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Nephrotic Syndrome

Updated : January 11, 2024





Background

Nephrotic syndrome is a kidney disorder characterized by high levels of protein in the urine, low levels of protein in the blood, and swelling of parts of the body due to fluid retention. It is usually caused by damage to the tiny blood vessels in the kidneys, which filter waste out of the blood and pass it out of the body in urine.

It is usually caused by damage to the tiny blood vessels in the kidneys, which filter waste out of the blood and pass it out of the body in urine. It is caused by increased permeability of the damaged basement membrane in the renal glomerulus due to an intrinsic renal disease or an underlying condition such as, systemic lupus, diabetes, neoplasia, or certain drug use.

Epidemiology

It is estimated that approximately 3 out of every 100,000 people in the United States have Nephrotic Syndrome. The prevalence of Nephrotic Syndrome is highest in children under the age of 10, with an estimated incidence of 20-40 cases per 100,000 children under the age of 5.

The mortality rate of varies depending on the underlying cause and severity of the condition. Approximately half of all Nephrotic syndrome patients reach complete remission, and long-term survival is possible. However, those with severe or end-stage kidney disease may have a poorer prognosis.

Anatomy

Pathophysiology

Nephrotic syndrome is caused by damage to the glomeruli. This damage leads to the leakage of proteins in the urine, which can cause proteinuria, edema, and hypoalbuminemia. The exact cause of glomerular damage is not known, but it is thought to be caused by autoimmune disorders, infections. The primary pathophysiology of nephrotic syndrome involves the loss of proteins, most notably albumin, in the urine. Enhanced glomerular permeability causes albuminuria, ultimately leading to hypoalbuminemia.

This reduction in plasma colloid osmotic pressure then causes an increase in transcapillary fluid filtration, leading to edema. The progress of edema is due to a decrease in intravascular oncotic pressure and an increase in hydrostatic capillary pressure, which results in an excessive amount of fluid being filtered from the vascular compartment into the interstitium. This excess fluid exceeds the maximal lymphatic flow, leading to a decrease in plasma volume and an increase in water and sodium retention in the kidneys.

Due to the damage to the glomeruli, they cannot retain proteins, causing them to be filtered out into the urine. As a result, the body cannot maintain the fluid balance in the bloodstream, leading to edema. Additionally, the loss of albumin in the urine causes hypoalbuminemia, leading to complications such as anemia and thrombosis. Long-term complications of nephrotic syndrome can include high cholesterol, kidney failure, and an increased risk of infection.

Etiology

Nephrotic syndrome is primarily caused by intrinsic kidney diseases, such as minimal-change nephropathy, membranous nephropathy, and focal glomerulosclerosis, as well as systemic diseases, such as diabetes mellitus, amyloidosis, and lupus erythematosus.

In some cases, it may be caused by genetic mutations in podocyte proteins, such as nephrin, podocin, or the cation channel 6 protein. Additionally, nephrotic syndrome can sometimes be triggered by an episode of infectious diseases of the upper respiratory tract, allergic reaction, insect bite, vaccination, or drugs of abuse, such as heroin.

Genetics

Prognostic Factors

The prognosis of the nephrotic syndrome depends on the underlying cause. In general, nephrotic syndrome can be managed with medications and lifestyle changes, and most people with the condition can lead a normal life. However, some underlying causes can cause permanent kidney damage and lead to end-stage renal disease.

Clinical History

Clinical History

The first sign in children is typically facial swelling. This can then be followed by swelling of the entire body. Adult patients may present with dependent edema. Other potential symptoms include frothy urine, tiredness, loss of appetite, and deep venous thrombosis (DVT) of the calf veins or a pulmonary embolus.

Depending on the cause of the nephrotic syndrome, additional features may be present in the patient’s history. For example, the recent initiation of NSAID therapy could suggest such drugs as the cause, while a more than ten year history of diabetes mellitus with symptomatic neuropathy could indicate diabetic nephropathy.

Physical Examination

Physical Examination

Edema is the hallmark symptom of nephrotic syndrome and is often first noted around the eyes and legs, eventually becoming generalized and leading to increased weight and the development of ascites or pleural effusions.

While hematuria and hypertension are not always found in those with nephrotic syndrome, they are more commonly seen in nephritic syndrome.

Depending upon the underlying cause of the nephrotic syndrome, there may be other physical findings such as diabetic retinopathy in those with longstanding diabetes mellitus or anemia, hypertension, or both in those with impaired renal function.

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

Differential Diagnoses

  • Hepatocellular cirrhosis
  • Budd-Chiari Syndrome
  • Hereditary angioneurotic edema
  • Diabetic nephropathy
  • Iga nephropathy
  • Minimal change disease

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

TREATMENT PARADIGM  

Symptomatic Management: Diuretics, particularly loop diuretics like furosemide, are used to manage edema. Sodium restriction is also recommended. 

Statins and dietary modifications are used to control elevated cholesterol levels. 

Angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) are commonly used to manage hypertension and reduce proteinuria. 

Use of immunosuppressive Therapy: In cases of minimal change disease and focal segmental glomerulosclerosis, corticosteroids are the first-line treatment. Additional immunosuppressive agents may be considered in steroid-resistant cases. 

Management of Complications: Patients with nephrotic syndrome are at an increased risk of thromboembolism. Anticoagulation therapy may be considered in high-risk cases. 

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Use of non-pharmacological approach for Nephrotic Syndrome

  • Dietary Modifications: As edema is a common symptom of nephrotic syndrome, limiting sodium intake is crucial. This includes reducing the consumption of processed foods, canned goods, and high-sodium snacks. 
  • Fluid Intake: Depending on the severity of edema and kidney function, fluid intake may need to be monitored.  
  • Lifestyle Modifications: Regular physical activity is generally beneficial for overall health, but the intensity and type of exercise may need to be adjusted based on individual health status.  
  • Rest and Stress Management: Adequate rest is essential for individuals with nephrotic syndrome. Stress management techniques, such as meditation or yoga, may also be helpful in maintaining overall well-being. 
  • Prevention of infection: Individuals with nephrotic syndrome are at an increased risk of infections due to immunosuppression. Practicing good hygiene, getting recommended vaccinations, and avoiding contact with sick individuals can help prevent infections. 
  • Regular Medical Follow-Up: Regular monitoring and follow-up appointments with a nephrologist or healthcare provider are essential. This includes monitoring blood pressure, renal function, and proteinuria levels to make necessary adjustments to the treatment plan. 
  • Prevention of Thrombosis: Due to an increased risk of thromboembolism in nephrotic syndrome, individuals may be advised to take measures to prevent blood clots.  

Role of Corticosteroids

Corticosteroids, such as prednisone, are often the first-line treatment for nephrotic syndrome, especially if the underlying cause is minimal change disease or focal segmental glomerulosclerosis. 

  • Prednisone: It is a potent anti-inflammatory medication that suppresses immune responses and inflammation. In nephrotic syndrome, inflammation within the glomeruli of the kidneys is play an important role in proteinuria and other symptoms.  

Use of Immunosuppressive Agents

In cases of immune-mediated glomerular diseases, additional immunosuppressive agents may be used to reduce inflammation and immune system activity. 

  • Cyclophosphamide: It is classified as an alkylating agent, and it possess immunosuppressive effects by interfering with the DNA synthesis and function of rapidly dividing cells, including immune cells. 

Use of Diuretics

Diuretics, especially loop diuretics like furosemide, are used to manage swelling by promoting the excretion of excess fluid and sodium. 

  • Furosemide: It inhibits the reabsorption of sodium and chloride in the loop of Henle in the kidneys, leading to increased urine production and subsequent fluid and electrolyte excretion. 

Angiotensin-Converting Enzyme (ACE) Inhibitors

ACE inhibitors are used to control hypertension and reduce proteinuria by dilating blood vessels and reducing the pressure within the glomeruli. 

  • Captopril: They inhibit the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. By blocking angiotensin II, captopril leads to vasodilation and a reduction in blood pressure. 

Use of Intervention with a procedure in treating Nephrotic Syndrome

  • Kidney Biopsy: A kidney biopsy may be performed to determine the underlying cause of nephrotic syndrome and guide treatment decisions. This procedure involves the removal of a small piece of kidney tissue for examination under a microscope. 
  • Plasmapheresis: Plasmapheresis involves removing blood plasma from the body, separating it from blood cells, and replacing it with a replacement solution. This procedure may be considered in certain cases of nephrotic syndrome, particularly those with rapidly progressive glomerulonephritis. 
  • Renal Angiography: Renal angiography is an imaging procedure used to visualize the blood vessels in the kidneys. It may be performed to assess the blood flow to the kidneys and identify any abnormalities. 
  • Renal Vein Thrombosis Intervention: If renal vein thrombosis is present, interventions such as anticoagulation therapy may be initiated to prevent further clot formation and promote blood flow. 

Use of phases in managing Nephrotic Syndrome

Diagnosis and Initial Evaluation: The process begins with a thorough medical history and physical examination to identify symptoms and potential risk factors. 

Urinalysis, blood tests (including serum albumin and lipid levels), and kidney function tests are performed. 

Imaging, such as ultrasound or CT scans, may be done to assess kidney structure and identify any abnormalities. 

Immunosuppressive Therapy: In cases of immune-mediated glomerular diseases, corticosteroids and other immunosuppressive medications may be initiated. 

Maintenance Therapy: Depending on the underlying cause, a long-term plan for immunosuppressive therapy may be established. This may include medications like corticosteroids, cyclophosphamide, mycophenolate mofetil, or rituximab. 

Blood Pressure Control: ACE inhibitors or angiotensin II receptor blockers (ARBs) are commonly used to control hypertension and reduce proteinuria. 

Cholesterol Management: Statins and dietary changes may be recommended to control elevated cholesterol levels. 

Complication Management: Individuals with nephrotic syndrome are at an increased risk of blood clots. Anticoagulation therapy may be considered in high-risk cases. 

Follow-Up Phase: Regular Check-ups: Patients with nephrotic syndrome require ongoing follow-up with a nephrologist or other specialists. 

Medication

 

corticotropin 

Administer dose of 40 to 80 units intramuscularly or subcutaneously every 1 to 3 days



 

prednisolone 

The first four weeks of treatment is 60 mg/m²/day or 2 mg/kg/day taken orally, divided into doses every 8 hours until urine is protein-free for three consecutive days. The treatment should not exceed 28 days, and the maximum daily dose should not exceed 80 mg
Subsequent four weeks: 40 mg/m²/day or 1-1.5 mg/kg/day orally every alternate day



corticotropin 

For <2 years: Safety and efficacy not determined
For ≥2 years old:
Administer dose of 40 to 80 units intramuscularly or subcutaneously every 1 to 3 days



 

Media Gallary

Nephrotic Syndrome

Updated : January 11, 2024




Nephrotic syndrome is a kidney disorder characterized by high levels of protein in the urine, low levels of protein in the blood, and swelling of parts of the body due to fluid retention. It is usually caused by damage to the tiny blood vessels in the kidneys, which filter waste out of the blood and pass it out of the body in urine.

It is usually caused by damage to the tiny blood vessels in the kidneys, which filter waste out of the blood and pass it out of the body in urine. It is caused by increased permeability of the damaged basement membrane in the renal glomerulus due to an intrinsic renal disease or an underlying condition such as, systemic lupus, diabetes, neoplasia, or certain drug use.

It is estimated that approximately 3 out of every 100,000 people in the United States have Nephrotic Syndrome. The prevalence of Nephrotic Syndrome is highest in children under the age of 10, with an estimated incidence of 20-40 cases per 100,000 children under the age of 5.

The mortality rate of varies depending on the underlying cause and severity of the condition. Approximately half of all Nephrotic syndrome patients reach complete remission, and long-term survival is possible. However, those with severe or end-stage kidney disease may have a poorer prognosis.

Nephrotic syndrome is caused by damage to the glomeruli. This damage leads to the leakage of proteins in the urine, which can cause proteinuria, edema, and hypoalbuminemia. The exact cause of glomerular damage is not known, but it is thought to be caused by autoimmune disorders, infections. The primary pathophysiology of nephrotic syndrome involves the loss of proteins, most notably albumin, in the urine. Enhanced glomerular permeability causes albuminuria, ultimately leading to hypoalbuminemia.

This reduction in plasma colloid osmotic pressure then causes an increase in transcapillary fluid filtration, leading to edema. The progress of edema is due to a decrease in intravascular oncotic pressure and an increase in hydrostatic capillary pressure, which results in an excessive amount of fluid being filtered from the vascular compartment into the interstitium. This excess fluid exceeds the maximal lymphatic flow, leading to a decrease in plasma volume and an increase in water and sodium retention in the kidneys.

Due to the damage to the glomeruli, they cannot retain proteins, causing them to be filtered out into the urine. As a result, the body cannot maintain the fluid balance in the bloodstream, leading to edema. Additionally, the loss of albumin in the urine causes hypoalbuminemia, leading to complications such as anemia and thrombosis. Long-term complications of nephrotic syndrome can include high cholesterol, kidney failure, and an increased risk of infection.

Nephrotic syndrome is primarily caused by intrinsic kidney diseases, such as minimal-change nephropathy, membranous nephropathy, and focal glomerulosclerosis, as well as systemic diseases, such as diabetes mellitus, amyloidosis, and lupus erythematosus.

In some cases, it may be caused by genetic mutations in podocyte proteins, such as nephrin, podocin, or the cation channel 6 protein. Additionally, nephrotic syndrome can sometimes be triggered by an episode of infectious diseases of the upper respiratory tract, allergic reaction, insect bite, vaccination, or drugs of abuse, such as heroin.

The prognosis of the nephrotic syndrome depends on the underlying cause. In general, nephrotic syndrome can be managed with medications and lifestyle changes, and most people with the condition can lead a normal life. However, some underlying causes can cause permanent kidney damage and lead to end-stage renal disease.

Clinical History

The first sign in children is typically facial swelling. This can then be followed by swelling of the entire body. Adult patients may present with dependent edema. Other potential symptoms include frothy urine, tiredness, loss of appetite, and deep venous thrombosis (DVT) of the calf veins or a pulmonary embolus.

Depending on the cause of the nephrotic syndrome, additional features may be present in the patient’s history. For example, the recent initiation of NSAID therapy could suggest such drugs as the cause, while a more than ten year history of diabetes mellitus with symptomatic neuropathy could indicate diabetic nephropathy.

Physical Examination

Edema is the hallmark symptom of nephrotic syndrome and is often first noted around the eyes and legs, eventually becoming generalized and leading to increased weight and the development of ascites or pleural effusions.

While hematuria and hypertension are not always found in those with nephrotic syndrome, they are more commonly seen in nephritic syndrome.

Depending upon the underlying cause of the nephrotic syndrome, there may be other physical findings such as diabetic retinopathy in those with longstanding diabetes mellitus or anemia, hypertension, or both in those with impaired renal function.

Differential Diagnoses

  • Hepatocellular cirrhosis
  • Budd-Chiari Syndrome
  • Hereditary angioneurotic edema
  • Diabetic nephropathy
  • Iga nephropathy
  • Minimal change disease

TREATMENT PARADIGM  

Symptomatic Management: Diuretics, particularly loop diuretics like furosemide, are used to manage edema. Sodium restriction is also recommended. 

Statins and dietary modifications are used to control elevated cholesterol levels. 

Angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) are commonly used to manage hypertension and reduce proteinuria. 

Use of immunosuppressive Therapy: In cases of minimal change disease and focal segmental glomerulosclerosis, corticosteroids are the first-line treatment. Additional immunosuppressive agents may be considered in steroid-resistant cases. 

Management of Complications: Patients with nephrotic syndrome are at an increased risk of thromboembolism. Anticoagulation therapy may be considered in high-risk cases. 

  • Dietary Modifications: As edema is a common symptom of nephrotic syndrome, limiting sodium intake is crucial. This includes reducing the consumption of processed foods, canned goods, and high-sodium snacks. 
  • Fluid Intake: Depending on the severity of edema and kidney function, fluid intake may need to be monitored.  
  • Lifestyle Modifications: Regular physical activity is generally beneficial for overall health, but the intensity and type of exercise may need to be adjusted based on individual health status.  
  • Rest and Stress Management: Adequate rest is essential for individuals with nephrotic syndrome. Stress management techniques, such as meditation or yoga, may also be helpful in maintaining overall well-being. 
  • Prevention of infection: Individuals with nephrotic syndrome are at an increased risk of infections due to immunosuppression. Practicing good hygiene, getting recommended vaccinations, and avoiding contact with sick individuals can help prevent infections. 
  • Regular Medical Follow-Up: Regular monitoring and follow-up appointments with a nephrologist or healthcare provider are essential. This includes monitoring blood pressure, renal function, and proteinuria levels to make necessary adjustments to the treatment plan. 
  • Prevention of Thrombosis: Due to an increased risk of thromboembolism in nephrotic syndrome, individuals may be advised to take measures to prevent blood clots.  

Corticosteroids, such as prednisone, are often the first-line treatment for nephrotic syndrome, especially if the underlying cause is minimal change disease or focal segmental glomerulosclerosis. 

  • Prednisone: It is a potent anti-inflammatory medication that suppresses immune responses and inflammation. In nephrotic syndrome, inflammation within the glomeruli of the kidneys is play an important role in proteinuria and other symptoms.  

In cases of immune-mediated glomerular diseases, additional immunosuppressive agents may be used to reduce inflammation and immune system activity. 

  • Cyclophosphamide: It is classified as an alkylating agent, and it possess immunosuppressive effects by interfering with the DNA synthesis and function of rapidly dividing cells, including immune cells. 

Diuretics, especially loop diuretics like furosemide, are used to manage swelling by promoting the excretion of excess fluid and sodium. 

  • Furosemide: It inhibits the reabsorption of sodium and chloride in the loop of Henle in the kidneys, leading to increased urine production and subsequent fluid and electrolyte excretion. 

ACE inhibitors are used to control hypertension and reduce proteinuria by dilating blood vessels and reducing the pressure within the glomeruli. 

  • Captopril: They inhibit the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. By blocking angiotensin II, captopril leads to vasodilation and a reduction in blood pressure. 

  • Kidney Biopsy: A kidney biopsy may be performed to determine the underlying cause of nephrotic syndrome and guide treatment decisions. This procedure involves the removal of a small piece of kidney tissue for examination under a microscope. 
  • Plasmapheresis: Plasmapheresis involves removing blood plasma from the body, separating it from blood cells, and replacing it with a replacement solution. This procedure may be considered in certain cases of nephrotic syndrome, particularly those with rapidly progressive glomerulonephritis. 
  • Renal Angiography: Renal angiography is an imaging procedure used to visualize the blood vessels in the kidneys. It may be performed to assess the blood flow to the kidneys and identify any abnormalities.