Nephrotic syndrome is a serious kidney disorder marked by high levels of protein in the urine (proteinuria), low levels of protein in the blood, swelling (especially in the legs and ankles), and high cholesterol. While the symptoms of nephrotic syndrome are well recognized, understanding its causes is essential for proper diagnosis, treatment, and prevention of complications.
While the symptoms of nephrotic syndrome are relatively well known, the underlying causes are diverse and complex. In many cases, this condition is a consequence of damage originating within the kidneys themselves referred to as primary nephrotic syndrome. In other situations, it develops as a result of another systemic illness or external factor what we call secondary nephrotic syndrome. Understanding these root causes is not just important for accurate diagnosis and treatment, but also for preventing long-term kidney damage and associated complications like high blood pressure, blood clots, and chronic kidney disease.
What Is Nephrotic Syndrome?
Before diving into the causes, it is important to briefly understand what nephrotic syndrome entails. It occurs when the tiny blood vessels in the kidneys, called glomeruli, become damaged. These glomeruli normally filter waste and excess fluids from the blood while retaining essential proteins. In nephrotic syndrome, this filtering function is compromised, leading to excessive loss of protein through the urine.
This condition can affect both children and adults and may develop gradually or suddenly depending on the underlying cause. The syndrome is not a disease itself but rather a sign of kidney damage resulting from various medical conditions.
Primary vs Secondary Causes of Nephrotic Syndrome
The causes of nephrotic syndrome are usually categorized into two main types: primary (idiopathic) causes, where the problem starts in the kidneys themselves, and secondary causes, where kidney damage results from a broader systemic condition.
Primary Causes of Nephrotic Syndrome
- Minimal Change Disease (MCD)
Minimal change disease is the most common cause of nephrotic syndrome in children, though it can also occur in adults. The name stems from the fact that the damage to the kidneys appears nearly normal under a regular microscope and requires an electron microscope to detect changes. The exact cause is unknown, but it may be linked to immune system dysfunction.
This condition often responds well to corticosteroids and has a good prognosis, especially in children. In many cases, the cause remains idiopathic, meaning no clear trigger is found.
- Focal Segmental Glomerulosclerosis (FSGS)
FSGS involves scarring (sclerosis) in some sections (segments) of the kidney’s filtering units. It is more common in adults and can lead to progressive kidney damage. FSGS may be primary or may occur as a secondary condition linked to obesity, infections, or drug toxicity.
Compared to minimal change disease, FSGS tends to be more resistant to treatment and may lead to chronic kidney disease if not managed effectively. Genetic mutations may also play a role in its development.
- Membranous Nephropathy
This condition is characterized by thickening of the glomerular basement membrane due to immune complex deposits. Membranous nephropathy is a common cause of nephrotic syndrome in adults and can be either idiopathic or secondary to infections, autoimmune diseases, or certain medications.
The idiopathic form is believed to be autoimmune in nature, involving antibodies attacking components of the kidney’s filtering system. Prognosis varies, and some patients may progress to end-stage kidney disease.
Secondary Causes of Nephrotic Syndrome
- Diabetes Mellitus (Diabetic Nephropathy)
One of the leading causes of nephrotic syndrome worldwide is diabetes, especially in long-standing or poorly controlled cases. High blood sugar levels over time damage the kidneys’ filtering system, leading to diabetic nephropathy.
This condition often develops gradually and is a sign of chronic kidney disease. It is critical for diabetic patients to maintain blood sugar control and follow regular kidney function tests to prevent progression.
- Systemic Lupus Erythematosus (Lupus Nephritis)
Lupus is an autoimmune disease that can affect multiple organs, including the kidneys. When the immune system attacks the kidney tissue, it leads to inflammation and damage to the glomeruli, resulting in nephrotic syndrome.
Lupus nephritis is more common in women and typically presents in individuals with an existing lupus diagnosis. Early treatment with immunosuppressive drugs can help preserve kidney function.
- Amyloidosis
Amyloidosis occurs when abnormal proteins called amyloids accumulate in organs, including the kidneys, disrupting normal function. This buildup can damage glomeruli and lead to nephrotic syndrome.
Although a rare cause, amyloidosis is serious and requires specific treatment targeting the underlying condition that produces the amyloid proteins.
- Infections
Certain chronic or acute infections can damage the kidneys and cause nephrotic syndrome. Notable infections include hepatitis B, hepatitis C, HIV, and malaria. These infections can directly injure the kidneys or trigger immune responses that result in glomerular inflammation.
Managing the underlying infection often helps in reversing or controlling the nephrotic symptoms, though persistent damage can occur in some cases.
- Medications and Toxins
Some medications are known to induce nephrotic syndrome as a side effect. Common culprits include nonsteroidal anti-inflammatory drugs (NSAIDs), certain antibiotics (like penicillamine), and some chemotherapeutic agents. These drugs may cause allergic or toxic reactions in the kidneys, leading to damage of the filtering units.
It is essential for patients on long-term medications to undergo routine kidney function tests to monitor any adverse effects.
- Cancer
Certain cancers, especially solid tumors and lymphomas, can be associated with nephrotic syndrome. The exact mechanism may involve immune system dysregulation or direct infiltration of kidney tissue by malignant cells.
Paraneoplastic syndromes conditions caused by immune responses to cancer can also lead to kidney damage and protein loss. Treating the underlying cancer often results in improvement of nephrotic symptoms.
Genetic and Hereditary Factors
Some forms of nephrotic syndrome are linked to genetic mutations, particularly in children. These hereditary conditions may lead to congenital or infantile nephrotic syndrome, often presenting within the first few months of life. Genetic testing and counseling are important in these cases, especially if there is a family history of kidney disease.
How Are the Causes Diagnosed?
Diagnosing the cause of nephrotic syndrome usually involves a combination of blood and urine tests, kidney function tests, imaging studies, and often a kidney biopsy. The biopsy helps in identifying the specific type of glomerular damage and guides the treatment plan. Identifying whether the cause is primary or secondary is crucial, as it determines the management strategy.
Conclusion
Nephrotic syndrome is not a disease but a manifestation of underlying kidney damage. Whether caused by a primary kidney disorder like minimal change disease or secondary to conditions like diabetes, lupus, or infections, timely diagnosis is key. Understanding the exact cause allows healthcare providers to offer targeted treatments that can reverse or slow down kidney damage.
