Lupus nephritis
OVERVIEW
What does lupus refer to in lupus nephritis?
Lupus is short for systemic lupus erythematosus (SLE), a systemic autoimmune connective tissue disease affecting multiple organs. Autoimmunity refers to the immune system attacking the body's own antigens, leading to tissue damage. Connective tissue disease means the body's connective tissues are harmed.
What is lupus nephritis?
When systemic lupus erythematosus affects the kidneys, it causes kidney inflammation, medically described as immune complex-mediated nephritis. It is a major complication and one of the leading causes of death in SLE, as well as a common secondary kidney disease.
Proper diagnosis and treatment of lupus nephritis are crucial for improving survival rates and prognosis (both lifespan and quality of life) in SLE patients.
Is lupus nephritis serious?
Nearly 100% of SLE patients experience kidney involvement, with 45%–85% showing clinical symptoms of kidney damage.
Is lupus nephritis common?
The prevalence in China is 1 in 1,000, higher than the 1 in 2,000 reported in Western countries. It is more common in women, with a male-to-female ratio of 1:8–9, particularly among women of childbearing age (20–40 years).
What is the function of the kidneys?
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The kidneys are vital organs responsible for producing urine to eliminate metabolic waste and toxins. They also reabsorb water and essential substances like glucose, proteins, amino acids, sodium, potassium, and bicarbonate to maintain fluid, electrolyte, and acid-base balance.
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The kidneys also have endocrine functions, producing renin, erythropoietin, active vitamin D3, prostaglandins, and kinins. They also serve as sites for degrading certain hormones and are target organs for extrarenal hormones. These functions ensure internal stability and normal metabolism.
SYMPTOMS
What are the symptoms of lupus nephritis?
Lupus nephritis generally presents with manifestations of systemic lupus erythematosus and clinical symptoms of kidney damage:
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Manifestations of systemic lupus erythematosus: Mainly include fever, fatigue, rash, weight loss, superficial lymphadenopathy, purpura, loss of appetite, nausea, vomiting, etc.
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Manifestations of kidney disease: Vary widely, ranging from asymptomatic proteinuria and/or hypertension to hematuria, edema, nephrotic syndrome, rapidly progressive nephritic syndrome, etc. The condition may gradually progress, leading to uremia in late stages. Some patients may present with chronic renal failure upon initial diagnosis.
What are the types of lupus nephritis?
The clinical manifestations of lupus nephritis correspond to some extent with pathological types but are not entirely parallel. Pathological classification includes 6 types, with varying clinical presentations as follows:
- Type I: Minimal mesangial lupus nephritis. Glomeruli appear normal under light microscopy, but immune complex deposits are visible in the mesangial area via immunofluorescence and/or electron microscopy. Typically asymptomatic with a favorable prognosis.
- Type II: Mesangial proliferative lupus nephritis. Light microscopy shows varying degrees of mesangial cell proliferation with or without increased mesangial matrix, accompanied by mesangial immune complex deposits. Immunofluorescence and electron microscopy may reveal sparse subepithelial or subendothelial immune complex deposits. Microscopic hematuria, proteinuria, or both may occur. Prognosis is relatively good.
- Type III: Focal proliferative type, with segmental endocapillary and extracapillary hypercellularity and inflammation in <50% of glomeruli. Common findings include hematuria and proteinuria. Hypertension, nephrotic syndrome, or elevated serum creatinine may occasionally occur. Prognosis is uncertain.
- Type IV: Diffuse lupus nephritis. Active or inactive lesions. Diffuse (≥50% of glomeruli) segmental or global endocapillary hypercellularity, membranoproliferative changes, moderate to severe mesangial proliferation, or crescentic glomerulonephritis. Characterized by diffuse subendothelial immune complex deposits, with or without mesangial involvement. Hematuria and proteinuria are common. Hypertension, nephrotic syndrome, and elevated serum creatinine are frequently observed.
- Type V: Membranous lupus nephritis. Diffuse thickening of the glomerular basement membrane with diffuse or segmental subepithelial immune complex deposits, with or without mesangial involvement. Nephrotic syndrome is common; microscopic hematuria or hypertension may occur occasionally. Serum creatinine is usually normal or mildly elevated. Prognosis is poor.
- Type VI: Advanced sclerosing lupus nephritis. Over 90% of glomeruli show global sclerosis without active lesions. Urinary sediment is mild, with end-stage renal disease or slowly rising serum creatinine. Prognosis is poor.
Patients diagnosed with lupus nephritis should undergo a kidney biopsy as early as possible to guide treatment planning based on specific pathological features.
CAUSES
How is lupus nephritis caused?
This disease is a complex autoimmune disorder caused by multiple factors, including:
- Genetic factors: Family incidence rates range from 3% to 12%;
- Infectious factors: Chronic viral infections such as measles, rubella, parainfluenza, mumps, etc.;
- Physical factors: Sunlight exposure, X-ray radiation, cold temperatures, intense electric light exposure, etc.;
- Endocrine factors: Estrogen, female contraceptives, etc.;
- Drug factors: Hydralazine, procainamide, chlorpromazine, phenytoin sodium, isoniazid, propylthiouracil, etc.
Why does systemic lupus erythematosus cause kidney damage?
Extensive research has long confirmed that lupus nephritis is a polygenic genetic disease. Its onset is not only directly related to multiple susceptibility genes but also closely associated with environmental factors, sex hormones, the intensity of immune responses, and the quantity of inflammatory mediators produced by the body in response to stimuli.
The formation and deposition of immune complexes in the bloodstream activate complement, leading to inflammatory cell infiltration, coagulation factor activation, and the release of inflammatory mediators, ultimately causing kidney damage.
Under what circumstances does lupus nephritis worsen or relapse?
Factors such as lupus activity, hypertension, proteinuria, nephrotoxic drugs, infections, poor cardiac function, excessive ultraviolet exposure, pregnancy, and other environmental factors can easily lead to disease exacerbation or relapse.
Is lupus nephritis contagious?
Lupus nephritis occurs when systemic lupus erythematosus affects the kidneys. It is an immune system disorder caused by immune dysfunction and is not contagious through any means. Therefore, contact and living with patients pose no risk.
Is lupus nephritis hereditary?
Lupus nephritis is a disorder of the autoimmune system and can occur at any age. Extensive epidemiological genetic studies have confirmed that lupus nephritis has a certain hereditary tendency, particularly among close relatives, where the genetic risk is highest.
DIAGNOSIS
What tests should be done when diagnosing lupus nephritis?
In addition to tests related to systemic lupus erythematosus, such as complete blood count, biochemistry, erythrocyte sedimentation rate, and various antibodies, if lupus nephritis is suspected, further tests like 24-hour urine protein quantification, urinalysis, renal function tests, kidney ultrasound, and renal biopsy should be performed to determine whether kidney damage has occurred.
How is lupus nephritis diagnosed?
Based on a confirmed diagnosis of SLE, if there are signs of kidney damage, such as persistent proteinuria (>0.5 g/d or >+++) or casts (which may be red blood cells, hemoglobin, granular, tubular, or mixed), lupus nephritis can be diagnosed. The gold standard for diagnosis is a renal biopsy (kidney puncture). It is important to note that a renal biopsy should be performed when possible to determine the pathological type and guide treatment. For cases of simple nephropathy, detailed examinations should be conducted to confirm whether it is lupus.
When is a renal biopsy needed for lupus nephritis?
- Urine protein ≥0.5g/24 h;
- Active urinary sediment: persistent hematuria and cellular casts;
- Unexplained elevation in serum creatinine.
What diseases are easily confused with lupus nephritis?
Lupus nephritis is often misdiagnosed as primary glomerular disease. Careful examination for signs of multi-system or multi-organ involvement, along with repeated tests for serum ANA, anti-dsDNA antibodies, and anti-Sm antibodies, can help differentiate the conditions.
What questions do doctors usually ask during a consultation for lupus nephritis?
During the consultation, doctors often ask: Are you sensitive to sunlight? How does your skin react after sun exposure? Do you experience hair loss, joint pain, fatigue, fever, changes in appetite, or mental abnormalities? Is there swelling, especially focusing on whether the urine is red, foamy, or if there is frequent nighttime urination or reduced urine output.
TREATMENT
Is Lupus Nephritis Treatment Necessary?
Patients with lupus nephritis face a high risk of cancer, primarily B-cell lymphoma. Due to common vasculitis, hypertension, abnormal blood lipids, and steroid use, there is also a significant risk of atherosclerotic complications (e.g., coronary heart disease, ischemic stroke).
Additionally, lupus nephritis can cause progressive kidney damage. Without timely diagnosis and treatment, it may lead to kidney failure or even death.
How Is Lupus Nephritis Treated?
Treatment Principles for Lupus Nephritis:
- While clinical manifestations and pathological types of lupus nephritis correlate, they are not entirely parallel. Therefore, treatment plans should not be based solely on clinical symptoms. Patients diagnosed with lupus nephritis should undergo a kidney biopsy as early as possible to tailor treatment according to pathological findings.
- Actively control SLE activity.
- Adhere to long-term, standardized, and rational drug therapy with close follow-up.
- Strive to restore or preserve residual kidney function, prevent recurrence, and minimize drug side effects.
Common Treatment Approaches:
- Angiotensin inhibition for hypertension or proteinuria.
- Cyclophosphamide and steroids for active, reversible cases.
- Immunosuppressive therapy is suitable for patients with disease activity, poor prognosis, or reversible damage, considering drug toxicity.
- Progressive and reversible lupus nephritis is typically type III or IV, while aggressive treatment for type V remains unclear.
- Proliferative lupus nephritis often requires combined cytotoxic drugs and corticosteroids, sometimes with other immunosuppressants.
- Acute, potentially reversible nephritis is treated with corticosteroids plus cyclophosphamide and/or mycophenolate mofetil.
- Kidney transplantation for end-stage renal disease.
What Are the Common Medications for Lupus Nephritis and Their Side Effects?
- Corticosteroids: Long-term use may cause infections, diabetes, osteoporosis, etc.
- Cyclophosphamide: Leukopenia, urinary symptoms, nausea/vomiting, hair loss.
- Azathioprine: Hair loss, rash, bone marrow suppression, liver damage, long-term cancer risk. Monitor blood counts and liver function.
- Cyclosporine: GI upset, gum hyperplasia, kidney damage, hypertension.
- Mycophenolate mofetil: GI issues, bleeding, anemia, infections, malignancy risk (e.g., skin cancer).
- Immunoglobulin: Allergic reactions, cardiovascular events in elderly, rare aseptic meningitis.
Is Surgery Required for Lupus Nephritis?
End-stage lupus nephritis patients stable on long-term dialysis (≥1 year) with inactive disease may undergo kidney transplantation. Recurrence in transplanted kidneys is rare among sustained remission SLE patients.
How Long Does Lupus Nephritis Treatment Take, and Is It Expensive?
Lifelong treatment is often needed, with duration varying by individual response and complications. Costs depend on hospital resources, therapy choice, disease severity, and regional policies. Avoid delaying treatment due to financial concerns.
What Risks Exist During Lupus Nephritis Treatment?
- Gonadal suppression and long-term carcinogenicity.
- Kidney biopsy bleeding.
- Osteoporosis.
- Pneumocystis pneumonia (risk of acute fulminant pneumonia).
- Antimalarial eye toxicity (corneal/ciliary/retinal damage).
- Pregnancy complications: fetal death, miscarriage, growth restriction, preterm birth.
Can Lupus Nephritis Be Cured, and Does It Recur?
Remission is possible, but recurrence is common, with progressive worsening trends. Improved diagnosis, early detection, and optimized drug use have raised 10-year survival rates to 80–90%.
How Crucial Is Standardized Treatment for Lupus Nephritis?
Early standardized treatment enables full remission. Inconsistent therapy leads to relapse or progression. Even in advanced stages, most patients achieve remission with proper drug regimens, doses, and adherence.
Is Frequent Follow-Up Needed for Lupus Nephritis?
During active disease, monitor every 1–2 months. When stable, extend to every 3 months.
What Is Hemodialysis in Lupus Nephritis? When Is It Required?
- Hemodialysis filters blood externally to remove waste, balance electrolytes/fluids, then returns purified blood.
- Initiate dialysis when chronic renal failure patients (GFR 6–10 mL/min) show overt uremic symptoms.
Does Dialysis Guarantee Survival for Lupus Nephritis Patients?
Dialysis replaces kidney function but requires adjunct therapies. Death may still occur if lupus attacks other systems (e.g., nervous system).
How to Manage Lupus Nephritis Relapse During Pregnancy?
Use corticosteroids ± azathioprine based on severity. Low-dose aspirin may reduce fetal loss. Seek immediate hospital care if relapse occurs.
DIET & LIFESTYLE
What should be noted in daily life for lupus nephritis?
- Do not fear or worry about the disease, avoid mental stress, maintain a happy mood, and build confidence in fighting the disease. Mental stress or a state of stress can trigger or worsen lupus nephritis by causing immune system disorders through the neuroendocrine system. During the active phase of lupus nephritis, rest and active treatment are essential. After the condition is controlled, patients can appropriately participate in some manageable work, and students may return to school. Avoid heavy physical labor and excessive fatigue in work and daily life, maintain a regular routine, and ensure adequate sleep.
- Avoid sun exposure and UV rays, especially for those sensitive to sunlight. Outdoor activities are best scheduled in the morning or evening, and try to avoid going out between 10 AM and 4 PM when sunlight is strongest. When going out, use sunscreen, carry a parasol, or wear a wide-brimmed hat, along with light-colored long-sleeved shirts and pants.
- In cold seasons, keep warm. Wear hats and masks when going out in winter to avoid catching colds and minimize infections such as the flu, as infections can definitely trigger lupus activity or worsen the existing condition.
- Avoid medications such as penicillamine, procainamide, chlorpromazine, and hydralazine, as these drugs may induce lupus or aggravate the condition. Women of childbearing age should also avoid taking contraceptives and estrogen-containing drugs.
Can lupus nephritis patients still work?
During the active phase of lupus nephritis, rest and active treatment are necessary. After the condition is controlled, patients can appropriately participate in some manageable work, usually limited to non-physical jobs.
What should lupus nephritis patients pay attention to in their diet?
- Lupus nephritis patients should avoid eating fungi such as shiitake mushrooms, as well as celery, spinach, and figs, as these foods may increase photosensitivity in lupus patients, potentially triggering or worsening the condition.
- Avoid seafood, as most patients are allergic and consuming seafood may trigger allergic reactions, leading to disease onset or aggravation.
- Limit salt intake, as excessive sodium can cause water retention, which is unfavorable for reducing edema and disease recovery.
- Due to long-term use of hormones and other medications, lupus nephritis patients are prone to deficiencies in nutrients such as vitamin B, vitamin C, vitamin D, calcium, zinc, and carotene. Therefore, they should consume foods rich in these nutrients:
- Foods rich in vitamin B include grains, liver, potatoes, and leafy greens.
- Foods rich in vitamin C include broccoli, cabbage, bell peppers, citrus fruits, and strawberries.
- Foods rich in vitamin D include eggs, butter, fish oil, and milk.
- Calcium-rich foods include milk, dairy products, and kale.
- Zinc-rich foods include poultry and eggs.
- Carotene-rich foods include carrots, corn, sweet potatoes, tomatoes, hawthorns, cherries, loquats, plums, and citrus fruits.
Can lupus nephritis patients get pregnant?
Patients who have not achieved complete remission should avoid pregnancy. Pregnancy during active lupus poses significant risks, including premature birth, miscarriage, or even fetal death.
On the other hand, pregnancy and childbirth can greatly affect the mother, potentially worsening proteinuria, hematuria, or even leading to acute kidney dysfunction. If pregnancy is strongly desired, patients must understand the high risks involved and ensure strict medical monitoring throughout the pregnancy.
When can lupus nephritis patients consider pregnancy, and what should they pay attention to?
Pregnancy may be considered six months after lupus nephritis has completely resolved. During pregnancy, close monitoring of proteinuria, blood pressure, and kidney function is essential. If abnormalities occur, termination of pregnancy may be necessary depending on the situation.
PREVENTION
How to Prevent Lupus Nephritis?
- The prevention of lupus nephritis primarily relies on preventing lupus itself, as well as early diagnosis and effective treatment of the primary disease. Preventing lupus flares can reduce complications like kidney damage, while proper treatment can prolong the patient's survival.
- Avoid factors that may trigger lupus flares, such as excessive sun exposure and UV radiation. When unavoidable, use an umbrella, wear a wide-brimmed hat, long sleeves, pants, and apply sunscreen when outdoors.
- Prevent cold exposure, as lupus patients are prone to colds, which can trigger relapse. Adjust clothing according to weather changes, and wear hats and gloves in winter to avoid catching a chill.
- Avoid medications that may induce lupus flares, such as hydralazine, procainamide, isoniazid, methyldopa, chlorpromazine, and quinidine. Do not use hormonal contraceptives.