membranous glomerulonephritis
Introduction
Introduction to membranous glomerulonephritis Membrane glomerulonephritis (membranous glomerulonephritis) is clinically characterized by massive proteinuria or nephrotic syndrome. Pathologically, the glomerular capillary basement membrane is uniformly thickened and characterized by diffuse subepithelial immune complex deposition. , without an independent disease with obvious cell proliferation. Pathological features are diffuse immune complex deposition under the glomerular basement membrane epithelial cells with diffuse thickening of the basement membrane. Clinical manifestations of nephrotic syndrome (NS) or asymptomatic proteinuria. basic knowledge The proportion of the disease: 0.3% - 0.6% (the incidence rate of the elderly over 50 years old is about 0.3% - 0.6%) Susceptible people: no specific population Mode of infection: non-infectious Complications: interstitial nephritis acute tubular necrosis renal failure
Cause
The cause of membranous glomerulonephritis
Etiology
The disease is caused by multiple causes, and idiopathic membranous nephropathy accounts for about 50% of adult nephrotic syndrome. This section mainly introduces idiopathic membranous nephritis, except for diagnosis, which is accompanied by other various reasons. Membranous nephropathy:
Malignant solid tumors (20%):
Among patients with membranous nephropathy older than 60 years, about 22% have malignant tumors, and among cancerous related nephritis, the most common membranous nephropathy accounts for 60% to 70%. Common tumors such as lung and mammary gland Gastrointestinal tract, ovary, renal cell carcinoma, lymphoma, leukemia and sarcoma.
Other (10%):
Accompanying may include: diabetes, sarcoidosis, thyroiditis, myasthenia gravis, sickle cell anemia, idiopathic thrombocytopenic purpura, multiple nodular polyarteritis, gangrenous pyoderma and bullous day Pem and so on.
Drugs (20%):
Penicillamine, gold, captopril, etc.
Connective tissue disease (10%):
Such as Sjogren's syndrome, systemic lupus erythematosus.
Mixed connective tissue disease and the like.
Infected with antigens and certain parasites: such as malaria, schistosomiasis, etc.
Hepatitis virus: Hepatitis B-associated glomerulonephritis (HBV-ASGN), hepatitis C virus membranous nephropathy.
Pathogenesis
The disease is a long-term immune complex, slowly deposited in epithelial cells (also known as chronic immune complex deposition disease), generally does not cause inflammatory cell response, and through the terminal components of complement C3b ~ C9 is the complement of the membrane attack system, resulting in Basement membrane damage, immunofluorescence showed granular IgG, C3 deposited in the glomerular basement membrane, Dixon et al. In animal experiments, 2 mg of low-dose heterologous protein was injected into rabbits every day to produce chronic serum disease, resulting in deposition of circulating immune complexes. Membranous nephropathy.
The epithelial immune complex of the basement membrane of the disease is mainly formed in situ, and the antigen may be "implanted" in advance, or the surface glycoprotein of the visceral epithelial cell and the corresponding antibody form an immune complex on the surface of the epithelial cell, and fall off the basement membrane. on.
Cell-mediated immune dysfunction is also one of the immunological features of this disease. There are data suggesting that, especially in the onset of nephrotic syndrome, abnormalities of T lymphocyte subsets, such as CD4, CD8 cells, absolute and absolute values, The former is higher and the latter is reduced.
Primary membranous nephropathy is significantly associated with immunological genetic markers; in Europe, such as the United Kingdom, Germany, Spain and Finland, the detection rate of HLA-DR3 is significantly increased in patients with primary membranous nephropathy, and patients with primary membranous nephropathy in the United States The B cell antigen MT2 was shown, and the detection rate of HLA-DR2 in patients with primary membranous nephropathy in Japan was significantly higher. In the United States and the United Kingdom, patients with B18-BfF1-DR3 monotype were more likely to have a worse prognosis than other types.
Prevention
Membranous glomerulonephritis prevention
1. Pay attention to rest, avoid fatigue, prevent infection, diet with low protein, pay attention to vitamin supplements. Avoid using drugs that damage the kidneys.
2. During the drug treatment, every 1 to 2 weeks of outpatient visits, observe urine routine, liver and kidney function, children should pay attention to growth and development to guide the completion of the course of treatment.
3. After the control of active lesions and after the completion of the course of treatment, renal biopsy should be repeated to observe the pathological changes of renal tissue to determine whether there is a chronic tendency, so as to take timely measures.
4. Pay attention to the protection of residual renal function, correct various factors that reduce renal blood flow (such as hypoproteinemia, dehydration, hypotension, etc.) and prevent infection, which are important links in prevention. For complications that affect patient outcomes and long-term prognosis, treatment should be actively treated:
(1) Infection: Hormone therapy is prone to infection. Once it is found, it should be promptly treated with antibiotics that are sensitive, potent and non-neotoxic to pathogenic bacteria. Those with clear infection should be removed as soon as possible.
(2) thrombosis and embolism complications: It is generally believed that when the plasma albumin concentration is lower than 20g / L, it indicates that there is a hypercoagulable state, that is, preventive anticoagulant therapy should be started. Anticoagulants should generally be used for more than half a year. Anticoagulation and thrombolytic therapy should avoid excessive drug bleeding.
(3) Acute renal failure: nephrotic syndrome complicated with acute renal failure can be life-threatening if not treated properly. Most patients are expected to recover if given timely treatment.
Complication
Membranous glomerulonephritis complications Complications interstitial nephritis acute tubular necrosis renal failure
1. Renal venous thrombosis Clinical evidence and continuous renal biopsy data prove that the disease is a chronic progressive disease. For example, during the course of the disease, sudden increase in urinary protein, or sudden deterioration of renal function, suggesting that renal vein thrombosis may be associated with a concomitant rate of up to 50%. Inducing factors include serum albumin too low (<2.0 ~ 2.5g / dl), strong excessive diuretic, long-term bed rest and so on.
2. Acute interstitial nephritis, tubular necrosis or crescentic nephritis are common complications of MN.
3. Patients with advanced renal failure have deteriorated renal function, decreased urine output, elevated urinary creatinine and urea nitrogen, and are prone to renal failure.
4. Infection Due to the large loss of immunoglobulin from the urine, the body's resistance is reduced, and various infections are often combined in the course of the disease.
Symptom
Membranous glomerular neuritis symptoms Common symptoms Urinary osmotic pressure decreased urinary filtration fraction decreased edema hematuria lower extremity edema edema with proteinuria plasma albumin decreased dyslipidemia glomerular sclerosis systemic persistent edema
For example, in adults with a large amount of proteinuria as the main manifestation, especially those with nephrotic syndrome, the possibility of this disease should be considered, and the diagnosis of this disease mainly relies on renal biopsy pathology. After diagnosis, it should be differentiated from primary or secondary. Sex.
1 early membranous nephropathy should be differentiated from mild lesions or focal glomerulosclerosis: sometimes can not be distinguished under light microscopy, mainly by electron microscopy of renal tissue.
2 Except for other secondary causes of membranous nephropathy: such as autoimmune disease systemic lupus erythematosus; can be used as ANA, anti-ds-DNA antibody, Sm antibody, RNP and serum complement, etc., combined with clinical manifestations; Related membranous nephropathy: In addition to the history of hepatitis B and serum immunological markers, it is mainly diagnosed by HBsAg immune complex deposition or HBV-DNA in renal tissues; refractory nephrotic syndrome is manifested in elderly people over 60 years old. Various relevant imaging examinations should be performed to exclude malignant tumor-associated membranous nephropathy.
3 whether there are comorbidities: such as clinical pulmonary embolism, acute lumbar abdominal pain, unexplained hematuria, increased proteinuria, acute renal impairment with single or bilateral renal volume increase, etc. should be highly suspected renal vein thrombosis, should For imaging examination, computed tomography (CT), B-ultrasound or Doppler ultrasound flow imaging, renal venography, etc., the most widely used clinically, percutaneous femoral vein puncture selective renal venography, If the vascular filling defect or the venous branch is not developed, the diagnosis can be confirmed. If only a local contrast agent drainage delay is observed, a small thrombus should be suspected in the site. The chronic type occurs especially in the left kidney, and sometimes the side can be seen. Branch cycle.
Examine
Examination of membranous glomerulonephritis
The diagnosis of this disease mainly relies on renal biopsy pathology.
Microscopic examination
By qualitative urine protein and microscopic examination of urine sediment, it is possible to preliminarily determine whether there is a glomerular lesion.
2. Urine routine examination
Urine color is generally no abnormality, urine protein is generally not much, leukocytosis in urine sediment (acute period often filled with visual field, chronic phase in 5 / high power field), sometimes white blood cell cast.
3. Urine bacteria examination
When the urine contains a large amount of bacteria, about 90% of the bacteria can be found due to gram staining in the urine sediment coating. This method is simple and has a high positive rate.
4. Urine cell count
In recent years, the 1-hour counting method has been used, and it is considered that the 12-hour urine sediment count is accurate and simple. The standard is that the number of white blood cells is more than 300,000 / hour is positive, less than 200,000 / hour can be considered as a normal range, between 20,300,000 / hour should be combined with clinical judgment; red blood cells greater than 100,000 / hour is positive.
Diagnosis
Diagnosis and differentiation of membranous glomerulonephritis
The diagnosis of primary membranous nephropathy is based on the exclusion of secondary factors, followed by several common secondary membranous nephropathy:
1. Membrane-type lupus nephritis has very similar pathological changes and idiopathic membranous nephropathy; histological changes have implications for lupus nephritis: electron dense deposits on the basement membrane of the tubule (100%), Deposition of subendothelial electron denses (77%), deposition of electron denses in the mesangial area (63%) and tubular corpuscular inclusions (61%). Type IV lupus nephritis, which is diffuse proliferative nephritis, is converted to membrane damage after intensive treatment, but this type of anti-DNA and anti-nuclear antibody titers are higher than membrane-type lupus nephritis. Unless the serum creatinine is elevated and the pathological tissue has inflammatory cell infiltration, the prognosis of membranous lupus nephritis and idiopathic membranous nephropathy is good, and the 10-year survival rate is above 85%. The incidence of renal vein thrombosis is also high. In addition to conventional serological examination, it differs from idiopathic membranous nephropathy in that pathologically, mesangial cells and endothelial cells proliferate, and there are also immune complex deposition under the renal endothelium in the mesangial area. IgG, IgM, IgA, C3 are all positive and help to identify.
2. Membrane nephropathy caused by tumors A variety of tumors, especially lung cancer, gastrointestinal tract and breast malignant lesions, can cause membranous nephropathy. Evidence for tumor-induced renal immunological damage: 1 tumor-specific antigen is present in the glomerular immune complex; 2 soluble immune complexes are detected in the serum of patients with tumor-bearing nephropathy, and tumor-specific antibodies are contained.
The immune pathogenesis may be: the tumor-associated antigen stimulates the host to produce anti-tumor antibodies, and the antigen and the antibody form a soluble immune complex deposited on the glomerulus; the tumor patient has a defect in immune surveillance function, and stimulates the body to produce an immune complex when exposed to an antigen. This causes kidney damage.
It has been reported that nephrotic syndrome often occurs 12 to 18 months before the diagnosis of the tumor, and it is particularly necessary to be alert to the tumor in the elderly with nephrotic syndrome.
3. Hepatitis virus infection and glomerulonephritis The most common pathological type of hepatitis B virus-associated nephritis is membranous nephropathy, which is more common in male children. The detection rate of HBsAg in the serum of children with membranous nephropathy in European and American countries with a hepatitis B virus carrying rate of 0.1% to 1.0% is 20% to 64%, while in the population, the hepatitis B virus carrying rate is 2% to 20% in Asia. 80% to 100%.
Hepatitis C virus infection is complicated by mesangial capillary glomerulonephritis (MCGN), but in recent years, membranous nephropathy has also been reported. Hepatitis C virus complicated with membranous nephropathy has no cryoglobulinemia, normal complement levels, and rheumatoid factor negative. These indicators are different from hepatitis C with mesangial capillary nephritis.
4. The recurrence rate of renal transplant after kidney transplantation is about 10%. Usually, proteinuria occurs from 1 week to 25 months after surgery. The recipient often has severe nephrotic syndrome, and in 6 months~ Loss of kidney transplant in 10 years, increased steroid dose is more effective.
5. Drug-induced membranous nephropathy Organic gold, mercury, D-penicillamine, captopril (captopril), non-steroidal anti-inflammatory drugs have reported membranous nephropathy. Should pay attention to the history of medication, timely withdrawal may ease the condition.
Early membranous nephropathy is often missed and misdiagnosed, so conventional electron microscopy and immunofluorescence can help diagnose.
