Mesangial proliferative glomerulonephritis

　　The etiology of mesangial proliferative glomerulonephritis is still unclear. Some cases have a history of infection before onset, mostly upper respiratory tract infection, but the pathogen is unknown, and the exact role of infection in mesangial proliferative glomerulonephritis is also unclear. Given the various manifestations of immunofluorescence examination, it is speculated that the pathogenic factors of mesangial proliferative glomerulonephritis may exist in various forms. The renal glomerular mesangial area of patients with mesangial proliferative glomerulonephritis has deposits of immunoglobulin and complement C3, suggesting an immune-mediated inflammatory disease. Certain antigens stimulate the body to produce corresponding antibodies, forming large, insoluble circulating immune complexes, which deposit in the glomerular mesangial area and cause mesangial cell proliferation. When the clearance function of mesangial tissue is low or suppressed, the function of the mononuclear phagocyte system is impaired, immune complexes cannot be cleared, and they remain in the mesangial area, leading to mesangial lesions. This pathogenesis has been verified in animal experiments. Although immune complexes are the main cause of mesangial damage, the nature of their antigens and antibodies and their exact damage process are still unclear. In addition, cell-mediated immunity plays an important role in the pathogenesis. In the study of the interaction between cytokine networks and mesangial cells, it was found that mesangial cells are target cells for inflammatory mediators in the inflammatory process, and with the autocrine and paracrine functions, they release various cytokines under the action of inflammatory mediators, thereby stimulating and activating mesangial cells, promoting mesangial cell proliferation. Mesangial cells produce extracellular matrix, which, through the signal transduction of receptors and integrins on the cell surface, affects the cell. Non-immunological factors such as hypertension, hyperperfusion state, and abnormal platelet function are also important factors leading to pathological changes in the mesangium.

　　The pathogenesis of membranous proliferative nephritis is not yet clear and can be roughly divided into immunological pathogenesis and non-immunological pathogenesis. The immunological pathogenesis includes the direct action of immune complexes and complement on mesangial cells due to immune reactions; inflammation-induced lymphocyte activation and abnormal secretion of cytokines lead to interactions between mesangial cells and cytokines. Non-immunological factors such as hypertension, hyperperfusion state, and platelet dysfunction can also lead to pathological changes in the mesangium. Some cases of membranous proliferative nephritis have the characteristic of negative immunofluorescence, and in some patients, the glomerular mesangial lesions continue to progress after the elimination of immunological factors, indicating that non-immunological factors have an impact on membranous proliferative nephritis.

　　Membranous proliferative glomerulonephritis can be complicated by infection, thrombosis, embolism, renal failure, and disorders of protein and fat metabolism. The specific complications are described as follows.

　　1. Infection:Membranous proliferative glomerulonephritis, when presenting as nephrotic syndrome, can lead to a decrease in body resistance, triggering the occurrence of infectious diseases, and clinical signs are often not obvious. Although there are various antibiotics available for selection, if treatment is not timely or thorough, it is still easy to cause recurrence of nephrotic syndrome, exacerbation of the condition, and even death of the patient.

　　2. Thrombosis and Embolism:The occurrence of complications in this column is due to increased blood viscosity caused by blood hypercoagulability (decreased effective blood volume) and hyperlipidemia. In addition, the large loss of protein and the increased compensatory synthesis of protein by the liver lead to an imbalance in the coagulation, anticoagulation, and fibrinolysis systems in the body. Moreover, during nephrotic syndrome, platelet function is hyperactive, and the use of diuretics and glucocorticoids and other medications can further worsen 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 showing no clinical symptoms due to slow formation. In addition, pulmonary vascular thrombosis and embolism, lower limb venous, inferior vena cava, coronary vascular thrombosis, and cerebrovascular thrombosis are 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 prerenal azotemia, and a few cases may develop acute renal failure. The high pressure in the renal tubular lumen can indirectly cause a sudden decrease in glomerular filtration rate, leading to acute renal parenchymal renal failure. It is common in patients over 50 years old, often with no obvious cause, manifested as oliguria or anuria, and ineffective with expansion and diuresis. Renal biopsy pathological examination shows mild glomerular lesions, diffuse severe edema of the renal interstitium, and the renal tubules may be normal or have a few cells showing变性, necrosis, 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, delayed growth and development in children; decreased immunoglobulins can cause decreased body immunity, making infections more likely; the loss of metal-binding proteins can lead to deficiencies in trace elements (such as iron, copper, zinc, etc.); insufficient endocrine binding proteins can induce endocrine disorders; decreased binding proteins may increase the concentration of free drugs in plasma and accelerate excretion, affecting drug efficacy. Disordered lipid metabolism increases blood viscosity, promoting the occurrence of thrombosis, embolism, and complications of the cardiovascular system, and accelerating the chronic progression of glomerulosclerosis and renal lesions.

　　Membranous proliferative glomerulonephritis can occur at any age, with a higher incidence in older children and young adults, and the peak age for membranous proliferative glomerulonephritis is 16 to 30 years, with a slight male predominance over females.

　　Membranous proliferative glomerulonephritis usually has an insidious onset, with upper respiratory tract infection as a prodromal symptom, with an incidence of 30.8% to 40.3%. The characteristics of membranous proliferative glomerulonephritis are diverse clinical manifestations, almost all types of primary glomerulonephritis pathogenesis and clinical manifestations can be seen in it. The mild form is mainly manifested as asymptomatic hematuria and/or proteinuria and chronic glomerulonephritis, while the severe form can manifest as nephrotic syndrome. 30% to 100% of patients have microscopic hematuria, and 20% to 30% have recurrent gross hematuria; most patients have moderate amounts of selective proteinuria; 30% of cases show mild hypertension, the majority of renal function is normal at the onset of the disease, and 10% to 25% of cases show decreased renal function in the later stage. In addition, some patients have back pain, which may be related to gross hematuria. The clinical manifestations of membranous proliferative glomerulonephritis are closely related to pathological changes, such as significant diffuse mesangial proliferation and typical nephrotic syndrome cases, which tend to develop into persistent proteinuria and progressive renal insufficiency. Mesangial proliferation with focal segmental sclerosis is also prone to renal insufficiency in clinical practice. Some patients with不明显 mesangial proliferation have a slow progression of the disease and a better prognosis.

　　The onset and prognosis of mesangial proliferative glomerulonephritis are related to many factors, so prevention should start with self-health. Pay attention to adequate rest, avoid overwork, have a reasonable diet, scientific exercise, enhance physical fitness, improve immunity, avoid contact with toxic substances, harmful drugs, and chemical substances, reduce their damage to the body, and prevent the occurrence of various diseases. For patients with severe mesangial proliferative glomerulonephritis, such as nephrotic syndrome or complications, they will directly affect the efficacy and long-term prognosis of the patients, so active prevention and symptomatic treatment should be carried out.

　　The examinations for mesangial proliferative glomerulonephritis include laboratory examinations and other auxiliary examinations. The specific examination methods are described as follows.

　　Firstly, laboratory examinations for mesangial proliferative glomerulonephritis

　　1. Urine tests:There are often significant abnormalities, and microscopic examination shows glomerular源性 hematuria, with red blood cells showing polymorphic changes. The incidence of hematuria accounts for 70% to 90%, and it is often microscopic hematuria. Urinary protein is often non-selective. Large molecular proteins such as complement C3 and α2-macroglobulin may appear in the urine.

　　2. Blood tests:Renal function is mostly normal in the early stage, with a decrease in glomerular filtration rate in a few cases. The level of serum immunoglobulin G (IgG) may slightly decrease, and in a very few cases, the level of C4 may decrease. In some cases, serum immunoglobulin M (IgM) or IgG circulating immune complexes are positive. The level of serum immunoglobulin A (IgA) is not high, complement C3 is normal, the titer of antistreptolysin 'O' is generally normal, and antinuclear antibodies and rheumatoid factors are negative.

　　Secondly, other auxiliary examinations for mesangial proliferative glomerulonephritis

　　1. Light microscopy:Diffuse proliferation of mesangial cells is the basic pathological feature of mesangial proliferative glomerulonephritis, which can be accompanied by widening of the mesangial area. This lesion usually affects more than 80% of the glomeruli, with most glomeruli showing similar degrees of lesions, known as diffuse proliferation. In the early stage, the main feature is an increase in the number of mesangial cells, with 4 to 5 mesangial cells in each mesangial area in moderate lesions. In more severe lesions, the number of mesangial cells in each mesangial area is usually more than 5, and mononuclear cell infiltration can also be seen in the mesangial area. Masson staining shows that about 50% of cases have mesangial area eosinophilic immune complex deposits. The glomerular capillary wall is normal, and the capillary lumen is well open. In most cases, the renal tubules, interstitial tissue, and intrarenal small arteries are normal.

　　2. Electron microscopy:Renal biopsy shows that more than 50% of the mesangial areas have electron-dense deposits, the composition is not yet clear, and it may contain IgM. Subendothelial electron-dense deposits can be found in some patients, but electron-dense deposits within the capillary wall are rarely found. Epithelial cell foot processes can present as diffuse swelling or disappearance, and occasionally, cytoplasmic fragmentation may be seen. Commonly, there are slight changes in the basement membrane, such as thickening or irregularity.

　　3. Immunofluorescence:

　　(1) Immunoglobulins dominated by IgM, accompanied or not by C3 deposits, often have IgM deposits in the mesangial area.

　　(2) 58% of patients have IgG and C3 deposits.

　　(3) Only complement C3 deposition.

　　(4) No precipitates, negative immunopathological examination.

　　The specific dietary注意事项for mesangial proliferative glomerulonephritis are described as follows:

　　1, Pay attention to light food, and it is best to eat easily digestible foods such as vegetable porridge and noodle soup.

　　2, You can eat more fresh fruits and vegetables to ensure the intake of vitamins.

　　3, Provide liquid or semi-liquid foods such as various porridge, rice soup, etc.

　　The treatment of mesangial proliferative glomerulonephritis should be selected based on clinical manifestations combined with pathological characteristics, and treatment plans should be adjusted through long-term follow-up. General treatment is the same as other renal diseases.

　　1, Simple hematuria:The pathological changes only show mild mesangial proliferation, with moderate or less proteinuria and/or hematuria, and 24-hour urine protein quantification less than 1.5g. Patients with mild or moderate mesangial proliferation do not require special treatment. For patients with urine protein quantification of 1-2g/24h, routine dosage of glucocorticoid therapy is helpful to shorten the remission time and alleviate renal pathological changes.

　　2, Large amounts of proteinuria or nephrotic syndrome:Patients with pathological changes, regardless of severity, should be treated with an adequate amount of glucocorticoid. Even if the pathological changes are mild mesangial proliferation without diffuse Ig and/or complement deposition, and without focal segmental glomerulosclerosis, prednisone (prednisone) treatment should still be given. For children, the dose is 60mg/(m².d)，Adult dosage is 40-60mg/d, and the dose should be gradually reduced to maintain over 4-6 months after routine treatment; or methylprednisolone (methylprednisone) 10g/d for 3 days, followed by oral prednisone (prednisone) 40mg/d, and the dose should be reduced after 4-8 weeks to maintain. Patients with positive immunofluorescence IgM and C3 are usually sensitive to hormone therapy and have a good prognosis. For patients with hormone-dependent and hormone-insensitive types, immunosuppressants such as cyclophosphamide, benzyl mustard, or azathioprine should be added while using hormones; cyclophosphamide is commonly used in clinical practice, 1g each time, once a month, for 12-16 months continuously, which is helpful to consolidate the efficacy, improve the remission rate, and prolong the remission period. It is reported that combined treatment can reduce recurrence in 60% of cases. In addition, anticoagulants or platelet inhibitors, angiotensin-converting enzyme inhibitors (ACEI), and heparin can also be added according to the condition. ACEI can reduce glomerular pressure and basement membrane permeability by reducing the effect of angiotensin II, inhibit mesangial cell proliferation, thus reducing proteinuria and protecting renal function. Heparin can significantly inhibit mesangial cell proliferation in vitro and has been proven to effectively inhibit mesangial cell proliferation, reduce the expression of mesangial cell, fibroblast growth factor, and PDGF receptors in the antithy-1 mesangial proliferative glomerulonephritis model, thereby inhibiting the synthesis of mesangial matrix. Heparin also has the effect of protecting or repairing the charge barrier of the glomerular basement membrane, so heparin may become a promising drug for the treatment of mesangial proliferative glomerulonephritis.

　　3. Complicated with hypertension and renal insufficiency:This type has the worst prognosis for the disease. Pathological changes show moderate to severe diffuse mesangial proliferation with focal segmental glomerulosclerosis, usually with poor response to hormones. If accompanied by cyst adhesion, tubular atrophy, and interstitial fibrosis, the response to hormone therapy is even worse. Such patients often manifest clinically with significant hematuria, persistent proteinuria, hypertension, and renal insufficiency, and gradually progress to end-stage renal failure. For patients with significant mesangial proliferation, treatment with a sufficient dose of hormones for 8 weeks is usually given, and if the effect is not satisfactory, the hormone treatment course is extended for more than 1 year, which may achieve a relatively satisfactory effect. Alternatively, immunosuppressants, anticoagulants, and antiplatelet drugs can be added to the conventional hormone treatment, but the effect is still uncertain. For patients who have entered chronic renal failure, timely implementation of hemodialysis and renal transplantation treatment should be carried out.