OVERVIEW
Non-IgA thylakoid proliferative nephritis is a group of diseases in which light microscopic pathologic changes are characterized by diffuse thylakoid cell proliferation and/or thylakoid stroma widening. In China, primary glomerular disease is a common disease, which was first clinicopathologically analyzed in 1988 at the First Hospital of Peking University in China.
Etiology
Most of the disease has an insidious onset, and some of them have a history of infection before the onset of the disease, with upper respiratory tract infections being the most common, and the aetiology is not clear, and the exact role of infection on the disease is still unclear. The pathogenesis of thylakoid proliferative nephritis is not clear, but immunofluorescence examination suggests that the disease is an immune complex disease, and the nature of antigens and antibodies is still not clear at the moment, although refractory and insoluble immune complexes are an important reason for the damage of thylakoid membranes, and the exact process is still not clear. The degree of thylakoid proliferation can be affected by a number of factors such as the size, number, charge and shape of the immune complexes. When the thylakoid function is depressed or inhibited, immune complexes or macromolecules that cannot be processed or transported can be retained in the thylakoid region, which can lead to thylakoid lesions. It is generally believed that this disease is an immune-mediated inflammatory disease, but like other glomerular diseases, non-immune factors (such as hypertension, proteinuria, hyperlipidemia, etc.) are involved in its disease progression, and the pathogenesis has the following two aspects: ① immune response, most of the glomerular thylakoid membranes in this type of disease have granular immunoglobulin and complement C3 deposition, which suggests that the immune complexes cause the disease. It is generally believed that circulating multivalent antigen and its high affinity antibody in almost equal amount or a slight excess of antibody binding, that is, the formation of insoluble larger molecules of immune complexes and deposition of the thylakoid membrane area, when the thylakoid membrane area is low-functioning or inhibited, the immune complex is not easy to be cleared, it will be able to activate the inflammatory response of the complement; the other kind of in situ immune complex formation can activate the complement of the pathogenesis; in addition, the cell-mediated immunity can play a role in the process of immune response. Another type of in situ immune complex formation can also activate complement pathogenesis; in addition, cell-mediated immunity can also play a role. Inflammatory response, glomerular mesangial cells are not only passive victims but also direct participants in the inflammatory process, and can play the role of inflammatory cells under specific conditions.
Symptoms
Glomerulonephritis can occur at any age, but it is more common in adolescents, slightly more in males than in females, often with insidious onset, in western countries, there is often no antecedent infections and other triggers, but in China, antecedent upper respiratory tract infections are more common, the clinical manifestations are varied, with acute nephritic syndrome as the mode of initiation of a minority of the people, and a minority of the people (children account for most of the cases) as the manifestations of nephrotic syndrome, and often Asymptomatic proteinuria and/or hematuria, hematuria incidence is very high, 70% to 90% of cases have hematuria, often microscopic hematuria, can be recurrent manifestations, but also can be visual hematuria or microscopic hematuria, proteinuria amount varies, but usually non-selective, a small number of patients with hypertension at the time of diagnosis, but often mildly elevated, there may be pain in the renal region, can be unilateral or bilateral, but rare, the majority of patients with renal function tests are normal at the time of diagnosis, and the majority of patients with renal function tests are normal at the time of diagnosis. Renal function tests were mostly normal at the time of consultation, and a few had mild decompensation. Immunopathology showed IgM nephropathy, with increased serum IGM concentration in a few patients, and some patients were positive for circulating immune complexes (containing IgM or IgG antibodies), serum complement components were generally normal, and blood immunoglobulin levels were seldom markedly abnormal, and the anti-streptococcalin “O ” titer is often normal.
Examination
1. Light microscopic examination
Diffuse thylakoid cell proliferation can be seen, early with thylakoid cell proliferation, each thylakoid area of 4 to 5, heavy cases can be more than 5; endothelial cells can also have hyperplasia, often lighter; hyperplasia in the cells may also have infiltrating mononuclear cells; late thylakoid stroma increased, although sometimes there can be segmental aggravation, but usually diffuse homogeneous performance; masson staining can sometimes be seen in thylakoid area and the paraxial area see Sparse eosinophilic red deposits are sometimes seen in the glomerular and paraglomerular areas; glomerular capillary walls are intact without plexiform necrosis; adhesions and sclerotic changes are usually absent; eosinophilic red deposits can be seen in the glomeruli of half of the patients, which are limited to the peritubular area, and occasionally there are eosinophilic red deposits and hyalinization in the basement membranes of glomerular capsule and walls of the arterioles, and the cells and stroma of the peritubular area are not inserted into the walls of peripheral capillaries. The cells and stroma of the peripheral capillaries are not inserted into the peripheral capillary wall, and the findings in immunofluorescence examination are quite diversified, and IgA nephropathy is IgA nephropathy if IgA is predominant. At present, most scholars advocate semi-quantitative analysis by the thylakoid stroma, commonly used classification criteria: ① Mild: thylakoid zone is mildly widened, the capillary lumen is not extruded and remains open. ②Moderate: the thylakoid zone is moderately wide, the capillary lumen has been squeezed, and it is mildly or moderately stenotic (the degree of stenosis is ﹤50% of the capillary lumen). ③Severe: severe widening of the tethering zone, the capillary lumen has been severely compressed, with severe stenosis (the degree of stenosis is >50% of the capillary lumen) or occlusion.
2. Electron microscopy
It can see proliferation of mesangial cells and increased stroma, and segmental mesangial insertion can be seen in severe cases. The glomerular basement membrane is normal.
3. Immunopathologic examination
There are five categories: ①IgM-based immunoglobulin and C3 deposition. ② IgG-based immunoglobulin and C3 deposition, common in China. (iii) Complement C1q deposition, often accompanied by weak C3 and immunoglobulin (IgM or IgG and IgA). ④Only C3 deposition. ⑤ Negative immunopathologic examination for those with clinical manifestations of non-nephrotic syndrome.4 and 5 are less common.
Diagnosis
The disease often occurs in adolescents, insidious onset, or acute episodes (the latter often have antecedent infections), clinical asymptomatic hematuria or (and) proteinuria, nephritis syndrome and nephrotic syndrome and other manifestations, the incidence of hematuria is high, the serum IgA and C3 is normal, the diagnosis of the disease needs to be done by pathology, diffuse glomerular plasma membrane cell hyperplasia accompanied with varying degrees of increase of the plasma membrane stroma is a characteristic of the disease, and need to be immunofluorescent examination IgA nephropathy can only be diagnosed with the exception of IgA nephropathy.
Treatment
1. Asymptomatic hematuria or (and) proteinuria
Avoid cold, overwork and application of nephrotoxic drugs, and observe the changes of the condition with regular checkups.
2. Chronic nephritis syndrome
Actively control hypertension and reduce proteinuria to slow down the progression of renal damage. It is generally believed that glucocorticoids and immunosuppressive drugs should not be applied to these patients.
3. Nephrotic syndrome
When the renal biopsy of the patient shows slight thylakoid proliferation, no immunoglobulin deposition or focal segmental glomerulosclerosis, the prognosis is often good. Most of these patients have a better response to glycoadrenocorticotropic hormone, only the course of treatment should be appropriately prolonged; to which is ineffective, or only partially relieved patients or recurrent relapses of patients, can be added with cytotoxic drugs, such as cyclophosphamide or phenylbutyric acid nitrogen mustard or thiazopurine, etc., and some of them can be effective or increase the rate of remission and reduce the recurrence of the disease.
Adult cases with nephrotic syndrome and renal biopsies showing superimposed manifestations of moderate to severe diffuse thylakoid hyperplasia with focal segmental glomerulosclerosis often respond poorly to glucocorticoids, tend to have persistent proteinuria, and slowly progress to renal insufficiency. These patients are worse with glomerular balloon adhesions, glomerulosclerotic destruction, tubular atrophy, and interstitial fibrosis. In these cases, after 8 weeks of trying the standard dose of prednisone, if it is ineffective, it is necessary to change to alternate-day treatment and reduce the dose, depending on the condition of the disease to determine the course of treatment and take care to prevent and minimize the side effects of hormone therapy. The usual dosing regimen is as follows:
(1) Dexamethasone + 10% dextrose IV.
(2) Nitrogen mustard hydrochloride injection. Four consecutive days as a course of treatment. Symptomatic treatments such as antiemetic and leukocyte elevation are given during the course of treatment. The second course of treatment should be given at an interval of 7 to 14 days. If the condition has not been relieved, depending on the patient’s condition, repeat the above treatment at intervals of 4 to 12 weeks; if the condition is relieved, then hospitalize for consolidation treatment 4 times at intervals of 1, 3, 6 and 12 months, each time for one course of treatment, and maintain with prednisone in between the courses of treatment.