Concept: nephroticsyndrome” (nephroticsyndromeNS) referred to as renal syndrome, refers to a variety of etiological causes, to increase the glomerular basement membrane permeability with glomerular filtration rate reduction and other glomerular pathology based on a group of syndromes clinically have four major characteristics: 1, large amounts of proteinuria more than 3, 5g / d, may have lipiduria; 2, low albumin Hemoglobinemia serum albumin less than 30g / L; 3, hyperlipidemia; 4, edema according to different etiology and pathology will be divided into three categories: primary nephrotic syndrome congenital nephrotic syndrome, secondary nephrotic syndrome. Typical manifestations: a large amount of proteinuria (daily >3,5g/1,73m2 body surface area), hypoalbuminemia (plasma albumin <30g/L), edema with or without hyperlipidemia diagnostic criteria should be a large amount of proteinuria and hypoproteinemia. Massive proteinuria is characteristic of glomerular disease, and it is rare to see such a large amount of proteinuria in renal vascular disease or tubulointerstitial disease. Since hypoproteinemia, hyperlipidemia, and edema are all consequences of massive proteinuria, it is believed that the criteria for diagnosis should be based on massive proteinuria. Etiology: Many diseases can cause damage to the glomerular capillary filtration membrane, leading to nephrotic syndrome. Two thirds of adults and most children have primary nephrotic syndrome, including primary glomerulonephropathy acute, chronic glomerulonephritis and acute progressive nephritis. The main diagnoses by pathology include: microscopic lesion nephropathy, membranous glomerulonephritis (membranous nephropathy), mesangial capillary proliferative nephritis (membranoproliferative nephritis) and focal segmental glomerulosclerosis. Their relative incidence and characteristics are shown in Table 1. Secondary nephrotic syndromes are caused by infections, drugs (mercury, organogold, penicillamine and heroin, etc.), toxins and allergies, neoplasms (solid tumors of the lungs, stomach, colon, and breast, and lymphomas, etc.), systemic lupus erythematosus, purpura fulminans amyloidosis and diabetes mellitus. 1/3 of adult nephrotic syndrome and 10% of children can be caused by secondary factors. Clinical manifestations (a) proteinuria Normal adult urinary protein excretion is not more than 150mg per day. large amount of proteinuria is due to glomerular filtration membrane abnormality. The normal glomerular filtration membrane has a selective filtration effect on plasma proteins, which can effectively prevent the vast majority of plasma proteins from glomerular filtration, and only a very small amount of plasma proteins into the glomerular filtrate. Factors affecting protein filtration may include: 1. Protein molecular size. The clearance of a substance by glomerular capillaries is inversely proportional to the effective molecular radius of the substance, and the larger the molecular weight of the protein, the less it is filtered or not filtered at all. In general, plasma proteins with molecular weights of 60,000 to 70,000 daltons (e.g., albumin) are less filtered, molecular weights greater than 200,000 daltons (e.g., α1 lipoproteins, etc.) cannot be filtered, and plasma proteins with smaller molecular weights (less than 40,000), such as lysozyme, β2-mg, and the light chains of immunoglobulins, are freely filtered. This barrier effect, in which filtration varies according to the molecular weight of the protein, is called the molecular selection barrier (mechanical barrier). This barrier effect is determined by the ultrastructure of the glomerular filtration membrane. The glomerular filtration membrane consists of the endothelium, glomerular basement membrane (GBM) and epithelial layer. The gap between the endothelial cells is 40 ~ 100nm, all soluble substances in plasma (including soluble immune complexes) can be passed; GBM consists of the inner sparse layer, dense layer and outer sparse layer, there is a filtration on the GBM, the pore radius of 3.5 ~ 4.2nm, forming a layer of coarse filter, which can allow part of the albumin (molecular radius of 3, 7nm) and transferrin to pass. Epithelial layer: the epithelial cells have a cleft between the peduncle, which has a septum, with small pores, pore size of 4 × 14nm, forming a layer of fine filters, so that molecules larger than albumin can not be filtered through. 2, protein charge situation glomerular basement membrane of the inner layer, outer layer, glomerular vascular collaterals of the endothelium, epithelial cell surface and thylakoid stroma is rich in aminopolysaccharide components (heparan sulfate) and salivary acid, both of which make the glomerular filtration membrane negatively charged, constituting an electrostatic barrier. Through the principle of repulsion of same-sex charge, the negatively charged proteins are cleared at the lowest rate, while the positively charged ones are cleared at the highest rate. Studies have demonstrated that in glomerular disease, the salivary acid component of the glomerular basement membrane is markedly reduced, allowing the filtration of negatively charged albumin to appear as proteinuria. In addition to the electrostatic barrier, the glomerular negatively charged field has the function of maintaining cell morphology and capillary structure. Therefore, the clinical loss of pure electrostatic barrier effect is rare, mostly accompanied by abnormal tissue structure function. 3, protein morphology and variability due to the glomerular mechanical barrier effect, so that the loosely arranged molecules in linear form are easier to pass through the glomerular filtration membrane than the tightly arranged molecules in spherical form. 4, hemodynamic changes in the glomerular filtration membrane permeability and glomerular intraglomerular pressure and renal blood flow are closely related. Decreased plasma flow in the small arteries of the incoming glomerulus and compensatory increase in hydrostatic pressure on both sides of the membrane are common hemodynamic regulatory mechanisms in glomerular damage. At this time, the individual glomerular filtration fraction increases and the protein concentration at the outgoing glomerular end is higher than normal, resulting in increased diffusion of plasma proteins through the glomerular capillary wall. Increased angiotensin II in the kidney causes constriction of the small glomerular arteries and increased capillary pressure in the glomerulus, which also increases protein leakage. Abnormalities of the charge barrier (e.g., microscopic lesions) lead mainly to albumin leakage, which manifests as selective proteinuria; there is no abnormality of glomerular structure under light microscopy, but a marked decrease in anions in the glomerular capillary wall can be detected with special staining techniques. An increased albumin clearance fraction may reflect the extent of the charge barrier defect. Mechanical barrier abnormalities, such as membranous nephritis, membranoproliferative nephritis or glomerular diseases accompanied by biochemical and structural changes in GBM, such as diabetes mellitus and hereditary nephritis can have significant structural changes, which increase the filtration of all plasma proteins, that is, it is manifested as nonselective proteinuria. (ii) Hypoalbuminemia Hypoalbuminemia is seen in most patients with nephrotic syndrome, i.e., serum albumin level below 30 g/L. The main cause is the loss of albumin in the urine, but the two are not exactly parallel, because the plasma albumin value is the result of the balance between albumin synthesis and catabolism. It is mainly affected by the following factors: 1. Increased hepatic synthesis of albumin. In hypoproteinemia and a decrease in the volume of the albumin pool, the absolute value of the albumin catabolic rate is normal or even decreases. The amount of compensatory hepatic synthesis of albumin is increased, and the patient's liver can synthesize up to 20 g or more of albumin per day if adequate protein and calories are given in the diet. Hypoproteinemia may not occur in patients who are fit and consume a high-protein diet. It has been suggested that plasma colloid osmotic pressure may play an important role in regulating hepatic synthesis of albumin. 2. The ability of renal tubules to break down albumin is increased. In normal people, 10% of the albumin synthesized by the liver is metabolized in the renal tubules. In nephrotic syndrome, due to the proximal tubule uptake and decomposition of filtered protein increased significantly, the renal metabolism can be increased to 16% to 30%. 3, severe edema, gastrointestinal absorption capacity is reduced, patients with nephrotic syndrome often show a negative nitrogen balance. Age, disease duration, chronic liver disease, malnutrition can affect plasma albumin level. Consumption of a high-protein diet in patients with nephrotic syndrome results in an increase in urinary protein with no or little increase in plasma albumin, whereas in severely malnourished individuals who are also taking angiotensin-converting enzyme inhibitors (which attenuates glomerular hyperfiltration), a high-protein diet may increase plasma albumin concentrations. If protein intake is restricted, urinary protein decreases and plasma albumin levels are mostly unchanged or minimal. Thus a new concept of control of dietary protein intake in patients with nephrotic syndrome has been developed. As a result of hypoalbuminemia, drug binding to albumin is reduced, resulting in elevated levels of free drug in the blood, which can produce toxic reactions even at routine doses. In hypoalbuminemia, there is reduced binding of arachidonic acid to plasma proteins, which contributes to platelet aggregation and increased thromboxane (TXA2), the latter of which can exacerbate proteinuria and renal damage. (iii) Oedema The presence of oedema and its severity correlate positively with the degree of hypoproteinemia. However exceptions are not uncommon. The body itself has the ability to resist the formation of edema, the mechanism of its regulation is: 1, when the plasma albumin concentration decreases, the plasma colloid osmotic pressure decreases at the same time, the tissue fluid from the lymphatic reflux greatly increased, thus taking away the protein in the tissue fluid, so that the colloid osmotic pressure of the tissue fluid at the same time decreases, and the difference in the gradient between the two is still maintained in the normal range. 2, the tissue fluid water increases, then its hydrostatic pressure rises, can make the small blood vessels in front of the capillary contraction, so that blood perfusion decreased, reducing the area of the capillary bed, so that the hydrostatic pressure in the capillary decreased, thus inhibiting the body fluids from the blood vessels to the intertissue escape. 3, the escape of water out of the vasculature causes tissue fluid protein concentrations to fall while intraplasma protein concentrations rise. In view of the limited ability of the lymphatic vessels to drain tissue fluid proteins, there is a certain limit to the ability of the above body fluid distribution to balance itself, and when the plasma colloid osmotic pressure further decreases, the colloid osmotic pressure of the tissue fluid cannot be regulated to the corresponding level, and the difference in the gradient between the two cannot be maintained at a normal level, which is what produces edema. Most patients with edema in nephrotic syndrome have normal or even increased blood volume, not necessarily all decreased, and plasma renin is normal or at a low level, suggesting that sodium retention in nephrotic syndrome is due to a disorder of renal regulation of sodium balance, and is not related to activation of the renin-angiotensin-aldosterone system by hypovolemia. The occurrence of edema in nephrotic syndrome cannot be explained by one mechanism alone. Changes in blood volume, only in some patients, may be a factor causing sodium retention and aggravating edema, but it cannot explain the occurrence of all edema, and the real mechanism of its formation, which is not yet clear, is likely to be related to the impairment of certain regulatory mechanisms within the kidney. (D) Hyperlipidemia Abnormalities of lipid metabolism in nephrotic syndrome are characterized by an increase in almost all kinds of lipoprotein components in plasma, a significant increase in plasma total cholesterol (Ch) and low-density lipoprotein cholesterol (LDL-Ch), and an elevation of triglycerides (TG) and very low-density lipoprotein cholesterol (VLDL-Ch). High-density lipoprotein cholesterol (HDL-Ch) concentrations can be elevated, normal, or decreased; abnormal distribution of HDL isoforms, i.e., an increase in HDL3 and a decrease in HDL2, suggests impaired maturation of HDL3. Increases in each lipid component occur at different times during the course of the disease, with elevated Ch appearing earliest, followed by phospholipids and TG. In addition to quantitative changes, the quality of the lipids is also altered, with the cholesterol/phospholipid and cholesterol/triglyceride ratios of the various lipoproteins being elevated. Apolipoproteins are also often abnormal, e.g., ApoB is markedly elevated and ApoC and ApoE are mildly elevated. The duration and severity of the lipid abnormalities correlate significantly with the course of the disease and the frequency of relapses, and prolonged hyperlipidemia may persist after the nephrotic syndrome has entered the recovery phase. Mechanisms of abnormal lipid metabolism in nephrotic syndrome: ① Increased hepatic synthesis of Ch, TG and lipoproteins. Lipid clearance is impaired by changes in the activity of lipid-regulating enzymes and in the activity or number of LDL receptors. (iii) Increased loss of HDL in the urine. In nephrotic syndrome, 50% to 100% of ApoA-Ⅰ of HDL can be lost in urine, and plasma HDL3 increases while HDL2 decreases in patients, suggesting that HDL3 is lost in urine before it is converted to larger HDL2 particles. The impact of hyperlipidemia on the incidence of cardiovascular disease in patients with nephrotic syndrome depends on the duration of hyperlipidemia, the LDL/HDL ratio, history of hypertension, and smoking. Prolonged hyperlipidemia, especially the rise in LDL and fall in HDL, can accelerate the development of coronary atherosclerosis and increase the risk of acute myocardial infarction in patients. In recent years, the effect of hyperlipidemia on the kidney has attracted the attention of many scholars. The role of lipid-induced glomerulosclerosis has been confirmed in the study of endogenous hyperlipidemia and so on. The mechanism of glomerular injury caused by lipid metabolism disorders and the factors affecting it are complex, and may be related to the following factors: intraglomerular lipoprotein deposition, tubulointerstitial lipoprotein deposition, LDL oxidation, monocyte infiltration, cytotoxicity caused by lipoproteins resulting in endothelial cell damage, the role of lipid mediators, and lipids increase matrix synthesis. (E) Changes in the concentration of other proteins in the blood The concentration of a variety of plasma proteins can change in nephrotic syndrome. For example, α2 and β globulin are elevated in serum protein electrophoresis, while α1 globulin may be normal or decreased, IgG levels may be significantly decreased, while IgA, IgM and IgE levels are mostly normal or elevated, but the changes in immunoglobulins are related to the primary disease. The lack of complement-activated bypass B factor can impair the body's regulation of bacteria and is one of the reasons why patients with nephrotic syndrome are susceptible to infections. Fibrinogen and coagulation factors V, VII, and X may be elevated; platelets may also be mildly elevated; antithrombin III may be lost from the urine resulting in a severe decrease; C protein and S protein concentrations are mostly normal or elevated, but their activity is reduced; increased platelet coagulability and elevated β-thromboglobulin may be a sign of latent spontaneous thrombosis. Characteristics of pediatric nephrotic syndrome: There are many causes of pediatric nephrotic syndrome. When you have a cold, the immune cells in your body will swallow the invading bacteria and viruses and generate an antibody that dies afterward, eliminating germs to ensure that the body is not affected. Children have fewer immune cells than normal people because of their weak physical condition, so their immune function is not strong enough, so the immune cells sometimes not only do not swallow the germs in children's bodies, but also temporarily contain the germs. This causes the antibodies to the germs in the child's body to combine with the germs themselves to form an immune complex that circulates in the bloodstream. When this immune complex reaches the child's kidneys, it is deposited into the basement membrane of the glomeruli, thus damaging the child's kidneys and causing a large amount of protein to be lost with the child's urine. This eventually leads to the development of nephrotic syndrome in children. In terms of nephrotic syndrome alone, it can occur at any age, but is more common in young people and children. Microscopic nephrotic syndrome occurs most often in children between the ages of 2 and 6 years, and is more common in boys than girls. Pediatric nephrotic syndrome is highly recurrent and prolonged, with a long duration of illness, usually occurring 1-4 weeks after infection with the organism. Generally speaking, pediatric nephrotic syndrome has pre-infectious symptoms. The prominent features of pediatric nephrotic syndrome are "three highs and one low", i.e., high swelling, high proteinuria, high cholesterolemia and hypoproteinemia. Within one to four weeks after a cold, children can have swelling in the lower limbs, head, face and trunk, especially in the areas where children have loose tissues. The most obvious and earliest appearance is eyelid swelling. In severe cases of nephrotic syndrome in children, the skin is thin and translucent, with pleural fluid, ascites, and oozing from the slightest damage to the skin. Harm: Nephrotic syndrome is not the name of a disease, but represents a group of symptoms behind a variety of chronic kidney disease. The most important complication of nephrotic syndrome Nephrotic syndrome patients have decreased resistance and are prone to infections, common respiratory tract infections and urinary tract infections, primary peritonitis, cellulitis. Due to the hypercoagulable state of the blood, they are prone to renal vein thrombosis, pulmonary embolism, and thrombophlebitis of the peripheral veins. It also causes vitamin D deficiency, as well as zinc deficiency, which can easily lead to weakness and slow wound healing. The most serious consequence of nephrotic syndrome is to cause acute renal failure; the proportion of chronic renal failure caused by long-term massive proteinuria is also much higher than that of the normal population.