Minimal change nephrotic syndrome

　　One, Etiology

　　MCN can be divided into primary and secondary types. The etiology of the primary type is unknown, and the onset may be related to infection and allergic reactions, and it is currently believed to be a disease related to immune response, mediated by abnormal T-lymphocyte clones. The pathogenesis of the secondary type may be related to antigens and human major histocompatibility complex. Patients are often highly sensitive, such as in allergic rhinitis, urticaria, and other allergic diseases, where the incidence rate is significantly increased. Common factors of the secondary type include allergens such as pollen, biological toxins, drugs (penicillamine, non-steroidal anti-inflammatory drugs), and lymphoma, as well as radiation therapy that can trigger MCN.

　　Two, Pathogenesis

　　The pathogenesis of MCN is still unclear, and it is generally believed to be related to immune mechanisms, but other factors may also be involved. Some people believe that abnormal T-lymphocyte subsets produce circulating glomerular toxic lymphokines that cause MCN. Because the condition of MCN patients can be alleviated after suffering from measles. Patients are prone to streptococcal infection and are sensitive to cyclophosphamide and glucocorticoid treatment.

　　1. Patients with humoral immunity are prone to infection, part of the reason is due to the decrease of IgG and IgA in plasma. The decrease of IgG is caused by the loss of IgG in urine and the change of CD4-lymphocyte regulatory function, leading to the impairment of B-cell production and maturation. During the recurrence period, the levels of IgG and IgA in plasma decrease, IgM increases, and these changes return to normal during the remission period. After the remission of MCN, IgG can maintain a low level for several years. In vitro studies suggest that B lymphocytes in MCN patients have difficulties in forming antibodies after antigen stimulation. Moreover, the titer of antibodies against Streptococcus and Streptococcus pneumoniae in the blood of MCN patients is lower than that in other patients with glomerular damage nephritis. Complement activation tests and immune complexes do not play a role in the pathological process of MCN, but complement factors B, D, and circulating immune complexes in MCN patients decrease, increase after hormone treatment, but are still lower than those in normal people. MCN is prone to infection due to low complement levels.

　　2. Cellular immunity MCN has a decreased delayed-type hypersensitivity to common antigens. After the disease is remitted, the body's response to antigens returns to normal. Most studies show that, compared with remission cases, there is an activation phenomenon in T lymphocytes during the relapse period, accompanied by increased expression of interleukin-2 receptor (IL-2R), CD69, and transferrin receptor, as well as increased production of IL-1 and IL-2. The total T lymphocytes (Leu4a/DR) and helper T lymphocytes (Leu3aCD4) in this disease decrease while suppressive T lymphocytes (Leu2a/DR) increase. In some patients, overactivation of suppressive T lymphocytes can be found. During the active phase of the disease, the concentration of activated lymphocyte products, such as soluble IL-2 receptor, in blood and urine increases and returns to normal with the remission of the disease. It is known that the IL-2 receptor acts to down-regulate the proliferative response of T lymphocytes, and clinical observation results also prove that when the IL-2 receptor is up-regulated, the response of T lymphocytes to mitogens decreases. This indicates that there is a defect in the function of T lymphocytes in this disease. In the renal interstitium, T lymphocytes activated by a complex cytokine network increase the permeability of glomeruli. In patients with renal disease responsive to hormones, inhibitory soluble immunosuppressive factors (SIRS) can be found in the body, while in patients with hormone-resistant renal disease, such a factor is not found. SIRS is produced by CD8 cells, with a molecular weight of 100-150 kDa, and can inhibit the response of T lymphocytes to antigens and the production of immunoglobulins mediated by B lymphocytes. Hormones can inhibit the production of SIRS. It has been reported that the concentration of type I soluble HLA antigen (sHLA-Ⅰ, a substance produced by mitogens, antigens, and cytokines that stimulate T and B lymphocytes) in urine is an indicator for predicting the effectiveness of hormone treatment for MCN.

　　3. Considering the histological changes of glomerular inflammation and the fact that proteinuria spontaneously disappears after treatment for lymphoma, many studies have focused on the search for humoral factors. Many humoral factors have been studied, such as interleukins, tumor necrosis factor (TNF), and interferons. Some reports suggest that the levels of these factors increase in the body of MCN patients. Other studies have found some new factors whose inhibitory effects are consistent with the activity of the disease. Stimulation of patients' neutrophils with mitogens can produce a substance called vascular permeability factor (VPF). Injecting this factor subcutaneously into guinea pigs can cause increased capillary permeability. During the remission period, the amount of VPF produced by neutrophils is less. As a related protein produced by tumor cells, vascular endothelial growth factor (VEGF) has mitogenic effects in vitro and promotes vascular growth in vivo. This factor can be detected in normal renal epithelial cells. Injecting VEGF into animals can cause proteinuria.

　　During the acute phase, using mitogen to stimulate the production of a 29kDa protein factor by the patient's neutrophils, which can increase the decomposition of sulfur-containing components in the glomerular basement membrane. Sulfur-containing components such as heparan sulfate are very abundant in the glomerular basement membrane, thereby exerting their charge barrier function. The decomposition of sulfur-containing components in the glomerular basement membrane decreases its negative charge, weakens the barrier function, and leads to changes in glomerular permeability, resulting in proteinuria. During the remission phase of MCN, this mediator produced by neutrophils does not have activity. Therefore, it has not yet been determined whether this mediator can cause animals to produce proteinuria. The T cell hybridoma formed by the lymphocytes of MCN patients can produce a glomerular permeability factor (GPF), which can directly increase the permeability of the glomerular basement membrane. Injecting GPF into rats can induce proteinuria and cause the disappearance of the pedicles of podocytes. GPF can cause necrosis of tumor cells derived from epithelial cells, with a molecular weight of 60-160kDa, similar to TNF, and is therefore inferred to be a tumor necrosis factor.

　　Long-term hypoproteinemia can lead to malnutrition and secondary infection in patients; hypercoagulability can lead to thrombosis; inappropriate diuresis and salt restriction can lead to hyponatremia or hypokalemia.

　　1. Infection

　　Before the advent of antibiotics, infection was a common cause of death in this disease, especially in pediatric patients. The pathogenic bacteria are mainly pneumococci, hemolytic streptococci, and others that cause peritonitis, pleurisy, subcutaneous infection, respiratory tract infection, and can also cause urinary tract infection. Especially in patients receiving adrenal cortical hormones and/or immunosuppressive drugs, the infection is often exacerbated, and the sensitivity to viral infection also increases, such as susceptibility to herpesvirus and measles virus. The mechanism by which this disease is prone to infection is:

　　1. Large amounts of IgG lost in urine;

　　2. Immune abnormalities:This disease can cause abnormalities in humoral and cellular immune functions, with a decrease in IgG synthesis by lymphocytes, a decrease in the conversion of IgM mediated by T cells to IgG, abnormal immune调理 function associated with the lack of factor B (complement alternative pathway component), and inhibition of T cell activity;

　　3. Malnutrition;

　　4. Hypotransferrinemia and hypozincemia:There is evidence that the iron-binding protein carries zinc, which plays an important role in the function of lymphocytes. Hypozincemia can lead to insufficient production of zinc-dependent thymic hormones, which can cause a decrease in the body's resistance.

　　Second, thrombotic and embolic complications

　　Thrombosis and thromboembolism of arteries and veins are common in patients with nephrotic syndrome, such as pulmonary artery thromboembolism and thrombosis, and peripheral arterial and venous thrombosis. Most renal vein thrombosis is subclinical, but it can also cause severe proteinuria, hematuria, and even renal failure. Thromboembolism of the femoral artery is one of the acute conditions of this disease, and if not treated with thrombolytic therapy in time, it can lead to necrosis of the extremities. The occurrence of this disease is related to factors that exacerbate the hypercoagulable state, such as hypovolemia, increased blood viscosity, diuretics, and long-term use of large amounts of glucocorticoids.

　　3. Hyperlipidemia

　　Long-term hyperlipidemia, especially with an increase in LDH and a decrease in HDL, may cause coronary heart disease and atherosclerosis. Studies have confirmed the existence of low-density lipoprotein receptors on mesangial cells, and low-density lipoprotein receptors can cause mesangial cell proliferation and mesangial matrix increase, thereby aggravating the progressive sclerosis of glomeruli.

　　4. Renal function injury

　　1. Acute renal injury:In patients with this disease, when severe hypovolemia occurs, clinical manifestations of acute renal failure such as oliguria, anuria, decreased urine sodium, cold extremities, decreased blood pressure, small pulse pressure, and increased hematocrit occur. This belongs to prerenal azotemia, which is easy to correct with plasma or plasma protein.

　　In some patients with a large amount of proteinuria without a decrease in blood volume, acute renal failure can also occur, which is related to factors such as a significant decrease in glomerular filtration rate, interstitial edema compressing the tubules, and proteinuria casts blocking the tubules.

　　2. Tubular dysfunction:Underlying diseases that cause nephrotic syndrome can all lead to tubular damage, with large amounts of urinary protein causing tubular atrophy and interstitial fibrosis, mainly due to the dysfunction of the proximal tubule, manifested as hypokalemia, renal diabetes, aminoaciduria, acidosis, and other symptoms.

　　Minimal change nephrotic syndrome often develops abruptly, often with edema as the initial manifestation, 50% of patients have a history of previous infection (more common in adults), and some patients have a history of bee stings and drug allergies. Regardless of age, patients often present with nephrotic syndrome, especially in infants, MCN accounts for 63% to 93% of nephrotic syndrome, and about 1/3 of adult cases have microscopic hematuria, and acute renal failure can occur when the blood volume is too low.

　　1. Edema:Marked edema is often the first manifestation of the disease, with children usually presenting with facial edema, while adults exhibit significant lower limb edema, accompanied by subungal edema (nail bed appears white), scrotal edema, pleural effusion, and ascites are also common. When a large amount of ascites or pulmonary edema occurs, patients may experience symptoms such as dyspnea and respiratory distress.

　　2. Proteinuria:Highly selective proteinuria, mainly albumin, with urine protein exceeding 10g per day, and urine disc electrophoresis shows selective middle molecular weight protein bands.

　　3. Hypoproteinemia:Plasma albumin is often significantly decreased, with some cases reaching below 10g/L. Hypoproteinemia is closely related to the amount of protein loss, and serum protein electrophoresis shows a decrease in albumin and gamma globulin, alpha-1 globulin is normal or slightly increased, while alpha-2 and beta globulins increase, immunoglobulins IgG and IgA decrease, IgM and IgE increase. Due to the changes in the quantity of different components of plasma proteins plus the changes in blood lipids, the patient's erythrocyte sedimentation rate (ESR) accelerates significantly (greater than 70mm/h). In addition, hypoproteinemia can cause a decrease in blood calcium, for every 10g/L decrease in blood albumin, blood calcium decreases by 8mg/L, but clinical symptoms are rarely observed, and hypophosphatemia does not occur.

　　4. Hyperlipidemia:MCN patients may exhibit disorders in lipid metabolism, with significantly elevated plasma cholesterol and triglycerides, serum may appear chylous, and patients with hyperlipidemia often have lipuria, in addition, pseudo-hyponatremia may also occur.

　　5. Hypertension, hypotension:Patients with significant hypoproteinemia and reduced effective blood volume may experience orthostatic hypotension, weak pulse, and other symptoms. At the same time, some patients may experience transient hypertension due to increased renin-angiotensin activity.

　　6. Hematuria:Some patients may present with microscopic hematuria (20% to 30%), which is mostly transient and rarely presents with gross hematuria.

　　7. Renal function:Most patients have normal renal function. In the early stage of the disease, due to the increased renal blood flow, the serum creatinine clearance rate shows a transient increase, which can rapidly return to normal with the increase in urine output. In patients with edema and severe hypovolemia, due to the increased urea cycle in the kidney and the increased protein catabolic metabolism of the body, the glomerular filtration rate can decrease (to 80% to 20% of normal), leading to oliguria and pre-renal azotemia. However, this phenomenon is reversible and does not affect the prognosis. Some patients, especially the elderly, may have renal insufficiency. The main reasons are forced diuresis, severe interstitial edema leading to tubular atrophy, and epithelial cell damage causing a decrease in glomerular filtration. Due to the secondary hyperemia caused by hypoproteinemia, the hemoglobin and hematocrit levels of patients are normal or increased. Renal insufficiency caused by renal parenchymal lesions is often accompanied by anemia.

　　The key to preventing this disease is to strengthen exercise, enhance physical fitness, and improve immunity. Children should pay attention to reducing visits to public places to avoid cross-infection. In case of infection, effective, sensitive, and minimally nephrotoxic antibiotics should be selected for treatment. If there is an obvious focus of infection, it should be removed promptly to prevent the spread of infection. At the same time, it is necessary to avoid contact with various toxic and harmful substances and reduce the occurrence of atopic diseases. Patients with the disease should actively treat the primary disease, control the occurrence and development of complications, and actively treat the complications that have appeared, striving to reverse or slow the progression of the disease.

　　Abnormal laboratory tests are mainly due to the large loss of protein in urine and the compensation after protein loss, as well as the secondary complications such as hypercoagulability due to the compensatory mechanism after loss.

　　First, hypoproteinemia

　　The plasma albumin of patients with this disease is usually below 25g/L, and a few can reach below 10g/L. When the plasma albumin drops below 20g/L, edema becomes more obvious. The concentration of plasma albumin is the result of a balance between the liver synthesis of albumin, albumin metabolism, and the loss from the gastrointestinal tract. With the increased filtration of albumin by MCN, it is speculated that after the albumin leaks out, it is reabsorbed, metabolized by the proximal renal tubules, and normally serves as a response to the decrease in colloidal osmotic pressure and viscosity in the sinusoid of the liver. The amount of albumin synthesized by the liver can increase by 300%, about 12g/d, while the metabolic rate of albumin in patients increases, and the absolute metabolic rate is decreasing. However, the speed of albumin synthesis by the liver does not keep up with the protein loss from urine plus the metabolic amount of albumin by the kidneys, partly due to insufficient protein intake.

　　Serum protein electrophoresis shows increased α2 and β globulins, α1 globulin is mostly normal or increased, γ globulin is decreased or depends on the primary disease. The levels of immunoglobulins IgG and IgA are significantly decreased, IgM and IgE levels change little or increase, complement C3, C1q, C8 can decrease; fibrinogen, factors II, VII, VIII, and X increase, which may be related to increased synthesis in the liver. Antithrombin III (heparin-related factor) decreases, possibly due to increased excretion in urine. Protein C and protein S levels are normal or increased, but the activity decreases, which is related to the formation of a hypercoagulable state. Factors IX, XI, and XII decrease, plasminogen, antiplasmin, and α1-antitrypsin levels also decrease. The urinary fibrin degradation products (FDP) mainly reflect glomerular permeability, not necessarily reflecting intraglomerular coagulation. Changes in transport proteins: trace metal-binding proteins in urine - ceruloplasmin, ferritin are lost from urine, causing proteins carrying important metal ions (iron, copper, zinc) in the blood to decrease, leading to decreased blood copper and iron concentrations, decreased iron content in red blood cells, resulting in iron deficiency anemia with small, hypochromic red blood cells. Two-thirds of the circulating zinc is bound to albumin, so hypoproteinemia and loss of zinc from urine can lead to decreased plasma zinc levels. The decrease in blood zinc hinders growth, leading to impaired immune function and delayed wound healing. The proteins and activity of important endocrine hormones (thyroxine, endothelin, prostaglandin) combined with and the binding proteins of 25-hydroxyvitamin D3 (25-OH vitamin D3) decrease.

　　Proteinuria

　　Urine examination can be detected by the dipstick method to roughly estimate the amount of urinary protein: + is equivalent to 30mg/dl, equivalent to 100mg/dl, equivalent to 300ml/dl, equivalent to 1000mg/dl. Some people use the IgG (molecular weight of 170kD) and ferritin (molecular weight of 88kD) clearance ratio to judge its selectivity, with a ratio of 0.2, indicating that the molecular barrier damage of the glomerular capillaries is significant, leading to the leakage of macromolecular proteins. Highly selective proteinuria is a feature of children with MCN. Adult patients have overlapping phenomena with other types of NS, and their value is not as high as that of children. Recent work has confirmed that protein selectivity does not have a definite clinical value, and it has no guiding significance for the response to treatment and the judgment of prognosis. Therefore, it is rarely used in clinical practice. As for glomerular permeability, although the retinol-binding protein and β2-microglobulin in urine are not specific, in patients with hormone-resistant NS, the excretion of these two proteins in urine is higher than that in patients with hormone-sensitive NS. The increase in the excretion of these two proteins in urine is a sign of damage to the proximal tubules, indicating significant renal parenchymal injury, and thus resistance to hormones. 23% of children with MCN may have microscopic hematuria.

　　In recent years, it has become a consensus that proteinuria, especially persistent and massive proteinuria, can exacerbate renal damage. However, its pathogenic mechanism has remained unclear for a long time. Previous studies have emphasized its role in aggravating glomerular hyperfiltration and promoting glomerulosclerosis. However, current research indicates that it primarily causes tubulointerstitial lesions, accelerating the progression of renal damage. The proximal tubular epithelial cells can reabsorb various proteins filtered by the glomerulus through endocytosis or receptor binding pathways. Complement components enter the cell and are activated by ammonia to produce C3a, C5a, and C5b-9. C3a and C5a are chemotactic factors, while C5b-9 can insert into the cell membrane, stimulating the release of inflammatory mediators such as interleukin-1 and tumor necrosis factor-α by the proximal tubular epithelial cells, and the synthesis of extracellular matrix fibronectin, thereby causing tubulointerstitial damage. Filtered insulin-like growth factor-1 can enter the proximal tubular epithelial cells through receptor-mediated pathways and then stimulate the synthesis of extracellular matrix components collagen I and IV, damaging the tubulointerstitium. Fatty acids bound to albumin can be reabsorbed by the proximal tubular epithelial cells after filtration, and then the lipids will be released back into the extracellular space, exerting chemotactic factor activity and damaging the tubulointerstitium. The filtered transferrin-iron complexes release iron in the acidic environment of the proximal tubules, and the divalent iron ions can reduce hydrogen peroxide to hydroxyl radicals, leading to lipid peroxidation reactions and damaging the tubulointerstitium. After the protein highly fills the organelles and cytoplasm of the proximal tubular epithelial cells, the cells are activated and subsequently release various inflammatory mediators, such as monocyte chemotactic protein through nuclear factor κB, endothelin, activated cells produce integrin αVβ5, and osteopontin, etc. These factors stimulate the proximal tubular epithelial cells to synthesize matrix, exert chemotactic and adhesion factor activities, and exacerbate tubulointerstitial damage. Moreover, after a large amount of filtered proteins are reabsorbed, lysosomes in the cells will release various enzymes to degrade these proteins. This process may damage the proximal tubular epithelial cells themselves, causing cell destruction and basement membrane rupture, leading to the leakage of tubular lumen and cell contents, and triggering interstitial inflammatory reactions. Various measures to reduce urinary protein levels will delay the progression of renal damage and protect renal function.

　　III. Hyperlipidemia and Lipuria

　　Hyperlipidemia may occur during the recurrence phase of MCN. Even after the condition is relieved and hormones are discontinued, hyperlipidemia can persist for a period of time, leading to a series of disturbances in blood lipids (Table 4). The loss of high-density lipoprotein and substances of unknown nature in urine, as well as the decrease in the colloid osmotic pressure of the portal vein of the liver, causes an increase in the synthesis of β-lipoprotein, leading to hyperlipidemia. MCN is always accompanied by hypercholesterolemia. Hyperlipidemia occurs only when the plasma albumin is significantly reduced. Patients with kidney disease often have an increase in low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL), and sometimes intermediate-density lipoprotein (IDL) is also increased. The level of high-density lipoprotein (HDL) can be normal, but the lipid and apolipoprotein components contained are not normal. Or due to the reduction of the activity of lecithin cholesterol acyltransferase (LCAT) caused by lipuria, it leads to the impairment of HDLs maturation. Hemolytic lecithin is generally combined with albumin, inhibiting LCAT, and LCAT is also lost in urine. Thus, the reduced activity of LCAT leads to the esterification of HDLs, a decrease in the transfer of cholesterol, an increase in free cholesterol, and a decrease in the activity of lipoprotein lipase. The HDL/LDL ratio decreases, and the content of lipified and non-lipified cholesterol in LDL and VLDL increases. The synthesis of cholesterol increases, and the concentration of cholesterol in plasma is inversely proportional to albumin and osmotic pressure, and positively correlated with the glomerular filtration rate of albumin in the kidney. The rate-limiting enzyme in the cholesterol biosynthesis process, 3-hydroxy-3-methylglutaryl-CoA reductase, is induced. Infusion of albumin and dextran can transiently increase osmotic pressure and reduce cholesterol levels. During the remission of MCN, cholesterol gradually returns to normal. Not all patients have hypertriglyceridemia. The synthesis of apolipoprotein A, B, and E increases. In experimental nephropathy, the mRNA content of these apolipoproteins increases. The ratio of triglycerides to albumin in chylomicrons and VLDLs increases. The clearance rate of peripheral tissues for chylomicrons, VLDLs, IDLs, and LDLs decreases. The conversion of VLDLs to LDLs is impaired. Due to the increase in inhibitors (free fatty acids) and the decrease in activators (glycosaminoglycans, ApoCⅡ), the activity of lipoprotein lipase decreases. Double-refractive fatty bodies appear in urine during lipuria, which may be epithelial cells or fatty casts containing cholesterol components.

　　Fourth, other

　　Water retention can cause a decrease in blood sodium concentration, long-term sodium restriction or acquired adrenal insufficiency can also lead to a decrease in blood sodium concentration. Hyperlipidemia can cause pseudo-hypochloremia. After the application of new experimental methods, pseudo-hypochloremia caused by hyperlipidemia is no longer common. Since platelets can release potassium ions in vitro, an increase in platelet count can also cause pseudo-hyperkalemia. Due to hyperparathyroidism and bone disease, some patients have an ionized calcium concentration that is not proportional to hypoalbuminemia. The transport of 25(OH) vitamin D3 concentration can be normal or decreased. The occurrence of MCN bone disease is related to the vitamin D3-parathyroid (PTH) axis, age of onset, duration of disease, frequency of recurrence, and use of hormones. Plasma thyroid-binding globulin (FBG), thyroxine (thyroxine, T4), triiodothyronine (T3), and thyroid-stimulating hormone (FSH) are generally normal in adult NS patients. Children with NS lose more TBG and T3 than adults, and the concentration of plasma TBG and T4 decreases, the concentration of TSH increases, but hypothyroidism does not occur. One-third of children may experience transiently elevated blood urea nitrogen and creatinine, decreased blood volume, which can cause an increase in hematocrit, normal white blood cells and classification, mild increase in platelets, and a slight decrease in glomerular filtration rate (GFR), which is generally 20% to 30% lower than normal.

　　Fifth, renal biopsy:

　　1. Light microscopy

　　Under light microscopy, renal glomeruli rarely show morphological changes, the capillary lumen can expand, but there is no cell proliferation. In cases with recurrent episodes, there may be a slight increase in mesangial cells and matrix, occasionally individual atrophic glomeruli, but without obvious tubular atrophy, interstitial or vascular changes are not prominent. Double-refractive fat droplets can be seen in the tubular epithelial cells, and vacuolar changes can be seen in the proximal tubular epithelial cells.

　　2. Electron microscopy

　　Under the electron microscope, the renal parenchyma shows widespread swelling of the epithelial cells, the foot processes lose their original scattered latticework and fuse into sheets, the filter pores are obstructed, accompanied by vacuolation of the epithelial cells, morphological changes of microvilli, increased protein absorption droplets, and lysosomes. These changes are not unique to the disease and can completely return to normal during the remission period. Research has confirmed that the disappearance or fusion of podocytes is the only glomerular pathological change in this disease, and this change is caused by the large amount of protein filtration. If a large amount of protein that can pass through the basement membrane is injected into animals, the same foot process changes can also be produced. In other types of kidney diseases with large amounts of proteinuria, the disappearance of foot processes can also be seen.

　　3. Immunofluorescence

　　Immunofluorescence examination is mostly negative, occasionally IgG and/or IgM, IgA, and C3 deposition is seen, which is more common in a few cases of mesangial expansion, while clinical manifestations indicate patients with hormone-dependent types.

　　1. Salt restriction:It should be determined according to the degree of edema of the patient. For those with severe edema, salt should be avoided; for those with reduced edema but not completely resolved, a low-salt diet (about 3 grams per day) should be followed. When the edema subsides and plasma protein returns to near normal, ordinary diet can be provided.

　　2. Protein intake:Nephrotic syndrome has a large amount of proteinuria, and hypoproteinemia often causes a decrease in colloid osmotic pressure, making edema stubborn and difficult to resolve. The body's resistance also decreases accordingly. Therefore, in the early stage of nephrotic syndrome, without renal failure, it is necessary to ensure that adults have an intake of approximately 0.7 to 1.0 grams of protein per kilogram of body weight per day to help alleviate hypoproteinemia and the complications that follow.

　　3. Fat:Patients with nephrotic syndrome often have hyperlipidemia. For patients with minimal change nephrotic syndrome, since they can improve in a short period of time, there is no restriction on fat intake; for patients with membranous nephropathy and other refractory nephrotic syndrome, long-term hyperlipidemia can cause atherosclerosis, so it is necessary to limit the intake of foods rich in animal fat, such as trotters, fatty meat, and foods rich in animal fat.

　　4. Intake of vitamins, calcium, and trace elements:In patients with nephrotic syndrome, due to the increased permeability of the glomerular basement membrane, in addition to the loss of protein in the urine, certain elements and hormones bound to protein can also be lost, which can indirectly cause a deficiency of calcium, magnesium, and zinc, etc. For this, drugs or food supplements can be used.

　　First, treatment

　　The goal of this disease treatment is to induce remission as soon as possible, reduce the adverse reactions of drugs, that is, to use the dose of drugs that produces the least adverse reactions, and try to maintain the remission state of the patient for a longer period of time. The use of corticosteroids is effective in more than 90% of patients, and the proteinuria gradually resolves and disappears, and clinical symptoms are alleviated within 7 to 28 days of the treatment course. Patients in the acute phase should be treated in the hospital. Follow-up visits should be conducted multiple times after discharge. The potential adverse reactions of hormones, such as weight gain, acne, slow growth, hair growth, hypertension, and changes in behavior and habits, should be clearly explained to the patients and their families.

　　1. General treatment

　　(1)Rest and activity: During the acute phase, bed rest should be the main approach. Bed rest can increase renal blood flow, which is beneficial for diuresis and prevents cross-infection. Appropriate bed activities should be maintained to prevent the formation of vascular thrombosis. After the condition improves, activities can be gradually increased, which is beneficial for reducing complications and lowering blood lipids. If urinary protein increases after activity (proteinuria after activity is often seen during the recovery period), then the activity should be reduced.

　　(2)Dietary treatment: Patients often have gastrointestinal edema and ascites, which affect digestion and absorption. Easy-to-digest, light, and semi-liquid foods should be consumed. Low-salt diet should be followed during edema. Daily salt intake should be controlled at 2 to 3 grams, and preserved foods should be avoided. The daily intake of sodium should be controlled at 1 to 2 grams to help alleviate edema and reduce the risk of hypertension. In the early and extreme stages of MCN, a normal amount of high-quality protein diet of 1 to 1.5 g/(kg·d) should be provided, and sufficient calories should be ensured to help alleviate hypoproteinemia and some associated complications. Due to the increased glomerular hyperfiltration caused by high-protein diet, it is easy to exacerbate the progression of kidney lesions, so it is generally no longer recommended to use this method at present.

　　Chronic patients should consume high-quality low-protein diet, with a protein intake of 0.65g/kg per day. If there is azotemia, the protein intake should be further reduced. The intake of fat should be controlled, and the cholesterol content in the diet should be low, with a high content of unsaturated fatty acids and fish oil, as well as soluble fiber such as oatmeal and rice bran, which is beneficial for lowering blood lipids. For patients with persistent proteinuria and hyperlipidemia, consideration should be given to the administration of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors (HMG-CoA reductase inhibitors).

　　Dietary control and drug treatment can reduce the risk of cardiovascular complications, especially for those with risk factors for ischemic heart disease. Appropriate supplementation of trace elements, such as copper, zinc, and iron, can be chosen for severe anorexia, with Chinese herbal medicine for spleen and dampness, digestion and stomach treatment. If there is significant hyperphagia, the intake of calories should be controlled to avoid excessive obesity. To prevent the side effects of hormones on bones, 1500mg of calcium and 400-800U of vitamin D (from diet and additional supplementation) should be consumed daily. Children should be adjusted appropriately according to age. In addition, for adults who have been using hormones for a long time, bone mineral density should be checked, and hormone replacement therapy (such as calcitonin) should be given if necessary.

　　After general treatment, including rest, diet, and bed rest, if diuresis and edema are not significant after one week, diuretics can be added. For severe cases, low molecular weight dextran or mannitol can be used, and human serum albumin should be used as little as possible. Repeated use of human serum albumin can cause tubular damage and lead to recurrent idiopathic nephrotic syndrome, increasing the recurrence rate of refractory nephropathy. In addition, for patients with obvious hypercoagulable states, anticoagulant therapy can be adopted, including heparin, dipyridamole (Pantoprazole), and compound salvia miltiorrhiza, etc.

　　(3) Diuretic therapy: The use of diuretics must be cautious, as it can easily cause a decrease in blood volume and exacerbation of azotemia. Generally, thiazide diuretics can be given, such as hydrochlorothiazide (dihydrochlorothiazide) 25-50mg, 2-3 times a day. If the effect is not good, potassium-sparing diuretics can be added, such as spironolactone (Antisterone), amiloride, etc. If the effect is still not good, loop diuretics can be changed, generally with furosemide 20-120mg/d, or bumetanide (Bumetanide) 1-5mg/d (the effect is 40 times that of furosemide at the same dose), taken orally or by intravenous injection in divided doses. For severe edema, osmotic diuretics should be given, commonly with sodium-free dextran 40 (low molecular weight dextran) or hydroxyethyl starch plasma substitute (706 plasma substitute) 250-500ml intravenously, once every other day. This drug, in combination with loop diuretics, has a good effect. However, for patients with oliguria (urine output

　　2. Special treatment

　　(1) Glucocorticoids: Glucocorticoid therapy for minimal change nephrotic syndrome is effective in the vast majority of patients, with a rapid response, but it is prone to recurrence. To reduce recurrence, the initial dose should be sufficient, the induction period should be long, the reduction in dose should be slow, and the reduction in dose should be small. The commonly used hormone treatment plan is a medium to long-term treatment plan, and this plan is often used in the initial treatment.

　　Glucocorticoids are the basic drugs for the treatment of minimal change glomerulonephritis, although the drug has adverse reactions, it cannot cure the disease, but for initial patients, it is still the first choice of medicine. The general principles and regimens for the use of hormones are:

　　① Starting with full dose: That is, at the beginning of treatment, the daily treatment dose should be large, and the commonly used drug is prednisone (Prednisone), with a pediatric dose of 60mg/(m2·d) or 1mg/(kg·d) (maximum dose 80mg/d), taken orally in 3 to 4 divided doses, for 4 to 6 weeks, and may be extended to 8 to 12 weeks if necessary. Another regimen is to take the above dose for 4 weeks, then change to 40mg/(m2·d), and continue for another 4 weeks; another regimen is to take the above dose once daily in the morning until the proteinuria turns negative for 3 days, if 4 weeks of treatment are ineffective, consider hormone resistance, and if the efficacy is satisfactory, the intermittent medication method can be transferred.

　　② Gradual dose reduction: After adequate treatment, the dose is gradually reduced by 10% every 1 to 2 weeks, and when the dose is reduced to about 20mg/d, symptoms are prone to recurrence, so the dose reduction should be slower.

　　③ Long-term maintenance: During this period, the minimum dose of prednisone (Prednisone) is usually 10mg/d, maintained for half a year to 1 year or even longer. Hormone administration can be taken as a single dose per day or every other day during the maintenance period, to reduce the adverse reactions of the drug.

　　According to the patient's response to hormones, they can be divided into three types: 'hormone-sensitive' (i.e., symptoms relieved within 8 weeks of medication), 'hormone-dependent', 'relapse during dose reduction', and 'hormone-resistant' (ineffective to hormone treatment). The treatment measures for each type are different. The use of high-dose hormone pulse therapy can quickly and completely inhibit the activity of some enzymes and make hormone-specific receptors reach saturation, exerting the maximum anti-inflammatory effect of hormones in a short period of time; on the other hand, the immunosuppressive and diuretic effects of high-dose hormones are generally more pronounced than those of conventional doses, so they can be used to treat refractory nephrotic syndrome that is ineffective to conventional hormones, and some patients' nephritis can be relieved. The most commonly used clinical treatment plan for idiopathic membranous nephropathy is the treatment plan proposed by the Italian scholar Ponticelli.

　　If the side effects of hormones are significant, it is more appropriate to follow the methylprednisolone (Methylprednisone) pulse therapy with low-dose hormone therapy than long-term high-dose hormone therapy. However, its therapeutic effect is generally not as good as that of conventional-dose hormone therapy. The reduction in medication should be conducted during urinalysis.

　　Another regimen is prednisone (Prednisone) 60mg/(m2·d), up to 80mg/d, taken once daily for 4 weeks; followed by prednisone (Prednisone) 40mg/(m2·d), taken for 3 days out of every 7 days, then maintained for another 4 weeks. The European Collaborative Group (APN) suggests that the second 4-week treatment regimen be given every other day, which may be more effective in preventing recurrence. These two regimens were tested in a randomized trial involving 48% of patients in group 1 with recurrence, and patients receiving prednisone (Prednisone) treatment every other day had a 50% reduction in the risk of recurrence per year compared to those receiving 3 days of treatment within 7 days. This difference only occurred within the first 6 months, and the recurrence rate was similar thereafter. However, it still indicates that the regimen of alternate-day administration for the second course is superior.

　　APN has also tried a new long-term initial hormone treatment regimen, which is to take prednisone (Prednisone) once a day for 6 consecutive weeks; followed by prednisone (Prednisone) once every other day for another 6 weeks. Compared with the standard regimen, this long-term treatment regimen has been proven to maintain remission in patients, which is twice as effective as conventional treatment, and recurrence is significantly reduced. Even if the total dose of initial hormone treatment is greater than the conventional regimen, the side effects of hormones have not increased. Because recurrence is reduced, the subsequent dose of hormones is also reduced. The average time from the start of treatment to remission for most patients is 2 weeks, and after 2 weeks of treatment, urinary protein can turn negative. By the end of 8 weeks, about 95% of patients can achieve remission. Children are prone to recurrence during the treatment of this disease, about 80% of patients have recurrent episodes, but they are still effective for hormone treatment. Some patients may become dependent on hormones. Research has found that children with complete remission and remission lasting for 6 months after the initial 8 weeks of conventional treatment have rare recurrence cases. However, recurrence rates are expected to be high in the following 3 years for cases that recur within 6 months. Children who do not remit after 8 weeks of treatment have 21% developing into renal insufficiency; therefore, for children with poor treatment response, intensive treatment should be carried out to reduce the recurrence rate. In summary, the recurrence rate of this disease decreases with the increase of patient age, and most patients no longer recur after entering puberty. Recurrence within the first 3 months of initial treatment is more common in patients with hormone dependence and resistance.

　　40% of adult patients with this disease can naturally remit, and patients with no symptoms can be treated with a low-sodium diet and diuretics. If general symptomatic treatment is ineffective, prednisone (Prednisone) 60-80mg/d can be administered in a single dose, or 100-200mg/d, once every other day. The remission rate for daily therapy for 8 weeks is 60%, and for 24 weeks is 80%. Adults may need 10-16 weeks of treatment to enter the remission period. Patients who receive daily medication for 2-3 months are more prone to recurrence than those who receive treatment every other day for 1 year. Therefore, those who take daily medication have a higher cumulative dose. Gradually discontinuing medication helps prevent recurrence and is also conducive to the production of endogenous hormones. 10%-15% of adult patients may be considered as resistant to hormone therapy if hormone treatment is ineffective after 16 weeks. Generally, as age increases, the proportion of patients with ineffective hormone treatment also increases. For patients with recurrent episodes, it is best to increase the dose, such as returning to the initial dose or changing from every other day to daily medication if the condition recurs after remission from hormone treatment or during dose reduction. Refractory nephrotic syndrome can be treated with high-dose, long-term intermittent therapy, with prednisone (Prednisone) 1.5-2.0mg/kg taken once every other day in the morning, for a course of 1/2 to 3 years, then gradually reducing the dose to 0.5-1mg/kg every other day, lasting for 3-5 years, and in some cases, nearly 10 years of the full course may achieve clinical complete or partial remission.

　　Regarding the effectiveness of different uses of steroids and their adverse reactions, it is generally believed that the effectiveness is: taking several times a day > taking all at once a day > taking every other day. The adverse reactions are similar: taking several times a day > taking all at once a day > taking every other day. Gastrointestinal adverse reactions are smaller when taken in several doses. The intensity of the first hormone treatment for minimal change disease determines the subsequent relapse rate. The optimal dose of the first dose of hormone should consider its cumulative toxicity, relapse rate, and re-treatment rate.

　　In the long-term hormone treatment, attention should be paid to the occurrence of side effects such as Cushing's syndrome, negative nitrogen balance, osteoporosis, diabetes, water and sodium retention, gastrointestinal symptoms, neurological and psychiatric symptoms, and the induction or spread of infection. There is also an antagonistic effect on growth hormone, affecting the growth and development of children.

　　(2) Cyclophosphamide (CTX) or busulfan: This class of alkylating drugs can induce a longer or complete remission in recurrent nephritis and reduce the risk of recurrence. However, it has significant side effects, such as leukopenia, alopecia, gastrointestinal reactions, hemorrhagic cystitis, and gonadal damage. Gonadal toxicity can cause male infertility, and reduced body resistance is prone to induce tumors. If patients have no history of chickenpox infection, they are also prone to develop chickenpox. Therefore, it is necessary to be cautious in the course and dose. If it is necessary to repeat the use, at least a one-year interval is required.

　　① Cyclophosphamide (CTX): It is a commonly used clinical drug, generally implemented on the basis of prednisone (steroid) administration. This drug is suitable for patients with relapse or frequent relapse and hormone dependence. The dose is 2mg/(kg·d), taken orally for 8 to 12 weeks, with a total dose not exceeding 0.2 to 0.25g/kg. For hormone-dependent patients, it is recommended to extend the course of treatment to 12 weeks. Grlkas et al. reported the use of pulse therapy, with a dose of 0.5 to 0.75g/m2 each time, once a month, for 6 to 12 times as a course of treatment. Hydration therapy should be provided on the day of treatment to ensure sufficient urine output of cyclophosphamide (CTX) metabolites, and appropriate sodium chloride should be supplemented during hydration therapy. There are reports that if the course of treatment reaches 8 to 12 weeks, at least 75% of patients can maintain non-proteinuria for at least 2 years.

　　Patients with this disease, especially children, 10% to 20% will experience 3 to 4 hormone treatments; about half of the children will frequently relapse or become hormone-dependent. The repeated or prolonged use of hormones brings significant side effects to frequent relapsers or hormone-dependent individuals, such as growth delay, osteoporosis, obesity, and cataracts. Research has found that cyclophosphamide (CTX) is effective for children with frequently relapsing minimal change disease. The combined use of cyclophosphamide (CTX) and prednisone (steroid) is superior to the treatment with prednisone (steroid) alone. In a prospective study, the cumulative remission rate of hormone-dependent patients receiving cyclophosphamide (CTX) treatment for 12 weeks was 67%, while the cumulative remission rate of those receiving treatment for 8 weeks was only 22%. The children receiving cyclophosphamide (CTX) treatment for 12 weeks were older than those receiving treatment for 8 weeks, and it may be this age difference that leads to better prognosis for the former. Currently, there is no conclusion on this.

　　② Busulfan: It has a definite curative effect on preventing recurrence and extending remission. The side effects include leukopenia and significant gonadal damage, so it is better to use it in low doses. The daily dose is 0.15 mg/kg, taken for 8 weeks, with a total dose not exceeding 10 mg/kg. After 8 weeks of using this drug, a more stable remission period is generally obtained than with cyclophosphamide (CTX), and it is even effective in some patients resistant to cyclophosphamide (CTX). Nitrogen mustard has a mild effect on gonadal suppression, and the method of use is to administer it by rapid intravenous infusion or slow intravenous push every other day. The initial dose is 1 mg or 2 mg, and the dose is increased by 1 mg each time, up to a maximum of 0.1 mg/kg, with 10 to 20 times as one course. The side effects are mainly gastrointestinal reactions, and sometimes phlebitis at the injection site occurs, so it should be given through a larger vein.

　　(3) Cyclosporine (CsA): It is suitable for patients with hormone-dependent and hormone-resistant types, with a dose of 6 mg/(kg·d) for children and 5 mg/(kg·d) for adults. For cases with frequent recurrence and hormone dependence, the initial dose can also be 0.1 to 0.15 g/m2 (5 to 7 mg/kg) per day, then adjust the dose to maintain a blood concentration of 100 to 200 mg/L, reduce the dose by 25% every 2 months, determine the minimum effective dose, and gradually stop the drug after two years. It can also be used with low-dose hormones or alone. Special attention should be paid to its nephrotoxicity during use, as the drug can cause changes in serum creatinine and renal interstitium, liver function damage, hypertension, hirsutism, gingival hyperplasia, hyperkalemia, and hypomagnesemia, among other side effects.

　　The treatment with cyclosporine (CsA) can reduce recurrence and decrease the total dose of hormones, which was discovered in research in the late 1980s. Later non-randomized studies also found that complete remission of hormone-dependent and frequently recurrent nephrotic syndrome could be achieved, so some children could discontinue hormone use.

　　For hormone-dependent nephropathy, cyclosporine (CsA) is less effective in extending remission than alkylating agents. Children and adults were randomly assigned to two groups receiving cyclophosphamide (CTX) and cyclosporine (CsA) treatment, both of which could relieve hormone-dependent and frequently recurrent nephropathy, with a longer remission period in the cyclophosphamide (CTX) group.

　　In a recent non-randomized retrospective study, it was found that in children with hormone-dependent and hormone-resistant nephropathy, especially those with certain focal segmental sclerosis, the use of cyclosporine (CsA) with an initial dose of 2.5 to 5.0 mg/(kg·d) has a good therapeutic effect. About half of the hormone-dependent patients and about 1/4 of the hormone-resistant patients recover their response to hormone treatment. After 7.5 years of hormone-dependent nephropathy and 5 years of hormone-resistant nephropathy, there is no significant change in serum creatinine, but not including some patients with focal segmental sclerosis. A small number of patients found interstitial fibrosis and tubular atrophy in renal biopsy, indicating the toxicity of cyclosporine (CsA), but there was no change in renal function. Cyclosporine (CsA) is an effective adjuvant treatment drug, but it has long-term renal toxicity.

　　Another randomized controlled trial on patients with hormone-dependent nephrotic syndrome and frequent recurrence compared the efficacy of cyclophosphamide (CTX) 2.5mg/(kg·d) for 8 weeks and cyclosporine (CsA) 6mg/(kg·d) (for adults) for 12 months. Cyclophosphamide (CTX) can very effectively prolong the remission period, with 63% of patients still in remission after 2 years of treatment, while only 25% of patients who received cyclosporine (CsA) therapy were in remission. It is also important to note the long-term nephrotoxicity of cyclosporine (CsA), especially in adults, where patients with renal tubular interstitial lesions who receive cyclosporine (CsA) treatment have a faster progression to end-stage renal failure.

　　(4) Levamisole: Levamisole, an antiparasitic drug, has immunomodulatory effects and has been used to treat diseases such as cancer. Levamisole alone or in combination with other drugs can increase the remission rate in children with minimal change disease. Levamisole has good tolerance, and side effects include neutropenia, rash, and liver damage. In recent years, the application of this drug in the treatment of nephritis has been rarely reported.

　　(5) Treatment of hormone-resistant nephritis: For hormone-resistant minimal change disease, re-biopsy should be performed to exclude focal segmental sclerosis, and cyclophosphamide (CTX) 2mg/(kg·d) should be administered continuously for 12 weeks, or cyclosporine (CsA) 6mg/(kg·d) (for children), 5mg/(kg·d) (for adults), but the duration of treatment is still uncertain.

　　Minimal change disease with hormone resistance is the most difficult to treat. These patients not only suffer from the toxicity of hormones but also increase the incidence of complications such as sepsis, malnutrition, delayed growth and development, and thrombosis due to the failure of nephritis to remit. In addition, this type of patient also increases the possibility of renal damage progressing to end-stage renal disease.

　　For patients with recurrent, hormone-dependent, and hormone-resistant minimal change disease, alkylating agent therapy should be the first choice. Cyclosporine (CsA) should be reserved for use after the failure of alkylating agent therapy. Especially for patients who cannot tolerate the side effects of hormones or those who are not suitable for hormone use during adolescence and growth. Due to the limited experience with cyclosporine (CsA), it is still difficult to guarantee that there will be no recurrence, and many children have recurred when the cyclosporine (CsA) was withdrawn. In addition, chronic CsA nephrotoxicity that is not proportional to the increase in serum creatinine requires repeated renal biopsies. Patients who have been treated with cyclosporine (CsA) for a long time should expand their blood volume, try to reduce the dose, and strictly control the concentration of cyclosporine (CsA), and nephrotoxicity may be avoided.

　　Another method is to add traditional Chinese medicine such as Astragalus membranaceus and Panax notoginseng to the long-term therapy of prednisone (prednisone) while using it. The dosage of Astragalus membranaceus should be large when used. The use of traditional Chinese medicine as an adjuvant therapy has no side effects and can improve efficacy. Studies have shown that Astragalus membranaceus and Panax notoginseng can correct the low serum cortisol levels in patients with refractory insulinoma, prevent side effects during hormone therapy; correct the abnormal proliferation and function of T lymphocytes; restore the body's immune regulatory function to glucocorticoids, so as to accelerate the relief of symptoms such as edema and diuresis, shorten the time to remission of nephritis, and at the same time, relieve nephritis in some cases with hormone resistance.

　　3. Anticoagulation Therapy

　　Such drugs can improve coagulation in the glomerular capillaries and are the main drugs in anticoagulant therapy; they have a suppressive effect on complement activity and kallikrein by inhibiting antithrombin and antithrombocyte aggregation, play a role in reducing edema and diuresis, and improve renal function by improving microcirculation. In addition to anticoagulation, they can also achieve the effect of fibrinolysis. Heparin 100 to 200U/kg is administered intravenously daily, and warfarin 1 to 2mg/d is taken orally for 6 months after 4 months; attention should be paid to the monitoring of prothrombin time, and it should be controlled within 2 times. Low-dose heparin subcutaneous injection can also achieve a good effect. Low molecular weight heparin calcium (nadroparin calcium), dalteparin sodium), with a long half-life, can be administered subcutaneously, is convenient to use, and requires a single subcutaneous dose per day. The drug has good efficacy and low bleeding risk, opening up a new path for anticoagulant therapy. Dipyridamole (Persantin) inhibits platelet aggregation and has the effects of antithrombosis and improving glomerular microcirculation, and can be used conventionally.

　　(1) Thrombolytic Therapy: Thrombolytic drugs can completely and rapidly dissolve thrombi. When renal venous thrombosis occurs, warfarin (sodium phenylbutyrate) can be administered first, followed by heparin intravenous therapy.

　　(2) Infection and Immunity: A PPD (tuberculin) test must be performed before the application of hormones. If there are no varicella antibodies in the patient's plasma, varicella-zoster immune globulin should be injected 96 hours before the administration of high-dose prednisone (>20mg/m2) or alkylating agents, with a dose of 125 to 625U/10kg. If the patient develops chickenpox or shingles while using high-dose hormones or alkylating agents, acyclovir should be administered. If the patient comes into contact with a measles patient, the immune status of the NS patient should be checked, and isolation and injection of gamma-globulin should be provided. If peritonitis is suspected, penicillin or cephalosporin treatment should be given. Some believe that vaccination can promote the relief of the disease, such as giving freeze-dried BCG vaccine. However, further research is needed on this aspect of treatment. Children receiving high-dose prednisone (>20mg/m2) or alkylating agents daily should not be vaccinated with live vaccines. For the siblings or family members of the child, it is also not recommended to give the oral polio vaccine. For adults and MCN patients over 2 years old, pneumococcal and Haemophilus influenzae type b vaccines can be administered during the period without hormone use. Because, although the pneumococcal and antibody levels are high at the beginning, 50% of the patients have their antibody levels drop to a level insufficient to exert protective effects after one year. There is no standard for intravenous use of immunoglobulins. Human blood gamma-globulin intravenous injection can be used when the adult IgG is below 6g/L, there are low natural antibodies, poor response to vaccination, and no protective effect against the pathogenic bacteria of infection.

　　II. Prognosis

　　This disease is characterized by spontaneous remission and recurrent attacks, with a high mortality rate before the use of hormones and antibiotics. Currently, the 10-year survival rate can reach 95%, but hormones cannot change the process of lesion development. Patients who only receive general supportive therapy have a spontaneous remission rate of 10% to 75%, while antibiotics effectively reduce the disability rate of patients. Hormonal treatment induces remission and prevents recurrence. A few children die from MCN itself or from complications of treatment, and most patients have a good prognosis. Elderly patients over 60 years of age have a poor prognosis, and the causes of death include thrombosis, sepsis, anuria, and cardiovascular diseases. The risk of recurrence decreases with age. The recurrence rate of children who have the disease before the age of 6 is 5.5% before the age of 10, and the frequency of recurrence in adults decreases. Adults receiving CTX treatment have a lower recurrence rate, among whom some patients can be relieved for more than 10 years, and about 5% of cases progress to end-stage kidney disease.