OVERVIEW

What is Minimal Change Disease?

Minimal change disease, also known as minimal change glomerulopathy, is a chronic condition caused by primary factors or secondary factors (such as medications, infections, tumors, allergies, etc.).

Its main manifestations include massive proteinuria, hypoalbuminemia, edema, and hyperlipidemia (collectively referred to as nephrotic syndrome).

It can be controlled with medications like glucocorticoids, but there is a possibility of recurrence.

Is Minimal Change Disease Common?

Primary minimal change disease is more common in children and adolescents, accounting for approximately 70%–90% of nephrotic syndrome cases in children under 10 years old and 10%–30% in adults. The incidence is lowest in middle-aged individuals and slightly increases in the elderly.

Male children are more affected than female children, while the gender ratio is more balanced in adult patients.

SYMPTOMS

What are the common manifestations of minimal change nephropathy?

Minimal change nephropathy often presents with nephrotic syndrome, typically occurring after upper respiratory or systemic infections. Specific manifestations include:

• Edema: Mostly pitting edema, usually starting in the lower limbs.

• Foamy urine (massive proteinuria): If the urine contains a large amount of fine, persistent foam, proteinuria should be suspected. Further tests such as urinalysis and 24-hour urine protein quantification are needed for confirmation.

• Most patients may have hyperlipidemia. Laboratory tests may reveal hypoalbuminemia (serum albumin may be <1.5–2.0 g/dL).

What diseases can minimal change nephropathy cause?

• Infection: Common sites include the respiratory tract, urinary tract, and skin. Symptoms may include fever, cough, sputum production, urinary frequency/urgency/pain, lower back pain, and skin redness/swelling.

• Thrombosis and embolism: The most common is renal vein thrombosis, but pulmonary embolism and deep vein thrombosis may also occur. These can be asymptomatic or present with symptoms like back pain, hematuria, dyspnea, chest pain, hemoptysis, and limb swelling/pain.

• Acute kidney injury: May present with reduced urine output. Diagnosis relies more on laboratory tests.

• Protein and lipid metabolism disorders: Can lead to edema, thrombosis, etc. Diagnosis primarily depends on laboratory tests.

CAUSES

What are the causes of minimal change nephropathy?

Minimal change nephropathy can be classified into primary, familial, and secondary types:

• For familial minimal change nephropathy, there have been only a few reports of familial clustering, and the pathogenic gene remains unclear.

• Secondary minimal change nephropathy is associated with the following factors:

  • Drug-related: Nonsteroidal anti-inflammatory drugs, antibiotics (penicillin, ampicillin, rifampin, etc.), interferon, lithium, gold preparations, methimazole, etc.;

  • Infection-related: AIDS (HIV infection), Guillain-Barre syndrome, syphilis, parasites (schistosomiasis, etc.);

  • Tumor-related: Hodgkin's disease, non-Hodgkin lymphoma, solid tumors, Kimura disease;

  • Allergy-related: Food, pollen, dust, insect bites, etc.

• Primary minimal change nephropathy:

  • The pathogenesis of this disease is still unclear. It is currently believed to be caused by certain damage to glomerular podocytes triggered by lymphokines secreted by abnormally functioning T lymphocytes in the immune system.
  • This damage may involve the widespread effacement of podocyte foot processes and alterations in the charge barrier of the glomerular basement membrane.

DIAGNOSIS

What tests are needed for minimal change nephropathy?

Since minimal change nephropathy is a type of nephrotic syndrome, it is first necessary to confirm whether it is nephrotic syndrome.

The diagnostic criteria for nephrotic syndrome are: massive proteinuria (24-hour urine protein quantification > 3.5 g/d); hypoalbuminemia (serum albumin < 30 g/L); edema; hyperlipidemia. The first two are essential diagnostic criteria. Therefore, the following tests are required:

• Urinalysis: Mainly used to detect proteinuria, hematuria, etc. Precautions for urinalysis include: avoid strenuous exercise 72 hours before urine collection; women should avoid collecting urine during menstruation. Morning urine samples are most suitable for urinalysis, while random urine samples are suitable for outpatient or emergency patients. Clean the external genitalia before collecting midstream urine.

• Urinary microalbumin or urinary microalbumin-to-creatinine ratio: Mainly used to identify the type of protein in proteinuria. Sample collection precautions are the same as for urinalysis.

• 24-hour urine protein quantification: Mainly used to measure the amount of protein in 24-hour urine. Collect all urine within 24 hours in a clean container, mix well, and measure the total volume with a measuring cup.

• Serum albumin: Mainly used to determine hypoalbuminemia. Conducted via venous blood draw.

• Blood lipids: Mainly used to detect hyperlipidemia. Conducted via venous blood draw.

Is a kidney biopsy necessary for minimal change nephropathy?

After confirming nephrotic syndrome, further tests are needed to determine whether it is minimal change nephropathy, with the most important being a kidney biopsy.

There are several methods for kidney biopsy, with the most widely used being percutaneous kidney biopsy, performed under ultrasound guidance through the skin of the lower back. A kidney biopsy can clarify the pathological type of kidney disease and is a crucial test.

What precautions should be taken for a kidney biopsy?

• During the biopsy, the patient is usually in a prone position with a pillow about 10 cm high placed under the abdomen.

• Patients scheduled for a kidney biopsy should practice this position and holding their breath in this posture.

• After the biopsy, the patient must lie flat, so they should practice urinating and defecating while lying in bed.

• After the biopsy, a follow-up urinalysis and kidney ultrasound are required.

TREATMENT

How should minimal change disease be treated?

Both adults and children require treatment once diagnosed with minimal change disease. Treatment can be divided into non-immunosuppressive therapy and immunosuppressive therapy.

• Non-immunosuppressive therapy includes diuresis and edema reduction (based on condition assessment), increasing plasma colloid osmotic pressure (e.g., albumin infusion), ACEI or ARB drugs for blood pressure control and proteinuria reduction, lipid-lowering therapy, and anticoagulation to prevent thrombosis.

• Children and adults with minimal change disease can undergo immunosuppressive therapy with glucocorticoids.

• For patients unresponsive to glucocorticoids or with frequent relapses, drugs such as cyclophosphamide, cyclosporine, tacrolimus, mycophenolate mofetil, or rituximab may be used.

What adverse reactions should be noted when using glucocorticoids for minimal change disease?

Common adverse reactions of glucocorticoids during treatment include:

Skin thinning and purpura, Cushingoid appearance and weight gain, sleep disturbances, elevated blood glucose, cataracts, increased intraocular pressure, heightened cardiovascular disease risk, elevated blood pressure, fluid retention and peripheral edema, increased risk of peptic ulcer disease and gastritis, potential osteoporosis, increased fracture risk, osteonecrosis, myopathy, effects on bone development and growth in children, and increased infection risk.

How long does glucocorticoid treatment typically last?

• Glucocorticoids work faster in children, with 50% responding within 2 weeks and nearly all children responding within 8 weeks.

• Adults generally respond more slowly, with over 25% of responders requiring 3–4 months or longer for complete remission, though relapse rates are usually lower than in children.

DIET & LIFESTYLE

What should patients with minimal change nephropathy pay attention to in daily life?

• Bed rest should be prioritized to reduce external contact and prevent cross-infection. However, appropriate in-bed and bedside activities should be maintained to prevent thrombosis. Activity levels can be gradually increased after symptom relief.

• A low-salt diet (daily salt intake of 2–3 g) and low-fat diet are recommended. In the early or acute phase of the disease, a relatively higher intake of high-quality protein [1–1.5g/(kg×d)] may help alleviate hypoalbuminemia and related complications.
  During the chronic or non-acute phase, a moderate amount of high-quality protein [0.7–1.0g/(kg×d)] is advised. If chronic kidney dysfunction occurs, corresponding adjustments should be made.

• Regular outpatient follow-ups are necessary, including blood tests, liver and kidney function tests, urinalysis, and 24-hour urine protein quantification to monitor disease progression and adjust medications accordingly.

PREVENTION

Can Minimal Change Disease Be Prevented? How to Prevent It?

Since the cause and pathogenesis of minimal change disease are not yet clear, there are currently no reliable prevention methods.

It is important to avoid factors that may lead to secondary minimal change disease, such as medications, infections, and allergies.

For patients already diagnosed with minimal change disease, avoiding fatigue, infections, and the use of suspicious medications can help reduce recurrence.