Membranous nephropathy (MN) is also known as membranous glomerulonephritis, characterized by diffuse immune complex deposition under the glomerular basement membrane epithelial cells and diffuse thickening of the basement membrane. Clinically, it is mainly manifested as nephrotic syndrome (NS) or asymptomatic proteinuria.
English | 中文 | Русский | Français | Deutsch | Español | Português | عربي | 日本語 | 한국어 | Italiano | Ελληνικά | ภาษาไทย | Tiếng Việt |
Membranous nephropathy
- Table of Contents
-
1. What are the causes of membranous nephropathy
2. What complications are likely to be caused by membranous nephropathy
3. What are the typical symptoms of membranous nephropathy
4. How to prevent membranous nephropathy
5. What laboratory tests are needed for membranous nephropathy
6. Dietary preferences and taboos for patients with membranous nephropathy
7. Conventional methods of Western medicine for the treatment of membranous nephropathy
1. What are the causes of membranous nephropathy
The exact etiology of membranous nephropathy (MN) has not been clarified. Clinically, it can be divided into two major categories: primary MN and secondary MN. The former has an unknown etiology, while the latter is often associated with autoimmune diseases such as systemic lupus erythematosus, hepatitis B, and hepatitis C. It is now widely believed that there is an autoimmune abnormality in this disease. Secondary causes of membranous nephropathy include:
1. Immune diseases: Systemic lupus erythematosus, rheumatoid arthritis, diabetes, Hashimoto's thyroiditis, Graves' disease, mixed connective tissue disease, Sjögren's syndrome, primary biliary cirrhosis, ankylosing spondylitis, and acute infectious polyneuritis.
2. Infections: Hepatitis B, hepatitis C, syphilis, leprosy, filariasis, schistosomiasis, and malaria.
3. Medications and toxins: Organic gold, mercury, D-penicillamine, captopril, and probenecid.
4. Tumors: Lung cancer, colon cancer, breast cancer, and lymphoma.
5. Others: Sarcoidosis, recurrent renal transplantation, sickle cell disease, and angiolymphoid hyperplasia (Kimura's disease). However, 75% of membranous nephropathy cases cannot find the above causes, which belong to primary membranous nephropathy.
Although little is known about the pathogenesis of primary membranous nephropathy at present, most scholars agree that immune injury is the basic mechanism of the disease. It is believed that membranous nephropathy is an autoimmune-mediated glomerular damage that targets the antigenic components on the normal glomerular epithelial cell membrane. The immune complexes are formed by the deposition of the epithelial cells on the basement membrane, which are typical immune complex deposition. The deposited immune complexes activate the complement, producing C5b-9 at this point. The complement membrane attack complex causes proteinuria, and the cytokines activated during the disease process cause changes in the extracellular matrix components of the basement membrane cells, leading to thickening of the basement membrane, further promoting the progression of the lesion.
2. What complications are easy to cause by membranous nephropathy
The main complications caused by membranous nephropathy include the following:
1. Renal vein thrombosis Clinical observations and continuous renal biopsy data have proven that this disease is a chronic progressive disease. If, during the course of the disease, there is a sudden increase in urinary protein or a sudden deterioration in renal function, it may indicate the occurrence of renal vein thrombosis, with an incidence rate of about 50%. The triggering factors include low serum albumin (
3. Infection Due to the large loss of immunoglobulins from the urine, the body's resistance decreases, and various infections often occur during the course of the disease.
3. What are the typical symptoms of membranous nephropathy?
Nephrotic syndrome (MN) can occur at any age, but most patients are diagnosed over 30 years old, with an average age of onset at 40 years, and the peak age groups are 30-40 years and 50-60 years. The disease usually develops slowly, with no history of preceding upper respiratory tract infection in most cases. A few patients present with asymptomatic proteinuria, while the majority of patients (70% to 80%) have significant proteinuria, manifesting as nephrotic syndrome. The latent period of MN is generally a few weeks to several months, during which subepithelial deposits in the glomeruli gradually form, but the increased excretion of urinary protein has not yet reached a level sufficient to form clinical symptoms and attract the attention of patients. About 80% of patients present with edema as the initial symptom, 20% seek medical attention due to proteinuria. The excretion of urinary protein in idiopathic MN is usually 5-10g per day, but may reach up to 20g/d, and is mostly non-selective proteinuria. The amount of urinary protein fluctuates greatly due to daily protein intake, body position, activity level, and renal hemodynamic indicators. Generally, there is no gross hematuria, and 50% of adults and most children have microscopic hematuria. Unlike many acute post-infection glomerulonephritis cases, there is usually no hypertension in the early stages of this disease, but with the progression of the disease, 30% to 50% of patients may experience a rise in blood pressure. Renal function is generally normal in the early stages, but renal insufficiency and uremia may gradually develop due to reduced glomerular filtration, interstitial lesions, and other factors a few weeks to several months after onset. This disease is prone to complications such as renal vein thrombosis, with an incidence rate of up to 40% in China. The triggering factors include low serum albumin (
The onset of MN patients is insidious, often表现为典型的肾病综合征, can be accompanied by hypertension or microscopic hematuria, gross hematuria is rare; proteinuria is selectively low, urinary C3, C5b-9 increased, blood C3 is generally normal; the condition often maintains for many years, some can be spontaneously relieved. According to the above clinical characteristics, MN can be diagnosed, but the final diagnosis still requires renal biopsy.
4. How to prevent membranous nephropathy?
To prevent membranous nephropathy, the following points should be done:
11. Pay attention to rest, avoid fatigue, prevent infection, and have a diet low in protein. Pay attention to vitamin supplementation. Avoid using drugs that damage the kidneys.
10. During the medication period, visit the outpatient department every 1-2 weeks to observe urine routine, liver and kidney function. For children, attention should be paid to the growth and development, in order to guide the completion of the treatment course.
9. After the control of active lesions and the completion of the treatment course, renal biopsy should be repeated to observe the pathological changes of the renal tissue, judge whether there is a tendency towards chronicization, and take timely measures.
8. Attention should be paid to protecting the residual renal function, correcting factors that reduce renal blood flow (such as hypoalbuminemia, dehydration, hypotension, etc.), and preventing infection, which are important links in prevention that should not be ignored.
5. What laboratory tests are needed for membranous nephropathy?
The examination of membranous nephropathy (MN) is as follows:
1. Pathological anatomy
From gross anatomy, the kidneys appear yellow and enlarged. Since all glomerular lesions in MN are almost uniform, the characteristics of kidney enlargement in other chronic kidney diseases are not seen in MN, which seems to explain the relatively smooth surface of the renal cortex. This is also true even in cases with progressive disease, where there may be scar formation under the capsule in patients with renal failure.
2. Microscopy examination
Microscopy shows diffuse thickening of the glomerular capillary wall caused by immunological deposits, with silver staining showing spike-like projections due to the protrusions of the basement membrane surrounding the stained immunological deposits. Early glomerular lesions are uniformly visible, with stiff glomerular capillary loops, thickened capillary walls, and no obvious cell proliferation. PAM staining reveals nail-like projections on the capillary loops and subepithelial deposits of immune complexes. Late lesions become more severe, with significantly thickened capillary walls, narrowed lumens, and occlusion. The mesangial matrix widens, and further development can lead to glomerulosclerosis and hyaline change. Epithelial cells in the proximal convoluted tubules show foamy changes (a characteristic change of nephrotic syndrome). In patients with hypertension, there is significant arteriosclerosis and small arteriosclerosis, and inflammation cell infiltration is visible in the interstitium. Mononuclear macrophages and lymphocytes are the main cell types in the interstitium, with helper/inducer T lymphocytes dominating.
3. Electron microscopy examination
The entire glomerular capillary loop shows characteristic subepithelial electron-dense deposits, which may be the only change in early lesions, and large immune complexes may be found deposited below the epithelium with electron-dense deposits, separated by spicules, and foot process cells with fused foot processes. The glomerular basement membrane (GBM) is initially normal, and then due to the deposition of dense materials, it appears concave, and finally the GBM completely envelops the dense materials. Another characteristic is the disappearance of electron-dense materials, and the appearance of translucent areas in the corresponding regions. According to electron microscopy, some residual basement membrane areas show repair phenomena on the outside. Primary MN often has interstitial fibrosis and tubular atrophy.
4. Immunofluorescence examination
Under the basement membrane, immune globulins and complement components are deposited in characteristic fine granular form uniformly on the capillary wall, showing the outline of the capillary loops, among which IgG is most common, with more than 95% of cases showing C3 deposition. In addition, there may also be deposits of IgA, IgM, or even IgE, and the amount of deposition varies with the course of the disease; initially small, then gradually increasing, and finally decreasing. In some cases, HBsAg and CEA may be found. MN nephropathy can be divided into 4 stages according to pathology:
Stage Ⅰ: Also known as the early subepithelial deposit stage, light microscopy shows no obvious pathological changes, and in some cases, the basement membrane may be slightly thickened. Electron microscopy reveals a small amount of immune complexes deposited below the epithelium, and in the deposition area, foot processes can be seen to fuse. It is worth noting that in the early stage of Stage Ⅰ, electron microscopy is often normal, while immunofluorescence shows a positive reaction, indicating that immunofluorescence examination is more sensitive for early diagnosis.
Stage Ⅱ: Also known as the spicule formation stage, light microscopy shows thickening of capillary loops, GBM reactive hyperplasia, showing comb-like changes - spicule formation, and immunofluorescence examination shows a large number of immune complexes deposited below the epithelium.
Stage Ⅲ: Also known as the intramembranous deposit stage, light microscopy shows the beginning of glomerular sclerosis, capillary lumens are blocked, spicules gradually merge into a mass, enveloping the deposits, forming double tracks, and electron microscopy reveals unclear boundaries of the deposits.
Stage Ⅳ: Also known as the sclerosis stage, GBM is severely irregularly thickened, capillary loops are twisted, glomeruli collapse and fibrosis appears, spicules disappear; interstitial tissue shows cell infiltration and fibrosis with tubular atrophy, and electron microscopy reveals deposits that are difficult to identify in the basement membrane. At this time, immunofluorescence examination is often negative.
6. Dietary preferences and taboos for patients with membranous nephropathy
The diet for patients with membranous nephropathy should pay attention to:
1. Caution should be exercised in the intake of salt and alkali.The daily salt intake for a normal adult is about 5-6 grams, while in some areas, the daily salt intake per person can reach 12 grams. Salt is sodium chloride, alkali is sodium carbonate, and baking soda is sodium bicarbonate. Excessive intake of salt and alkali containing sodium can easily cause water retention in the human body, induce edema, so renal edema patients should control the intake of salt and alkali. Taking 2-3 grams of salt per person is considered a low-sodium diet. It is also not scientific to have a salt-free diet, as it can easily lead to fatigue, dizziness, and other symptoms over time.
2. Adequate water intake.The normal urine volume for a person is generally 1-2 kilograms per day. For patients with acute nephritis, acute renal failure oliguria phase, nephrotic syndrome, chronic renal failure with oliguria and edema, water intake should be controlled. Because water consumed cannot be excreted, water retention in the body worsens edema and is also prone to increase hypertension. At this time, the water intake should be about 500 milliliters more than the urine output. After the urine output increases, the water intake can be relaxed. For patients with normal urine output, there is no limit to water intake. In addition, for patients with urinary tract infections such as acute pyelonephritis, urethritis, cystitis, etc., drinking plenty of water and urinating frequently is very beneficial to the recovery of the disease.
3. Selection of ingredients.Patients with membranous nephropathy can eat fish, shrimp, eggs, and meat. These foods are high-quality proteins. In cases with allergic diseases such as allergic purpura or nephritis, or those with a history of allergic reactions to fish and shrimp, caution should be exercised due to suspected allergen protein sensitivity or a history of fish and shrimp allergies. Generally, there is no need to avoid these foods. Fish, shrimp, eggs, and meat contain abundant animal protein, which is the main structural material for human cells and tissues and is of great importance to the human body. After consuming protein-rich foods, the liver breaks them down, and the kidneys excrete them. Therefore, when renal function declines, it is necessary to appropriately reduce protein intake to meet the body's metabolic nutritional needs without increasing the burden on the kidneys. It is incorrect for some patients to avoid protein intake due to a mild kidney disease or to ignore protein intake when the disease requires it.
7. Conventional Western treatment methods for membranous nephropathy
For a long time, there has been controversy in the treatment of primary membranous nephropathy (MN). Some patients may experience spontaneous remission a few months or even several years after onset, while glucocorticoids and cytotoxic drugs themselves have side effects. To avoid delaying the disease due to prolonged observation, some experts suggest that for patients with persistent proteinuria, regardless of the severity, a 6-month close dynamic follow-up should be conducted before treatment, and general symptomatic treatment should be given, with medication as necessary.
One, General Management
1. Rest and Activity: When nephrotic syndrome occurs, bed rest should be the main method to increase renal blood flow and promote diuresis. However, moderate activity should be ensured to prevent the formation of thrombi and the occurrence of thromboembolic complications. After the nephrotic syndrome improves, gradually increase the amount of activity.
2. Diet: When edema is obvious, a low-sodium diet should be followed. Regarding protein intake, it is now universally recognized that limiting protein intake can delay the progression of renal dysfunction. A low-protein diet combined with essential amino acid therapy can reduce proteinuria while ensuring the patient's nutrition, thereby protecting renal function. This disease often accompanies hyperlipidemia, so it is recommended to follow a low-fat diet to reduce the occurrence of complications such as atherosclerosis caused by hyperlipidemia. One report states that providing animals with abundant polyunsaturated fatty acids can reduce animal blood lipids, decrease urine protein, and alleviate glomerulosclerosis.
3. Diuretic treatment: Selectively use various diuretics according to the condition and in moderation.
4. Lipid-lowering treatment: Hyperlipidemia can promote glomerulosclerosis and increase the occurrence of cardiovascular and cerebrovascular complications. In addition to changes in the amount of lipoproteins, hyperlipidemia in nephrotic syndrome also exists in changes in the composition of lipoproteins and changes in the lipoprotein profile. Therefore, in recent years, more attention has been paid to lipid-lowering treatment. Fibrates reduce plasma cholesterol concentration by interfering with the synthesis of triglycerides and cholesterol in the liver. Probucol (propyl gallate) can increase cholesterol degradation, antioxidant activity, and prevent the formation of oxidized low-density lipoprotein.
5. Anticoagulation: This disease has a hypercoagulable state, which is related to multiple factors such as the changes in coagulation and fibrinolysis factors in nephrotic syndrome, blood concentration, and so on. The use of strong diuretics and long-term and large doses of corticosteroids further aggravates this tendency. Anticoagulant drugs should be used preventively for these patients.
6. Reducing proteinuria: In addition to low-protein diet, the following drugs can also be used: angiotensin-converting enzyme inhibitors (ACEI), non-steroidal anti-inflammatory drugs, and traditional Chinese medicine Raiforgia royleana.
7. Immunostimulants: Levamisole can stimulate T cell function and strengthen immune regulation. The use of freeze-dried BCG vaccine in the treatment of refractory nephrotic syndrome has achieved good efficacy.
8. Intravenous administration of immunoglobulins: Use IgG to treat membranous nephropathy, and the specific use of IgG is 0.4g/kg, administered continuously for 3 days a week for 2 months, and then changed to 0.4g/kg, once every 3 weeks for 10 months.
2. Corticosteroids and Cytotoxic Drugs
1. Corticosteroids: There is still controversy about the efficacy of hormone treatment alone for MN. There are three large prospective randomized controlled studies, and their evaluation of hormone efficacy is inconsistent. It is not advisable to use corticosteroids alone for patients with primary membranous nephropathy.
2. Cytotoxic drugs:
(1) Combination of cyclophosphamide (CTX) with corticosteroids;
(2) Combination of busulfan with corticosteroids.
3. Cyclosporine (CsA)
Some studies have reported that cyclosporine (CsA) mainly reduces proteinuria by increasing the selectivity of the basement membrane pore size and charge, reducing shunt filtration, and promoting the reconstruction of podocytes. However, it should be noted that cyclosporine (CsA) has adverse reactions such as hypertension, increased blood creatinine levels, and interstitial nephritis.
Recommend: Chronic pyelonephritis , Urolithiasis , Horseshoe kidney , Urethral diverticulum , Urethral vestibular polyps , Urinary retention