Rapidly progressive glomerulonephritis
Introduction
Introduction to rapid glomerulonephritis Rapidly progressive glomerulonephritis (RPGN) is a group of clinical syndromes characterized by hematuria, proteinuria, and progressive renal dysfunction. It is the most serious type of glomerulonephritis. The pathology of renal biopsy usually shows a new moon. Sore nephritis. The incidence of RPGN accounts for 2% of patients with renal puncture, and the population rate is 7/million. It is a common critical illness in the nephrology department. The disease begins rapidly and the disease develops rapidly. If not treated in time, more than 90% of the patients die within 6 months or rely on dialysis to survive. Therefore, it is necessary to make a clear diagnosis according to the early stage of renal pathology, and take timely and correct treatment measures for different causes to improve the prognosis of patients. basic knowledge The proportion of illness: 0.0007% Susceptible people: no special people Mode of infection: non-infectious Complications: renal failure, hypertension, chronic heart failure, pleural effusion, ascites, anemia
Cause
Cause of rapid glomerulonephritis
(1) Causes of the disease
There are many causes of this disease, generally there will be extrarenal manifestations or clear primary disease is called secondary acute nephritis, such as secondary to allergic purpura, systemic lupus erythematosus, etc., occasionally secondary to certain Primary glomerular diseases, such as mesangial capillary nephritis and membranous nephropathy, the cause is unknown, referred to as primary acute nephritis, these diseases are the focus of this description, primary acute nephritis About half of the patients have a history of pre-infection of the upper respiratory tract, and a few of them have typical streptococcal infections. Others have viral respiratory infections. The patients have serological evidence of Coxsackievirus B5 infection, but influenza and other common respiratory viruses. The serum titer did not increase significantly, so the relationship between the disease and viral infection remains to be further observed. In addition, a small number of patients with progressive nephritis have a history of Mycobacterium tuberculosis antigen sensitization (history of tuberculosis infection), which occurs during the treatment with rifampicin. In this disease, individual intestinal inflammatory diseases may also be associated with the disease, and various causes are classified as follows:
Primary glomerular disease
2. Idiopathic crescentic glomerulonephritis (this disease)
(1) Type I: anti-glomerular basement membrane antibody type (without pulmonary hemorrhage).
(2) Type II: immune complex type.
(3) Type III: micro-immunoglobulin deposition type (70% to 80% of which are small vasculitis nephritis or ANCA-positive nephritis).
3. Membrane proliferative nephritis
(1) Membranous nephropathy.
(2) IgA nephropathy.
(3) Secondary glomerular disease.
4.Goodpasture syndrome (pulmonary hemorrhage - nephritis syndrome)
5. Post-infection nephritis
(1) Nephritis after streptococcal infection.
(2) Nephritis after endocarditis.
(3) sepsis and other post-infectious nephritis.
6. Secondary to other system diseases
(1) purpuric nephritis.
(2) Lupus nephritis.
(3) Multiple arteritis.
(4) Wegener granuloma.
(5) Scleroderma.
(6) cryoglobulinemia.
(7) Others: Some chemical poisons may also be the cause of acute nephritis (anti-basement membrane antibody type), in which the contamination of various hydrocarbon compounds is closely related to the occurrence of this disease, and may occur after application of penicillamine-D. The disease may be related to the activation of polyclonal B cells to form autoantibodies. The case of the antihypertensive drug hydralazine has also been reported. The immune susceptibility may be related to the disease. HLA-DR2 is found in more than 85% of type I patients. The type II DR2, MT3 and BfF frequencies increase.
(two) pathogenesis
Acute nephritis can be divided into three types according to immunopathology, and its pathogenesis is different.
1. Anti-glomerular basement membrane (GBM) antibody deposition (type I)
About 30% of patients with RPGN have linear immunoglobulin deposition in GBM. The main component is IgG, even IgA, often accompanied by C3. It has been observed that C3 can be deposited in granular form, accompanied by electron microscopic deposition under electron microscope, and circulating anti-GBM. Positive for antibodies.
Animal experiments have shown that injection of anti-GBM antibody can cause IgG deposition on the glomerulus (GBM) of experimental animals, and lead to serious pathological process, rapid RPGN, the antigen of this disease is GBM component, GBM antigen It is associated with glomerular basement membrane (TBM) and lung basement membrane antigen, and anti-GBM antibodies can also cause renal interstitial damage and pulmonary hemorrhage (Goodpasture syndrome).
2. Deposition of glomerular immune complexes (type II)
About 30% of the patients with this disease can be positive for serum immune complexes. Immunological examination shows glomerular capillary vasospasm and mesangial immunoglobulin deposition in the mesangial area. The main components are IgG, IgM, occasionally IgA and C3, this type Relating to circulating immune and/or in situ immune complexes formed by antigen (infectious or autoantigen) antibodies.
3. Neutrophil and neutrophil cytoplasmic home antibodies (type III)
This type of patient's glomerular capillary blood stasis lacks immune deposition, but there are obvious focal segmental necrosis and polymorphonuclear leukocyte exudation, vasculitis-associated nephritis patients, serum tests for common anti-neutrophil cytoplasmic antibodies (ANCA) positive, ANCA can recognize the surface of neutrophil membrane (protease 3), activate neutrophils, the latter can release lysosomal enzyme, elastase and reactive oxygen free radicals degrade GBM; ANCA can lead to neutral Increased granulocyte enzyme activity mediates cellular immune responses, so changes in ANCA are closely related to disease activity.
4. Cellular immune-mediated mechanisms
About one-third of RPGN patients lack the deposition of glomerular immune complexes. In such RPGN patients, there are a large number of mononuclear macrophages and T lymphocytes infiltrating the glomeruli and renal interstitial, and T cells and macrophage infiltration are often present. Consistency, mainly CD4, CD8 and IL-2 receptor cells, experiments have shown that the degree of glomerular cell infiltration is consistent with the amount of proteinuria, after depletion of macrophages or CD8 T cells, can reduce proteinuria, And prevent the occurrence and development of renal tissue damage, in addition, peripheral blood lymphocytes of patients with delayed allergic reaction to GBM, also suggest the existence of cellular immune-mediated mechanisms.
In summary, the disease is a group of syndromes including multiple diseases caused by multiple etiology and different pathogenesis. The basic mechanism of crescent formation is related to glomerular basement membrane perforation, anti-GBM antibody and immunity. Complex-mediated immune response and polymorphonuclear leukocyte and macrophage infiltration, resulting in GBM injury, blood protein components (fibrinogen and fibrin), and a large number of mononuclear macrophages in blood vessels escape to the kidney capsule The latter is one of the cellular components that make up the crescent, and plays a key role in fibrin deposition. The crescentic cells begin to express the gel gene in 1-2 days, while the interstitial fibroblasts pass through the broken kidney capsule. Enter, secrete collagen to form fibrosis.
Prevention
Rapid glomerulonephritis prevention
1. Pay attention to rest, avoid fatigue, prevent infection, diet with low protein, pay attention to vitamin supplements, and avoid using drugs that damage the kidneys.
2. During the drug treatment, the clinic will be reviewed every 1 to 2 weeks to observe the urine routine, liver and kidney function, and growth and development to guide the completion of the treatment.
3. After the control of active lesions and after the completion of the course of treatment, renal biopsy should be repeated to evaluate the pathological changes of renal tissue and to observe whether there is a chronic tendency, so as to take timely measures.
In short, pay attention to the protection of residual renal function, correct various factors that reduce renal blood flow (such as hypoproteinemia, dehydration, hypotension, etc.) and prevent infection, are important links in prevention.
Complication
Rapid glomerulonephritis complications Complications, renal failure, hypertension, chronic heart failure, pleural effusion, ascites anemia
More common renal failure, high blood pressure, cardiac insufficiency, pleural effusion, ascites, anemia and so on.
Symptom
Rapid glomerular nephritis symptoms common symptoms proteinuria oliguria anuria hematuria
Mostly sudden onset, mainly manifested as oliguria or anuria, hematuria (often gross hematuria and recurrent), a large number of proteinuria, red blood cell cast with or without edema and hypertension, the disease progresses rapidly, the disease continues to attack, Causes progressive damage to kidney function, which can progress to the end stage of renal failure in weeks or months. It can have three outcomes: 1 rapid development into uremia within a few weeks, showing acute renal failure; 2 renal dysfunction is slower, develops into uremia within a few months or 1 year; 3 minority patients After treatment, the condition is stable, and even healed or residual kidney damage.
Examine
Acute glomerulonephritis
Urine analysis
Common gross hematuria, massive proteinuria, white blood cell urine and tubular urine, urine specific gravity and osmotic pressure are reduced.
2. Blood routine
There are many severe anemias, and white blood cells and platelets can be normal or increased.
3. Renal insufficiency
It is characterized by blood urea nitrogen, creatinine concentration is progressively increased, creatinine clearance rate is significantly reduced, and phenol red excretion experiment is significantly reduced.
Immunoglobulin
Increased, the performance of gamma globulin increased, IgG increased, C3 can be normal or decreased, decreased mainly in patients with lupus nephritis, acute streptococcal infection after nephritis.
5. Anti-glomerular basement membrane antibody in blood
Positive is mainly seen in Goodpasture syndrome, and the concentration of anti-glomerular basement membrane antibody can also be quantitatively detected by ELISA. Generally, complement C3 is normal, and the decrease is seen in streptococcal infection after nephritis, lupus nephritis and membranous proliferative nephritis.
6. Anti-neutrophil cytoplasmic antibody (ANCA)
Positive in ANCA-positive RPGN, ANCA can be divided into C-ANCA and p-ANCA, the former is mainly seen in Wegger granuloma, the latter is mainly seen in microscopic nodular polyarteritis, the so-called idiopathic RPGN, the disease It may be a special form of nodular polyarteritis under the microscope, limited to the glomerular capillaries.
1. Pathological and biopsy of acute glomerulonephritis
(1) Light microscopy: The epithelial cells of the normal glomerular capsule wall layer are monolayer cells. Under pathological conditions, the proliferation of parietal epithelial cells causes the cells to increase (more than three layers) to form a crescent, rapidly progressive glomerulonephritis. The pathological features are extensive crescent formation, rapid crescent nephritis, large volume of the crescent, often involving more than 50% of the glomerular capsule, and more extensive, usually more than 50% of the glomerulus has a crescent, new The formation of the lunate is the result of severe damage to the glomerular capillary vasospasm. Therefore, glomerular capillary vasospasm adjacent to the crescentic body is often seen with sputum necrosis. The crescents of different subtypes of acute nephritis are slightly different. The crescentic membrane against basal glomerulonephritis is consistent. In the early stage of the disease, all crescents are cellular crescents; at a later stage, the cellular crescents are transformed into new fibrillar cells. In the lunar body, the disease progresses quite rapidly. After 4 weeks of onset, the renal biopsy can see fibrotic crescent and glomerular sclerosis. The glomerular capillaries adjacent to the crescent are often fibrin-like necrosis. But normal or almost normal glomeruli can also be seen, "all or nothing" Phenomenon, glomerular lesions with crescent formation are quite serious and glomeruli without involvement can be almost normal, glomerular basement membrane staining (PAS staining or hexammine silver staining) can be seen glomerular basement membrane integrity Destruction and rupture of the basement membrane of the glomerular capsule (Bowman's capsule). In severe cases, there may be global glomerular capillary necrosis, annular crescent formation and extensive rupture and disappearance of the glomerular basement membrane, tubular damage and The glomerular disease is consistent, there is severe tubulointerstitial damage in the severe glomerular lesion, there may be tubulitis; the renal interstitial has a large number of inflammatory cell infiltration, and even the formation of multinucleated giant cells, vascular lesions are usually not significant, If there is necrotic inflammation of the arteries or arterioles, it may indicate that vasculitis (type IV acute nephritis) may be combined.
The number of crescents in immune complex type acute glomerulonephritis is not more than anti-GBM nephritis, and the volume of crescent is also relatively small. The glomerular capillary vasospasm adjacent to the crescent is characterized by nuclear fragmentation and other necrosis, but fiber The necrosis of necrosis is rare, the basement membrane of the glomerular capsule is destroyed, the fracture is relatively rare, and the damage around the glomerulus and tubulointerstitial is relatively light. Unlike the anti-GBM nephritis, the former is "all or nothing", and the immune complex Types of glomeruli without a crescentic body also have mesangial hyperplasia, thickening of the basement membrane or endothelial cell hyperplasia, and the pathological features mainly depend on the underlying diseases, such as membranous nephropathy with diffuse thickening of the basement membrane.
The light microscopic findings of non-immune complex type progressive nephritis are similar to those of anti-GBM nephritis. Glomerular capillary necrosis of glomerular capillary is common, with extensive large crescent formation, glomerular basement membrane rupture and small renal Severe tubulointerstitial inflammation around the ball is similar to anti-GBM nephritis. Unaffected glomeruli can be normal. Inflammatory cells of glomerular and tubulointerstitial infiltration include various cellular components and neutrophils. , eosinophils, lymphocytes, monocytes and macrophages, and even multinucleated giant cells, granulomatous changes, this type of lesions can be confined to the kidney only (called primary non-immune complex type rapid Nephritis), which may also be secondary to systemic vasculitis such as microscopic polyangiitis (MPA) or Wegnei's granulomatosis. The kidney lesions are basically the same, but secondary to systemic blood vessels. There are extrarenal lesions in the inflammatory person. If there is small vasculitis in the kidney, it is often suggested to be secondary to systemic vasculitis. The course of vasculitis may be a seizure-relieving chronic process. Therefore, there are fresh active lesions seen during renal biopsy, such as fibrinoid necrosis, cell proliferation and cellular crescent, as well as chronic lesions such as fibrous crescent, glomerular sclerosis and renal interstitial fibers. Different from anti-GBM nephritis, the latter's pathological changes are relatively consistent. In general, the pathological changes of immune complex type progressive nephritis (especially secondary to other glomerulonephritis) are relatively light, crescentic The number is relatively small, the volume is also small, the proportion of macrophages and epithelial cells in the crescent is lower; while the anti-glomerular basement membrane type and non-immune complex type are pathological changes, and the crescent is large and large. The proportion of macrophages and epithelial cells in the crescent is higher.
(2) Immunofluorescence: Immunopathology is the main basis for distinguishing three kinds of rapid progressive nephritis. The thin line deposition of IgG along the glomerular capillary basement membrane is the most characteristic manifestation of anti-GBM nephritis. Almost all glomerular IgG staining It is moderately positive to strong positive, other immunoglobulins are generally negative, and IgA type anti-GBM nephritis has been reported. The main manifestation is that IgA is deposited along the basement membrane linearly. If the chain is also linear, it indicates heavy chain deposition disease. This type shows that C3 is continuous or discontinuous linear or fine-grained deposition along the basement membrane, but only 2/3 of C3 patients are positive, and sometimes IgG is deposited along the basement membrane of the renal tubule. In diabetic nephropathy, IgG is sometimes seen. The basement membrane is linearly deposited, but the clinical manifestations and light microscopy characteristics of the two are easily identified. The IgG deposition of diabetic nephropathy is due to the non-specific deposition of plasma proteins (including IgG and albumin) due to increased vascular permeability. Albumin staining was positive.
The immunofluorescence of immune complex type acute glomerulonephritis is mainly characterized by coarse granular deposition of IgG and C3. Since this type can be secondary to various immune complex nephritis, it is secondary to the progressive nephritis of immune complex nephritis. There is also the immunofluorescence of the primary disease, such as secondary to IgA nephropathy, mainly in the mesangial area IgA deposition; secondary nephritis secondary to infection after glomerulonephritis is characterized by coarse particles or agglomerate deposition Secondary to membranous nephropathy, IgG can be deposited along the capillaries in fine granular form. Membranous nephropathy can be combined with anti-GBM nephritis. At this time, IgG is deposited along the fine line of the capillary basement membrane under the fine granular deposit.
As the name suggests, non-immune complex type acute nephritis kidney immunofluorescence staining is generally negative or weakly positive, occasionally scattered IgM and C3 deposition, may have fibrinogen staining positive in crescent or thrombus, some scholars reported that the new moon The less glomerular immunoglobulin deposition in nephritis, the greater the chance of serum ANCA positive.
(3) Electron microscopy: The electron microscopic findings of acute nephritis correspond to light microscopy and immunopathology. Anti-GBM nephritis and non-immune complex type rapid nephritis have no electron dense (immune complex) deposition under electron microscope, and capillary base can be seen. Membrane and glomerular basement membrane rupture, accompanied by neutrophil and monocyte infiltration, and the electron microscopic features of immune complex type progressive nephritis are characterized by the deposition of a large number of electron-dense immune complexes, mainly in the mesangial area. Deposition, the progressive deposition of electron dense substance secondary to immune complex nephritis depends on the type of primary glomerulonephritis, which can be seen in the mesangial area, subepithelial or subendothelial, and sometimes capillaries and small kidneys. The basement membrane of the balloon has a broken gap, but it is rarer than other subtypes of rapid progressive nephritis.
2. Imaging examination
The radionuclide kidney map shows a reduction in renal perfusion and filtration; digital subtraction angiography (DSA) reveals a non-functional cortical area, and a plain abdominal examination reveals an enlarged or normal size of the kidney with a neat contour, but the cortical and medullary junction Unclear, intravenous pyelography (IVP) showed poor, but the diameter of the renal angiography was normal, blood flow was not reduced, even in systemic vasculitis.
3. Ultrasound examination of the kidney
The kidneys can be found to be enlarged or normal in size and neatly contoured, but the junction of the skin and medulla is unclear.
Diagnosis
Diagnosis and differentiation of acute glomerulonephritis
For patients with acute nephritic syndrome (acute onset, oliguria, edema, hypertension, proteinuria, hematuria) and severe hematuria, marked oliguria and progressive renal failure, the disease should be considered and promptly performed. Kidney biopsy. The diagnosis of RPGN includes two major aspects: 1 histopathological diagnosis; 2 etiology diagnosis. The pathological diagnosis criteria of crescentic nephritis must emphasize two points: 1 The newly emerging crescent is a large crescent moon that occludes more than 50% of the glomerular capsule, excluding small or partial crescent; 2 with large The number of glomeruli in the crescent must exceed or equal to 50% of the total number of glomeruli. RPGN is a group of clinical syndromes with similar clinical manifestations and pathological changes but different causes. Therefore, the diagnosis of RPGN should be made. Detailed medical history, active search for extra-renal manifestations and signs of multi-system diseases, and related tests (such as anti-nuclear antibodies, anti-ds-DNA antibodies, ANCA, ASO, etc.). Only after determining the cause, the type of immunity, the stage of development of the disease, and the activity, you can choose reasonable treatment, weigh the pros and cons of the treatment and the risk, and make a prognosis.
RPGN should be differentiated from the following diseases: 1 acute tubular necrosis often has a clear cause, such as poisoning factors (drugs, fish gallbladder poisoning, etc.), shock, crush injury, atypical blood transfusion, etc., the lesion is mainly in the renal tubules, so see urine Low, low specific gravity urine and low osmotic pressure urine, a large number of renal tubular epithelial cells characteristic of urine, generally no acute nephritis syndrome. 2 urinary tract obstructive renal failure is common in renal pelvis or bilateral ureteral stones, or one side of non-functional kidney with other side stone obstruction, bladder or prostate tumor compression or clot obstruction. Patients often have sudden or sudden anuria, history of renal colic or obvious low back pain, but no acute nephritis syndrome, B-ultrasound, cystoscopy or retrograde urography can confirm the presence of urinary tract obstruction. 3 acute allergic interstitial nephritis can be caused by acute renal failure, but often accompanied by fever, rash, eosinophilia and other allergic manifestations, elevated eosinophils in the urine. Often the cause of drug allergy can be detected. 4 bilateral renal cortical necrosis in the late pregnancy, especially in patients with early placental exfoliation, or various serious infections and dehydration also occur. The disease is caused by the contraction of small arteries (especially 2 / 3 small arteries in the outer layer of the renal cortex), and the history and renal biopsy can help identify. There was no deformed red blood cells in the urine of the above diseases, no renal proteinuria, no anti-GBM antibody in the blood, and ANCA negative.
