:**
- **Frequent Check-Ups:** Regular visits to a healthcare provider to monitor kidney function and general health.
- **Blood Pressure Monitoring:** Keep track of blood pressure to avoid hypertension-related complications.
5. **Avoid Over-the-Counter Medications:**
- Some non-prescription drugs like NSAIDs can worsen kidney function. Always consult with a healthcare provider before taking new medications.
6. **Smoking Cessation and Alcohol Moderation:**
- Quit smoking and limit alcohol intake to reduce additional strain on the kidneys and overall health.
7. **Manage Other Health Conditions:**
- Keep other conditions like diabetes or hypertension well-controlled as they can exacerbate kidney issues.
8. **Vaccinations:**
- Stay up-to-date with vaccinations to reduce the risk of infections, as nephrotic syndrome can affect the immune system.
Collaborating with a dietitian, nephrologist, and primary care physician can help tailor these recommendations to individual needs. - Medication
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Nephrotic syndrome type 2, also known as steroid-resistant nephrotic syndrome (SRNS), is a genetic disorder affecting kidney function. Treatment often involves medications such as:
1. **Angiotensin-converting enzyme (ACE) inhibitors** or **Angiotensin II receptor blockers (ARBs)**: These help reduce proteinuria (protein in the urine) and control blood pressure.
2. **Immunosuppressive agents**: Drugs such as calcineurin inhibitors (e.g., cyclosporine, tacrolimus), mycophenolate mofetil, or rituximab might be prescribed to suppress the immune response.
3. **Diuretics**: To manage swelling (edema) by helping the kidneys remove excess fluid.
4. **Anticoagulants**: To prevent blood clots, which can be a complication of nephrotic syndrome.
5. **Statins**: To manage hyperlipidemia (high levels of lipids in the blood).
It's important to monitor and manage any associated complications, and treatments are usually tailored to the individual patient based on their specific needs and underlying genetic causes. - Repurposable Drugs
- Repurposable drugs for Nephrotic Syndrome Type 2 are not well established in the medical literature. Treatment typically focuses on managing symptoms and underlying causes using corticosteroids, immunosuppressants like cyclosporine or tacrolimus, and angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) to control blood pressure and reduce proteinuria. However, ongoing research may identify new uses for existing medications.
- Metabolites
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Nephrotic syndrome type 2 is associated with metabolites such as:
1. **Albumin**: Decreased levels due to excessive loss in the urine.
2. **Cholesterol**: Elevated levels commonly found in nephrotic syndrome due to altered lipid metabolism.
3. **Triglycerides**: Increased levels as a secondary effect of nephrotic syndrome.
4. **Serum Creatinine**: May be elevated if kidney function is impaired.
5. **Urea**: Levels can be increased if there is significant impairment in kidney function.
These metabolites are commonly monitored to assess the severity and progression of nephrotic syndrome and its treatment. - Nutraceuticals
- Nutraceuticals for nephrotic syndrome type 2 are not well-established, but supportive approaches may include omega-3 fatty acids for their anti-inflammatory properties and vitamin D to support bone health. Always consult healthcare providers before starting any supplement regimen.
- Peptides
- Nephrotic syndrome type 2 (NS2) is a genetic disorder characterized by the loss of protein in urine, leading to symptoms such as edema, hypoalbuminemia, and hyperlipidemia. The disorder is typically caused by mutations in the NPHS2 gene, which encodes podocin, an important protein in the kidney's filtering system. Treatment focuses on managing symptoms and may include the use of medications such as corticosteroids, immunosuppressants, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin II receptor blockers (ARBs). Peptides and nanoparticles (nan) have not been established as standard therapies for NS2. Research is ongoing into potential novel treatments, including targeted therapies and the use of bioengineered solutions.