thin glomerular basement membrane disease

　　1. Etiology

　　The genetic mode of this disease is mostly autosomal dominant inheritance, but it has also been found that there are autosomal recessive inheritance pedigrees in recent years. Recently, Smeets et al. found that the mutated genes are also COL4A3 and COL4A4, located on chromosome 2. Why some COL4A3 and COL4A4 mutations cause hereditary progressive glomerulonephritis while others cause familial benign hematuria remains to be studied. Some authors have used specific antibodies against Goodpasture syndrome antigens to stain the GBM of this disease, and the results showed that it could be stained, suggesting that the changes in collagen IV of this disease are different from those of hereditary progressive glomerulonephritis.

　　2, Pathogenesis

　　The pathogenesis of thin basement membrane nephropathy is still unclear. It can be said that the glomerular basement membrane of patients with thin basement membrane nephropathy does not lack any of the main components (such as type IV collagen, laminin, nidogen, heparan sulfate, and proteoglycan). Aasosa et al. found that type IV collagen is mainly located in the central area of the glomerular basement membrane, while the subepithelial part of the glomerular basement membrane becomes thin.

　　It appears in adulthood. Hematuria is usually persistent, but some patients have intermittent hematuria, and their hematuria seems to persist into old age. Urine microscopic examination shows变形红细胞血尿, and red cell casts can be seen. Sudden gross hematuria is often related to infection, and obvious gross hematuria after upper respiratory tract infection or strenuous exercise. Patients usually do not have proteinuria, edema, and hypertension, and renal function is always normal; there is also no sensorineural hearing loss and eye abnormalities.

　　The clinical manifestations of this disease are similar to those of Alport syndrome. The most important finding of various thin glomerular basement membrane diseases is microscopic hematuria, which usually appears in childhood, and some in adulthood. Hematuria is usually persistent, but some patients have intermittent hematuria, and their hematuria seems to persist into old age. Urine microscopic examination shows变形红细胞血尿, and red cell casts can be seen. Sudden gross hematuria is often related to infection, and obvious gross hematuria after upper respiratory tract infection or strenuous exercise. Patients usually do not have proteinuria, edema, and hypertension, and renal function is always normal; there is also no sensorineural hearing loss and eye abnormalities.

　　1, Most patients with thin glomerular basement membrane disease, including familial benign hematuria, do not have obvious proteinuria. Dische et al. reported that 9 patients with thin glomerular basement membrane disease had obvious proteinuria, which was related to hypertension or renal insufficiency, or both.

　　2, It is commonly equated in the literature to benign familial hematuria, which is obviously not appropriate. It should be considered that the pathological feature of familial benign hematuria is thin basement membrane nephropathy. However, about half or more patients with thin basement membrane nephropathy do not belong to benign familial hematuria. Thin basement membrane nephropathy is an electron microscopic pathological diagnosis, which is not a clinical syndrome. These patients may have hematuria, obvious proteinuria, and even nephrotic syndrome in clinical practice. In some pedigrees, a few patients have even been found to have renal failure. There are also reports that thin basement membrane nephropathy can coexist with other kidney diseases such as IgA nephropathy, leading to diverse clinical manifestations. Only 30% to 40% of patients with this disease have a positive family history, so most of this disease is not a genetic disease. Familial benign hematuria is a benign disease that does not require treatment. It is still necessary to avoid colds, fatigue, and nephrotoxic drugs, and regular urinalysis and renal function tests should be performed.

　　2. For young and middle-aged patients with asymptomatic hematuria (mainly persistent or intermittent microscopic hematuria) and a positive family history (autosomal dominant or recessive inheritance), if electron microscopy of renal biopsy reveals diffuse thinning of GBM, this disease should be considered. However, the thinning of the glomerular basement membrane does not equal the diagnosis of thin glomerular basement membrane disease. There must be renal biopsy showing no separation and lamellar changes in the dense layer of the glomerular basement membrane to make the diagnosis.

　　3. Caution is required for the diagnosis of benign familial thin glomerular basement membrane disease (familial benign hematuria). Only after years of follow-up and observation without progression of kidney disease, and renal biopsy showing no separation and lamellar changes in the dense layer of the glomerular basement membrane, can the diagnosis be established. Regular nephrological examinations should be performed for patients diagnosed with this disease, with particular attention to the appearance of proteinuria, and it is best to perform urine tests on family members.

　　4. Due to the variability of normal glomerular basement membrane thickness and different tissue fixation and embedding methods, the definition of thin glomerular basement membrane in the literature is inconsistent. In addition, the thickness of the glomerular basement membrane is age- and sex-dependent. Vogler found that in the first two years after birth, the thickness of the glomerular basement membrane and the dense layer increased rapidly, from (169±30)nm and (98±23)nm at birth to (245±49)nm and (189±42)nm at 2 years old, respectively. After that, these structures gradually increased naturally. At the age of 11, the glomerular basement membrane reached (285±39)nm, and the dense layer reached (219±42)nm. After adulthood, the basement membrane thickness of males (373±42)nm exceeds that of females (326±45)nm.

　　5. Based on retrospective studies, diagnostic principles for thin glomerular basement membrane disease have been established. Steles et al. and Tiebosch et al. reported using 250nm as the threshold, while some laboratories have higher normal values at 330nm, which is used for diagnosing thin glomerular basement membrane disease in adults. For pediatric patients, a glomerular basement membrane thickness below 250nm is considered to be thinning, so caution should be exercised in diagnosing thin glomerular basement membrane disease in children. Tiebosch et al. reported that the basement membrane thickness of thin glomerular basement membrane disease patients varies in different locations, and 2 to 3 glomeruli should be measured to obtain the most accurate results. Each laboratory should try to establish its own normal mean and standard deviation of glomerular basement membrane thickness and decide whether to prioritize arithmetic mean or geometric mean.

　　The incidence of thin glomerular basement membrane disease varies among different reports, and it is estimated to be as high as 5% to 9%, accounting for about 20% of primary asymptomatic hematuria. The disease can occur at any age, with equal opportunities for men and women, and the vast majority of onset ages are under 40 years old. Some cases have been reported to be discovered only after the age of 80.

　　Therapeutic diet:

　　1. Take 150-250 grams of shepherd's purse (50-100 grams of dried shepherd's purse flowers), 5 grams of red skin (peanut skin), and 100 grams of glutinous rice. Cut the shepherd's purse into fine pieces (if using dried shepherd's purse flowers, you can boil the water to extract the juice. Remove the dregs), and cook the rice and red skin with water in the usual way to make porridge. Take it warm in the morning and evening every day for 15 days.

　　1. Take 15 grams of black plum, 120 grams of lotus seeds, and about 1000 milliliters of water, boil to 500-600 milliliters, and take it in three doses. It has a hemostatic effect and is more suitable for taking when there is hemoglobinuria, myoglobinuria, or microscopic hematuria.

　　2. Take 200 grams of shepherd's purse and 200 grams of bamboo shoots, fry in oil, and add a little salt and seasonings such as monosodium glutamate. Eat after the vegetables are cooked. This recipe can clear heat and eliminate dampness, cool blood and stop bleeding, and is suitable for chronic nephritis patients with hematuria.

　　Therapeutic diet: Take 5 grams of black fungus, wash and soak for half a day, chop, and cook with 100 grams of glutinous rice and appropriate amount of rock sugar to make porridge. This product has the effect of cooling blood and stopping bleeding, and can be tried for hematuria.

　　First, routine examination

　　Blood complement, plasma protein electrophoresis, antinuclear antibody, platelet count, blood urea nitrogen, and creatinine are all normal. Clinically, patients may have hematuria, and the microscopic examination of urine red blood cell phase shows red blood cells of different sizes and various shapes, with about 1/3 of the patients having red blood cell casts, but generally no obvious proteinuria or nephrotic syndrome changes.

　　Second, renal biopsy tissue examination

　　1. Light microscopy

　　Generally, no abnormalities are found. Under light microscopy, the glomeruli are usually normal, with red blood cell casts in the tubules, and occasionally some non-specific mild glomerular changes can be seen, such as mild mesangial proliferation, which has no diagnostic significance. Some reports also find global glomerulosclerosis, focal tubular atrophy, mild mesangial widening, and immature glomeruli.

　　2. Immunofluorescence examination

　　Immunoglobulins and complement are usually negative in the glomeruli of patients with this disease, and there are also reports of small amounts of IgG, IgM, IgA, and C3 deposited along the glomerular basement membrane, combined with anti-glomerular basement membrane autoantibodies, as well as the ability to bind to monoclonal antibodies against Goodpasture antigen, which are normal or slightly reduced.

　　3. Ultrastructure

　　The main ultrastructural feature is the thinning of the glomerular basement membrane, and characteristic changes of the disease can be observed under an electron microscope, such as diffuse thinning of the GBM, with a thickness only 1/3 to 2/3 of the normal thickness, even thinner, without thickening, and segments of split GBM appear. In some families, the glomerular basement membrane thickness is normal in individual adult patients, while the other family members have thinning glomerular basement membranes. In some families with familial benign hematuria, the glomerular basement membrane thickness is normal, even in families with glomerular basement membrane thinning, not all vascular loops have thinning walls. Mesangial thickening and focal capillary wall rupture can be found in patients of all ages. In a few cases, segmental irregularities of vascular contours and deposition of mesangial granular substances can be found.

　　The following food therapies can be adopted for patients with hematuria symptoms:

　　1. Take 150-250 grams of shepherd's purse (50-100 grams of dried shepherd's purse flowers), 5 grams of red skin (peanut skin), and 100 grams of glutinous rice. Cut the shepherd's purse into fine pieces (if using dried shepherd's purse flowers, you can boil the water to extract the juice. Remove the dregs), and cook the rice and red skin with water in the usual way to make porridge. Take it warm in the morning and evening every day for 15 days.

　　1. Take 15 grams of black plum, 120 grams of lotus seeds, and about 1000 milliliters of water, boil to 500-600 milliliters, and take it in three doses. It has a hemostatic effect and is more suitable for taking when there is hemoglobinuria, myoglobinuria, or microscopic hematuria.

　　2. Take 200 grams of shepherd's purse and 200 grams of bamboo shoots, fry in oil, and add a little salt and seasonings such as monosodium glutamate. Eat after the vegetables are cooked. This recipe can clear heat and eliminate dampness, cool blood and stop bleeding, and is suitable for chronic nephritis patients with hematuria.

　　3. Take 5 grams of black fungus, wash and soak for half a day, chop, and cook with 100 grams of glutinous rice and an appropriate amount of rock sugar to make porridge. This product has the effect of cooling blood and stopping bleeding, and can be tried for hematuria. This food therapy comes from netizen sharing, unreviewed by doctors, for reference only.

　　1. Western Medical Treatment Methods

　　Thin basement membrane nephropathy is a benign disease that does not require special treatment. For a small number of patients with hypertension symptoms, blood pressure should be controlled in a timely manner, but unnecessary treatment and the use of nephrotoxic drugs should be avoided; when there is gross hematuria, attention should be paid to whether there is an upper respiratory tract infection, and corresponding treatment can be performed. For progressive thin glomerular basement membrane disease, symptomatic treatment should be carried out; for a small number of patients with progressive renal failure, as well as those with recurrent gross hematuria, proteinuria, and lumbar pain, angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists can be given. It is reported that ACEI drugs have a definite effect on reducing proteinuria. In addition, a low-protein diet and traditional Chinese medicine with protein-reducing effects, such as Shen Gan Ning, formulas containing Astragalus membranaceus, etc., can be given; for hypertension and chronic renal insufficiency, treatment should be followed according to the corresponding treatment principles.

　　2. Prognosis

　　This disease mostly progresses benignly, with no significant damage to kidney function, and has a good prognosis. However, a small number of patients may experience changes in kidney function, so long-term follow-up should be noted.