Immune-mediated kidney disease

Introduction to immune-mediated kidney disease Immune-mediated kidney disease refers to a kidney disease caused by the host immune mechanism, glomerular, vascular and tubulointerstitial. Immune-mediated kidney disease is an immune response elicited by an antigen. The list of related antigens is very large and continues to expand. These antigens are classified into renal and non-renal according to their origin from the kidney or the kidney. It is self or foreign antigen (endogenous or exogenous to humans), but the causative antigen is often unknown. basic knowledge Sickness ratio: 0.05% Susceptible people: no special people Mode of infection: non-infectious Complications: acute renal failure nephrotic syndrome rapid progressive nephritis lupus nephritis uremia hypotension acute tubular necrosis interstitial nephritis pneumonia meningitis peritonitis sepsis sepsis urinary tract infection

The cause of immune-mediated nephropathy

IgE mediated (35%):

The IgE-mediated immune response is triggered by the release of allergen-sensitive T cells in contact with specific allergens to release allergic interleukins IL-4, IL-5, which promote IgE production and activate mast cells and Alkaline cells, IgE-coated mast cells, basophils release vasoactive proteins (such as histamine) and chemokines (such as IL-4) in the presence of allergens, causing vasospasm, prostaglandin synthesis, Platelet-mediated coagulation, thrombosis, and fibrin deposition. In several renal inflammatory diseases, there may be deposition of IgE and infiltration of eosinophils, especially by the use of penicillin (especially methicillin). The occurrence of tubulointerstitial nephropathy is partly due to IgE-mediated hypersensitivity, accompanied by eosinophilia, renal eosinophil infiltration and IgE deposition, which is effective in the treatment of corticosteroids, often in the cause of discontinuation. Sex drugs soon improved.

Cytotoxic antibody mediated (25%):

The renal damage is caused by the linear deposition of type IV collagen-specific antibodies in GBM. The antibodies bind to the corresponding antigens to form an immune complex to activate the complement system, which is a group of enzyme-active, chemoattractant, binding and regulatory properties. Plasma and membrane proteins, complement can be activated by C1 (classical pathway) or C3 (alternative pathway) to form a protein called membrane attack complex (MAC), which is composed of complement component C5-9, MAC-to-tissue Injury, directly through the membrane channel, can also indirectly attract other inflammatory cells to participate in the immune response, such as the complement fragment C5-7 will attract neutrophils to the site of inflammation, neutrophils can release lysosomes, further causing tissue damage, and Can directly damage and penetrate GBM, but also generate reactive oxygen species (ie, free radicals, superoxides), eicosanoids, and can interact with platelets to activate the coagulation system, stimulate fibrin deposition, therefore, In anti-glomerular basement membrane disease, cytotoxic antibodies are deposited linearly along GBM. Although the distribution of complement is irregular and intermittent, it is also linearly distributed. Science glomerular damage is characterized by necrotizing structure, fibrin deposition of fibrous epithelial cells crescent formation.

Anti-neutrophil cytoplasmic antibodies (ANCA) also cause cytotoxic antibody-mediated immune kidney disease, play a role in Wegener glomerulonephritis and other vasculitic kidney diseases, although there is no immunity in immunoblotting The deposition of components is characterized by oligo-immunity. It is best to classify ANCA-associated kidney disease into the category of immune-mediated kidney disease because ANCA plays a causative role, although there are different types of ANCA, each of which Identify a specific neutrophil cytoplasmic component (eg myeloperoxidase, lysozyme, elastase, protease 3, lactoferrin, cathepsin B, D, G), but most of the plasma containing ANCA only Specifically specific for one antigen, virtually all C-ANCA specifically targets protease 3, while P-ANCA is directed against myeloperoxidase, which is the prototype of ANCA-mediated kidney disease, almost all cases Related to ANCA.

The initiating factors generated by ANCA are not known, but it has been thought that the interaction of ANCA with neutrophil cytoplasmic antigen activates neutrophils, upregulates cell surface integrin, attracts neutrophils and causes them along the kidney or The vascular endothelial cells of other affected organs roll during vasculitis, and the adhesion of neutrophils to endothelial cells up-regulates the ligands on the surface of endothelial cells, with intracellular adhesion molecule-1, endothelial-leukocyte adhesion molecule- 1, these ligands enhance the binding between activated neutrophils and endothelial cells, leading to a variety of immune inflammatory reactions, such as the formation of reactive oxygen species, lysosome degranulation, T cell activation and release of lymph Factor, causing damage to endothelial cells.

Damaged (30%):

The glomerular vascular endothelial cells are particularly vulnerable. Although immunoglobulin deposition is rare, the positive charge of protease 3 or the autoantigen of myeloperoxidase has been proposed to make ANCA and protease 3 or myeloperoxidase. The complex can bind to the endothelium along GBM. The ANCA-antigen immune complex initiates ANCA-mediated renal injury along the implantation of GBM and enlarges it. The histopathological features of clinical Wegener granulomatosis are necrotic and rapid new moon. Somatic glomerulonephritis and renal and respiratory T cell mediated granuloma formation.

Idiopathic necrotizing glomerulonephritis and progressive glomerulonephritis (without involving the respiratory tract), microscopic arteritis, a common renal vasculitis, small blood vessels involving the kidneys or other organs, no granuloma or immunity In globulin deposition, ANCA activation of neutrophils may also be the cause of the disease.

Immune complex-mediated (type III hypersensitivity) kidney complex immune complex localization in the mesangium, glomerular capillary wall or renal interstitial, and often found in the circulation, renal biopsy showed antibodies and complement Deposited in these areas as "clumps".

The basic mechanism may be the same as in animal model experiments. In animal experiments, parenteral administration of heterologous proteins stimulates the production of specific compounds, which combine with antigens to form immune complexes. After the antigen has been implanted in the kidney, or the antigen is circulating, it is subsequently deposited. The implanted antigen attracts circulating antibodies, forms local immune complexes, increases antibody production, forms circulating immune complexes, increases the size of circulating immune complexes, and is easily cleared by the reticuloendothelial cells from the circulation or localized to the mesentery. Or capillary wall, because small immune complexes are difficult to deposit, and bulky complexes are easily removed by reticuloendothelial organs (such as liver, spleen and lymphatic system), reducing deposition in the kidney, in immunity In the formation of complexes, various endogenous and exogenous substances can act as antigens. For example, in lupus nephritis, endogenous nuclear proteins can lead to the formation of DNA-anti-DNA immune complexes. In the glomerulonephritis after streptococcal infection, the streptococcal cell wall antigen can form an immune complex.

There is growing evidence that immune complexes are grown through a number of mechanisms, some of which have specific affinity for GBM, and some that are implanted may be altered natural antigens or viruses that pass through the circulation to the kidney tissue, except The type and source of antigens may be affected by a variety of factors, such as the release of vasoactive substances, increased vascular permeability, size of immune complexes, shape and ratio of antigen to antibody, and glomerular epithelial cells. Whether there are receptors that activate C3b and the presence or absence of receptors with mesenchymal cells and IgG Fc segments on mesenchymal cells.

The immune complex is deposited on the glomerular capillary wall, mainly in the subepithelial area. The localization of immune complexes and the activation of complement are the basic pathogenesis of immune complex type progressive glomerulonephritis, and the activation of complement is stimulated. Immunizations, including the attraction of neutrophils and the release of lysosomes, the release of other lymphocytes and cytokines, virtually all pathological types of the kidney can be observed, including minimal lesions, mesangial proliferative, membranous, membrane Proliferative, mesangial capillary, necrotic, and rapidly progressive glomerulonephritis.

Kidney disease mediated by cell (type IV or delayed type hypersensitivity) This type of prototype is a kidney transplant. The kidney transplant between the monozygotic twins is the same as the host antigen, and no immune response is induced, but almost all Non-monozygotic twin transplantation, the transplanted kidney's heterologous antigen triggers immunity, mainly cell-mediated immune response, HLA in transplanted kidney cells is treated by monocytes and macrophages, IL-1 is released, and helper T cells are activated. Activated helper T cells stimulate other T cells with the participation of IL-2 and convert them into cytotoxic T cells, which can attack foreign antigens on the transplanted kidney, causing cell-mediated immune inflammation, if the host is transplanted Pre-sensitization of the antigen on the kidney can stimulate hyper-excitation, an antibody-mediated attack on the renal capillary endothelium, leading to acute renal ischemia, infarction, and loss of transplanted kidney.

Immune-mediated kidney disease prevention

First, the diagnosis and treatment are different, and the course of treatment may be longer. Some patients need to perform a renal biopsy to confirm the diagnosis, guide the treatment and judge the development of the disease. If the patient has a basic understanding of the relevant knowledge, the blind fear can be reduced. And strengthen cooperation with doctors.

Second, do not despise the cold, most chronic kidney disease is an immune disease, cold or infection can induce immunity, thereby accelerating disease development.

Third, work and rest combine to rest, the body's metabolites increase after the work, increase the workload of the kidneys, can make the condition worse, so avoiding the tired rest is beneficial to the recovery of kidney function.

Fourth, adjust diet to help nutrition, patients with chronic kidney disease should be light, avoid alcohol and irritating foods, when kidney function damage occurs, it is necessary to limit protein intake in the diet, mainly egg, milk, lean meat and other animal proteins, And oral essential amino acid agents to prevent malnutrition.

Immune-mediated renal disease complications Complications acute renal failure nephrotic syndrome rapid progressive nephritis lupus nephritis uremia hypotension acute tubular necrosis interstitial nephritis pneumonia meningitis peritonitis sepsis sepsis urinary tract infection

1, acute renal failure: patients with nephrotic syndrome appear oliguria, renal function suddenly worsening, serum creatinine rise first consider the primary disease caused by renal impairment such as acute nephritis type II, lupus nephritis type IV, at this time clinical Produces a large amount of proteinuria, azotemia and even uremia, severe hypoalbuminemia of nephrotic syndrome, a significant decrease in blood volume can produce pre-renal azotemia, patient orthostatic hypotension, weak veins of jugular vein collapse, Reduced pulse pressure and other manifestations of insufficient blood volume, decreased urine output, increased urine specific gravity and urinary permeation, increased hemoglobin concentration and hematocrit, increased plasma product and albumin concentration and hematocrit, infusion of plasma Products and albumin urinary silk can be increased, nephrotic drugs such as nephrotic syndrome gentamicin can cause acute tubular necrosis, non-solid drunk anti-inflammatory drugs, contrast agents can produce acute interstitial nephritis-induced acute renal failure.

2, infection: infection is a common complication of primary nephrotic syndrome, accounting for about 20% of patients with nephrotic syndrome, before the antibiotics and corticosteroid treatment is the main cause of death in children with nephrotic syndrome, died of hemolytic streptococcus Pneumonia, meningitis and peritonitis, K1ebsNla sepsis, etc., nephrotic syndrome with urinary tract infection is not uncommon, should pay attention to urine sediment smear to find bacteria and urine culture, such as urinary nucleated cells should not be easily diagnosed as urinary tract infection, Renal tubular epithelial cells also appear in the urine during nephrotic syndrome.

3, thrombosis and embolism and disease.

4, blood lipid disorders.

5, abnormal renal tubular function.

Immune-mediated kidney disease symptoms Common symptoms Immunity decreased proteinuria nephrotic syndrome nocturia increased diabetes hematuria oliguria urinary nephropathy edema face

Renal biopsy and microscopy of stained tissue provide the best method for diagnosing immune-mediated kidney disease, estimating its prognosis and selecting treatment, and using fluorescein-labeled, given that different immune mechanisms can cause similar morphological changes. Immunofluorescence microscopy of specific antibodies often helps to identify the type and location of immune components in the kidney.

The type and form of complement deposition contributes to the diagnosis. The deposition of complement usually follows the deposition of immune complexes or immunoglobulins, or both, but without the deposition of immunoglobulins, C1q or C4, C3 deposition. Type II membranous proliferative glomerulonephritis that can be activated by an alternative route can occur.

Electron microscopy revealed submicroscopic changes in glomerular and tubular structure thickening and its components, and clarified the presence and location of immunoprecipitation.

Urine analysis often helps to check for protein and components in the urine. In fact, nephrotic syndrome is found in various types of immune-mediated kidney disease. A large amount of protein and fat-rich tubular epithelial cells are often seen in the urine (polarization). Light microscope ellipsoidal fat body is "Malta cross"). Although nephrotic syndrome can occur in non-immune kidney disease (such as diabetes), proteinuria in the range of nephropathy often suggests a potential immune mechanism.

Causes necrotic damage, such as acute cytotoxic damage in glomerular basement membrane disease, can cause obvious hematuria, immune complex type damage (such as glomerulonephritis after streptococcal infection) and hematuria and red blood cell cast , hematuria, leukocyteuria, erythrocyte casts and epithelial cell casts are associated with active SLE and other collagen-vascular diseases, membranous proliferative glomerulonephritis and membranous glomerulonephritis with significant proteinuria, membrane Hypertrophic glomerulonephritis often occurs in hematuria, but membranous glomerulonephritis is rare in hematuria. Small lesions and focal sclerosing glomerulonephritis may have only proteinuria.

Serological tests can be found in cytotoxic antibodies mediated by renal diseases (such as anti-basement membrane antibodies, anti-HLA antibodies) cytotoxic antibodies, such as C1q binding and Raji cell assays, can mediate kidneys in various immune complexes Circulating immune complexes are found in the disease, and ANCA can be found in the circulation of ANCA-mediated kidney disease (such as Wegener granulomatosis).

Different levels of complement protein can often be used to identify the type of immune-mediated kidney disease, when activated by alternative pathways (such as membranous proliferative glomerulonephritis and most streptococcal infection after glomerulonephritis), when complement consumption Started by activated C3, so what? C1q, C4 and C2) are not reduced, such as activation by classical pathways (such as SLE), consumption begins with early components, so early components are reduced, as long as C3 nephritis factor is present, C3 is reduced, and C1q, C4 and C2 are normal, then diagnosis is possible. Membrane proliferative glomerulonephritis activated by an alternative route.

Other useful serological tests include an increase in antibody titers against streptococcal antigens in glomerulonephritis following streptococcal infection, and other post-infection glomerulonephritis can also be diagnosed based on serological tests, such as a syphilis-positive test, hepatitis-related Sexual antigens, or increased titers of antibodies to other infectious microorganisms, AIDS can be diagnosed using polymerase technology to detect HIV antibodies or HIV antigens.

Histocompatibility testing can help diagnose certain types of immune-mediated nephropathy, such as glomerulonephritis associated with HLA-B12 after streptococcal infection, IgA nephropathy associated with HLA-B35, HLA-DR4, and anti-basement membrane or Goodpasture The syndrome is associated with HLA-DR2.

Immune-mediated kidney disease examination

1. Renal biopsy and microscopy of stained tissue provide the best method for diagnosing immune-mediated renal disease, estimating its prognosis and selecting treatment.

2. Electron microscopy can reveal the thickening of glomerular and tubular structures and the submicroscopic changes of their components, and can clarify the existence and localization of immune deposition.

3. Urine analysis often helps to check for protein and constituents in the urine.

4. Serological examination Cytotoxic antibodies can be found in the circulation of cytotoxic antibodies mediated renal diseases (such as anti-basement membrane antibodies, anti-HLA antibodies).

5. Histocompatibility testing can help diagnose certain types of immune-mediated nephropathy.

Diagnosis and differentiation of immune-mediated nephropathy

Diagnosis can be based on medical history, clinical symptoms, and laboratory findings.

Mainly differentiated from secondary kidney disease, including diabetic nephropathy, uric acid nephropathy, amyloidosis nephropathy and lipoprotein glomerulopathy.

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