Rapidly progressive nephritis in the elderly

Introduction to acute progressive nephritis in the elderly Rapidly progressive nephritis, also known as rapidly-progressive glomerulonephritis (RPGN), was first proposed by Ellis in 1942. It is a clinically acute nephritic syndrome. It is a group of kidneys with clinical manifestations and similar pathological changes but different causes. Small ball nephritis, clinical manifestations of rapid development of the disease, proteinuria, rapid development of hematuria, renal failure within months or even weeks. Glomerulonephritis with poor prognosis. The pathological change of this disease is cell proliferation in the glomerular capsule, fibrin deposition, so it is also called crescentic nephritis. Although the incidence of this group of diseases is low, timely diagnosis and adequate treatment can effectively change the prognosis of the disease, and therefore, cause a high degree of clinical attention. basic knowledge The proportion of sickness: 0.5%-0.7% Susceptible people: the elderly Mode of infection: non-infectious Complications: heart disease

The cause of acute progressive nephritis in the elderly

Anti-glomerular basement membrane antibody type nephritis (type I) (20%):

Accounted for 10% to 30% of the disease, immunofluorescence showed diffuse fine linear deposition on the glomerular basement membrane (GBM), the main component is IgG, occasionally IgA often accompanied by C3, it has also been observed that C3 can be particles Deposition, even IgG can also become granular deposition, accompanied by electron microscopic deposition of electron dense deposits, it is now recognized that this is the result of anti-glomerular basement membrane (GBM) antibody and glomerular corresponding antigen binding.

Immune complex type nephritis (type II) (20%):

It accounts for about 30% of the disease. In China, it is mainly type-based. The author summarizes that 17 of the 20 cases are type II. The serum immune complex can be positive. The immunofluorescence confirms that the glomerular basement membrane and mesangial area are diffuse. Granular deposition, the main components are IgC, IgM, occasionally IgA, accompanied by C3, the pathological and immunopathology of this type is particularly similar to immune complex-mediated experimental nephritis, suggesting this type and antigen (infectious or Circulating immune complexes formed by autoantigen antibodies and/or in situ immune complexes.

Other mechanisms (type III) (10%):

About 50% of the patients with this disease had no or only micro-immune deposits by immunofluorescence and electron microscopy. The circulating anti-GBM antibody and immune complex were also negative, which may be non-immune mechanism or cell-mediated immune pathogenesis. 70% to 80% of patients with this type of vasculitis are small vasculitis or small vasculitis that is simply involved in the kidney. Some scholars believe that because renal biopsy is only a stage of the dynamic process of the disease, this type of patient may have early stage of the disease. Immunoglobulins are deposited, but are then phagocytosed or digested by infiltrating neutrophil monocytes to become negative or trace.

Cellular immune-mediated inflammation (20%):

Through the nephrotoxic serum nephritis model and patient materials, the cellular immune-mediated inflammation mechanism of this disease has been fully studied. Macrophages and T lymphocytes have a positive infiltration in the glomeruli and renal interstitial of patients and experimental animals. Macrophages in glomeruli are the main infiltrating cells.

Macrophages and T lymphocytes infiltrating into the kidney mainly cause pathogenic effects by producing cytokines. For example, macrophages can produce IL-1, IL-6, TNF-, transforming growth (TGF), and platelet source growth. Factor (PDGF) and platelet activating factor (PAF), etc. In recent years, studies have shown that IL1 activity in glomerular culture medium of patients with this disease is accompanied by histological examination of macrophage infiltration; and the application of IL1 receptor antagonist in experimental new After lupus nephritis, proteinuria is reduced, renal function is maintained, histological lesions are alleviated, and macrophage infiltration is also significantly reduced. T lymphocytes can produce interferon (IFN-y), IL-2, IL-4 and Colony-stimulating factor (CM-CSF), etc. In addition, these two kinds of cells can function as antigen presenting cells (APC), especially the role of T cells in attracting and activating other inflammatory cells is mainly in glomerular inflammation. The mechanism of action.

The role of neutrophils in the early stages of inflammation in this disease has also been confirmed. In addition to phagocytosis, neutrophil production of proteases and activated oxygen molecules cause serious damage to the kidneys, but animal experiments have shown that neutrophil infiltration occurs in The first 12 hours of the disease.

In summary, the disease is caused by a variety of causes and different pathogenesis, including a variety of disease syndrome.

The basic mechanism of crescent formation is related to the glomerular basement membrane, which causes the plasma components and mononuclear macrophages in the blood vessels to escape to the renal capsule, which is one of the main cellular components that make up the crescent. Can release a large amount of polypeptide cell growth factors, such as IL1, PDGF, stimulate the proliferation and differentiation of parietal epithelial cells, and macrophages play a key role in fibrin deposition during the formation of crescent. Experimental studies have shown that depletion of macrophages After the cells, fibrin deposition can be prevented, and the cells of the crescent are beginning to express the collagen gene in 1-2 days. At the same time, the interstitial fibroblasts enter through the ruptured renal capsule wall, secreting collagen to form fibrosis. It was confirmed that the degree of renal capsule wall fracture was proportional to the degree of crescentic fibrosis.

Pathological changes (10%):

In the acute phase, the kidney is swollen, the surface is smooth, pale or dark, and it can be a bit or flaky bleeding point. Therefore, it can be said that the "bite kidney" and "big color kidney" cut surface can be thickened in the renal cortex and medullary congestion.

(1) Seen by optical microscope:

1 The crescent in the renal capsule, the affected glomerulus accounted for 50% to 70%, up to 100%, characteristic morphological changes of this type of nephritis, renal small cell wall cells in 2 to 3 layers The degree of lesions of the affected renal sac can be different. Only a small amount of cells in the renal capsule are in the light. In severe cases, the entire renal capsule is filled, occluded, and the glomerular vasospasm is compressed, and even a "ring" diagnosis is formed. The standard of this disease is different. It is generally believed that the crescent moon exceeds 50% of the renal capsule area, and the number of affected glomeruli exceeds 50%. Those who are lower than this standard say that small small crescent formation is not included in the disease. diagnosis.

In the early stage of the disease, the crescent is mainly composed of cellular components called the cell crescent. The cellular components of the crescent are consistent with the degree of lesions. The lesions are severe and extensive, and the renal capsules are broken, and macrophage infiltration is the main; The lesion is mild, the renal capsule and the glomerular basement membrane integrity are maintained, and the wall epithelial cell proliferation is the main factor. The collagen component appears in the second day after the onset of the disease, so the disease hardens rapidly and the collagen fiber is mainly deposited. It is called the fiber crescent, and then the crescent can appear in the crescent, which makes the closed renal capsule appear partially recanalized.

The crescent can be divided into 3 types:

1 cell crescent;

2 fibrous cell crescent;

3 fibrous crescentic body, cellular crescent is the initial stage of crescent formation. When the fibroblasts around the glomerulus enter the renal capsule through the damage of the renal capsule wall, it gradually evolves into Fibrocytic and fibrous crescentic, cellular crescentic, mainly accumulation of cells in the renal sac, with little or no collagen deposition, and the composition of the cellular crescent is still controversial, some studies have shown Its main component is epithelial cells, while other experiments have proved that its main component is macrophages, which indicates that the cellular crescent is highly heterogeneous, and the cellular crescent sometimes dissolves spontaneously, especially the kidney. When the small sac is intact and the epithelial cells accumulate in the sac, the chance of spontaneous lysis is greater, but if the macrophages in the renal sac continue to accumulate, the cellular crescent will develop further, and then the glomerulus The surrounding fibroblasts and T cells also enter the renal small cyst, leading to collagen deposition, which becomes a fibrocellular crescent. At the same time, as the collagen deposition increases, the cells in the cyst gradually decrease. Lost, become a fibrous crescent.

2 glomerular capillary vasospasm varies with the degree of vasospasm of the crescentic body itself, caused by segmental fibrinoid necrosis, ischemia and thrombosis, and even vascular ganglion segmental sclerosis; In the basement membrane nephritis, the glomerular capillary basement membrane is broken, and the glomerular capillary sputum cell proliferation is very mild; but after infection, acute nephritis (type II) capillary sputum cell proliferation is obvious, accompanied by neutrophil infiltration and subepithelial hobby The complex red pigment is widely deposited.

The mesangial matrix often proliferates, sometimes with pseudo-lobes to separate the glomeruli. The monoclonal antibody was identified by immunohistochemical technique. The CD4+, CD8+ T cells and the number of mononuclear macrophages in the glomeruli were found. Significantly increased.

3 renal tubules: renal tubular disease and glomerular and renal interstitial lesion severity have a corresponding relationship, renal tubular epithelial cells may appear drop-like degeneration, steatosis and atrophy changes, it has been found that this type of nephritis often has anti-renal tubules The basement membrane antibody is present, so the renal tubular epithelial cells are often exfoliated in large numbers, and even some of the renal tubules exhibit necrotic changes.

4 renal interstitial and renal vascular: this disease is often accompanied by extensive renal interstitial lesions, the initial renal interstitial neutrophils and eosinophilic infiltration, the disease progress is diffuse or focal single Infiltration of nuclear macrophages, lymphocytes and plasma cells, interstitial edema and fibrosis are particularly evident around the diseased glomerulus.

5 renal fibrosis: rapid development, clinical and animal experiments have shown that glomerular collagen fibrosis begins in this disease at the time of inflammatory hyperplasia, once the crescent occurs, it soon develops into glomerular sclerosis, interstitial Fibrosis, tubule atrophy.

(2) Electron microscopy: The basement membrane and mesangial area of glomerular capillaries may be electron dense or non-electron dense in different parts depending on the cause, and common cellulose deposition and microthrombus formation, in type III primary new In lunate nephritis, there is no electron dense substance in the mesangial area or capillary wall. Type II primary crescentic nephritis can be seen. The electron dense substance is distributed in the whole mesangial area and is irregularly distributed under the endothelium. The glomerular capillaries The vascular wall is widened and the subcutaneous endothelial cells of the capillaries are separated from the basal segment. There is fibrin in the capillary lumen, which is directly attached to the basement membrane and the renal sac and mixed with the cells. The capillary plexus partially or completely collapses. The basement membrane may have fissures, local or extensive separation. These lesions can be found in various types of primary crescentic nephritis, but more common in type I, the extent and location of sediments for primary and secondary crescents Somatic glomerulonephritis; if the sediment is mainly under the epithelium and has a hump-like structure, it suggests the presence of pathogenic factors after infection; subepithelial compacts with basal-like substance "nail-like" changes are potential Indications for membranous nephropathy; large The mechanized structure of the subendothelial sediment ("fingerprint"), suggesting IgG/IgM cryoglobulinemia or systemic lupus erythematosus; the deposition of electron dense deposits of the mesangial membrane suggests membrane proliferative glomerulonephritis type II (dense Sediment disease).

Under electron microscope, more macrophages, neutral polymorphonuclear granulocytes, and cellulose deposition were observed in the early stage of the crescent. In the later stage, epithelial cell hyperplasia, basal membrane-like substance formation, and fibroblast proliferation were observed. Collagen fibers are formed.

(3) Immunofluorescence: Immunofluorescence is of great value in identifying the pathogenic mechanism of primary crescentic nephritis. In type I primary crescentic nephritis, most show smooth linear IgG (a few IgA) deposits along the glomerular capillary wall, occasionally with C3 deposited in the same way, but in severely damaged glomeruli, it is difficult to identify the morphology of the sediment, C3 deposits may also be irregular, or even Granular, there are some patients with linear IgG deposition and clear granular C3 deposition, C3 is related to electronic dense matter, in addition, linear IgG deposits may also develop into granules, making it with other forms of primary Confused with crescentic nephritis, type II primary crescentic nephritis shows IgG and IgM deposits in the scattered mesangial area and surrounding capillary wall under immunofluorescence, but not necessarily associated with C3 deposition, if any Extensive IgG, IgM and IgA deposits, especially with C1q, C4 and C3, should be highly suspected of SLE; if the deposit is predominantly IgA, it should be classified as IgA nephropathy or allergic purpura; mesangial area or surrounding capillaries Isolated C3 deposits of blood vessels should be suspected of membrane hyperplasia The presence of glomerulonephritis, no or only micro-immunoglobulin deposits under the fluorescence of type III primary crescentic nephritis, all of the crescentic nephritis immunofluorescence can prove fibrin-related in the crescent The presence of antigen.

Elderly progressive nephritis prevention

Pay attention to protecting residual kidney function, such as avoiding the application of drugs that damage the kidneys; correcting various factors that reduce renal blood flow (such as hypoproteinemia, dehydration, hypotension, etc.) and preventing infection are important links that cannot be ignored in treatment. .

Complications of acute progressive nephritis in the elderly Complications

In the short term, blood pressure continues to rise, and heart and brain complications can occur.

Acute progressive renal syndrome in the elderly Common symptoms Abdominal pain, nausea, loss of appetite, edema, nephrotic syndrome, hypertension, proteinuria, azotemia, renal failure, fatigue

The disease accounts for 2% to 5% of patients with renal perforation, 2% for China, 2:1 for males and females, and 2 peaks for young and middle-aged people. The clinical signs of acute nephritis are acute renal failure and active nephritis. Acute onset, but most of the insidious onset, often seen in the initial diagnosis of azotemia, often with weakness, fatigue and fever as the most significant symptoms, nausea, loss of appetite, vomiting, joint pain, abdominal pain are also common before the onset of half There are flu-like symptoms. A few weeks or months after onset, renal function deteriorates very rapidly and requires dialysis.

The main symptoms:

1. Urine changes: The patient's urine volume is significantly reduced, oliguria or anuria occurs, some patients have gross hematuria, microscopic hematuria persists, proteinuria often occurs, and urine protein can be large (>3g/d).

2. Edema: About half of the patients develop edema at the onset, the edema is mainly on the face and the lower extremities; 25% to 30% of patients have high edema, a large amount of proteinuria, which is characterized by nephrotic syndrome, which often persists after edema Exist, it is not easy to subside.

3. Hypertension: Some patients may have high blood pressure, and blood pressure continues to rise, and heart and brain complications can occur in a short period of time.

4. Renal dysfunction: progressive persistent renal dysfunction is a characteristic of this disease, glomerular filtration rate decreased significantly in the short term, urinary enrichment dysfunction, serum creatinine, urea nitrogen continued to increase, and finally uremia syndrome .

5. Systemic symptoms: According to different causes, there may be some different systemic manifestations, such as purpura, hemoptysis, fecal occult blood, skin lesions, etc., which is helpful for clinical differential diagnosis.

Elderly rapid nephritis check

1. Urine routine examination shows a large number of red blood cells or gross hematuria, common red blood cell casts and small or medium amount of protein, urinary white blood cells are often increased (> 30,000 / ml), neutrophils, monocytes, auxiliary and Inhibitory T cells, the specific gravity of urine is generally not reduced.

2. Often severe anemia, sometimes microvascular hemolytic anemia, sometimes accompanied by increased white blood cells and platelets, and C-reactive protein positive coexistence suggests acute inflammation.

3. Blood urea nitrogen and creatinine are progressively increased, the anti-basal membrane type complement components are basically normal, the immune complex type complement components are decreased, the anti-basement membrane type patients are early onset, the blood anti-basement membrane antibody is positive, and the human kidney is small. The basement membrane of the ball is used as an antigen for radioimmunoassay. The positive rate of early type I patients is over 95%. The antibodies are mostly IgG type. IgA antibodies are occasionally reported. The immune complex type patients may have circulating immune complexes and cold globulin blood. Symptoms, anti-neutrophil cytoplasmic antibodies (ANCA) are closely related to small vasculitis RPGN.

4. Immunoglobulin IgG class ANCA is found in 75% to 90% of patients with ANCA-associated acute nephritis. P-ANCA is more common in C-ANCA. Serological examination is very useful for the differential diagnosis of diseases. The cause may have some specific positive results, such as anti-DNA, IgA, fibronectin, hemolysis, thrombocytopenia, elevated ASO, and the like.

5. Abdominal plain film and kidney ultrasonography can be found that the kidney is enlarged or normal size and neatly contoured, but the skin and medulla are unclear (related to renal edema).

Diagnosis and differentiation of acute progressive nephritis in the elderly

In the performance of acute nephritic syndrome (acute onset, oliguria, edema, hypertension, protein, hematuria) and severe hematuria, prominent oliguria and progressive renal failure should be considered in this case, any doubt The patient should have early renal biopsy, such as 50% glomerulus with a large crescent body diagnosis can be established.

Differential diagnosis

1. Acute oliguria or anuria-free uremia caused by non-glomerular damage

(1) Acute tubular necrosis: The disease has the following characteristics:

1 often have a clear cause of the disease, such as poisoning factors (drugs, fish gallbladder poisoning, etc.) shock, crush injury, heterotypic blood transfusion.

2 lesions mainly in the renal tubules, so the urine is not and the urine specific gravity is less than 1.010. The renal tubular absorption is impaired. The urinary sodium often exceeds 20~30mEq/L. (In the case of acute progressive nephritis, there is less urinary output and less urinary sodium excretion) A large number of characteristic tubular epithelial cells can be seen.

(2) urinary tract obstructive renal failure (renal uremia): common in renal pelvis or ureteral bilateral stones, or one side of non-functional kidney with other side stone obstruction, bladder or prostate tumor compression or clot obstruction, etc. The characteristics of the disease are:

1 If the original urine volume is normal and suddenly reduced to no urine, the possibility of obstruction is large.

2 have a history of renal colic or obvious low back pain.

3 Ultrasound examination revealed bladder or hydronephrosis; X-ray plain film may have stones and kidney enlargement; isotope kidney map has excretion barrier.

4 cystoscopy and retrograde pyelography can be found in obstruction lesions and sites.

(3) acute interstitial nephritis: can also be caused by acute renal failure, but often accompanied by fever, rash, eosinophilia and other allergic manifestations, elevated eosinophils in the urine, often can be found to cause drug allergies.

(4) Renal medullary necrosis (nephrotic necrosis): more common in patients with diabetes or long-term use of analgesics for urinary tract infections, before oliguria, anuria and uremia, first fulminant pyelonephritis and bacteremia The performance (high fever, low back pain, pyuria), urinary sediment visible exfoliated tissue fragments, intravenous pyelography can help identify.

(5) Acute renal vein thrombosis: a history of blood concentration and increased platelet adhesion; severe back pain, abdominal gastrointestinal symptoms; ultrasound and renal scan showed obvious enlargement of the kidney; renal venography can confirm the diagnosis.

(6) renal artery embolism: occurs in the elderly, with a history of arteriosclerosis or renal artery injury.

(7) renal atherosclerotic plaque embolism: seen in elderly patients with hyperlipidemia atherosclerosis, acute renal failure with hematuria, hypo-complementemia and eosinophilia, confirmed by kidney biopsy.

2. Acute glomerulonephritis

Acute nephritis can also occur in a few cases of crescentic body, clinical manifestations of progressive renal dysfunction, but there are still typical clinical manifestations and laboratory findings of acute nephritis, and renal dysfunction may be self-healing, clinical identification is difficult Early diagnosis of renal puncture pathology.

Once the disease is diagnosed, the type of disease immunity, the stage of development of the disease, and whether the disease is active should be further determined to facilitate the selection of reasonable treatment, to evaluate the pros and cons and to weigh the pros and cons and risks.

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