Patient's question:
What is kidney syndrome? How is it caused? What are the treatment options?Doctor's answer:
Nephrotic syndrome is a clinical syndrome characterized by massive proteinuria (proteinuria exceeding 3.5 grams per 24 hours), hyperlipidemia, and varying degrees of severity. It is classified into primary and secondary types. Secondary nephrotic syndrome can be caused by immune diseases (such as systemic lupus erythematosus), diabetes, secondary infections (such as bacteria, hepatitis B virus), circulatory system diseases, drug toxicity, and other factors. In the early stages of this disease, the basement membrane lesions are relatively mild. As the lesions progress, a large amount of protein is excreted in the urine, which is a significant or causative factor in reducing plasma protein levels. The reduction in plasma protein levels, especially a significant decrease in albumin, leads to a decrease in plasma colloid osmotic pressure, promoting the exudation of fluid from the blood vessels into the tissues, resulting in tissue edema and a decrease in effective blood volume. The mechanism by which nephrotic syndrome causes hyperlipidemia is not yet fully understood. When a large amount of protein is lost in the urine, liver synthesis of albumin increases, and the synthesis of lipoproteins also increases, becoming a cause of hyperlipidemia. In addition, a decrease in the activity of lipoprotein lipase reduces the clearance of lipids, which may also be a contributing factor or cause.Symptom Manifestations
1. Simple Primary Nephrotic Syndrome
- Most commonly occurs in children and adolescents. The male-to-female ratio is approximately 2:1.
(1) Pitting edema throughout the body, most noticeable in the face, lower limbs, and scrotum. Ascites is common, but the general condition is usually good, with no hypertension.
(2) Decreased urine output, with proteinuria often ranging from ++ to ++++, with a quantification greater than 0.1 g/(kg·d). Occasional red blood cells may be observed in urine microscopy.
(3) Total plasma protein is below normal, with a more significant reduction in albumin (less than 30 g/L). Serum protein electrophoresis shows a reduced proportion of albumin and an increased proportion of globulins, with a decrease in r-globulin. Blood cholesterol is significantly elevated (greater than 5.7 mmol/L), and serum complement levels are normal.
(4) Renal function is generally normal, but during the edema phase with significant oliguria, temporary mild azotemia may occur.
2. Nephritic Nephrotic Syndrome
- Most commonly affects children aged 7 and older, with less severe edema.
(1) Blood pressure may be elevated to varying degrees, with recurrent or persistent hypertension and hematuria.
(2) Serum complement levels may be reduced, with varying degrees of azotemia.
3. Congenital Nephrotic Syndrome
- Rare, often an inherited disease, and typically manifests in the neonatal period or within the first three months after birth, with symptoms similar to simple nephrotic syndrome.
4. Complications
(1) Infection: Upper respiratory tract infections, skin infections, and peritonitis.
(2) Electrolyte Imbalance: Hypokalemia, hyponatremia, and hypocalcemia.
(3) Thrombosis: Renal vein thrombosis is common, along with pulmonary artery and vein thrombosis, pulmonary embolism, and peripheral venous thrombophlebitis. These are primarily caused by hyperlipidemia, severe blood concentration, increased blood viscosity, and changes in coagulation function.
Etiology and Pathology
Due to changes in the permeability of the glomerular filtration membrane, proteins leak excessively, forming massive proteinuria. The permeability changes of the glomerular filtration membrane are related not only to pathological changes but also to changes in the surface charge of the glomerular epithelial cell membrane. Normal membranes have sialic acid proteins with a negative charge, and albumin molecules, at pH 7.4, also carry a negative charge. Due to electrostatic repulsion, albumin is not easily filtered. In simple nephrotic syndrome, sialic acid protein levels decrease, increasing protein filtration. Massive proteinuria leads to hypoalbuminemia, particularly a significant reduction in albumin, which lowers plasma colloid osmotic pressure. This causes water and electrolytes to shift from the blood vessels to the interstitial spaces. Combined with increased secretion of aldosterone and antidiuretic hormone, and decreased secretion of natriuretic factor, edema is further exacerbated. The occurrence of hypercholesterolemia is primarily due to compensatory increases in liver synthesis, with secondary factors being reduced lipoprotein catabolism.
Pathological Classification and Prognosis
1. Minimal Change Nephrotic Syndrome
- Most common, accounting for approximately 80% of primary nephrotic syndrome in children and 25% in adults. About 30-40% of this type may spontaneously resolve within months of onset, and 90% respond well to hormone therapy. However, the recurrence rate is as high as 60%.
2. Mesangial Proliferative Glomerulonephritis
- Accounts for about 30% of primary nephrotic syndrome in China, with most patients having a preceding infection. Prognosis depends on the severity of pathological changes, with better outcomes in milder cases.
3. Mesangial Capillary Glomerulonephritis
- Accounts for about 10% of primary nephrotic syndrome in China. Treatment is challenging, with hormone and cytotoxic therapies effective only in some pediatric cases. Adult outcomes are poor, with rapid disease progression, and about 50% may progress to chronic kidney failure within 10 years.
4. Membranous Nephropathy
- More common in middle-aged and elderly patients, accounting for about 30% of primary nephrotic syndrome in adults. It has an insidious onset and slow progression, with a high risk of thrombosis and embolism. Renal damage typically appears 5-10 years after onset.
5. Focal Segmental Glomerulosclerosis
- Some patients with this type may transform from minimal change nephrotic syndrome. Hormone and cytotoxic therapy responses are slow, but 50% of patients achieve clinical remission after treatment.
Diagnosis and Examination
Primary and secondary nephrotic syndromes share similar clinical manifestations but differ significantly in etiology, pathogenesis, and treatment. Therefore, differentiation between the two is essential. The diagnosis of secondary nephrotic syndrome should focus on the following:
(1) Detailed medical history: Search for underlying causes and identify the primary disease.
(2) Systemic extrarenal manifestations: Do not focus solely on kidney disease symptoms.
(3) Age and gender: Young female patients should be monitored for systemic lupus erythematosus. Children and adolescents aged 7-10 should be checked for allergic purpura. Middle-aged and older patients should be evaluated for diabetic nephropathy, multiple myeloma, and polyarteritis nodosa.
(4) Laboratory tests: Targeted tests should be performed in patients without systemic diseases.
(5) Renal biopsy: Primary nephrotic syndrome should only be diagnosed after excluding secondary nephrotic syndrome. If treatment is ineffective or the condition recurs, a renal biopsy is necessary to determine the pathological type.
Common Complications of Primary Nephrotic Syndrome and Their Prevention
(1) Infection: Maintain skin and living to reduce the risk of skin and respiratory infections. Use antibiotics promptly if infections occur, but avoid long-term use of broad-spectrum antibiotics to prevent resistance and dysbiosis.
(2) Hypovolemic Shock and Acute Renal Failure: Severe edema can lead to low blood volume due to reduced colloid osmotic pressure. Strict salt and water restriction, combined with strong diuretics or infections, can exacerbate this. Patients should not excessively limit fluid intake. Strong diuretics should not be used continuously or without volume expansion. In cases of pre-renal failure, intravenous albumin, plasma, and plasma substitutes should be administered to correct shock.
(3) Thrombosis: Anticoagulants (e.g., heparin), fibrinolytics (e.g., ancrod), and platelet aggregation inhibitors should be administered to patients suspected of thrombosis.
Treatment Measures
1. Corticosteroid Therapy
- Prednisone is commonly used. Depending on the disease type and the child's response, treatment may be short-term (8 weeks), medium-term (4-6 months), or long-term (9-12 months). Short-term therapy is used for first-time simple nephrotic syndrome, while medium and long-term therapy is used for recurrent or multiple-recurrent simple nephrotic syndrome or nephritic nephrotic syndrome.
- Efficacy Evaluation:
- Steroid-sensitive: Urine protein becomes negative within 8 weeks of treatment, and edema resolves.
- Partially steroid-sensitive: Edema resolves within 8 weeks, but urine protein remains + to ++.
- Steroid-resistant: Proteinuria remains ++ or higher after 8 weeks of treatment.
- Steroid-dependent: Urine protein becomes negative after treatment, but reappears after stopping or reducing the dose. The patient requires two or more cycles of treatment to achieve a protein-negative response (excluding infections and other factors).
2. Immunosuppressive Agents
- Used for cases with poor steroid response or severe side effects. Common agents include vincristine, tripterygium glycosides, cyclophosphamide, mercaptopurine, and cyclosporine A.
3. Diuretics
- Not typically needed for steroid-sensitive cases, as diuresis usually occurs within 7-10 days of treatment. Severe edema may require diuretics, such as furosemide () administered intravenously. Low-molecular-weight dextran should be infused first for better diuretic effects.
4. Side Effects of Corticosteroids
- 1. Weight gain.
- 2. Can cause osteoporosis and femoral head necrosis.
- 3. Decreased immunity, elevated blood sugar, steroid symptoms, gastrointestinal ulcers, and electrolyte imbalances.
- Both corticosteroids and immunosuppressants can affect sexual function. Long-term, high-dose corticosteroids (e.g., prednisone) can exacerbate sexual dysfunction. Most immunosuppressants can cause testicular atrophy, ovarian damage, reduced or lost sperm production, decreased libido, and impotence.
Traditional Chinese Medicine Treatment
Traditional Chinese medicine (TCM) herbal formulas have shown excellent and stable results with no side effects. While TCM and Western medicine each have their strengths, Western medicine lacks effective methods for treating various types of nephritis, nephrotic syndrome, kidney failure, and uremia. Western steroid and immunosuppressive therapies have limited efficacy, significant side effects, and are costly, often leading to recurrent conditions and only treating symptoms rather than the root cause. Patients suffer greatly, and long-term complications arise. Dialysis for uremia and kidney failure can lead to gradual organ atrophy, and kidney transplantation has limited survival rates with unresolved rejection issues. Hormone therapy has notable side effects and recurrence risks, while dialysis and transplantation are expensive, often unaffordable for many patients.
Prevention and Health Care
1. Rest
- Bed rest is recommended during severe edema and hypertension. Generally, strict activity restrictions are not needed, but appropriate recreational activities should be arranged to keep children happy.
2. Diet
- Ensure adequate calorie intake, with protein restricted to approximately 2 g/kg per day. In cases of severe edema or hypertension, salt restriction may be necessary for a short period.
3. Skin Care
- Maintain skin cleanliness and dryness, avoiding friction and pressure. Turn the patient regularly. Bedding should be soft. Rubber air cushions or cotton rings can be used for the buttocks and limbs. Air mattresses can be used if available. Swollen scrotums can be supported with cotton pads or straps. Cover broken skin with sterile dressings to prevent infection.
4. Avoid Muscle Injections in Severe Edema
- Severe edema can lead to drug retention, poor absorption, or leakage after injection, causing local moisture, erosion, or infection. If injections are necessary, strict sterilization is required, and prolonged pressure should be applied after injection to prevent leakage.
5. Monitor Edema Changes
- Record 24-hour fluid intake and output, daily abdominal circumference and weight, and send urine tests 2-3 times per week.
6. Prevent Infections
- Nephrotic children should be housed separately from those with infectious diseases. Avoid exposure to cold and crowded places.
7. Monitor Drug Efficacy and Side Effects
- (1) Strictly follow medical instructions for prednisone administration to ensure compliance and prevent (concealment) leading to incorrect efficacy assessments. Monitor for steroid side effects, such as Cushing's syndrome, hypertension, peptic ulcers, and osteoporosis.
- (2) During diuretic use, monitor urine output. If output is excessive, contact the doctor to adjust or discontinue the drug to prevent electrolyte imbalances.
- (3) When using immunosuppressants (e.g., cyclophosphamide), monitor for leukopenia, hair loss, gastrointestinal reactions, and hemorrhagic cystitis. Increase fluid intake and perform regular blood tests. Treatment duration should not exceed 12 weeks to avoid gonadal damage.
Health Education
- Explain the importance of steroid treatment to patients and families to ensure active cooperation and adherence to the treatment plan.
- Children with nephrotic syndrome often have long hospital stays, so a structured schedule should be arranged, with appropriate learning activities after symptom relief.
- Ensure safety, avoiding running and roughhousing to prevent falls and fractures.
- Educate patients and families that infection is the most common complication and recurrence trigger, making prevention critical.
- Teach parents or older children to monitor urine protein changes using test strips.
Childhood Nephrotic Syndrome
The most prominent feature of childhood nephrotic syndrome is severe edema. Swelling can occur in the lower limbs, face, and torso, especially in looser tissues, such as eyelids. The scrotum of boys may swell like a lightbulb, accompanied by effusions in visceral serous cavities, such as pleural effusion and ascites. Severe edema can make the skin thin and translucent, with slight damage causing fluid leakage. Edema affects blood circulation, reducing local resistance and making infections more likely. Urine tests show high protein levels, with proteinuria ranging from ++ to ++++, and 24-hour urine protein output is elevated. Blood tests reveal reduced plasma albumin, altering the normal albumin/globulin ratio (from 1:1.5 to 0.5) and causing inversion. Plasma cholesterol is elevated. Some children may develop skin streaks resembling those of pregnant women on thighs, upper arms, abdomen, and chest. Urine output is significantly reduced. Due to long-term protein loss, malnutrition may occur, with symptoms such as dry, yellowish hair, hair follicle hyperkeratosis, dry skin, white transverse ridges on nails, delayed development, and anemia with increased susceptibility to infections. Some children may experience hematuria and hypertension. Nephrotic syndrome has a prolonged course and is prone to recurrence. The greatest risk is secondary infection, such as skin erysipelas, intestinal infections, pneumonia, primary peritonitis, and sepsis, any of which can be fatal.