OVERVIEW

What is Nephrotic Syndrome?

Nephrotic syndrome is a group of syndromes caused by various pathological types of glomerular lesions that lead to abnormal kidney filtration function. The main manifestations of this condition are "three highs and one low": massive proteinuria, hyperlipidemia, severe edema, and hypoalbuminemia. Currently, clinical treatment primarily involves medication, and the prognosis mainly depends on the pathological type, disease severity, and the effectiveness of drug therapy. Some cases of nephrotic syndrome can be cured, while a small number may progress to end-stage renal disease (i.e., uremia)^[1,2].

What Are the Common Types of Nephrotic Syndrome?

Based on etiology, this condition can be divided into primary nephrotic syndrome and secondary nephrotic syndrome.

1. Primary nephrotic syndrome: Related to autoimmune dysfunction, it generally includes the following common pathological types.
   • Minimal change disease: More common in males than females, frequently seen in children, with lower incidence in adults, though the rate rises again after age 60.
   • Mesangial proliferative glomerulonephritis: More prevalent in adolescents, with males affected more than females.
   • Focal segmental glomerulosclerosis: More common in adolescents, with males affected more than females; some cases may develop from minimal change disease.
   • Membranous nephropathy: More prevalent in middle-aged and elderly individuals, with males affected more than females; the peak age of onset is 50–60 years.
   • Mesangiocapillary glomerulonephritis: More common in adolescents, with roughly equal incidence in males and females.
2. Secondary nephrotic syndrome: Often secondary to other diseases.
   • Henoch-Schönlein purpura nephritis: Kidney damage caused by Henoch-Schönlein purpura, mostly seen in children.
   • Hepatitis B virus-associated glomerulonephritis: Glomerulonephritis caused by the hepatitis B virus; it can occur in anyone infected with the virus.
   • Lupus nephritis: Kidney damage caused by systemic lupus erythematosus, most common in women aged 20–40.
   • Diabetic nephropathy: Kidney damage caused by diabetes, which can occur in both type I and type II diabetes. It may affect individuals of any age^[2].

Is Nephrotic Syndrome Serious?

It cannot be generalized. Because nephrotic syndrome is not a single disease but a group of syndromes caused by various conditions, its severity depends on the specific pathological type. For example, minimal change disease and mild mesangial proliferative glomerulonephritis have a better prognosis and are relatively less severe. In contrast, mesangiocapillary glomerulonephritis, focal segmental glomerulosclerosis, and severe mesangial proliferative glomerulonephritis have a poorer prognosis and are relatively more serious^[2].

SYMPTOMS

What are the common symptoms and manifestations of nephrotic syndrome?

The symptoms of nephrotic syndrome are related to abnormal kidney filtration function, leading to excessive protein loss in urine and reduced plasma protein levels. The primary manifestations are known as the "three highs and one low": massive proteinuria, hyperlipidemia, severe edema, and hypoalbuminemia.

1. Massive proteinuria: Early-stage proteinuria is often unnoticed. Patients typically seek medical attention only after edema develops. Some may notice increased foam in their urine.
2. Edema: Due to decreased plasma protein, the body cannot retain water, causing fluid to leak from blood vessels and resulting in edema. Early-stage edema appears as morning eyelid swelling. Prolonged standing or walking may lead to swelling in the lower limbs and ankles, while severe cases involve generalized edema. Pressing on swollen lower limbs leaves a pit that slowly rebounds. Additionally, fluid retention can cause weight gain.
3. Hyperlipidemia: Patients often develop hyperlipidemia because excessive protein loss triggers the body to accelerate protein synthesis for balance. Since protein and lipid synthesis share the same metabolic pathway, increased protein production also raises fat synthesis, leading to elevated blood lipids. Patients usually experience no obvious discomfort.
4. Hypoalbuminemia: Mainly caused by excessive protein loss through the kidneys, reducing blood protein levels. Besides edema, patients may also experience malnutrition, fatigue, weakness, dizziness, and increased susceptibility to infections^[2].

What other diseases can nephrotic syndrome easily cause?

Common complications include:

1. Infections: Related to malnutrition, immune dysfunction, and immunosuppressant use. Patients may develop respiratory, gastrointestinal, or urinary tract infections.
2. Thrombosis: Associated with blood concentration, increased lipid synthesis by the liver, and imbalance between anticoagulation and procoagulation factors. The renal veins are most prone to thrombosis, though symptoms are usually absent.
3. Acute kidney injury: A small number of patients may experience acute kidney injury, presenting as oliguria (urine output <400 mL in 24 hours) or even anuria (urine output <100 mL in 24 hours or no urine for 12 hours)^[2].

Can nephrotic syndrome progress to uremia?

Not necessarily. The causes of nephrotic syndrome vary, and treatment outcomes differ significantly.

Generally, some types respond well to steroid therapy and are less likely to progress to uremia with proper treatment, such as minimal change disease. Others, like membranoproliferative glomerulonephritis, respond poorly to steroids and various immunosuppressants. Long-term massive proteinuria in such cases may lead to uremia^[1,2].

CAUSES

What are the causes of nephrotic syndrome?

Based on the etiology, nephrotic syndrome can be divided into two major categories: primary and secondary.

1. Primary nephrotic syndrome: The exact cause is unknown. It may be due to immune dysfunction in the body, leading to an autoimmune attack on the kidneys (self-damage), or triggered by certain factors (such as colds, vaccinations, etc.) that induce the production of substances (immune complexes) damaging the glomeruli, thereby disrupting the glomerular filtration barrier^[3].
2. Secondary nephrotic syndrome: This type usually has clear underlying causes and often occurs secondary to pre-existing diseases such as diabetes, systemic lupus erythematosus, hepatitis B, renal amyloidosis, etc.^[4].

Is nephrotic syndrome hereditary?

Not necessarily. Nephrotic syndrome is caused by various types of glomerular diseases, most of which are idiopathic and generally not considered hereditary. However, certain pathological types may be inherited, such as focal segmental glomerulosclerosis^[5].

DIAGNOSIS

What tests should be done for nephrotic syndrome?

1. Blood biochemical tests: Usually performed on fasting blood samples, mainly to check serum albumin levels, blood lipid status, and assess liver and kidney function to determine the presence of hypoalbuminemia, hyperlipidemia, and whether liver and kidney function indicators are normal.
2. Coagulation status: For example, D-dimer can help determine if thrombosis has occurred. Due to fluid loss and increased compensatory lipid synthesis by the liver in nephrotic syndrome patients, the blood tends to be hypercoagulable (commonly referred to as "thick blood"), increasing the risk of thrombosis.
3. Urinalysis: Evaluates whether there is protein in the urine for preliminary diagnosis of the condition.
4. 24-hour urine protein quantification: Measures the amount of protein in the urine, typically requiring the patient to collect urine over 24 hours. A daily urine protein excretion >3.5 g further confirms the diagnosis.
5. Renal biopsy: Involves taking a small sample of kidney tissue for testing, which is an invasive procedure. It helps clarify the pathological type and guides subsequent treatment^[1,2].

What are the diagnostic criteria for nephrotic syndrome?

The diagnostic criteria for nephrotic syndrome include massive proteinuria (>3.5 g per day), hypoalbuminemia (plasma albumin <30 g/L), edema, and hyperlipidemia. Among these, massive proteinuria and hypoalbuminemia are essential requirements^[2].

Is a renal biopsy necessary for nephrotic syndrome?

Yes, it is recommended as long as there are no contraindications. Since nephrotic syndrome has various types, a biopsy is necessary to identify the specific type and guide further treatment. Primary nephrotic syndrome includes membranous nephropathy, minimal change disease, focal segmental glomerulosclerosis, and mesangiocapillary glomerulonephritis. Secondary causes include Henoch-Schönlein purpura nephritis, diabetic nephropathy, lupus nephritis, and hepatitis B virus-associated nephritis, among others.

Because the treatment approaches differ depending on the underlying cause, a renal biopsy should be performed to determine the specific pathological type and direct subsequent therapy^[1,2].

What are the contraindications for renal biopsy in nephrotic syndrome patients?

Renal biopsy is an invasive procedure, usually performed under local anesthesia and completed within about half an hour. However, to ensure a smooth procedure and reduce postoperative complications, the following conditions are contraindications:

1. Patients with coagulation disorders: Since bleeding is the most common complication after renal biopsy, those with clotting abnormalities are not suitable for this test.
2. Local kidney infection: The biopsy may spread or worsen the infection.
3. Others: Patients with poor cooperation or communication difficulties, as well as those with a solitary kidney, are also unsuitable for this procedure^[6].

TREATMENT

Which department should I visit for nephrotic syndrome?

Nephrology.

How is nephrotic syndrome treated?

Nephrotic syndrome is mainly treated with medications, commonly including glucocorticoids and immunosuppressants.
In addition, other drugs may be used for symptomatic treatment, such as diuretics, antihypertensives, and lipid-lowering drugs. Common treatments include:

1. For severe edema: Diuretics (e.g., hydrochlorothiazide, furosemide) can be used to reduce swelling and promote diuresis, along with sodium restriction.
2. For severe proteinuria: Antihypertensives (e.g., benazepril, valsartan) may be used to reduce proteinuria.
3. For hyperlipidemia: Lipid-lowering drugs (e.g., atorvastatin, rosuvastatin) can be prescribed, along with limiting saturated fat and cholesterol intake^[1,2].

Can nephrotic syndrome be cured?

Not necessarily. Since the exact causes of nephrotic syndrome remain unclear and involve various pathological changes, it is difficult to definitively determine whether it can be cured.

Some patients (e.g., those with minimal change disease) may achieve complete remission and discontinue immunosuppressants. However, others, such as those with membranoproliferative glomerulonephritis or focal segmental glomerulosclerosis, may respond poorly to combined immunosuppressive therapy and have a poorer prognosis^[2].

What are the common medications for nephrotic syndrome?

Common treatments include glucocorticoids and immunosuppressants, as well as symptomatic medications like diuretics, antihypertensives, and lipid-lowering drugs.

1. Glucocorticoids: These suppress immune-inflammatory responses, promote diuresis, and reduce proteinuria, making them the first-line treatment. Prednisone is commonly used, but methylprednisolone may be substituted if ineffective. Side effects may include Cushingoid features (e.g., moon face, buffalo hump), menstrual irregularities, and osteoporosis. These drugs should be used under medical supervision.
2. Immunosuppressants: These strongly inhibit immune responses and are often combined with glucocorticoids. Common drugs include cyclophosphamide, mycophenolate mofetil, tacrolimus, and cyclosporine, typically for patients unresponsive to glucocorticoids alone. Side effects may include bone marrow suppression, liver damage, hair loss, gastrointestinal issues, and hemorrhagic cystitis.
3. Diuretics: Used for severe edema (e.g., hydrochlorothiazide, furosemide). Side effects may include electrolyte imbalances (e.g., low potassium, sodium).
4. Antihypertensives: Reduce proteinuria and control blood pressure (e.g., benazepril, valsartan). Side effects may include headache, dizziness, and nausea.
5. Lipid-lowering drugs: Lower cholesterol and lipids (e.g., atorvastatin, rosuvastatin). Side effects may include liver damage, muscle pain, and fatigue^[1,2].

Can "folk remedies" treat nephrotic syndrome?

No.
Unverified "secret remedies" should never be used, as they may delay proper treatment and worsen kidney damage.

What are the side effects of glucocorticoid therapy for nephrotic syndrome?

Short-term use may not cause noticeable side effects, but long-term use can lead to Cushing's syndrome, characterized by moon face, central obesity, acne, hypertension, secondary diabetes, osteoporosis, and even avascular necrosis of the femoral head^[7].

Doctors tailor treatment plans to minimize side effects, monitoring patients to adjust dosages and mitigate risks^[7].

What should be noted during glucocorticoid therapy for nephrotic syndrome?

1. Low-salt, low-sugar diet: To prevent metabolic disturbances, limit salt (<5g/day) and sugar (<25g/day)^[8].
2. Calcium supplementation: Prevents osteoporosis and bone loss.
3. Skin care: Maintain hygiene and moisturize to manage acne and striae. Avoid irritants and consume vitamin C-rich foods^[7,9].

How should nephrotic syndrome patients treat a cold?

Due to immunosuppressant use and hypoalbuminemia, these patients are prone to colds, which may worsen their condition. Seek medical advice for proper treatment to avoid kidney-damaging medications.

How often should nephrotic syndrome patients follow up?

Early-stage patients should check every 2–4 weeks for treatment adjustments. In remission, follow-ups can be every 1–3 months. After 2 years of stable results, annual urine tests suffice^[1,2].

When should nephrotic syndrome patients receive albumin supplementation?

Albumin infusion is controversial and reserved for severe cases:

1. Severe edema unresponsive to diuretics.
2. Hypovolemia post-diuretic use.
3. Acute kidney injury due to interstitial edema^[10].

DIET & LIFESTYLE

What should patients with nephrotic syndrome pay attention to in daily life?

1. Take medications regularly as prescribed by the doctor, and do not stop taking them immediately after proteinuria turns negative.
2. During the acute phase (severe edema, massive proteinuria), rest appropriately and avoid public places to prevent infection.
3. Patients with stable conditions should engage in moderate activity to prevent venous thrombosis, enhance immunity, and avoid relapse.

What should patients with nephrotic syndrome pay attention to in their diet?

1. Patients with edema should limit salt intake, generally less than 3 grams per day.
2. Protein intake should be reasonable, with a preference for high-quality protein such as milk, eggs, and beef. Generally, the daily intake of high-quality protein is 0.8–1 g per kilogram of body weight. For example, a person weighing 50 kg requires 40–50 g of high-quality protein per day. To put this into perspective, one egg contains about 6 g of protein, 100 mL of milk contains about 3 g, and 100 g of beef contains about 25–26 g. Patients can adjust their diet accordingly.
3. Follow a low-fat diet, reducing animal fats like butter and lard. Opt for vegetable oil or fish oil when cooking^[2].
4. Avoid taking unverified medications, such as unknown Chinese herbal medicines or drugs that may harm the kidneys.

Can patients with nephrotic syndrome consume salt?

This has been a common misunderstanding among many patients. Doctors generally recommend limiting salt intake (less than 3 g per day) when edema and proteinuria are present, as it can worsen swelling.

However, for patients whose urine tests are negative and who no longer have edema, normal salt intake (like healthy individuals, following the Chinese Dietary Guidelines recommendation of less than 5 g per day) is necessary. Otherwise, it may lead to hyponatremia or hypokalemia, causing symptoms like fatigue and muscle weakness^[8].

How much water should patients with nephrotic syndrome drink?

During edema, patients should moderately restrict water and sodium intake. The daily water intake is typically based on the previous day's urine output plus 500 mL, ensuring both edema relief and kidney perfusion. If swelling has subsided and creatinine (a kidney function indicator) is normal, normal water intake is acceptable^[11].

Can patients with nephrotic syndrome conceive and have children?

Since some nephrotic syndrome patients are women of childbearing age, fertility concerns arise. Such patients must consult obstetricians and nephrologists before conception to assess pregnancy feasibility and necessary monitoring during pregnancy.

What should nephrotic syndrome patients pay attention to during pregnancy?

1. Blood pressure, blood sugar, and lipid levels may be higher in pregnant nephrotic syndrome patients, with increased blood viscosity. Regular monitoring of blood pressure, blood sugar, coagulation function, urine, and kidney function is essential.
2. Certain medications for nephrotic syndrome, such as steroids and immunosuppressants, may affect the fetus. These should be avoided in early pregnancy, but a doctor's evaluation is necessary.
3. Monitor fetal development. If growth issues arise, or if proteinuria worsens or kidney function declines, consult nephrologists and obstetricians to consider terminating the pregnancy^[12].

Can patients with nephrotic syndrome drink alcohol?

Patients should abstain from alcohol. Alcohol reduces renal blood flow, worsens kidney function, and increases cardiac strain, especially for those with hypertension or hyperlipidemia^[11].

How should patients with nephrotic syndrome exercise?

1. During active disease: Rest in bed is recommended, with gentle movements to prevent thrombosis, such as leg massages or knee lifts.
2. Recovered patients: Moderate exercise can boost immunity and prevent relapse. Aerobic exercises like walking, jogging, swimming, cycling, or dancing are suitable, as they are low-intensity, rhythmic, and sustained.

Can patients with nephrotic syndrome have a normal sex life?

Yes. Traditional beliefs wrongly associate kidney disease with sexual dysfunction, causing unnecessary anxiety. Nephrotic syndrome itself does not affect sexual function, though some medications (e.g., steroids) may reduce libido^[7]. Patients need not worry excessively, as sexual function usually normalizes after stopping such medications.

PREVENTION

Can the recurrence of nephrotic syndrome be prevented?

1. Primary nephrotic syndrome is related to autoimmunity, so there are no effective preventive measures. However, improving immunity may reduce the likelihood of its occurrence. Common methods include:
   • Eat more fresh vegetables, fruits, milk, eggs, lean meat, etc., to supplement vitamins and protein;
   • Balance work and rest, avoid staying up late or overexertion;
   • Exercise regularly, such as jogging, swimming, or cycling.
2. Secondary nephrotic syndrome often results from other diseases. Therefore, patients with underlying conditions should seek early medical treatment and actively manage the primary disease to prevent progression to nephrotic syndrome.