Rapidly progressive glomerulonephritis in children
Introduction
Brief introduction of pediatric rapid glomerulonephritis Rapidly progressive glomerulonephritis (RPGN) is a group of acute acute glomerulonephritis syndrome, which is rapidly developed from hematuria and proteinuria to oliguria or anuria until acute renal failure. Clinically, renal function is acute. Progressive deterioration often results in a glomerular filtration rate (GFR) of more than 50% within 3 months, and progression to end-stage renal failure is usually weeks or months. The disease progresses rapidly, the condition is critical, and the prognosis is poor. The pathological changes are characterized by cell proliferation and fibrin deposition in the glomerular capsule, which is characterized by extensive crescent formation, so it is also called crescentic nephritis (CGN). The incidence of this group of diseases is low, the risk is high, timely diagnosis and adequate treatment can effectively change the prognosis of the disease, and should be highly valued clinically. basic knowledge The proportion of illness: the incidence rate is about 0.0002%-0.0005% Susceptible people: children Mode of infection: non-infectious Complications: hypertension, renal failure, pleural effusion, ascites, anemia
Cause
The cause of acute glomerulonephritis in children
(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), which may be related to the activation of polyclonal B cells to form autoantibodies. The case of antihypertensive drug yttrium is also induced by this disease. It has been reported that immune genetic susceptibility may be related to this disease. HLA-DR2 is seen in more than 85% of type I patients; and type II DR2, MT3 and BfF are increased.
(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 RPGN patients with GBM have linear immunoglobulin deposition, the main component is IgG, occasionally IgA, often accompanied by C3, it was observed C3 can be deposited in the form of particles, accompanied by electron microscopic deposition under electron microscopy, and circulating anti-GBM antibody positive. 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 occurrence of RPGN, the antigen of this disease is GBM component, GBM antigen and glomerular basement membrane (TBM) and lung basement membrane antigen cross-over, anti-GBM antibody can also cause renal interstitial damage And pulmonary hemorrhage (Goodpasture syndrome).
2. Deposition of glomerular immune complex (type II): About 30% of patients with this disease can be positive for serum immune complexes. Immunological examination can be seen in glomerular capillary vasospasm and mesangial immunoglobulin deposition in the mesangial area. The main components are IgG, IgM, and occasionally IgA and C3, which are involved in circulating immune compounds and/or in situ immune complexes formed by antigen (infective or autoantigen) antibodies.
3. Neutrophil and neutrophil cytoplasmic autoantibodies (type III): glomerular capillary blood stasis in this type of patient lacks immunoprecipitation, but has obvious focal segmental necrosis and polymorphonuclear leukocyte infiltration Out, patients with vasculitis-associated nephritis, 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 be dissolved Enzymatic enzymes, elastase and reactive oxygen species degrade GBM; ANCA can lead to increased neutrophil enzymatic activity and mediate 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 into the glomeruli and renal interstitium. T cells and macrophage infiltration are often consistent, 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, in the depletion of macrophages or CD8 T After the cells, the proteinuria can be alleviated, and the occurrence and development of renal tissue damage can be prevented. In addition, the peripheral blood lymphocytes of the patient have a delayed allergic reaction to GBM, which also indicates the existence of a cellular immune-mediated mechanism. Disease is a group of syndromes involving 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 immune complex-mediated immunity. Reaction and polymorphonuclear leukocyte and macrophage infiltration, causing GBM damage, blood protein components (fibrinogen and fibrin), and mononuclear macrophages in blood vessels to escape to the kidney capsule, the latter is a new composition Cell formation of the moon One of them, 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 enter through the broken kidney capsule, secreting collagen to form fibrosis.
Prevention
Pediatric 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 tissues and to observe whether there is a tendency to chronicize, so as to take timely measures. In short, pay attention to protect residual renal function and correct renal blood flow. Various factors (such as hypoproteinemia, dehydration, hypotension, etc.) and prevention of infection are important links in prevention.
Complication
Pediatric acute glomerulonephritis complications Complications Hypertension Renal failure Pleural effusion Ascites anemia
More common renal failure, high blood pressure, cardiac insufficiency, pleural effusion, ascites, anemia and so on.
Pathological condition in which some or all of the kidney function is lost. According to the rapid onset of the attack, it is divided into acute and chronic. Acute renal failure is caused by a variety of diseases, causing the two kidneys to lose excretory function in a short time, referred to as acute renal failure. Chronic renal failure is a syndrome that consists of a group of clinical symptoms that arise from the development of chronic kidney disease caused by various causes to the advanced stage. Chronic renal failure was divided into 4 stages according to the degree of renal dysfunction: 1 renal reserve function decreased, and the patient was asymptomatic. 2 renal insufficiency compensation period. 3 renal decompensation (nitrogenemia), patients with fatigue, loss of appetite and anemia. 4 uremia stage, there are symptoms of uremia.
Hypertension is the most common chronic disease and the most important risk factor for cardiovascular and cerebrovascular diseases. Stroke, myocardial infarction, heart failure and chronic kidney disease are the main complications.
Cardiac insufficiency (heart failure) is an abnormality of the heart's systolic and diastolic function caused by different causes, so that when the circulating blood volume and vasomotor function are normal, the blood pumped by the heart does not meet the needs of the tissue, or can only be filled in the ventricle. When the pressure is increased, the metabolic needs are met; at this time, the neurohumoral factors are activated to participate in the compensation, forming a clinical syndrome with various features of hemodynamic function director and neurohumoral activation.
Symptom
Pediatric acute glomerular nephritis symptoms common symptoms fatigue expression apathy edema complexion pale proteinuria anuria hypertension low urinary abdominal pain nausea
The main clinical features are:
1. Onset and prodromal symptoms: This disease occurs mostly in older children, more boys than girls, 1/3 to 1/2 have a history of prodromal history, showing fever, fatigue, joint pain within 2 to 3 weeks before the disease, Symptoms or non-specific manifestations such as myalgia.
2. Acute nephritis: early onset is similar to acute glomerulonephritis, manifested as edema, oliguria, hematuria, proteinuria, hypertension, etc., but after 2 to 3 weeks, the above symptoms can not only be alleviated, but intensified, appearing Persistent oliguria, severe hypertension and circulatory congestion.
3. Progressive renal function decline: renal function is progressively reduced within 2 to 3 months. Symptoms of uremia and acidosis: nausea, vomiting, anorexia, pale, itchy skin, nosebleeds, cyanosis, breathing Deep, weak, and indifferent.
4. All kinds of primary disease manifestations of RPGN: such as those caused by allergic purpura, there may be bilateral lower extremity symmetrical purpura, abdominal pain, blood in the stool, joint pain and other symptoms; caused by systemic lupus erythematosus (SLE) A variety of SLE manifestations may occur; those caused by Goodpasture syndrome may have hemoptysis and other symptoms.
Examine
Examination of pediatric rapid 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 May be nodular polyarteritis under the microscope.
7. Pathological and biopsy of acute glomerulonephritis
(1) Light mirror
The normal glomerular capsule wall epithelial cells are monolayer cells. Under pathological conditions, the proliferation of parietal epithelial cells causes the cells to grow (more than three layers) to form a crescent. The pathological features of rapid glomerulonephritis are extensive new. The formation of the lunate, the rapid crescent nephritis has a large volume of the crescent, often involving more than 50% of the glomerular capsule, and is more extensive, usually more than 50% of the glomeruli have a crescent, and the formation of the crescent is small The result of severe damage to the capillary capillaries, so the glomerular capillaries adjacent to the crescentic body are often seen with tendon necrosis. The crescents of different subtypes of acute nephritis are slightly different, against the basement membrane glomerulus. The crescent of nephritis is relatively consistent. In the early stage of the disease, all crescents are cellular crescents; at a later stage, the cellular crescents are transformed into fibrotic crescents, and the disease progresses. Very fast, 4 months after onset, renal biopsy can see fibrotic crescent and glomerular sclerosis, glomerular capillary vasospasm adjacent to the crescent is often fibrinous necrosis, but can also be seen normal or Basically normal glomeruli, showing "all or nothing", ie Glomerular lesions with crescent formation are quite severe and the glomeruli that are not affected can be almost normal. Glomerular basement membrane staining (PAS staining or hexammine silver staining) shows glomerular basement membrane integrity destruction and kidney The basement membrane of the small balloon (Bowman's capsule) is broken. 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 glomeruli. The disease is consistent, there is severe tubulointerstitial damage in the glomerular lesions, there may be tubule inflammation; 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 are arteries Or small arterial necroinflammation, suggesting that there may be a combination of vasculitis (type IV acute nephritis), the number of crescentic complexes of immune complex type progressive nephritis is not more anti-GBM nephritis, the volume of the new moon is also relatively small, and Necrotic capillary vasospasm adjacent to the crescentic body can be seen as nucleus fragmentation and other necrosis, but fibrinoid necrosis is rare, glomerular capsule basement membrane destruction, fracture is relatively rare, around the glomerulus and tubulointerstitial The damage is also relatively light. Unlike the anti-GBM nephritis, the former is all or nothing, while the immune complex type has no glomerular growth of the glomerulus, and there are also mesangial hyperplasia, thickening of the basement membrane or endothelial cell hyperplasia. The characteristics of the lesion mainly depend on its underlying diseases, such as membranous nephropathy with diffuse thickening of the basement membrane, light microscopic findings of non-immune complex type progressive nephritis and anti-GBM nephritis, glomerular capillary cellulose-like necrosis More common, with extensive large crescent formation, glomerular basement membrane rupture and severe tubulointerstitial inflammation around the glomerulus similar to anti-GBM nephritis, unaffected glomeruli can be normal, small renal Inflammatory cells infiltrating between the ball and tubules include various cellular components, including neutrophils, eosinophils, lymphocytes, monocytes, and macrophages, and even multinucleated giant cells, which are granulomatous. Change, this type of lesion can be limited to the kidney (called primary non-immune complex type rapid progressive nephritis), but also secondary to systemic vasculitis such as microscopic polyangiitis (microscopic polyangiitis, M PA) or Wegner's granulomatosis, the kidney lesions are basically the same, but there are extrarenal lesions secondary to systemic vasculitis. If there is small vasculitis in the kidney, it is often prompted to be systemic. Vasculitis Kidney damage, because the course of vasculitis can be a seizure-relieving alternating chronic process, so there are fresh active lesions seen during renal biopsy, such as fibrinoid necrosis, cell proliferation and cellular crescents. To chronic lesions, such as fibrous crescents, glomerular sclerosis and renal interstitial fibrosis, this is different from anti-GBM nephritis, the latter has a relatively consistent pace, in general, immune complex type rapid progressive nephritis (special The pathological changes secondary to other glomerulonephritis are relatively light, the number of crescents is relatively small, the volume is small, and the proportion of macrophages and epithelial cells in the crescent is low.
(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 is moderately positive to strong. Positive, other immunoglobulins are generally negative, there are reports of IgA anti-GBM nephritis, mainly as IgA linear deposition along the basement membrane, if the chain is also linear deposition, it suggests heavy chain deposition disease, this type can be seen C3 along the base The membrane is continuous or discontinuous in the form of linear or fine particles, 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 deposited along the basement membrane. However, the clinical manifestations and light microscopy characteristics of the two are easy to identify. 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, so the former is positive for albumin staining. The immunofluorescence of complex type of acute nephritis 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 immunity. Acute nephritis of nephritis also has immunofluorescence manifestations of primary disease, such as those secondary to IgA nephropathy, mainly manifested as mesangial area IgA deposition; secondary nephritis secondary to post-infection glomerulonephritis is Coarse granules or agglomerate deposition; secondary to membranous nephropathy, IgG can be deposited along the capillaries in fine-grained form, membranous nephropathy can be combined with anti-GBM nephritis, when IgG deposits along the thin line of the capillary basement membrane Below the fine-grained deposition, 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 have reported that the less glomerular immunoglobulin deposition in crescentic nephritis, the greater the chance of serum ANCA.
(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 basement membrane and glomerulus can be seen. The capsular basement membrane is ruptured with 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 deposited in the mesangial area, secondary to Immune complex nephritis Rapid nephritis The deposition of electron dense matter depends on the type of primary glomerulonephritis, which can be seen in the mesangial area, subepithelial or subendothelial, and sometimes the capillaries and glomerular balloon basement membrane are also visible. Breaking the gap, but less common than other subtypes of acute nephritis.
8. 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.
9. 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 in children
diagnosis
The clinical diagnosis of RPGN is not difficult. Anyone with progressive renal function decline within 3 months of onset, gradually oliguria or no urine, and proteinuria, hematuria and other renal parenchymal damage should be considered as acute nephritis, if kidney Histopathology suggests that more than 50% of the glomeruli form a crescent and the crescent area accounts for more than 50% of the glomerular cross-sectional area. The diagnosis can be confirmed. Laboratory tests and renal pathological examination are expected to determine the cause of RPGN.
Differential diagnosis
RPGN is a clinical syndrome with different prognosis and treatment. Therefore, in addition to differentiation from other clinical syndromes, differential diagnosis of its etiology is needed.
1. Nephritis after acute streptococcal infection
At the beginning of the disease, there was a history of streptococcal infection, the anti-"O" was high, the duration of oliguria was short (about 2 weeks), and the C3 in the final stage decreased more, but gradually recovered with the improvement of the condition. Although there may be azotemia in the early stage, More rapid recovery, rapid oliguria lasts longer, C3 does not decrease, renal function continues to decline and progressive deterioration, renal biopsy is mainly characterized by crescent formation, pathological changes are mainly endothelial and mesangial cells Proliferation and exudation of polymorphonuclear leukocytes.
2. Hemolytic uremic syndrome
More common in infants and young children, mainly manifested as hemolytic anemia, acute renal insufficiency, hematuria (or hemoglobinuria) need to be identified with this disease, but more anemia, more reticulocytes, abnormal red blood cell morphology, more visible Broken red blood cells, helmet-shaped red blood cells and other abnormal cells, thrombocytopenia, bleeding tendency is obvious, helpful for identification.
3. Secondary glomerular disease
Such as systemic lupus erythematosus, allergic purpura, necrotizing vasculitis, pulmonary hemorrhagic nephritis syndrome can cause acute nephritis, systemic symptoms can be inconspicuous or neglected or concealed, easy to cause misdiagnosis, the identification is mainly to improve the primary The understanding of the disease, pay attention to the symptoms of the system, and carry out the necessary examination for the possible primary disease to confirm the diagnosis.
