thin glomerular basement membrane disease
Introduction
Brief introduction of thin glomerular basement membrane disease Thinlomerular basement membrane disease is defined as a type of disease in which the glomerular basement membrane is thinned and clinically characterized by glomerular hematuria, but genetically no genetic mutation. basic knowledge The proportion of illness: 0.001% Susceptible people: no specific people Mode of infection: non-infectious Complications: high blood pressure
Cause
Causes of thin glomerular basement membrane disease
Genetic factors (85%):
The genetic pattern of the disease is mostly autosomal dominant inheritance, but in recent years, it has also been found that there are autosomal recessive hereditary families. Recently, Smeets et al found that the mutant genes are also COL4A3 and COL4A4, which are located on autosome 2, why some COL4A3 and COL4A4 mutation causes hereditary progressive nephritis, while some cause familial benign hematuria remains to be studied. Some authors have used specific antibodies against the Goodpasture syndrome antigen to stain the disease GBM, and the results can be stained, suggesting that the disease collagen IV The change is different from hereditary progressive nephritis.
Pathogenesis
At present, the pathogenesis of thin basement membrane nephropathy remains unclear. It can be said that the glomerular basement membrane of patients with thin basement membrane nephropathy does not lack any major components (such as type IV collagen, laminin, nidogen, heparin sulfate and protein glycoside). ), Aasosa et al found that type IV collagen is mainly in the central region of the glomerular basement membrane, while the subepithelial portion of the glomerular basement membrane is thinned.
Prevention
Thin glomerular basement membrane disease prevention
There is no special treatment for this disease, and it is necessary to avoid colds and excessive fatigue. There have been reports in the literature that there are very few cases of gross hematuria and red blood cell casts, or when there is proteinuria, it should be alert to symptomatic treatment. It is better to use TCM syndrome differentiation to prevent slow renal insufficiency.
Complication
Thin glomerular basement membrane disease complications Complications
Appeared in adulthood. Hematuria is usually persistent, but some patients have intermittent hematuria, which seems to persist until old age. Urine microscopy is a variant of red blood cell hematuria, visible red blood cell cast. Paroxysmal gross hematuria is often associated with infection. Gross hematuria is evident after upper respiratory tract infection or strenuous exercise. Patients usually have no proteinuria, edema, and high blood pressure, and kidney function is always normal; there are no neurological deafness and abnormal eye.
Symptom
Thin glomerular basement membrane disease symptoms common symptoms deafness hypertensive proteinuria protein
The clinical manifestations of this disease are similar to those of Alport syndrome. The main findings of various thin glomerular basement membrane diseases are microscopic hematuria. Usually hematuria begins to appear in childhood, and some appear in adulthood. Hematuria usually lasts. Sexually, but some patients are intermittent hematuria. These patients seem to have hematuria that lasts until the elderly. Urine microscopy is deformed red blood cell hematuria. Red blood cell casts are seen. Paroxysmal hematuria is often associated with infection. After upper respiratory tract infection or strenuous exercise. Gross hematuria is obvious, patients usually have no proteinuria, edema and high blood pressure, renal function is always normal; there is no neurological deafness and abnormal eye.
Most patients with thin glomerular basement membrane disease, including familial benign hematuria, have no obvious proteinuria. Dische et al reported 9 patients with thin glomerular basement membrane disease with significant proteinuria, proteinuria and hypertension or with kidney It is related to insufficiency or related to both.
It is now inappropriate to use thin basement membrane nephropathy with benign familial hematuria in the literature. This is obviously inappropriate. It should be considered that the pathological features of familial benign hematuria are thin basement membrane nephropathy, but about half or more patients with thin basement membrane nephropathy are not It is a benign familial hematuria. Thin basement membrane nephropathy is an electron microscopic pathological diagnosis. It is not a clinical syndrome. These patients may have hematuria in the clinic, obvious proteinuria and even nephrotic syndrome. It has even been found in some families. A small number of patients have renal failure. It is also reported that thin basement membrane nephropathy can coexist with other kidney diseases such as IgA nephropathy, which leads to the diversification of clinical manifestations. Only 30% to 40% of patients with this disease have a positive family history, so most of the disease is Non-genetic diseases, familial benign hematuria is a benign disease, no treatment, avoiding colds, fatigue and avoiding nephrotoxic drugs are still necessary, and urine routine and renal function should be checked regularly.
Any young adult with clinically asymptomatic hematuria (mainly with persistent or intermittent microscopic hematuria) and a positive family history (autosomal dominant or recessive inheritance), if renal biopsy reveals diffuse GBM changes Thin should consider the disease, but found that glomerular basement membrane thinning is not equal to the diagnosis of thin glomerular basement membrane disease, renal biopsy must show that the glomerular basement membrane dense layer without separation and lamellar changes, In order to make a diagnosis of this disease.
If you want to further diagnose the benign familial thin glomerular basement membrane disease (familial benign hematuria), you must be cautious. Only after years of follow-up observation, there is no progression of nephropathy. Renal biopsy shows no separation and plate of glomerular basement membrane dense layer. A layered change can be used to establish a diagnosis. Patients with a diagnosis of this disease are required to undergo regular nephrology, especially in the presence of urinary protein. It is best to have a urine test on family members.
Because of the variability of normal glomerular basement membrane thickness and tissue fixation and embedding methods, the definition of thin glomerular basement membrane is inconsistent in the literature. In addition, the thickness of glomerular basement membrane is age- and gender-dependent. Vogler found that the thickness of the glomerular basement membrane and dense layer increased rapidly from the first two years after birth, from (169 ± 30) nm and (98 ± 23) nm at birth to (245 ± 49) at 2 years of age. After nm and (189±42) nm, these structures gradually increased gradually. At 11 years old, the glomerular basement membrane reached (285±39) nm, and the dense layer reached (219±42) nm. After adulthood, the male basement membrane thickness ( 373 ± 42) nm, exceeding the thickness of women (326 ± 45) nm.
The diagnostic principles of thin glomerular basement membrane disease have been established on the basis of retrospective studies. Stelles et al. and Tiebosch et al. reported using 250 nm as the cutoff value, while some laboratories have higher normal values, 330 nm, which are used to diagnose adult thin. Glomerular basement membrane disease; for pediatric patients, the glomerular basement membrane is considered to be thinner than 250nm, so it is prudent to diagnose thin glomerular basement membrane disease in children, Tiebosch et al reported thin kidney There is a change in the thickness of the basement membrane in different parts of patients with basal membranous disease. Two or three glomeruli should be measured to obtain the most accurate results. Each laboratory should try to establish the normal thickness of the glomerular basement membrane. The number and standard deviations and decide whether to prefer the arithmetic mean or the geometric mean.
Examine
Examination of thin glomerular basement membrane disease
Routine inspection
Blood complement, plasma protein electrophoresis, antinuclear antibody, platelet count, urea ammonia, and hepatic anhydride are normal. Patients may have hematuria in the clinic. The urinary red blood cell phase microscopy is of different sizes and is characterized by various forms of glomerular red blood cells. About 1/3 of patients have red blood cell casts, but generally no significant changes in proteinuria and nephrotic syndrome.
Kidney biopsy examination:
Light microscopy
Usually no abnormal findings, glomeruli under normal light microscope, red blood cell casts in the renal tubules, occasionally some non-specific slight glomerular changes, such as mild mesangial hyperplasia, no diagnostic significance, there are some reports found Spherical glomerular sclerosis, focal tubule atrophy, mild mesangial widening and immature glomeruli.
2. Immunofluorescence
Immunoglobulins and complements are usually negative in the glomeruli of patients with this disease, and small amounts of IgG, IgM, IgA, and C3 are deposited along the glomerular basement membrane, combined with autoantibodies against the glomerular basement membrane, and The binding ability of monoclonal antibodies against the Goodpasture antigen is normal or slightly reduced.
3. Ultrastructure
The main ultrastructural feature is the thinning of the glomerular basement membrane. The characteristic changes of the disease can be seen under electron microscope. The diffuse GBM is thinner, and the thickness of GBM is only 1/3 to 2/3 of the normal thickness, or even thinner. There is no thickening, and the cleft palate GBM segment appears. In some families, the glomerular basement membrane thickness is normal in some adult patients, while the glomerular basement membrane is thinner in other members of the family, in some cases of familial benign hematuria. Family, glomerular basement membrane thickness is normal, even in the family of glomerular basement membrane thinning, not all vascular fistula wall thinning, thickening of the peri-membrane can be found in patients of all ages It is associated with focal capillary wall rupture. In a few cases, segmental irregularities of the vessel contour and deposition of mesangial particulate matter can be found.
Diagnosis
Diagnosis and differentiation of thin glomerular basement membrane disease
Diagnostic criteria
Basta-Jovanovic et al reported that the thickness of the dense layer was significantly reduced in thin glomerular basement membrane disease. For biopsy specimens of hematuria patients, if the edge of the dense layer is clearly seen, the thickness of the dense layer can be determined to aid diagnosis.
Dische found that the female to male ratio of thin glomerular basement membrane disease was approximately 2:1, which may be related to the lower normal value of the glomerular basement membrane in women. One study showed that in the non-selected population of school-age children, once The incidence of microhematuria was 4%.
The diagnosis points of this disease:
1. Age of occurrence: Thin basement membrane nephropathy can occur at any age, and the smallest is reported to be 1 year old and the maximum age is 86 years.
2. Symptoms: Most patients are asymptomatic, or occasionally found microscopic hematuria, no or mild proteinuria, normal blood pressure and normal renal function, gross hematuria, proteinuria during upper respiratory tract infection or after infection or strenuous exercise, Rarely, repeated low back pain similar to IgA nephropathy is an initial symptom.
3. Laboratory examination: blood complement, plasma protein electrophoresis, anti-nuclear antibody, platelet count, urea ammonia, and hepatic anhydride are normal. The patient's urinary red blood cell phase microscopy is of different sizes and various forms of glomerular red blood cells. About one-third of patients have red blood cell casts.
4. Renal biopsy light microscopy: normal or mild abnormalities, glomerular mesangial mild to moderate hyperplasia, immunofluorescence negative, only diffuse GBM thinning under electron microscope, no electron dense deposits, this is also The only or most important pathological characteristics of the disease, the normal basement membrane width is 300-400 nm, and the basement membrane width is only 150-225 nm, and the thinnest glomerular basement membrane is 110 nm, which is 1/3 of normal people. ~2/3, according to the above points, the diagnosis of thin basement nephropathy can be established.
Differential diagnosis
1.Alport syndrome (hereditary nephritis): Because of early histology, thin basement membrane nephropathy may be difficult to distinguish from hereditary nephritis. Alport syndrome is generally only seen in adolescents, renal function is progressively reduced, and males are more severe, such as There are deafness, ocular lesions and familial hematuria and progressive renal dysfunction, suggesting the possibility of Alport syndrome, patients with thin basement nephropathy have no typical extrarenal manifestations or significant renal failure and family history, Alport under electron microscope Syndrome GBM thickening and multi-layer structure can form a network, which contains dense particles, accompanied by segmental GBM thinning; thin basement membrane nephropathy diffuse GBM thinning without electron dense deposits, therefore, the two Identification of the disease should not be difficult, but benign familial thin glomerular basement membrane disease can coexist with deafness, so renal biopsy should be performed to confirm the absence of separation and lamellar changes in the dense layer of the glomerular basement membrane, if any Diagnosed as Alport syndrome.
Patients with a diagnosis of thin glomerular basement membrane disease have obvious proteinuria, especially when accompanied by hypertension or renal insufficiency, suggesting that the patient is not a benign familial thin glomerular basement membrane disease and should be considered progressive. Thin glomerular basement membrane disease; or suggest that the patient may be other diseases, such as IgA nephropathy or familial proliferative glomerulonephritis, repeat renal biopsy and observe the presence or absence of glomerular basement membrane dense layer and lamellar change.
2. Mesangial IgA nephropathy: IgA nephropathy patients with hematuria as the main clinical manifestation, often no family history of hematuria, and immunofluorescence of renal biopsy see IgA-based immunoglobulin deposition, electron microscopically visible large electron dense Sedimentation, these characteristics make mesangial IgA nephropathy and thin basement nephropathy identification is not difficult. Recently, reports of thin basement nephropathy with mesangial IgA nephropathy have attracted attention and further discussion.
3. Other diseases: thin basement nephropathy must be associated with surgical hematuria (such as stones, tumors, tuberculosis, etc.), urinary tract infections, and some primary glomerular diseases with hematuria as the main manifestation (such as mesangial proliferation) Nephritis, nephritis after acute streptococcal infection) and secondary glomerular disease (such as purpura kidney, lupus kidney, vasculitic kidney damage) can be distinguished according to the clinical characteristics of the above diseases, laboratory examination and pathological changes .
