Human Immunodeficiency Virus Infectious Kidney Damage

Introduction to human immunodeficiency virus infectious kidney damage Human immunodeficiency virus infection, also known as AIDS, is the transliteration of AIDS, the full name is acquiredimmunodeficieneysyndrome, meaning acquired immunodeficiency syndrome, AIDS patients are due to acquired immunodeficiency, mainly manifested as conditional infection and malignant tumor, and Often accompanied by renal complications, according to renal biopsy or autopsy results found to be 20% to 30%. basic knowledge The proportion of illness: the probability of illness is 0.0002% Susceptible people: no special people Mode of infection: sexual intercourse, drug injection, blood transfusion or blood product transmission Complications: Pneumocystis carinii pneumonia diarrhea tuberculosis tuberculous pleurisy interstitial nephritis hypotension diabetes adrenal crisis

Etiology of human immunodeficiency virus infectious renal damage

(1) Causes of the disease

In 1983, the pathogen isolated from Montanier in France was named LAV. The AIDS pathogen discovered by Gallo in the United States in 1983 and reported in 1984 was named HTIV-III. The study proved that the two viruses are the same virus. The HIV Nomenclature Committee recommended that the human immunodeficiency virus (HIV) be named as a pathogen.

HIV is an RNA retrovirus, mostly round or elliptical, with 9213 nucleotide structures and 9749 base pairs. HIV is highly antigenic and can quickly occupy free immunoglobulin after invading the human body. It stimulates the body to produce antibodies, which are divided into anti-viral antibodies and neutralizing antibodies. The serum antibody titers of the individual vary greatly. The titer of serious AIDS cases is lower than that of mild cases. In the early stage of the disease, the virus can cause lymphocytes. After proliferation, the helper T lymphocytes (CD4 cells) are killed, the function of the helper B cells is lost, and the function of the antibody is weakened. Therefore, the destruction of CD4 cells by HIV is the central link of AIDS.

(two) pathogenesis

HIV is a T-lymphocyte virus that selectively attacks CD4 cells after infection. After HIV invades CD4 lymphocytes, the virus binds to the HIV receptor on the tissue membrane and enters the cell, and removes the envelope, intracellular, viral RNA. Reverse transcription into DNA, which then integrates into the host cell chromosome. When the infected cell is activated, the integrated proviral DNA transcribes RNA, synthesizes the protein, and finally forms intact HIV particles, which are released from the cell surface in a bud form. Blood circulation, re-infection of new CD4 cells, resulting in massive destruction of CD4 cells in patients leads to immunodeficiency. At the same time, loss of helper effect on B lymphocytes causes humoral immune disorders, loss of normal immune function, and reduction of CD4 cells can cause relative CD4/CD8 Inversion of (inhibition of T lymphocytes).

Due to the inhibition of cellular immune function, AIDS is prone to various infections, especially conditional pathogenic infections; due to the loss of immune surveillance and self-stabilizing functions, malignant tumors often occur, both of which are the leading causes of death.

The pathogenesis of HIVAN has not yet been elucidated. Most scholars believe that HIV is directly involved in the invasion of the kidney, causing the entire renal parenchyma cells to be involved, resulting in a variety of renal pathological changes. Cohen et al. found HIV and HIV serum with HIV nucleic acid and p24 antigen probes. Positive glomerular and tubular epithelial cells in patients with focal segmental sclerosis and tubulointerstitial lesions, and recent DNA in situ hybridization confirmed that renal biopsy and autopsy specimens of renal tubular and glomerular epithelial cells in HIV patients have HIV The presence of the genome strongly suggests that HIVAN's viral invasion theory, including immunological damage, infection, tumor, drug toxicity, long-term intravenous drug use, and renal hemodynamic changes, may be direct and/or caused by HIVA. Indirect cause.

Pathogen infection (37%):

The most common conditional pathogenic infections in AIDS patients are Pneumocystis carinii pneumonia, cytomegalovirus (CMV), mycobacterium avium infection, oral or esophageal Candida albicans infection, and herpes virus, Cryptococcus neoformans meningitis , Toxoplasmosis, Giardia infection, etc. According to the literature, CMV can often be detected in immune complex nephropathy, which proves that CMV infection can also cause nephritis, which may be associated with severe tubulointerstitial lesions. Some people found that CMV can be borrowed. Kidney transplantation spread, in vitro culture showed that CMV can infect and reproduce mesangial cells, and there are reports of HBsAg and HBeAg found in glomeruli.

Drugs (25%):

Intravenous injection of diacetal morphine has long been reported in the literature, and about 50% of AIDS patients have a history of drug addiction, and the pathological changes of HIVAN and HAN are very similar. It is often difficult to distinguish the pathological changes of these two nephropathy. There are glomerular lesions such as glomerular segmental sclerosis, capillary collapse and intermittent balloon dilation, and small tubule lesions, including microcapsule expansion, plasma protein tube type, cytoplasmic inclusion bodies on the ultrastructure Nuclear changes, as well as typical tubular network structures, Chander believes that HAN does not have a tubular network.

In addition, the size of the kidney of the HIVAN is higher than normal in the early or late stage, while the kidney in the late HAN is significantly reduced; the time to the end-stage renal failure is mostly from March to April, and the latter is from 2 to 4 years; There is no hypertension, the latter often has high blood pressure; the prognosis of the two is also significantly different, the duration of HIVH is short and the mortality rate is high, while the condition of HAN is relatively stable, and life can be prolonged by dialysis treatment.

Tumor (13%):

In the autopsy of 36 AIDS patients, Pardo found that there were 17 cases of glomerular pathological changes, 10 of which had Kaposi sarcoma. Bennett et al found that 25 cases of FSGS had pathological changes in 170 cases of AIDS patients, including 2 cases. There are Kaposi sarcoma, and cases of lymphoma and renal cell carcinoma are also found.

1. Nephrotoxic drugs Nephrotoxic drugs can cause kidney damage in AIDS patients. Therefore, nephrotoxic drugs, especially aminoglycoside antibiotics, amphotericin B, cyclosporine, and chemotherapy drugs should be used with caution in patients with AIDS. In addition to the direct toxicity of the kidney, the drug can also cause allergic interstitial nephritis.

2. Hemodynamic changes in body fluid loss or abnormal distribution, sepsis, shock, etc. can cause kidney damage in AIDS patients, so the cause of blood volume changes should be paid attention to.

3. Immune dysfunction AIDS patients with immune dysfunction, it has been proved that the incidence of nephrotic syndrome may be related to T lymphocyte function, lymphocytes produced by lymphocytes, can increase vascular permeability, and have direct toxicity to the glomerular basement membrane Role; regarding the role of humoral immunity in HIVAN, it is thought that the pathogenesis associated with immune complexes is not related, but in a few cases, the deposition of granular immunoglobulin and complement can often be detected in glomerular capillaries or mesangium. .

Among the above various pathogenic factors, some are relatively clear, such as nephrotoxicity, but some factors are complex. Since AIDS is a multi-factorial disease, damage to the kidney must be caused by many factors.

Human immunodeficiency virus infectious kidney damage prevention

The prevention of AIDS has attracted the attention of all countries in the world. All countries have established corresponding prevention and research institutions and adopted a series of preventive measures.

1. Management measures

(1) Establishing a management organization for prevention and treatment. At present, WHO has set up a special committee. In 1986, China also established a working group on prevention of AIDS.

(2) Limiting behaviors such as homosexuality.

(3) Drugs are banned and drug abuse is strictly prohibited.

(4) Do a good job in the management of patients and infected persons. Patients and infected persons should be sexually isolated. Pregnant AIDS patients or infected persons should stop pregnancy.

5 Do a good job in publicity, publicize AIDS knowledge, consciously protect yourself, and resist homosexuality and drug abuse.

2. Technical measures

(1) Import and use of imported blood and blood products are prohibited.

(2) Vaccine development: The AIDS vaccine is currently being developed using genetic engineering, and preliminary results have been obtained.

(3) Do a good job in customs quarantine and AIDS testing, and find patients and infected people in time.

(4) Do a good job in disinfection of patients' families and hospitals. Experiments have confirmed that HIV is very sensitive to disinfectants. It should be disinfected in places where patients, hospitals, and patients are polluted, such as 70% ethanol, 3% hydrogen peroxide, and 1% pentane. Dialdehyde, 0.2% to 0.5% sodium hypochlorite, 0.9% formaldehyde, 0.08% quaternary ammonium chloride, chlorine-containing lime, etc. all have the effect of killing HIV.

In short, the active implementation of the above preventive measures to control HIV infection, as well as early treatment of HIV patients, can effectively reduce the risk of kidney disease occurrence and development.

Complications of human immunodeficiency virus infectious renal damage Complications Pneumocystis carinii pneumonia diarrhea tuberculosis tuberculous pleurisy interstitial nephritis hypotension diabetes adrenal crisis

Complications of AIDS mainly include severe infection, progressive renal insufficiency and multiple systems, multiple organ dysfunction, and various primary and secondary malignant tumors. Common complications include:

1. Pneumocystis carinii pneumonia: X-ray films show patchy shadows around the two hilars, showing interstitial pneumonia.

2. Enteritis: Symptoms of diarrhea.

3. Tuberculosis: Among them, tuberculosis, tuberculous pleurisy is more common.

4. Skin, mucous membrane damage.

5. Fungal infection: visible in patients with tongue, buccal mucosa, soft palate and posterior pharyngeal wall with a thick white film.

6. Concurrent renal dysfunction can cause interstitial nephritis and tubular necrosis, proteinuria, oliguria, high edema, azotemia and renal failure.

7. Endocrine system damage: adrenal insufficiency and hyporenalemia, hypotension, persistent hyponatremia and hyperkalemia, hypothyroidism, diabetes and adrenal crisis.

Human immunodeficiency virus infectious kidney damage symptoms Common symptoms HIV infection lymphadenopathy Proteinuria Diarrhea Immunodeficiency Hypoproteinemia Powerless fatigue Night sweats and edema

1. The clinical manifestations of AIDS are very complicated. Due to irreversible immunodeficiency, AIDS has obvious systemic symptoms, often complicated by conditional infections and malignant tumors. Because there is no specific treatment, the final outcome is death.

The disease is usually from HIV infection to HIV antibody production for 2 months, and 10% to 15% of HIV-positive HIV-infected patients can develop into AIDS patients. The incubation period is not 1 to 3 years before clinical symptoms occur. In the shortest 6 months, the elderly can reach 4 to 8 years, and the clinical stage is generally:

(1) recessive period: also known as subclinical infection period, those who have HIV infection but no clinical symptoms are recessive, but can detect HIV antibodies or isolate HIV virus and CD4 cells in laboratory tests. There are three possibilities for this period: one is long-term recessive state; the other is long-term insidious state; the third is AIDS-related syndrome after 1 to 3 years of incubation.

(2) AIDS-related complex (ARC): the body may have irregular fever, night sweats, loss of appetite, fatigue, diarrhea and other symptoms, systemic lymphadenopathy, biopsy showed lymphocytosis, follicular Degeneration, increased plasma cells, lymphatic tissue atrophy, immune system changes, CD4/CD8 inversion, thrombocytopenia, etc.

(3) Clinical AIDS period: also known as AIDS episode, the patient has suffered a large number of CD4 cell destruction, forming a serious irreversible immunodeficiency, systemic symptoms are more obvious, fever, sweating, general weakness, weight loss, cachexia, etc. Various pathogenic infections and conditional pathogenic infections (such as PCP), as well as a variety of primary and secondary malignancies, Kaposi sarcoma, non-Hodgkin's lymphoma, brain tumors , mediastinal lymphosarcoma, prostate cancer, etc.

2. The clinical manifestation of HIVAN is about 10% of patients with nephrotic syndrome. The patients have a large amount of proteinuria (>3g/d), hypoproteinemia (<2.5g/L), with normal renal function or Different degrees of renal failure, occasionally manifested as hematuria (microscopic or gross), 25% to 35% of patients with moderate proteinuria, peripheral edema is generally not obvious, most patients (>95%) at the beginning (compensation The blood pressure is normal, and the blood pressure remains normal when the renal function declines. The kidney B-ultrasound and autopsy prove that the kidney is enlarged and the renal parenchyma echo is enhanced. The typical clinical process of HIVA is rapid glomerular filtration rate (GFR). Decreased, often develops into end-stage renal failure within 8 to 16 weeks. Although there is dialysis support treatment, the survival time is often less than 1 year. A small number of patients with end-stage renal failure have prolonged life by maintaining dialysis or kidney transplantation. .

Examination of human immunodeficiency virus infectious kidney damage

Blood routine examination

(1) White blood cell count: Leukopenia in AIDS patients is often less than 4 × 10 ⁹ /L.

(2) Lymphocyte count: often less than 1 × 10 ⁹ /L (normal people are higher than 1.5 × 10 ⁹ /L).

(3) Platelet count: often less than 0.1 × 10 ¹² /L.

(4) Eosinophilia.

2. Immunological examination

(1) The ratio of CD4/CD8 decreased, the ratio was often less than 1, and the severity decreased to 0.02, mainly due to the decrease of CD4 cells.

(2) Lymphocytes react to PHA, ConA, PWM and other mitogens and react with antigens such as tuberculin.

(3) The amount of interferon produced is reduced, and the ability to kill the virus is weakened.

(4) The number of NK cells is normal, but the activity is decreased.

(5) Delayed or abnormal skin allergic reaction.

(6) Anti-lymphocyte antibodies, anti-nuclear antibodies and anti-sperm antibodies positive.

3. Pathogen examination

(1) HIV examination: HIV can be found by electron microscopy of blood or tissue biopsy specimens.

(2) Pneumocystis carinii examination: sputum smear, lung biopsy.

(3) Candida albicans examination: direct microscopic examination and culture of lesions and secretions.

(4) Examination of pathogens of other infections.

4. Serological examination

The serological examination of AIDS can determine the presence of HIV antibodies, is the main tool for detecting AIDS, and is also an important basis for the diagnosis of AIDS and an important means of epidemiological investigation. The current detection methods are as follows:

(1) Enzyme-linked immunosorbent assay (ELISA): It is one of the most widely used methods, and it is easy to operate and sensitive.

(2) Immunofluorescence (IFA): After HIV infection, the virus antigen is often expressed on the cell membrane, and the antibody of the antigen is detected by immunofluorescence. The method is simple and can be used for screening blood donors for blood donors.

(3) Western blot (WB): This method is highly sensitive and specific, but the operation is more complicated, generally can be used as a method to verify other serological tests.

(4) Radioimmunoprecipitation test (RIP): including solid phase radioimmunoassay and competitive radioimmunoassay, which have high sensitivity and specificity and are of great value for the diagnosis of AIDS.

(5) Gelatin particle agglutination test (GPAT): This method is rapid, simple, and sensitive, but may have a false positive.

(6) Polyribozyme chain reaction (PCR): amplification of HIV DNA sequences in vitro for DNA molecular hybridization, which is the most specific and sensitive method for detection, is rapidly being promoted.

Other auxiliary inspections:

1. Pathological changes of HIVAN The glomerular pathological changes were found in 30% to 50% of renal biopsy and autopsy in AIDS patients, mainly characterized by focal segmental glomerulosclerosis (FSGS) accounting for 83%. Proliferative glomerulonephritis accounted for 6%, minimal lesions accounted for 3%, and other glomerular lesions (including diabetic glomerular sclerosis, post-infection glomerulonephritis, membranous or proliferative glomerulonephritis) accounted for 6%.

2. Renal biopsy revealed pathological changes in FSGS in HIV nephropathy.

(1) Light microscopy: visible swelling and hyperplasia of glomerular visceral epithelial cells, with large vacuole formation or protein reabsorption microdroplets in the cytoplasm, extensive capillary wall collapse and often spherical collapse, collapsed blood vessels The plexus is "crowned" by a layer of hypertrophic visceral epithelial cells. Foam cells are visible in the still open lumen. The mesangial matrix proliferates, and there are a large number of invasive lesions. The renal capsules are often dilated and filled with protein. In addition, There are obvious tubular lesions, such as the disappearance of the brush-like edge of the proximal convoluted tubule, the cells flatten, the microtubules are dilated, and the epithelial cells of the tubule contain a large number of protein reabsorption droplets, accompanied by various degeneration, necrosis and regeneration. Dilated tubules are found throughout the cortex and medulla, especially at the junction of the pulp and pulp. The lumen is filled with large casts, but some tubules are still atrophied, interstitial diffuse edema, on the contrary, interstitial fibrotic lesions, lymphocytes Very little infiltration with monocytes and lack of hypertensive arteriolar lesions.

(2) Immunofluorescence: IgM, C3 and C1q are observed in the segmental and mesangial areas of glomerular sclerosis, showing granular segmental deposition, and circulating immune complexes of IgG or IgA, C3 can also be detected. The immunological characteristics are similar to those of type I membranous proliferative nephritis.

(3) Electron microscopy: visible visceral epithelial cell foot process fusion, epithelial cells and basement membrane separation, especially in the segment of glomerular sclerosis, there are various complex inclusion bodies in the nucleus and cytoplasm of various cells. Rich tubular network structure (TRS) appears in endothelial cells and interstitial cells. This inclusion body is numerous, bulky and fused to each other. The presence of such inclusion bodies in renal biopsies of HIV-infected asymptomatic FSGS. It can be considered as a strong evidence of the state of HIV carrying, parallel deposits and column-to-cell changes (CCC) are also seen in the cytoplasm of renal tubular epithelial cells and other cells, which are also known as test tube and ring-like changes.

The above-mentioned pathological features of FSGS in HIV nephropathy contribute to the identification of FSGS caused by other kidney diseases, but still lack specificity, especially similar to diacetal morphine nephropathy (HAN), which should be carefully identified.

Diagnosis and diagnosis of human immunodeficiency virus infectious renal damage

diagnosis

1. Diagnosis of AIDS In addition to epidemiological data, detailed medical history and comprehensive physical examination, the key is to conduct laboratory tests of HIV and comprehensive analysis of clinical manifestations to help diagnose AIDS.

(1) Gay history: Whether the patient has a typical medical history, whether there are AIDS patients with confirmed gammon.

(2) History of intravenous drug use: whether it is drug dependent, whether there is a history of intravenous drug use, whether the syringe is strictly disinfected, and whether the syringe is used in series with each other.

(3) Blood transfusion or blood products: It is also the main source of infection of AIDS. Pay special attention to whether hemophilia patients use factor VIII.

(4) Others: AIDS infection factors, such as heterosexual and chaotic relationship, HIV infection in pregnancy, organ transplantation, etc., in addition to systemic physical examination of suspected AIDS patients, mainly for conditional infection and Kaposi sarcoma examination.

2. Diagnosis of HIVAN First, the diagnosis of AIDS should be determined according to the International Centers for Disease Control (CDC) diagnosis of AIDS, and then the diagnosis of the disease should be based on the comprehensive analysis of the clinical manifestations and laboratory results of kidney disease, such as through serology and virus research. It is confirmed that there is HIV infection, many HIV seropositive but clinically healthy people have clinical manifestations of kidney disease. The main clinical manifestations of HIVA are proteinuria, some are nephrotic syndrome, and renal function is rapidly declining in a short period of time. There is pathological change of FSGS in renal biopsy. And other causes of diagnosis, including drug addiction, tumors, immune factors and nephrotoxicity can induce and promote various kidney lesions in AIDS patients.

Differential diagnosis

It should be identified with the following diseases:

1. Primary immunodeficiency disease.

2. Secondary immunodeficiency disease, corticosteroids, chemotherapy, secondary immunological diseases caused by radiotherapy or malignant tumors.

3. Idiopathic CD4 T lymphopenia, similar to AIDS, but no HIV infection.

4. Autoimmune diseases Connective tissue diseases, blood diseases, etc., AIDS has fever, and weight loss needs to be identified with the above diseases.

5. Lymph node enlargement diseases such as KS, Hodgkin's disease, lymphoma, blood disease.

6. Pseudo AIDS Syndrome AIDS phobia, British gays have seen some neurological symptoms similar to the early symptoms of AIDS.

7. Central nervous system diseases Brain damage can be caused by AIDS or other causes and needs to be identified.

8. The pathological features of FSGS for differential diagnosis of HIV nephropathy caused by nephrotic syndrome or other kidney diseases are helpful for identification with other kidney diseases, but still lack specificity, especially with the pathological features of diacetal morphine nephropathy (HAN). Should be carefully identified.

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