Lupus nephritis

Introduction to lupus nephritis Systemic lupuserythematosis (SLE) is an autoimmune disease characterized by multiple systemic damage characterized by multiple autoantibody formations. The patient can produce antibodies against his own nucleus, cytoplasm and membrane antigen, which often manifests as fever, facial erythema, pleomorphic rash, photoallergic, multiple oral ulcers, arthritis, multiple serositis, vasculitis , nephritis and central nervous system symptoms. The condition varies greatly, often due to a prominent system or an organ lesion, which is easily misdiagnosed or missed. The main manifestation of kidney damage is called systemic lupus erythematosus. basic knowledge The proportion of illness: 0.004% Susceptible people: no special people Mode of infection: non-infectious Complications: chronic nephritis nephrotic syndrome

Causes of lupus nephritis

(1) Causes of the disease

The etiology of SLE and lupus nephritis (LN) is not completely clear. It is mainly thought to be caused by multiple factors, such as heredity, viral infection, immune abnormalities, exposure to sunlight or ultraviolet light, autoimmune caused by certain drugs and estrogen. Sexual disease, which causes kidney disease (ie, LN) is a typical autoimmune complex nephritis.

Immune genetic defects (30%):

The occurrence of SLE is related to hereditary factors. The family incidence rate is as high as 3% to 12%, and there is a tendency of family aggregation. After extensive research on HLA of SLE patients, it is found that some genes closely related to SLE are mainly in HLA. At the gene locus, especially in the HLA DR region, the HLA phenotype is polymorphic. The study confirmed that there is a haploid HLA B8/DR2 in the population, which is more likely to produce hypersensitivity reactions of cells and body fluids; this may be due to T and B lymphocytes and antigens are caused by HLA-encoded polymorphism in cells, which is characterized by T-suppressor cell dysfunction, autoantibodies and globulins. Some people think that SLE susceptibility genes are genes of different structures of T cell antigen receptors. Recently, some peptide structures of T-cell B chain have been found in the same individual as HLA DR, which increases the possibility of SLE. In addition, there are many complement defects in SLE, such as C2, C1q, C1r, C1s, C4. , C5, C8 and Bf, TNF, C1 esterase inhibitor deficiency, etc., these complement components or genetic defects can affect the traditional activation pathway of complement, increase the body's sensitivity to infection and other stimulating factors and SLE Susceptibility related.

External environmental factors (30%):

There are many external factors that induce or aggravate SLE, among which chronic infection, drugs, physical factors, emotional stimulation, and living environment are all important.

(1) Chronic infection: Commonly known as chronic viral infection, it is found under electron microscopy that there is a tubular corpuscular inclusion in the tissue of SLE patients, which is similar to the nuclear structure of the paramyxovirus nuclear protein and core, but further studies consider this to be Non-specific manifestations of cell damage, others have found inclusion-like substances from glomerular endothelial cytoplasm, vascular endothelial cells, and lesions in SLE patients, but the virus has not been isolated from tissues containing inclusion body-like substances. Therefore, the relationship between these substances and viral infections remains to be confirmed. In SLE patients, there are a variety of high titer anti-viral antibodies, such as anti-measles, anti-rubella, anti-parainfluenza, anti-EB virus, anti-mumps, anti-adhesive Antibodies such as viruses also have anti-reverse virus antibodies such as ds-DNA, dsRNA and RNA-DNA in patients' serum. It is also suggested that the pathogenesis of SLE is closely related to C-type RNA virus. In general, there are many signs. It indicates that viral infection may be one of the causes of SLE, but it has not been confirmed that viral infection is associated with immunoregulation and autoimmunity in SLE patients. In addition, some people think that the incidence of SLE is related to tuberculosis or Cocci infection.

(2) Drugs: A variety of drugs are associated with the pathogenesis of SLE, but the pathogenesis is different.

1 The drugs that induce SLE symptoms include penicillin, sulfonamides, phenylbutazone, gold preparations, etc. These drugs enter the body, causing allergic reactions, then stimulating the quality of lupus or causing the onset of SLE patients, or making patients with SLE Exacerbation, withdrawal can not prevent the disease from developing.

2 The drugs that cause lupus-like syndrome include hydralazine, procainamide, chlorpromazine, phenytoin, isoniazid, propyl and thiouracil, etc. After long-term high-dose use of these drugs, patients The clinical symptoms and laboratory changes of SLE may occur, but the pathogenesis is still unclear. Some people think that chlorpromazine binds to soluble nuclear protein to enhance its immunity after UV irradiation. The hydralazine binds to soluble protein and enhances its own tissues in vivo. The immunogenicity of the components, such patients can resolve spontaneously after withdrawal or a few symptoms remain. With the emergence of new drugs, some people believe that drugs can be used as exogenous carriers to bind to host tissue determinants. Inducing autoantibody production, therefore, the clinical use of drugs should pay attention to the occurrence of drug-induced lupus.

(3) Physical factors: About 1/3 of patients with SLE are allergic to sunlight, ultraviolet light can induce skin lesions or aggravate the original skin lesions. In a few cases, systemic lesions can be induced or aggravated, and double-stranded DNA in normal human skin tissues is exposed to ultraviolet rays. Dimerization can occur after irradiation to form thymine dimer, which can repair depolymerization after UV irradiation, SLE patients have defects in repairing dimerized DNA, and excessive thymine dimer may become pathogenic Sexual antigens, some people think that ultraviolet radiation can damage skin cells, anti-nuclear factors can enter the cells, and play a role in the nucleus, resulting in skin damage. In addition, X-ray irradiation, cold, strong electro-optic irradiation can also induce or aggravate SLE Condition.

(4) Diet: Foods containing psoralen, such as celery, figs, European windproof, etc., have the potential to enhance the light sensitivity of patients with SLE; mushrooms containing hydrazine gene, smoked food, food dyes and tobacco can induce Drug-induced lupus; seeds of alfalfa containing L-concandin, sprouts and other pods can also induce lupus, limiting calorie and fatty acid intake can reduce the severity of lupus, presumably this may be for patients with SLE Good.

(5) Others: Asbestos, silica, vinyl chloride and hair dyes containing reactive aromatic amines may be involved in the pathogenesis of SLE. Severe physiological and psychological stress can induce sudden onset of SLE.

Endocrine factors (30%):

SLE mainly affects women. The prevalence of women of childbearing age is 9-13 times higher than that of men of the same age. However, the prevalence of prepubertal and postmenopausal women is only slightly higher than that of men. Therefore, estrogen is considered to be related to SLE, regardless of male or In women with SLE, the levels of 16-hydroxyated estrone and estriol are significantly increased. Female contraceptives can sometimes induce lupus-like syndrome. Both human and animal studies have shown that estrogen can increase the production of DNA by B cells. Antibodies, and androgen can inhibit this reaction, recently found that serum levels of prolactin in SLE patients, leading to secondary changes in sex hormones, further research confirmed.

(two) pathogenesis

Although the research on the pathogenesis of LN has been greatly developed in recent years, so far, the complex mechanism of this multi-factor and many aspects has not been fully understood.

1. It is currently accepted that LN is a typical autoimmune complex nephritis. The evidence is:

(1) Plasma globulin, gamma globulin and IgG increased.

(2) There are a large number of autoantibodies in the body, including anti-mono, double-stranded DNA, anti-SM, anti-RNP, anti-nuclear protein, etc. in the nucleus; anti-La, Ro, etc. in the cytoplasm; anti-lymphocyte, anti-platelet The anti-endothelial cells and the like, as well as certain component proteins of the extracellular matrix, such as type IV collagen on the basement membrane, wherein the DNA-anti-DNA antibody is one of the main immune complexes causing kidney damage.

(3) The immune complex was positive in the patient's circulation, and immunofluorescence confirmed that the kidney tissue had DNA-anti-DNA immune complex deposition.

(4) There is hypocomplementemia.

(5) Histological changes are characterized by immune responses, including lymphocyte and plasma cell infiltration.

(6) Treatment with corticosteroids and cytotoxic drugs is effective.

2. The formation and deposition of immune complexes is the main mechanism of LN-induced renal damage

(1) Circulating immune complexes in the kidney deposit: some foreign antigens (such as viruses) and endogenous antigens (such as DNA, immunoglobulins, lymphocyte surface antigens, etc.) act on patients with abnormal immune regulation function, making B lymphocytes Highly active proliferation, production of a large number of autoantibodies, and binding with the corresponding antigen to form an immune complex deposited in the kidney and cause glomerular damage, which is the main pathogenesis, the process is subject to the size of the circulating immune complex, charge, affinity And glomerular mesangial effect on its clearance, local hemodynamics, etc., this form mainly leads to mesangial proliferation and hair cell vascular endothelial proliferation pathological changes.

(2) Implantation of antigen: Nuclear antigen or other antigen is pre-exposed under the glomerular epithelium to form a so-called implanted antigen, which is then combined with the corresponding circulating antibody to form an in situ immune complex.

(3) In situ immune complex formation: circulating antibodies and glomeruli, renal tubular or vascular wall basement membrane endogenous antigens combine to form an in situ immune complex.

Lupus nephritis prevention

The prevention of SLE renal damage mainly depends on the prevention of lupus and the early diagnosis and reasonable and effective treatment of primary disease. The prevention of lupus can reduce the occurrence of complications such as kidney damage. Reasonable and effective treatment can prolong the survival of patients. Mainly infection, renal failure and central nervous system diseases, the 5-year and 10-year survival rates of SLE in recent years are 95% and 85%, respectively, which is closely related to the early diagnosis and reasonable and effective treatment of primary disease.

Lupus nephritis complications Complications Chronic nephritis nephrotic syndrome

Mainly complicated by acute and chronic nephritis syndrome, nephrotic syndrome, renal tubular syndrome, and may be combined with larger renal vascular thromboembolism, renal capillary thrombotic microvascular disease, causing renal dysfunction, especially renal failure.

Lupus nephritis symptoms common symptoms fatigue weight loss consumptive weight loss discoid erythema joint pain muscle atrophy hepatomegaly lymph node enlargement liver function abnormal mania

SLE women are more common, the ratio of male to female is 1:13, but male and female patients have the same high renal involvement rate, the average age of onset is 27 to 29 years old, 85% of patients are under 55 years old, SLE is a systemic disease Can affect multiple systems and organs, clinical manifestations are diverse, about 70% of patients have clinical manifestations of renal damage, combined with renal biopsy tissue immunofluorescence and electron microscopy, SLE 100% have kidney involvement, often due to infection Cold, sun exposure, alcohol abuse, stress, overwork or mental stress can lead to the onset or aggravation of the disease. It can also cause recurrence due to improper application of hormones, excessive reduction or sudden withdrawal of drugs, and every recurrence will cause involvement. The damage to the organs is even worse, and even functional failure.

(1) General symptoms: Most patients may have generalized weakness, weight loss, and weight loss. 90% of patients have fever, 65% of which are the first symptoms, and the heat type is uncertain. It can be intermittent heat, relaxation heat, and heat retention. Or chronic hypothermia, 40% can exceed 39 ° C, should pay attention to whether it is caused by infection, especially patients treated with large doses of hormones.

(2) Skin mucosal damage: SLE has a variety of skin mucosal damage, the incidence rate is more than 80%, 50% of patients may have butterfly erythema, edematous erythema (nose) with butterfly shape on the bridge of the nose and the cheeks There is no skin lesion in the lip groove, there may be telangiectasia and scales. When the exudation is serious, there may be blisters and ecdysis. After the erythema is regressed, no scar is left. 20% to 30% of patients may have discoid erythema. The skin at the exposed part is a ring-shaped, round or elliptical red ridged patch with scaly and horny plugs on the surface. Scars often remain after the lesions have subsided. Butterfly erythema and discoid erythema are characteristic of SLE. Skin lesions, sun or ultraviolet radiation will increase, 35% to 58% of SLE patients may have photoallergies, 50% to 71% of patients may have hair loss, is one of the sensitive indicators of SLE activity, about 50% of patients may appear Vascular skin lesions, caused by small blood vessels and capillary inflammation or spasm, including reticular bluish, vasculitic skin lesions, Raynaud's phenomenon, periungual erythema, urticaria-like lesions, frostbite-like lupus-like lesions and capillaries Vasodilatation, etc., 7% to 14% of patients may have mucosa Erosive or painless ulcers.

(3) joint and muscle lesions: about 95% of patients may have joint pain and arthritis, common in limbs and small joints, 5% to 10% of patients have aseptic femoral head necrosis, mostly due to long-term, large, irregular Due to the use of hormones, half of the patients have myalgia and myopathy, and even obvious symptoms of muscle weakness or muscle atrophy. Joint muscle disease is often associated with disease activity.

(4) Lung and pleural lesions: 28% to 50% of patients may have pleurisy, pleural effusion, effusion mostly yellow exudate, mainly monocytes, need to be differentiated from tuberculous pleurisy, there is thought, chest The effusion ANA1:160, or pleural effusion/serum titer 1, or SM antibody positive, contributes to the diagnosis of SLE pleural effusion, 2.7% to 10.1% have acute lupus pneumonia, and the mortality rate is high. The main cause of death is respiratory failure and pulmonary embolism. The symptoms of acute lupus pneumonia are more severe. The X-ray shows diffuse speckled shadows in both lungs. There are more lung fields and more shadow changes. The effect of large doses of hormone therapy is obvious.

(5) Cardiovascular system performance: 50% to 55% of patients with SLE may have heart disease, including pericarditis, myocarditis, heart valve disease, arrhythmia and hypertension.

(6) Blood system lesions: 50% to 75% of patients have positive pigmented cell anemia, which may be autoimmune hemolytic anemia, partly related to inflammation of SLE, renal insufficiency, blood loss, eating disorders, drug effects, etc. 50% to 60% of patients may have leukopenia, mostly below 4.0 × 109 / L, lymphopenia (<1.5 × 109 / L) more common in the disease activity period, 20% to 50% of patients can be concurrent Mild thrombocytopenia, mostly in (50 ~ 150) × 109 / L, 5% ~ 10% of patients can be less than 50.0 × 109 / L, is a common clinical manifestation of SLE disease activity, in addition, 25% of SLE Patients with a variety of lupus anticoagulant substances, such as anti-VIII, IX, XI, XII, clotting factors, etc., lead to abnormal blood coagulation.

(7) Gastrointestinal symptoms: 25% to 50% of patients may have loss of appetite, nausea, vomiting, abdominal pain, diarrhea, 30% of patients may have hepatomegaly and abnormal liver function, a few have splenomegaly.

(8) Neurological manifestations: 50% to 60% may have neuropsychiatric disorders, and the clinical manifestations are complex and diverse. Symptoms include mental disorders (such as depression, mania, mental defects, confusion, etc.), epilepsy, hemiplegia, migraine, Chorea, peripheral neuritis and retinopathy, most of which are related to lupus disease activity, poor prognosis, is an important cause of death in SLE.

(9) Others: Irregular menstruation, dysmenorrhea, excessive or too little menstruation, some patients may have painless lymphadenopathy, parotid swelling, conjunctivitis and so on.

Examination of lupus nephritis

1. Urine routine examination changes in urine composition are important for the diagnosis and curative effect observation of lupus nephritis. LN patients may have hematuria, proteinuria, leukocyte urine and tubular urine. When renal insufficiency may have a decrease in urine specific gravity, and Uremic performance, urea nitrogen, creatinine were significantly increased.

2. Blood routine examination SLE patients with blood system involvement may appear:

(1) Red blood cell reduction, hemoglobin reduction, and may be accompanied by reticulocyte increase, Coombs test positive.

(2) Leukopenia can be below 4.0 × 109 / L, patients with larger doses of hormone therapy, may have increased white blood cells and neutrophils.

(3) thrombocytopenia, often below 100 × 109 / L.

3. Blood chemistry examination Patients with active SLE almost all have erythrocyte sedimentation rate. Some patients still have high erythrocyte sedimentation rate even during remission. Most patients with lupus activity have hyperglobulinemia, mainly -globulin. A small number of patients have a decrease in cryoglobulinemia and complement levels (C3, C4, CH50, especially C3); there may be an increase in circulating immune complexes (CIC), a variety of cytokines in the blood such as IL-1, IL-2, IL-6, IL-2 receptor, tumor necrosis factor increase, unless the infection is combined, C-reactive protein is generally not high.

4. Autoantibodies When SLE is examined, a variety of autoantibodies can be present in the blood, which is important for diagnosis.

(1) Antinuclear antibody (ANA): high positive rate, 95%, specificity of about 70%, can be used as a good screening test. Peripheral or homogeneous type has a greater significance for the diagnosis of SLE, while spot type and nucleolus The type can be seen in other connective tissue diseases, and is quite specific for diagnosis when ANA 1/80.

(2) Anti-ds-DNA antibody: anti-ds-DNA antibody positive rate of about 72%, high specificity, up to 96%, in patients with untreated SLE, only occasionally in Sjogren's syndrome, rheumatoid Arthritis and chronic active hepatitis, the concentration of anti-ds-DNA antibodies have a certain value in distinguishing SLE activities.

(3) Anti-Sm antibody: The positive rate is low, only found in 25% of patients with SLE, but the specificity is extremely high, up to 99%.

(4) anti-histone antibody: positive rate of 25% to 60%, high specificity, drug-induced lupus 90% positive, even in rheumatoid arthritis and Sjogren's syndrome.

(5) Anti-SSA (Ro) and anti-SSB (La) antibodies: Both antibodies have poor sensitivity and specificity for the diagnosis of SLE, mainly in patients with Sjogren's syndrome.

(6) Other antibodies: There are also a variety of autoantibodies in SLE, such as anti-RNP antibodies, antiphospholipid antibodies, anti-neutrophil cytoplasmic antibodies (ANCA), anti-erythrocyte antibodies, anti-platelet antibodies, anti-lymphocyte antibodies , anti-skeletal muscle cells, anti-smooth muscle cell antibodies, anti-thyroid epithelial cell antibodies, etc.

5. Renal biopsy and skin lupus belt test (LBT) Renal biopsy combined with immunofluorescence and electron microscopy, the diagnosis rate of SLE is almost 100%, and the pathological type of lupus nephritis can be determined and the activity and chronic degree of disease can be judged. .

Skin LBT has a high value for the diagnosis of SLE. Generally, the skin of the site is non-skinned at the exposed site, and the skin with normal appearance on the wrist is taken. The false positive rate is high in the lesion, and the skin is directly immunofluorescent. A yellow-green fluorescent band consisting of IgG, IgM and/or other immunoglobulins and complements is found in the epidermis and the dermis junction or the basal membrane of the dermatological accessory. It is homogeneous or granular and is positive for the LBT test. For LN without extrarenal manifestations, skin LBT is important when there is difficulty in differential diagnosis.

SLE has a variety of renal lesions, and its pathological changes are characterized by:

(1) "iron coil"-like lesions: thickening of the basement membrane due to subendothelial deposits, electron microscopy and immunofluorescence have a large number of subendothelial deposits, which is an important feature of SLE renal damage.

(2) Hematoxylin body: It is generally believed that antinuclear antibodies cause cell damage in situ, and are stained by highly coagulated nuclei.

(3) necrotizing vasculitis: micro-arteries and capillaries are fibrin-like necrosis.

(4) Electronic dense deposits, nuclear fragmentation, virus-like particles and inclusion bodies can be seen under electron microscope.

(5) Immunofluorescence: immunoglobulin deposition.

Diagnosis and diagnosis of lupus nephritis

Diagnostic points

The diagnosis of LN is mainly based on the clear diagnosis of SLE. The typical SLE diagnosis is not difficult. There are often multiple systems and multiple organ involvement, but atypical or early SLE is easily missed or misdiagnosed as other diseases.

At present, the diagnostic criteria for SLE are mostly based on the SLE diagnostic criteria revised by the American College of Rheumatology in 1982 (Table 1). Four of the 11 criteria can be diagnosed, with high sensitivity and specificity, respectively 93.1. % and 96.4%.

This standard is easy to miss diagnosis of some early, mild or atypical cases. In order to improve the sensitivity of SLE diagnosis, a diagnostic standard was proposed in 1982, which added skin LBT examination and serum complement test based on American standards. Serum complement, such as lower than normal, helps to diagnose SLE with a sensitivity of 97.5% and a specificity of 93.6%.

The diagnosis of lupus nephritis should pay attention to two points. First, those who are diagnosed with SLE should pay attention to the presence or absence of kidney disease. If there are conditions, renal biopsy should be performed. Second, because about 6% of patients with SLE, Renal damage is the first and only clinical manifestation, so anyone with glomerular disease should pay attention to whether it is caused by SLE. According to the detailed medical history, physical examination, laboratory examination, pathological examination, contrast SLE The diagnostic criteria often make a correct diagnosis.

Differential diagnosis

SLE has a common immunological basis with primary glomerular disease. Lupus nephritis can be used as the first manifestation of SLE and as the main or only manifestation of SLE, so it is easily misdiagnosed as primary glomerular disease. The following points are identified:

1. Primary glomerular disease does not produce fever unless it is combined with infection.

2. Nephritis with extra-renal manifestations such as joint pain, rash, etc., especially young women, should be highly suspected of lupus nephritis.

3. Before the diagnosis of primary glomerular disease, patients with conditions should routinely perform serum immunological tests such as ANA, anti-ds-DNA antibodies, anti-Sm antibodies, etc., in order to avoid misdiagnosis.

4. If necessary, immunopathological examination (skin lupus test and renal biopsy) will also help identify.

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