familial hemorrhagic nephritis
Introduction
Introduction to familial hemorrhagic nephritis Familial hemorrhagic nephritis (Alport syndrome, AS) is a hereditary disease. Samuelson first reported in 1874 and Dickinson in 1875. In the literature, it is called hereditary nephritis, hereditary progressive nephritis, hereditary chronic progressive. Nephritis, hereditary chronic nephritis, clinical manifestations of hematuria, neurological deafness, eye disease and chronic renal insufficiency. basic knowledge The proportion of illness: 0.003% Susceptible people: no specific population Mode of infection: non-infectious Complications: posterior optic neuritis, ascending aortic aneurysm
Cause
Causes of familial hemorrhagic nephritis
Sexually linked dominant inheritance (35%):
The main inheritance of this disease, because the disease-causing gene is on the X chromosome, the inheritance is related to gender, the mother-in-law is also passed on to the female, and the children have equal chances of getting sick, 50%, the father does not pass the child, but all the daughters are passed. Thus, there are more female patients than male patients in the family, but the male is heavier than female, because the female has a normal homologous chromosome (heterozygous), while the male has no (semi-zygote).
Autosomal dominant inheritance (30%):
1/7~1/3 families are inherited in this way. Because the disease-causing gene is on the autosome, the inheritance has nothing to do with gender. The sick or the mother's children have the same chance of getting sick, about half, the father can pass the child, the patient The severity of the disease has nothing to do with gender. The severity of male and female illnesses is similar.
Autosomal recessive inheritance (25%):
This disease has been reported in this disease after 1981, and it is now recognized, but the family that is so inherited is rare. The pathogenic gene is also on the autosome, but the heterozygous phenotype is normal, but the homozygous is only Patients with clinical symptoms are often children of close relatives (parents are carriers of disease-causing genes, and their children have a 1/4 chance of becoming a disease-bearing gene carrier with normal phenotype. /2), the location of the causative gene on the chromosome was also recently identified, also COL4A3 and COL4A4 on chromosome 2.
Pathogenesis
Hereditary nephritis is a basement membrane disease, and collagen IV is the main component of the basement membrane. Therefore, before discussing the pathogenesis of this disease, briefly review the modern understanding of collagen IV structure.
The collagen IV molecule is composed of three (IV) peptide chains and has a triple helix structure. Except for the central helix region, the amino terminus is the TS region, the carboxyl terminus is the terminally expanded non-collagen NC1 region, and the four collagen IV molecules are amino groups. The ends are connected, and the carboxyl terminals of the two collagen IV molecules are connected to each other to form a network-like stent.
Five kinds of chain subunits constituting collagen IV molecules are known, namely 1(IV) to 5(IV), and in recent years, the sixth type 6(IV) has been found, among which 1(IV), 3(IV) and 5 ( The amino acid sequences of IV) are similar, while the amino acid sequences of 2(IV), 4(IV) and 6(IV) are similar and can be divided into two types, which are composed of 1(IV) and 2(IV). The isoforms of collagen IV molecules are composed of 3(IV) to 6(IV). It is known that 1(IV) and 2(IV) peptide chains are widely distributed in various basement membranes, and 3(IV), The 4(IV) and 5(IV) peptide chains have only limited tissue distribution, mainly distributed in GBM, anterior lens membrane and retina (the inner ear basement membrane has not been studied due to difficulty in examination), that is, the main lesion of the disease, 6 ( IV) The tissue distribution of the peptide chain is not fully understood. Preliminary data show that it is also a finite distribution, so it can be inferred that the mutated collagen IV chain in the basement membrane of this disease should be in 3(IV) to 6(IV).
As mentioned above, the mutations of COL4A3 to COL4A6 have been confirmed in this disease. The most mutated form of COL4A5 has been studied. Some mutations have been reported, and mutations, deletions, and insertions, repetitive and deletion complexes have been reported, or Repeated and inverted complex gene rearrangement, etc., it has been inferred that gene mutations lead to enzymatic diseases, enzyme abnormalities cause collagen IV molecular synthesis barrier or decomposition rate to cause basement membrane disease, but so far no evidence of enzymology, this The hypothesis cannot be established. It is now believed that genetic diseases can directly lead to abnormalities in collagen IV, because the mutated DNA can play a role in the process of transcription, translation, and translation of peptide chain modification and peptide chain formation of collagen IV.
As described above, the pathological GBM of the patient lacks the Goodpasture syndrome antigen, which is known to be the NC1 region of the 3(IV) peptide chain. In patients with autosomal dominant or recessive inheritance of the disease, there is a mutation. The COL4A3 gene, which causes the 3(IV) peptide chain abnormality, makes the Goodpasture syndrome antigen absent, which is easy to understand, but how does the COL4A5 gene mutation lead to the absence of Goodpasture syndrome antigen in patients with this disease-linked dominant dominant gene? Some people have made a variety of speculations that the greatest possibility is that the constitutive variant 5(IV) peptide chain after COL4A6 mutation destroys the stable structure of mature collagen IV, making the 3(IV) peptide chain unable to enter this collagen IV molecule, or rapidly The removal of collagen IV leads to the absence of 3(IV) in GBM. This explanation is reasonable and needs to be verified. When Reeders explained this in 1992, mutations in COL4A6 and COL4A4 have not been found, and how these two gene mutations lead to Goodpasture synthesis. The lack of antigen is not yet explained, the pathogenesis of this disease may have the following points:
1. Molecular biology Type IV collagen is the main collagen component of the basement membrane. A single type IV collagen chain enters the cell to form a triple helix molecule, and then secretes the cell into the extracellular matrix. In the mammalian basement membrane, at least 5 Genetically distinct type IV collagen molecules, which are identical to other collagens. The procollagen IV chain consists of a major collagen region and a carboxy-terminal non-collagen region, and the collagen region contains a glycine-XY triplet repeat. , X and Y represent various other amino acids, and the formation of the triple helix of the type IV collagen molecule starts from the formation of a disulfide bond at the carboxy terminal non-collagen region of the relevant chain, and the chains are folded into a triple helix structure and proceed to the amino terminus. This process is similar to pulling a zipper. Type IV collagen and interstitial collagen are important in two aspects. These characteristics affect the macromolecular structure that it can form. First, interstitial collagen loses its secretion from the endocrine. The non-collagen region at the carboxy terminus, while the type IV collagen triple helix retains its carboxy terminal region, and secondly, the type IV collagen chain is spaced apart. -XY glycine repeats, thus increasing the triple helical spring, collagen triple helix is formed by a network structure between molecules of different types of connections:
(1) Terminal-to-end ligation: that is, the carboxy termini of two type IV collagen triple helices are linked.
(2) Four triple helices produce a covalent effect at their amino terminus.
(3) Lateral junction: the carboxy terminus of a triple helix is attached to the collagen region of another triple helix. These interactions form a resilient, non-fibrillar, multi-lateral scaffold, and 6 coding IVs have been cloned. The genes of collagen encode 1(IV) and 2(IV), respectively, and the genes of COL4A1 and COL4A2 of the chain are located on chromosome 13; the genes COL4A3 and COL4A4 encoding 3(IV) and 4(IV) are located on chromosome 2 The genes COL4A5 and COL4A6 encoding the 5(IV) and 6(IV) chains are located on the long arm of the X chromosome; COL4A1 and COL4A2, COL4A3 and COL4A4, COL4A5 and COL4A6 are arranged head-to-head, respectively, sharing a bidirectional promoter. Genes have similarities, each gene has about 50 exons, and several exons at the 3' end of the gene are ligated to the coding carboxy terminal region, and the difference in the sequence encoding the carboxy terminus results in antigen specificity, molecular size. And the heterogeneity of charge and so on.
Habib et al. and DiBona found that the basement membrane hydroxyproline content of Alport syndrome was reduced compared with the control group, but the decrease in basal membrane hydroxyproline content was also characteristic of many non-Alport syndrome kidney disease progression. Tina et al found that the increase in urinary excretion of hydroxylysine glycosides in patients with Alport syndrome, which means that the decomposition of collagen is strengthened, but Schroeder et al found that patients with Alport syndrome and other small ball disease patients discharged from the urine. There is no difference in hydroxylysine glycosides.
Kleppel et al reported that the glomerular basement membrane of male patients with Alport syndrome lacks the 3 and 4 chains of type IV collagen, and it was later proved that the lack of these chains was due to mutation of the COL4A5 gene encoding the 5(IV) chain. And indirect evidence suggests a special relationship between the 3(IV), 4(IV) and 5(IV) chains in the glomerular basement membrane and other basement membranes, which are simultaneously distributed in the kidneys, eyes, cochlea and In the basement membrane of the choroid plexus, it can be explained that the syndrome can have both eye and ear abnormalities.
The 3(IV) and 4(IV) chains together with the 5(IV) chain can form a triple helix, so the COL4A5 gene mutation prevents these chains from forming the glomerular basement membrane. It is currently suspected that there are two 5(IV) chains encoding The mutation type of the COL4A5 gene prevents the 3(IV) and 4(IV) chains from constituting the basement membrane, and any mutation affecting the carboxy terminal region of the 5(IV) chain prevents its linkage to the 3(IV) and 4(IV) chains. In order to prevent the formation of triple helix, mutations that alter the glycine residue of the 5(IV) collagen region can prevent normal folding into a triple helix, leading to degradation of all chains (procollagen suicide), genetically engineered COL4A5 mutant cells or The method of transgenic animals can confirm this hypothesis.
2. Mechanism of renal damage progression
It is unclear what path COL4A5 ultimately leads to renal failure, although the glomerular basement membrane at birth is deficient in 3(IV), 4(IV), 5(IV) chains in men with Alport syndrome. Significant glomerular filtration and selective permeability abnormalities occur many years later, at the histological level, from the glomerular basement membrane of male children with Alber syndrome to the diffuse glomerulus of adult males Thickening and stratification of the basement membrane requires a considerable period of time, which is parallel to the natural course of glomerular filtration and selective permeability changes. Therefore, it is necessary to study the molecular composition of the basement membrane during this process. What changes, the process of glomerular sclerosis in this disease is unique, and which aspects are similar to the glomerular changes of non-Alport syndrome.
The 1 (IV) and 2 (IV) chains are often found in the subendothelial region of the mesentery and glomerular basement membrane. In the course of diabetic nephropathy and membrane proliferative glomerulonephritis, these chains are from the glomerular basement membrane. Disappeared, but still present in the widened mesangium. In the Alport syndrome, there is no such change in the distribution of the 1(IV) and 2(IV) chains, which are present throughout the glomerular basement membrane. Collagen V and VI are only distributed in the basement membrane under the mesangium and endothelium at normal time, but in the whole layer of the glomerular basement membrane in the case of Alport syndrome, and with the glomerular sclerosis Accumulation, but disappears from the glomerular basement membrane in diabetic nephropathy and membrane proliferative glomerulonephritis, in the Alport syndrome, other matrix components of the glomerulus such as the A and B chains of laminin, The distribution of heparin sulfate, nidogen and protein glycosides is also abnormal.
Melvin et al observed a deletion of amyloid P in the glomerular basement membrane of male patients with Alport syndrome, a substance that is a normal glycoprotein component of the glomerular basement membrane, mesangial and vascular wall, although starch is known. The protein P can bind to the carboxy terminal non-collagen region of type IV collagen, but its ligand on the glomerular basement membrane in vivo has not yet been identified.
It is unclear whether the abnormalities of these glomerular basement membrane components are functionally important, but it is certain that mutations in the COL4A5 gene alter the biosynthesis and secretion of certain basement membrane components in some respects.
Prevention
Familial hemorrhagic nephritis prevention
Should pay attention to avoid infection, fatigue and pregnancy, should also disable nephrotoxic drugs to prevent the disease.
Complication
Familial hemorrhagic nephritis complications Complications posterior optic neuritis ascending aortic aneurysm
In the family of hereditary nephritis, patients often have many non-specific lesions, such as thyroid disease, IgA deficiency, retrobulbar optic neuritis, ascending aortic aneurysm, anorectal malformation, psychosis and fibromuscular dysplasia.
Symptom
Familial hemorrhagic nephritis symptoms Common symptoms Urea clearance disorder Deafness bleeding tendency Clitoris hypertrophy Thrombocytopenia Urine protein protein Urine hematuria Hypertension Nephrotic syndrome
1. Kidney performance
The main clinical manifestation of Alport syndrome is hematuria. The affected male patients show persistent microscopic hematuria. Within 20 years of age, many patients often have episodes of gross hematuria after upper respiratory tract infection. Women are often heterozygous and may exhibit intermittent hematuria. 10% to 15% of heterozygous women have never had hematuria. The affected boy may have hematuria within 1 year of age and is likely to occur at birth. A boy who has not had hematuria within 10 years of age is no longer possible.
Male patients with this disease often end up with proteinuria. At the beginning, it is only microalbuminuria. Urine protein gradually increases with age, and often develops to nephrotic syndrome. The incidence and severity of hypertension also increase with age. Although the syndrome can progress to renal failure before the age of 10, most patients develop end-stage renal disease between the ages of 20 and 50. The prognosis of male patients is poor. All male patients develop end-stage renal disease, and the speed of development Significant inter-family variation, some scholars have observed that the rate of progression to renal failure within the same family is fairly fixed, and the heterogeneity of this phenotype was thought to reflect the association with specific genes or environmental factors. The effect is now considered to be the heterogeneity of alleles that are secondary to mutations at a single site on the X chromosome, and the rate of progression of renal failure in male patients in the same family has been reported.
Female patients in the family have a good prognosis, most of whom are older and have only milder kidney disease. Grunfeld et al found that childhood gross hematuria, nephrotic syndrome and diffuse glomerular basement membrane thickening under electron microscopy suggest women Characteristics of nephritis progression, sensory neurological deafness and impaired crystals also suggest a poor prognosis. Female patients with progressive nephritis remain adequately functioning until the later years (50-75 years), and renal function in patients with mild disease No significant effect, but may accelerate the deterioration of renal function in more severe patients.
2. Hearing loss
Hearing loss in patients with Alport syndrome is not congenital, but occurs in male patients around the age of 15 years. In members of the family with Alport syndrome, hearing damage is often accompanied by kidney damage, but deafness Men without kidney disease will not pass Alport syndrome to their offspring. In the early stage, hearing loss can only be found by hearing test. The hearing is reduced to 2000-8000 Hz. The loss of hearing in male patients is progressive. In the end, it will affect other frequencies, including the frequency of vocalization. In female patients, hearing loss is less and tends to occur at a greater age. Female patients with progressive hearing loss predict poor outcomes of kidney disease.
The location of the auditory injury of the disease is the cochlea, and the vestibular function can also be impaired, but it has no clinical significance.
It has been reported that some patients with Alport syndrome have improved hearing after kidney transplantation, while others have no change or even worsened hearing after kidney transplantation. Uremia itself can make hearing worse. The literature indicates that the hearing improves after the kidney transplant. All patients with the disease were combined with other diseases.
3. Eye defects
Although eye defects are not as common as deafness, they are also common, with an incidence of 15% to 30%. The anterior cone lens (ie, the central portion of the lens forms a conical anterior sac) is essentially a characteristic of Alport syndrome. In the lesion, Nielson found that all patients with conical crystals were able to obtain evidence of chronic nephritis and sensorineural deafness after careful examination. Atkin et al. observed that anterior conical crystals were limited to those that rapidly progressed to end-stage renal disease and deafness. In the family of special syndromes, it can be seen that the anterior conical crystal appears to have a conical or globular protrusion into the anterior chamber in the central part of the crystal surface. The base of the protrusion is circular, 2.5 to 4 mm in diameter, and the front cone crystal is in the patient. It is usually not born at birth. It usually appears in the age of 20 to 30 years. It can develop progressive crystal deformation with deepening myopia. Crystal opacity can occur at the same time as the conical crystals appear, occasionally caused by rupture of the anterior lens capsule. Electron microscopy showed that the front lens capsule of the conical crystal region was significantly thinner, and Streeten et al. observed many verticals in the front lens capsule of the conical crystal. To fracture.
There are many other eye damages in patients with Alport syndrome, the most common being pigmentation in the macula, with yellow or white particles around the fove, and some patients, especially children, the only observed Abnormalities may be the disappearance of foveal reflexes, and corneal endothelium vesicles may be present in other patients, and are quite common, suggesting abnormalities of the posterior corneal elastic layer. These lesions often coexist with the pre-conical crystals, but may not be accompanied by cone-shaped crystals. Govan believes that these lesions are localized to the basement membrane supporting the pigmented epithelium and are similar to the glomerular basement membrane in the collagen component, so it is concluded that abnormalities in the kidneys and eyes are due to mutations that cause changes in the basement membrane composition.
4. Platelet defects
In 1922, Epstein et al reported two families of hereditary nephritis and deafness with giant platelet disease. Patients often showed bleeding tendency in early years, and were diagnosed with idiopathic thrombocytopenic purpura, followed by hematuria. Proteinuria and sensorineural deafness, nephropathy is progressive, and the characteristics of light microscopy are consistent with the Allport syndrome. In the family reported by Parsa et al, the transmission to the father is an autosomal dominant inheritance. Three patients had no positive family history, probably due to new mutations, and two of them reported renal biopsy with focal glomerular basement membrane thickening and stratification.
5. Diffuse leiomyomatosis
It is reported that some families with Alport syndrome are accompanied by leiomyomatosis of the upper digestive tract and tracheobronchial tree. In these families, some female patients present with typical genital leiomyoma, clitoris hypertrophy and labia and Different changes in the uterus, patients in these families often have posterior subcapsular type, bilateral cataract.
The diagnosis of Alport syndrome should include two levels of clinical-pathological diagnosis and genetic diagnosis. The latter is currently being tested. If the genetic diagnosis is successful, both asymptomatic pathogen carriers (mostly female) can be detected. Making prenatal diagnosis will play a major role in prenatal and postnatal care.
Examine
Examination of familial hemorrhagic nephritis
Hematuria and proteinuria, male patients with persistent microscopic hematuria, initially only microalbuminuria, urine protein gradually increased with age, often developed to nephrotic syndrome proteinuria, may have platelet defects and obvious bleeding tendency, In the event of renal failure, there may be changes in urea nitrogen and creatinine.
Light mirror
Under the light microscope, the renal lesions are non-specific, and the glomerular lesions in the early stage of the disease are generally normal. Only the mild focal segmental mesangial tissue hyperplasia, with the progression of the lesion, the glomerular progression to glomerular sclerosis, the late renal small The ball appears fibrosis and spheroidal sclerosis, and the renal interstitial can progress from inflammatory cell infiltration to fibrosis with tubular atrophy.
The disease is common in the kidney skin, medullary junction interstitial foam cells, the foam cell cytoplasm contains neutral fat, mucopolysaccharide, cholesterol and phospholipids, the lesion is not specific to the disease, but the incidence of this disease is high, the prompt This syndrome is still important.
In addition, 10% to 25% of patients with Alport syndrome have fetal glomeruli, and fetal glomeruli can also be seen in children with non-Alport syndrome, especially infants with congenital nephrotic syndrome, but after 5 years of age, non-Alport It is difficult to see this disease again in the syndrome. This fetal glomerulus is mainly seen in children before the age of 10, especially in infants before the age of 5, and it is rare in adults with Alport syndrome.
Electron microscope
The ultrastructural changes of the glomerular basement membrane (GBM) have diagnostic significance for this disease, and it is earlier than the optical microscope. There are three main types of lesions: GBM thickening, thinning, and thinning of the GBM. Only 1/4 of the normal thickness, more common in children and women; thickened GBM can reach 2 to 5 times the normal thickness, the epithelial side edge is often irregular wave shape, thickened dense band longitudinal splitting Layers, interlaced into nets, containing lipid particles in the mesh, more common in adults and men. If thickened GBM is widely present and appears with thinned GBM, it is of great significance for the diagnosis of this disease, without GBM thickening. The pure GBM thinning is more common in benign familial hematuria, ie thin basement membrane nephropathy. Some authors have found that GBM thickening and rupture are parallel with the degree of proteinuria. GBM is obviously thickened and the disease is often progressed, and the prognosis is poor (male) This is especially true for patients).
3. Immunofluorescence
Immunofluorescence and immunohistochemistry were mostly negative, suggesting that no humoral immunity is involved in the disease, but occasionally a small number of glomerular capillaries have IgM and C3 deposits. Immunofluorescence also found that GBM lacks Goodpasture in patients with Alport syndrome. Antigen, also lacks amyloid P, amyloid P is present in normal human plasma and GBM, and the significance of GBM deficiency of amyloid P in patients with Alport syndrome remains to be studied.
In addition, the authors used anti-GBM antibodies produced by kidney transplantation in patients with Alport syndrome or directly anti-5 (IV) antibodies to incubate the skin slices of patients with this disease treated with acid-urea. As a result, the epidermal basement membrane of male patients with Alport syndrome was completely No coloration, female patients only segmental coloration, similar to the results of GBM staining, this theory theoretically suggests that the GBM and epidermal basement membrane of patients with this disease lacks Goodpasture syndrome antigen, and in practice it is possible to provide a diagnosis of this disease. means.
Diagnosis
Diagnosis and diagnosis of familial hemorrhagic nephritis
Diagnostic criteria
In the clinical-pathological diagnosis, the standards are not unified. Based on the opinions of various experts, we believe that the following aspects are diagnostic points:
1. Positive family history, the majority of hereditary methods are sexually linked dominant inheritance, followed by autosomal dominant inheritance, and very few are autosomal recessive inheritance.
2. Clinically presented nephropathy (hematuria and progressive renal impairment), ear lesions (high frequency neurological deafness) and ocular lesions (pre-spherical crystals and microparticles around the fovea).
3. The pathological examination of renal tissue showed that GBM was extensively thickened, ruptured, and coexisted with thinned GBM.
4. Anti-collagen IVNC1 antibody was used for immunofluorescence, and the epidermal basement membrane and GBM were not stained (male) or only segmental light-stained (female).
Flinter et al. listed positive family history, nephropathy (including typical changes in GBM under electron microscope), ear and eye lesions as 4, and considered that 3 of them could diagnose the disease. However, the shortcoming of this diagnostic criterion is that if the patient is sick It is only a nephropathy, and it is easy to miss the diagnosis when there is no characteristic deafness and eye disease.
Differential diagnosis
Alport syndrome needs to be identified with the following diseases:
1. Familial benign thin basement membrane disease (familial benign hematuria)
Familial benign thin basement membrane disease is autosomal dominant inheritance, clinical features of recurrent episodes of gross hematuria, non-progressive diseases, good prognosis, no renal failure, no ear, eye disease, renal biopsy under normal light microscope, immunity Fluorescence was negative, and GBM was diffuse and thin under electron microscope.
Although diffuse basement membrane thinning is considered a hallmark of benign familial hematuria, some patients with diffuse basement membrane thinning have a family history of progressive renal failure, and diffuse glomerular basement membrane thinning may be In the early stages of Orport syndrome or in the early stages of glomerular basement membrane changes, young children and adult women with Alport syndrome often show thinning of the basement membrane, while older patients tend to Significantly thickened basement and basket-like, Rumpelt found that the glomerular basement membrane deepens in the male patients with increasing age, while in women it remains in the thin basement membrane state, in other words, the glomerulus Thinning of the basement membrane does not necessarily indicate a benign thin basement membrane disease. It is only found that thinning of the glomerular basement membrane may lead to erroneous clinical pathological findings. Therefore, when the dense layer of the renal biopsy specimen is found to be thin, the patient is carefully asked. Family history, followed by examination for proteinuria, hearing impairment, ophthalmologic abnormalities to identify Allport syndrome and thin basement membrane disease, but sensory neurological deafness for Ort comprehensive The diagnosis of the association is not required.
2. Chronic glomerulonephritis
The clinical manifestations are similar to those of Alport's syndrome, but there is no obvious family history and ear, eye abnormalities, and renal biopsy can be identified.
3. Chronic tubulointerstitial nephritis
Because of the main pathological manifestations of light microscopy in patients with Alport syndrome during renal biopsy, extensive interstitial inflammation and fibrosis require differentiation with various chronic tubulointerstitial nephritis. Electron microscopy is necessary.
4. A- syndrome
For autosomal dominant inheritance, there are nail dysplasia and bone and joint hypoplasia and other diseases, and no deafness and eye disease, about half of the cases have kidney damage, kidney disease mainly manifested as proteinuria, microscopic hematuria, edema and hypertension, the condition Relatively benign, only 10% of cases develop renal failure, bone and joint mainly manifested as multiple skeletal malformations, including sacral dysplasia or dysplasia, nail atrophy and longitudinal fissure defect, eyelid drooping, X-ray examination helps identify, kidney Biopsy light microscopy and immunofluorescence showed no specificity, but GBM thickening under the electron microscope was spotted or worm-like and intramembranous fibrils could be identified.
5. Other diseases with basement membrane deposits
Under the electron microscope, the basement membrane deposit can be seen in other kidney diseases, and needs to be differentiated from other diseases other than Alport syndrome. It should also consider whether the immune complex-mediated glomerulonephritis is combined.
6. Other diseases with dense basement membrane changes
Recent studies have questioned the specificity of glomerular basement membrane changes in this disease. In the two groups of non-selective renal biopsy specimens, 6% to 15% of the specimens showed focal layered and separated dense layers, mainly Occurrence of post-infection glomerulonephritis, focal segmental glomerulosclerosis and hyaline degeneration, IgA nephropathy and mesangial proliferative glomerulonephritis with nephrotic syndrome, so when considering Alport synthesis At the time of diagnosis, clinical connection should be made, and immunofluorescence microscopy of the renal tissue, diffuse glomerular basement membrane thickening and separation is an important basis for the diagnosis of Alport syndrome, such as the discovery of IgM, C3, properdin , C4 and other deposition under the endothelium, consider IgM nephropathy, membrane proliferative glomerulonephritis and other immune complex-mediated glomerulonephritis.
