- Nephrotic Syndrome is a collection of symptoms that occur when the kidneys’ filtering units (glomeruli) are damaged, leading to excessive loss of protein in the urine (proteinuria). This condition represents a nonspecific kidney disorder that can be caused by various diseases affecting the glomeruli. The hallmark features include severe proteinuria, hypoalbuminemia, edema, and hyperlipidemia.
- The primary defect in nephrotic syndrome involves damage to the glomerular filtration barrier, specifically the podocytes and their slit diaphragms. This damage increases the permeability of the glomerular basement membrane, allowing proteins (primarily albumin) to leak into the urine. The loss of protein in the urine leads to decreased oncotic pressure in the blood, resulting in fluid movement into the interstitial spaces and causing edema.
- The clinical presentation typically includes peripheral edema, which often begins around the eyes and ankles and can become generalized. Patients may notice foamy urine due to high protein content, and weight gain from fluid retention. Other symptoms can include fatigue, loss of appetite, and general malaise. In children, the onset is often sudden and may follow an upper respiratory infection.
- The syndrome can be classified as primary (idiopathic) or secondary to various conditions. Primary causes include minimal change disease (most common in children), focal segmental glomerulosclerosis (FSGS), and membranous nephropathy. Secondary causes include diabetes, lupus, infections (such as HIV, hepatitis B or C), certain medications, and various malignancies.
- Complications of nephrotic syndrome are numerous and can be serious. These include thromboembolism due to loss of anticoagulant proteins, increased risk of infections due to loss of immunoglobulins, acute kidney injury, and accelerated atherosclerosis from hyperlipidemia. The risk of thromboembolism is particularly concerning and may require prophylactic anticoagulation in some cases.
- Diagnosis typically begins with urinalysis and quantification of protein excretion, usually through a 24-hour urine collection or spot urine protein-to-creatinine ratio. Blood tests are performed to assess albumin levels, lipid profile, kidney function, and to screen for potential underlying causes. A kidney biopsy may be necessary to determine the specific cause and guide treatment decisions.
- Treatment approaches vary depending on the underlying cause and severity of the condition. General measures include dietary sodium restriction, diuretics for edema management, and ACE inhibitors or ARBs to reduce proteinuria. Specific treatments depend on the underlying cause and may include corticosteroids, immunosuppressive medications, or other targeted therapies.
- In minimal change disease, especially in children, corticosteroids are typically the first-line treatment and often result in complete remission. However, relapses are common, and some patients may become steroid-dependent or steroid-resistant. Other forms of nephrotic syndrome may require different treatment approaches, and some may be resistant to various therapies.
- Monitoring of patients with nephrotic syndrome is crucial and includes regular assessment of protein excretion, kidney function, complications, and response to therapy. Patients need to be educated about dietary modifications, medication compliance, and signs of complications that require immediate medical attention.
- The prognosis varies significantly depending on the underlying cause and response to treatment. Minimal change disease generally has an excellent prognosis, especially in children. Other forms, particularly FSGS and certain secondary causes, may have a more progressive course and can lead to end-stage kidney disease requiring dialysis or transplantation.
- Prevention of complications is an important aspect of management. This includes maintaining adequate nutrition, preventing infections through appropriate vaccinations, and careful monitoring for thrombotic complications. Some patients may require prophylactic anticoagulation, particularly those with severe hypoalbuminemia or additional risk factors for thrombosis.
- Research continues in understanding the molecular mechanisms of various causes of nephrotic syndrome, which has led to the development of new targeted therapies. Genetic testing is becoming increasingly important, particularly in children and in cases resistant to standard treatments, as specific genetic causes may respond better to certain therapeutic approaches.
