Membranous glomerulonephritis

　　First, etiology

　　Membranous proliferative nephritis is divided into primary and secondary glomerulonephritis according to its clinical and laboratory characteristics:

　　1. The etiology of primary membranous proliferative nephritis is unknown, and it is generally believed that Type I is an immune complex disease; Type II is an immune complex and autoimmune antibody disease, which may be related to heredity.

　　2. In secondary membranous proliferative nephritis, there are three subtypes of mixed cryoglobulinemia. Type I cryoglobulinemia is a monospecific globulin, usually myeloma protein. Type II is usually a monospecific IgM globulin bound to IgG, also known as anti-IgG rheumatoid factor, while Type III is a polyvalent immunoglobulin. Type II and III cryoglobulinemia are prone to renal damage. The pathological features are massive proliferation of mesangial cells, infiltration of white blood cells, especially monocytes, thickening of the glomerular basement membrane with double track phenomenon. About 1/3 cases have medium and small artery inflammation, and microthrombi form in the capillaries. The etiology and pathogenesis of MPGN are not very clear. Type I MPGN is considered an immune complex disease, caused by the repeated and continuous deposition of relatively large, insoluble immune complexes. Type II MPGN patients also have immune complexes in the serum, cryoglobulinemia, abnormal complement, and persistent decrease in serum C3. All these suggest the role of immune complexes in Type II MPGN. C3 nephritogenic factor (C3NeF) can be detected in the serum of Type II MPGN patients, which is an autoantibody against C3bBb converting enzyme, enhancing the action of C3bBb, leading to the continuous activation of the complement alternative pathway, producing persistent hypocomplementemia and basement membrane变性. Therefore, complement metabolism disorder is the central link.

　　(1) In addition, Type II MPGN often recurs after renal transplantation, possibly due to the deposition of substances in the basement membrane that can cause abnormal glycoprotein formation in the patient's serum, leading to nephritis.

　　(2) This disease may be related to heredity, and HLA-B7 is often found in patients with Type II MPGN. Most patients with Type I MPGN have specific B cell alloantigens.

　　Second, pathogenesis

　　The pathogenesis of MPGN is not yet clear, and it is currently believed to be related to immunological mechanisms. 50% to 60% of MPGN patients show decreased complement C3, C1q, and C4 in the blood, indicating that both the alternative pathway and the classical pathway are activated, leading to decreased complement in the blood. It is also accompanied by mild increase in immune complexes and cryoglobulinemia, with deposition of immunoglobulins and complements in the glomeruli. However, the relationship between the abnormality of complement and the disease, as well as the role of immune complexes, needs further investigation.

　　MPGN is divided into three types based on the form and degree of immune complex deposition in the glomerular basement membrane and mesangial area.

　　1. The primary focus is on complex deposits in the subcutaneous and mesenteric areas. Type I is associated with viral, bacterial, and parasitic infections, as well as some immune complex diseases (such as hereditary complement deficiency, SLE, mixed cryoglobulinemia, SBE, shunt nephritis, lymphoma, schistosomiasis), but it is often idiopathic. In patients with Type I MPGN, 33% to 50% show hypocomplementemia, 25% to 30% have decreased Clq, C4, and C5, and 15% to 20% have decreased B factor.

　　2. Type II is known as an autoimmune disease, and under the electron microscope, a uniform and consistent band-like deposition of laminin can be observed along the basement membrane. This type is also known as dense deposit disease (DDD), and it often accompanied by subepithelial deposits similar to hump-shaped deposits. PAS staining sometimes shows a strip-like deep staining on the capillary loops. Type II is mainly believed to be related to streptococcal infection, as streptococci can cross-react with kidney antigens, causing antibody-mediated kidney damage. Type II often complicates with low plasma C3 levels, as some patients have complement activators, a type of autoantibody, also known as nephritogenic factor or C3 nephritogenic factor, which directly antagonizes C3bBb, altering the C3 alternative pathway conversion, by binding to the converter enzyme, blocking the action of some normal inhibitory factors such as H factor, and increasing the activation and consumption of complement. The nephritogenic factor is common in both type I and type II MPGN, especially more common in type II. Some are related to lipid malnutrition. Since type II MPGN mainly causes damage to the basement membrane, with a large amount of dense deposits deposited on the basement membrane, these deposits can activate complement, which is usually activated by specific substances such as ribonuclease, and can also activate the alternative pathway, causing the secondary and persistent increase of the nephritogenic factor in the blood, leading to a decrease in complement C3 in the blood. In type II MPGN, 70% of patients have reduced levels of complement C3 and B factor.

　　3. Deposits are present in the subendothelial, mesangial, and subepithelial areas of type III. The difference between type III and type I lies in the presence of deposits under the epithelium. With the passage of time, the pathological changes of MPGN often change from proliferation to obvious sclerosis. When the subtype is focal MPGN, the lesions can shift to diffuse classic MPGN. Some children or adolescents may start with diffuse MPGN, with the subtype mostly being lobular, which can then shift to focal or complete remission.

　　1. Infection:When nephrotic syndrome is present, the loss of a large amount of protein, malnutrition, immune function disorder, and the use of glucocorticoids for treatment can all lead to a decrease in the body's resistance, triggering the occurrence of infectious diseases. Clinical signs are often not obvious. Although there are many antibiotics to choose from, if treatment is not timely or thorough, it is still easy to cause recurrence of nephrotic syndrome and exacerbation of the condition, even leading to death of the patient.

　　2. Thrombosis and embolism complications:Due to the increase in blood viscosity caused by blood concentration (reduction in effective blood volume) and hyperlipidemia; the loss of a large amount of protein and the compensatory synthesis of protein by the liver can lead to an imbalance in the coagulation, anticoagulation, and fibrinolysis systems of the body. In addition, during nephrotic syndrome, platelet function is hyperactive, and the use of diuretics and glucocorticoids and other medications can further exacerbate the hypercoagulable state, making thrombosis and embolism complications more likely. Among them, renal vein thrombosis is the most common, with 3/4 of the cases not showing obvious clinical symptoms due to slow formation. In addition, pulmonary vascular thrombosis and embolism, lower limb venous, inferior vena cava, coronary vascular thrombosis, and cerebral vascular thrombosis are also not uncommon. Thrombosis and embolism complications are important factors directly affecting the treatment effect and prognosis of nephrotic syndrome.

　　3. Renal failure:Patients with nephrotic syndrome may experience a decrease in renal blood flow due to insufficient effective blood volume, which can trigger pre-renal azotemia. A few cases may present with acute renal failure. Due to the high pressure within the renal tubular lumen, it indirectly causes a sudden decrease in glomerular filtration rate, leading to acute renal tubular renal failure. It is common in patients over 50 years old, and the onset is often without obvious triggers, manifested as oliguria or anuria, with ineffective expansion and diuresis. Renal biopsy pathological examination shows mild glomerular lesions, diffuse severe edema in the renal interstitium, normal or a few cells showing变性, necrosis in the renal tubules, and a large amount of protein casts in the renal tubular lumen.

　　4. Disordered protein and fat metabolism:Long-term protein loss can lead to malnutrition and delayed growth and development in children; decreased immunoglobulin levels can cause decreased body immunity, making it prone to infection; the loss of metal-binding proteins can lead to deficiencies in trace elements (such as iron, copper, and zinc); insufficient endocrine-binding proteins can induce endocrine disorders; a decrease in binding proteins may increase the concentration of free drugs in plasma and accelerate excretion, affecting drug efficacy. Disordered lipid metabolism increases blood viscosity, promoting thrombosis, embolism, and cardiovascular complications, and accelerating the chronic progression of renal glomerular sclerosis and renal lesions.

　　This group of diseases is relatively rare in primary glomerulonephritis and is one of the few proliferative nephritis cases in nephrotic syndrome. The clinical manifestations of various pathological types are basically similar. Regardless of the clinical syndrome of this disease, almost all have simultaneous proteinuria and hematuria. Proteinuria is non-selective, and hematuria is often microscopic persistent hematuria. 10% to 20% of patients often have paroxysmal gross hematuria after respiratory tract infection, which is severe and shows glomerular hematuria with various urinary red blood cell deformities. More than 1/3 of patients have hypertension, the degree of which is generally mild, but there are also individual cases, especially type II patients, who may develop severe hypertension. Large doses of hormone therapy may also induce a hypertensive crisis. At least half of the patients have acute or chronic renal insufficiency. Renal insufficiency at the onset of the disease often indicates a poor prognosis. Patients often have a relatively severe normocytic normochromic anemia at the onset of the disease, manifested as pale complexion, shortness of breath, fatigue, and the degree of anemia is not proportional to the degree of renal function decline. The mechanism of occurrence is not yet clear, and it may be related to complement activation on the surface of red blood cells, or it may be due to capillary lesions that shorten the lifespan of red blood cells.

　　When this disease occurs, at least half of the patients have nephrotic syndrome, about 1/4 of the patients have asymptomatic hematuria and proteinuria, and 1/4 to 1/3 of the patients have acute glomerulonephritis syndrome, accompanied by red blood cells and red cell casts in urine, hypertension, and renal insufficiency. About half of the patients may have a history of precursor respiratory tract infection, 40% have an increased titer of anti-O and other evidence of streptococcal infection before onset. Some patients may develop partial lipoprotein malnutrition (Barraquar-Simmons disease), especially in type II lesions, which can even occur before the clinical manifestations of kidney disease. Some patients may show X-linked inheritance, and congenital deficiency of complement and a1-antitrypsin is also prone to occur in this disease type I. In nephrotic syndrome, renal vein thrombosis may occur. Although there is a high degree of individual variability in the development of the disease, the overall course of the disease is generally a slow progressive progression. Because the histopathological and immunopathological changes of this disease type I and II are different and they are morphologically two types, it is generally believed in clinical practice that they represent different diseases. Type II is more inclined to manifest as glomerulonephritis signs, with a high incidence of crescentic glomerulonephritis and acute renal failure. Type I has more characteristics of nephritis, often with precursor infection and anemia. Serum complement levels in type II patients are often persistently low, and the age of onset is usually younger than 20 years. Although there are exceptions, type II is also more prone to recurrence after renal transplantation.

　　Type III is rare, mainly occurring in children and young adults, with a peak age of 10 to 20 years, and it is rare before 2 years and after 40 years. The incidence is close to that of men and women. There are few descriptions of the clinical manifestations of this type, which are basically similar to the long-term clinical changes of type I. According to Strife's description, type III has a decrease in C3 levels, but without C3 nephritis factor, the prognosis of non-nephrotic proteinuria is better than that of nephrotic syndrome. The individual differences in entering end-stage renal disease are large in this type. During the long course of the disease, some patients' conditions can be relatively stable or even gradually improve.

　　The course of this disease type 3 is basically the same. Prevention should start with personal health, avoid overexertion, have a reasonable diet, scientific exercise, enhance physical fitness, and improve the body's immune function to prevent the occurrence of disease. For patients who have the disease and have complications, active and effective prevention and treatment of the primary disease and complications should be carried out. Once infection is detected, it is necessary to promptly select antibiotics that are sensitive to the pathogenic bacteria, strong in efficacy, and non-nephrotoxic for treatment. If there is a clear focus of infection, it should be removed as soon as possible to prevent the progressive development of renal insufficiency.

　　Patients with this disease almost always have hematuria, including microscopic or gross hematuria. Proteinuria can be relatively mild, with about 30% presenting with asymptomatic proteinuria, but half of the patients have urine protein > 3.5g/24h. More than 90% of patients have poor selective proteinuria, and urine FDP and C3 may be elevated.

　　A characteristic change in laboratory tests is the decrease in blood complement. About 75% of patients with this disease have a persistent decrease in C3, which is more common in type II lesions, accounting for 80% to 90%. About 10% of patients have a significant decrease below 20 to 30 mg/dl. In type I lesions, the average C3 concentration decreases to 68% of normal, and in type II, it decreases to 47% of normal. Moreover, type II lasts longer than type I. Early acting complement components (such as C1q, CA) decrease to varying degrees in type I lesions, while they are usually normal or slightly decreased in type II. However, type II often has a decrease in late acting complement components C5b-9. Without any change in the condition or treatment, the serum C3 level may fluctuate and may tend to recover to normal over time, indicating that the change in complement is not related to the condition or treatment. Nephrotic syndrome secondary to lupus nephritis, late liver disease, monoclonal gammopathy, leukemia, and metastatic cancer can have a decrease in C3. However, C3 decrease is rare in other primary nephrotic syndromes, except for post-streptococcal glomerulonephritis. Therefore, persistent complement decrease has a significant suggestive role in the diagnosis of the disease. Unlike this disease, the C3 level in post-streptococcal glomerulonephritis often decreases but typically returns to normal levels within 6 to 8 weeks. In the nephrotic syndrome of capillary glomerulonephritis, complement remains low for more than 2 months. The low level of C3 is the result of activation and decreased synthesis of the complement pathway. While C3 decreases, the classical pathway C1q and C4 are generally normal, indicating that the alternative pathway may be activated. However, in membranoproliferative glomerulonephritis secondary to cryoglobulinemia, the decrease in C4 is more significant than that of C3.

　　Patients in this group have a heat-stable factor in their blood, also known as the C3 nephritis factor (C3NF). This is an antibody against the self-C3 converting enzyme. More than 60% of type II patients are positive for C3NF, while only 10% to 20% of type I patients are positive. This may be one of the reasons for the persistent low C3 levels in these patients. C3NF and its analogs are also found in other glomerular diseases related to nephritis. Other factors that degrade C3 can be detected in acute nephritis, especially lupus nephritis.

　　The serum complement component C3 levels are usually normal. If the C3 level decreases, the complement component C3 level may also slightly decrease. The serum level of factor B is usually normal or slightly decreased. Circulating immune complexes and cryoglobulins may be positive. More than 75% of type I have special B cell alloantigens, indicating a genetic basis for susceptibility. HLA-AB7 and familial BIH deficiency are associated with type II disease.

　　Clinically, some patients may have azotemia, which often indicates acute nephritis syndrome. The glomerular filtration rate is often reduced, but it can also be normal, even showing severe glomerular damage in renal biopsy, with GFR sometimes normal. It is often accompanied by water and sodium retention, leading to hypertension. More than half of the patients may have normocytic normochromic anemia, which can be very severe and not proportional to the severity of azotemia. The lifespan of red blood cells and platelets can be shortened, and the titer of anti-streptococcal antibodies in 40% to 60% of patients increases.

　　Pathology and biopsy examination of type I membranous proliferative glomerulonephritis

　　1. Light microscopy:The main changes of type I membranous proliferative glomerulonephritis are diffuse thickening of the capillary wall and intravascular cell proliferation, as well as infiltration of mononuclear leukocytes and neutrophils. The mesangial area and capillary wall show varying degrees of expansion due to cell proliferation and matrix increase, usually affecting almost all lobules uniformly, which can cause the lobulated structure of the capillary plexus to be prominent. Therefore, this lesion was early called lobular glomerulonephritis. Whether there is a causal or sequential relationship between lobulated and non-lobulated lesions is yet to be determined. The mesangial area is significantly expanded to form nodules, and there may be sclerosis foci in the central area of the nodules, similar to the lesions of diabetic glomerulosclerosis or light chain deposition disease. However, combined with the results of light microscopy, immunofluorescence, and electron microscopy, it is easy to distinguish this disease from other diseases. Another obvious but not specific manifestation is the thickening of the glomerular basement membrane, which can be easily seen as double tracks or multi-layers with appropriate staining (such as silver staining or periodic acid-Schiff staining). This is due to the extension and insertion of proliferated mesangial cells and their matrix between the basement membrane and endothelial cells, forming an interposition, that is, the inserted mesangium forms a pseudo-basement membrane, rather than the commonly believed basement membrane splitting. Occasionally, eosinophilic deposits can be seen in the subendothelial area, and a few patients may have crescents, but rarely involving more than 50% of glomeruli. Like other nephritis, a large number of crescents suggests a poor prognosis. In the late stage, patients often have interstitial fibrosis, tubular atrophy, and infiltration of mononuclear inflammatory cells in the interstitium. 'Transparent thrombi' appear in the capillary lumen, suggesting that the lesion may be secondary to cryoglobulinemia or systemic lupus erythematosus. 'Transparent thrombi' are not true thrombi but are filled with immune complexes in the capillary lumen.

　　Renal biopsy under light microscopy can classify MPGN into 5 subtypes: ① Lobulated type: The capillary loops show obvious lobulated shape, mainly characterized by cell proliferation, and can also be accompanied by varying degrees of sclerosis; ② Classic type (bifid type): Due to mesangial insertion, the basement membrane becomes diffusely thickened, forming a double track, with atypical lobulated shape; ③ Mixed type: Although mesangial insertion and lobulated shape are not atypical, there are immune complexes deposited under the basement membrane, both in the subendothelial and mesangial areas, with mesangial cell proliferation and matrix proliferation, and the basement membrane becomes significantly thickened. This type is very similar to the diffuse proliferative type of lupus nephritis, and some people call it mixed membranous and proliferative glomerulonephritis; ④ Focal type: The changes of MPGN occupy less than 50% of all glomeruli; ⑤ Crescentic type: More than 50% of glomeruli show crescents.

　　 2. Electron microscopy:The typical ultrastructural feature is the extension and interposition of mesangial cells and matrix between the glomerular capillary basement membrane and the endothelial cells. There is electron-dense immune complex deposition. The name 'mesangiocapillary glomerulonephritis' comes from the changes in mesangium and capillaries in type I lesions. New basement membrane substances can be seen around the subendothelial deposits and near the cytoplasm of mesangial cells. In the areas of mesangial proliferation and mesangial matrix expansion, there is usually scattered dense deposits. Subepithelial electron-dense deposits can vary in quantity. When the number is sufficient, it is similar to membranous nephropathy, and some renal pathologists call it 'mixed membranous and proliferative glomerulonephritis', or 'type III mesangiocapillary glomerulonephritis' proposed by Burkholder. In a few lesions, the glomerular damage is similar to that of type I under light microscopy and immunofluorescence, but the ultrastructure is characterized by irregular thickening of the glomerular basement membrane and unevenly dense deposits within the membrane. Such lesions are also classified as type III. There may be infiltration of monocytes or neutrophils between the mesangial matrix and basement membrane. In some renal biopsy tissues, there may be a small to moderate amount of extramesangial deposits呈 'hump-shaped'. The epithelial pedicles often disappear. The hyaline thrombi observed under light microscopy are spherical dense substances in the vascular lumen. When these structures or any other electron-dense deposits present microtubular structures, it suggests possible cold agglutinin disease or immune touch-like nephropathy.

　　 3. Immunofluorescence:The characteristic changes are the granular or streaky distribution of complement, especially C3 and immunoglobulins, which can display the outline of the lobular periphery. This is consistent with the site of subendothelial immune complex deposition observed under the electron microscope. The morphology of the deposits is usually less symmetrical than in membranous nephropathy, and the granules are not as prominent. The B factor and C1 esterase inhibitor also show a similar distribution. The granular deposition of mesangial substances can be明显 or not, and in a few cases of type I, immune complexes can be deposited along the tubular basement membrane and/or extraglomerular blood vessels outside the glomerulus. The composition of the deposited immune complexes can be very different, possibly reflecting the multiple causes of type I. Most patients show a more pronounced deposition of C3 than any immunoglobulin, with some mainly IgG or IgM; and a very few mainly IgA, which can be considered as IgA nephropathy with a mesangiocapillary glomerulonephritis manifestation. Early acting complement components such as C1q and C4 are slightly less common than C3, and in a few patients, Ig (especially IgM and IgG) can be seen in a segmental granular distribution on the capillary wall, occasionally also in the mesangial area. A large amount of immunoglobulins and complements deposited in the capillary lumen form spherical structures, which are consistent with the hyaline thrombi observed under light microscopy, suggesting that the lesion is secondary to systemic lupus erythematosus or cryoglobulinemia.

　　2. Pathology and biopsy examination of Type II membranous proliferative glomerulonephritis

　　1. Light microscopy:The light microscopic changes in Type II are more than those in Type I, not only membrane proliferation changes. This makes some renal pathologists believe that calling it dense deposit disease is more accurate than Type II mesangial capillary glomerulonephritis. In 1995, WHO classified it as a secondary metabolic disease. Histologically, it is manifested as proliferation of glomerular mesangial cells and matrix. When proliferation is obvious, it can form obvious lobular structures and thickening of the capillary wall. Some capillaries may appear as double tracks due to mesangial interposition. These typical membranous proliferative changes are similar to those in Type I, but some have obvious thickening of the capillary wall, cell proliferation呈灶状 or without cell proliferation. There are also some with focal or diffuse cell proliferation without obvious thickening of the capillary wall. The degree of mesangial changes has a significant individual difference. The increase of mesangial cells and matrix can be very mild or very severe. Circular eosinophilic deposits are often visible in the mesangial area with Masson trichrome staining. Some may have subepithelial 'hump'-like deposits. The number of neutrophils in the capillary lumen often increases, and a few have crescent formation. The interstitium may have leukocyte infiltration and fibrosis. Therefore, the light microscopic changes of Type II can be similar to other nephritis, and accurate judgment requires the results of electron microscopy and immunofluorescence. There are some reports that patients with this type do not have mesangial proliferative changes, so they are different from Type I.

　　2. Electron microscopy:Type II is also known as dense deposit disease, and the diagnostic feature of this disease is the formation of discontinuous electron-dense bands on the glomerular basement membrane, accompanied by mesangial spherical or irregular dense deposits. Sometimes, there are also deposits under the endothelium and subepithelium. Some changes are similar to the 'hump' after streptococcal infection glomerulonephritis. The basement membrane is significantly widened and has extremely electron-dense structures, which have great diagnostic significance. However, in some glomeruli, there may be no such lesions as mentioned above, and the dense structures may be spindle-shaped, spherical, or sausage-shaped, with a clear boundary between them and the normal structure. Mesangial cells and matrix often extend to the periphery and interpose, but not as obvious as in Type I. The podocytes of the epithelial cells often completely disappear. Many patients often have circular electron-dense deposits in the mesangial area. If there are electron-dense deposits in the basement membrane of the renal tubules, it highly suggests Type II lesions.

　　3. Immunofluorescence:Large amounts of C3 are deposited in a linear or band-like manner in the basement membrane of the glomerular capillary wall, with C3 exhibiting discontinuous linear types, which can display the outline of the capillary wall, glomerular capsule, and renal tubules. The mesangial deposits are scattered in needle-like or annular shapes, with annular shapes resulting from the staining of only the outer side of the deposits. Additionally, many capillary walls may have granular C3 deposits, and the fluorescence of linear capillary walls appears as a double track, due to the deposition of C3 on both sides of the basement membrane. Other complement components are only seen in less than 50% of biopsy cases, and immunoglobulin deposits are rare.

　　3, other types of mesangiocapillary glomerulonephritis

　　It is still uncertain whether they are variant types of type I damage or independent lesions. These types are almost identified based on electron microscopy. Burkholder proposed type III damage, which is characterized by more prominent subepithelial immune complex deposition in addition to the common pathological changes of type I, with fine vascular walls accompanied by isolated extramembranous deposits, isolated by the protuberances of the basement membrane material (similar to the spike-like protuberances of the basement membrane of membranous glomerulonephritis). Some scholars believe that this type is a mixed type of membranous and proliferative glomerulonephritis. In addition, in recent years, some scholars have reported various variant types, such as type IV, which is characterized by stratified splitting of the basement membrane, accompanied by subepithelial and subendothelial deposits, and the rest is not elaborated here.

　　Can kidney patients eat salt and alkali?The normal daily salt intake of an 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. Eating too much salt and alkali containing sodium can easily cause water retention in the human body, induce edema, so for patients with renal edema, the intake of salt and alkali should be controlled. Eating 2-3 grams of salt per person is considered a low-salt diet. A salt-free diet is also not scientific, as it can easily lead to fatigue and dizziness over time.

　　How much water should membranous nephropathy patients drink?The normal urine volume of a healthy person is generally 1-2 kilograms per day. During the oliguria phase of acute nephritis, acute renal failure, nephrotic syndrome, and chronic renal failure with oliguria and edema, the intake of water should be controlled. Because the water taken in cannot be excreted, it accumulates in the human body, aggravating edema, and also easily increasing hypertension. At this time, the intake of water should be about 500 milliliters more than the urine output. After the urine output increases, the intake of water can be relaxed. While for patients with normal urine output, there is no limit to the intake of water. In addition, for patients with urinary tract infections such as acute pyelonephritis, urethritis, and cystitis, in addition to timely medical treatment and taking medication, drinking plenty of water and urinating frequently are very beneficial for the recovery of the disease.

　　Can membranous nephropathy patients eat fish, shrimp, eggs, and meat foods?Fish and shrimp foods, some kidney patients feel that they should not eat them, thinking that they are bad for the kidneys. In fact, such foods are high-quality proteins. In cases with allergic diseases such as allergic purpura and purpuric nephritis, those who suspect allergy to foreign proteins or have a history of fish and shrimp allergy should use them with caution. Generally, they are not prohibited. Fish, shrimp, eggs, and meat foods contain abundant animal proteins, which are the main construction materials for human cells and tissues and are very important for the human body. After eating protein foods, the liver breaks them down and the kidneys excrete them. Therefore, when kidney function decreases, it is necessary to appropriately reduce the intake of protein to meet the body's metabolic and nutritional needs without increasing the burden on the kidneys. It is incorrect for some patients with kidney disease not to eat protein because their condition is not serious, or to ignore it when their condition requires protein restriction.

　　4. Some kidney patients have a long course and slow recovery:They often discuss and exchange information and experiences. It should be noted that everyone has their own characteristics and should not imitate each other.

　　First, treatment

　　The treatment of nephrotic syndrome caused by this disease is often difficult. Low-dose prednisone treatment every other day may be beneficial for improving renal function. West et al. used long-term treatment with oral glucocorticoids every other day and compared renal biopsies before and after treatment, which proved that this method is beneficial for renal survival. At present, most nephrologists only do symptomatic treatment.

　　1. In the treatment of type I, in addition to glucocorticoids, other drugs such as immunosuppressants and anticoagulants can also be used.

　　(1) For patients with MPGN of all ages, if renal function is normal and only asymptomatic mild proteinuria is present, there is no need for hormone or immunosuppressive therapy. It is only necessary to follow up every 3-4 months, closely observing renal function, proteinuria, and blood pressure control. For adults and children with primary MPGN, hormone and immunosuppressive therapy can be given when urine protein is more than 3g/d, renal dysfunction, and renal interstitial lesions are found in biopsies.

　　(2) For children with primary MPGN who have proteinuria (more than 3g/d) or renal dysfunction, high-dose glucocorticoids 40mg/m2 every other day may be effective after 6-12 months of treatment. If ineffective, stop taking glucocorticoids and suggest close follow-up, focusing on conservative treatment (i.e., controlling blood pressure, using drugs to reduce urine protein, and correcting metabolic disorders).

　　(3) For adult primary MPGN patients with proteinuria (more than 3g/d) or renal dysfunction, aspirin (325mg/d) and dipyridamole (Persantin) therapy (75-100mg, twice daily) should be administered, or both should be used in combination for 12 months. If this treatment plan is ineffective, it should be discontinued. It is important to consider factors that can delay renal dysfunction and close follow-up should be part of the treatment plan.

　　Several treatment studies have reported the results of the use of oral glucocorticoids every other day or daily, intravenous injection of high-dose glucocorticoids, and the combined application of both: one more rigorous study confirmed that for children with MPGN, hormone therapy is effective in slowing the decline in glomerular filtration rate (GFR) and stabilizing renal function. Most of the 80 children with MPGN were of type I MPGN, and they were treated with prednisone (Prednisone) 40mg/m2 every other day, with an average treatment duration of 13 months. 61% of the children in the treatment group had stable renal function during the study period, while only 12% in the placebo group. This proved that the use of glucocorticoids in children with MPGN is effective. The study showed that early application of high-dose prednisone (Prednisone) in children with MPGN can effectively shorten the course of the disease. However, there is still controversy, and it is necessary to use strict randomized controlled trials to verify it.

　　Danadio et al. separately studied the effects of dipyridamole (Panshending), aspirin, and warfarin on renal outcomes (including proteinuria excretion rate) and platelet half-life (bleeding tendency) in the treatment of MPGN. The results showed that the proteinuria excretion rate decreased, but there was no significant change in GFR. Cattran et al. studied the efficacy of cyclophosphamide, warfarin, and dipyridamole (Panshending) in 59 patients with MPGN, with a treatment duration of 18 months. The authors explained in detail that this study only has a clear treatment for type I MPGN patients, and there is not enough strong evidence to draw conclusions for type II disease.

　　2. Currently, there is no very effective treatment for type II. Due to controversy over the rational treatment plan for this disease, careful consideration should be given to the balance between efficacy and treatment adverse reactions when choosing a treatment plan. Ye Ren et al. recommend the following regimen: dipyridamole (Panshending) 50-300mg/d, taken in three divided doses. For patients with nephrotic syndrome, symptomatic treatment can be used, and a standard course of hormone can be tried. When the dose is reduced to maintenance dose (morning administration of prednisone 0.4mg/kg every other day), longer-term application should be maintained. If hypertension is present, it is recommended to use the new stepwise antihypertensive treatment method. Close observation of toxic and side effects should be made during the implementation of the treatment plan to achieve the therapeutic effect.

　　3. Other treatments include lipid-lowering drugs, ACEIs, ARBs, low-molecular-weight heparin, etc. In recent years, some scholars have reported the use of mycophenolate mofetil (MMF) to treat this disease, showing preliminary efficacy, but the number of cases is still small, and there is a lack of controlled and long-term observation studies.

　　4. In addition, cytotoxic drug use, plasma exchange methods, and traditional Chinese medicine treatment have shown some efficacy in some research studies.

　　When clinical doctors decide what type of patient to treat and when, they must consider the expected course and outcome of the disease, as well as the benefits and risks of treatment, the progressive development of renal insufficiency, and poor adherence to drug treatment and other factors.

　　Two, Prognosis

　　Extensive research confirms that the 10-year renal survival rate of primary MPGN is between 60% and 65%, and the course and prognosis of various types of MPGN are similar. Nephrotic syndrome (large amounts of proteinuria) and the presence of renal interstitial lesions are major signs of poor prognosis. Clinically, nephrotic syndrome with persistent hypertension and decreasing GFR has a poor prognosis. Younger age and good prognosis in pediatric patients; in adults, the disease progresses progressively and has a poor prognosis. Glomerular mesangial cell proliferation and basement membrane thickening are not significantly related to prognosis, while the extent of focal crescent formation is significantly related to prognosis, and the severity of interstitial changes is significantly related to prognosis. Poor prognosis is associated with crescent formation and severe tubulointerstitial lesions. About 50% of patients with nephrotic syndrome develop ESRF within 10 years, 50% of patients have their nephrotic syndrome disappear after several years, and renal function remains normal. After renal transplantation, the disease can recur, but less than 10% of patients lead to loss of the transplanted kidney. Patients receiving combined treatment with glucocorticoids, immunosuppressants, and anticoagulants can maintain stable renal function or achieve significant improvement.

　　In summary, the individual differences in entering end-stage renal disease are quite large, with type I patients usually 1/3 can spontaneously remit, 1/3 show progressive development, and 1/3 of the disease progresses slowly but cannot be completely remitted.

　　1. Adverse prognostic factors for primary type I lesions include: hypertension, renal dysfunction, proteinuria formation within the scope of nephrotic syndrome, cellular crescentic lesions found during renal biopsy, combined with arterial lesions, and damage to renal tubules and interstitium. Cameron in the UK found that the 10-year survival rate for patients with proteinuria within the scope of nephrotic syndrome in type I is 40%, while the 10-year survival rate for patients with proteinuria outside the scope of nephrotic syndrome is 85%; however, another study believes that there is no difference in prognosis between the two, and hematuria, even gross hematuria, has no effect on prognosis, and age and gender do not affect the prognosis of the disease.

　　2. The prognosis of type II is worse than that of type I, which may be due to type II being a dense deposit disease, where renal biopsy often reveals crescentic and interstitial tubular lesions. Clinical remission rarely occurs in type II, and the remission rate in pediatric patients is less than 5%. Patients usually enter renal failure in the 8th to 12th year of the disease course. Type II patients often relapse after renal transplantation, especially those with crescentic changes found in the biopsy before renal transplantation. Type I may also recur after renal transplantation, but it is not as frequent as type II.