minimal change nephropathy
Introduction
Introduction to minimally pathological nephropathy Minimalchangenephrosis (MCN), formerly known as lipoid nephrosis. The disease is a group of glomeruli under light microscopy is normal, proximal tubule epithelial cell steatosis, electron microscopic glomerular epithelial podocyte process protrusion fusion and disappearance. Primary glomerular disease characterized by no mesangial cell proliferation matrix broadening and immunoprecipitation. basic knowledge The proportion of illness: 0.002% - 0.004% Susceptible people: children Mode of infection: non-infectious Complications: malnutrition thrombosis hypokalemia peritonitis pleurisy venous thrombosis renal failure hyperlipidemia coronary heart disease arteriosclerosis acute renal failure renal diabetic
Cause
Causes of minimally pathological nephropathy
Virus infection (25%):
MCN can be divided into primary and secondary types. The primary cause is unknown. The onset may be related to infection and allergic reaction. It is now considered to be an immune system mediated by abnormal T-lymphocyte cloning. Reaction-related diseases.
Allergic factors (45%):
Secondary onset may be associated with antigens and major histocompatibility complexes in humans. Patients often have a significantly higher incidence of specific hypersensitivity such as allergic rhinitis, urticaria and other allergic diseases. Secondary common factors are allergens such as pollen biotoxin drugs (penicillamine, non-steroidal anti-inflammatory drugs) and lymphoma and other radiation treatments can also trigger the possibility of MCN related to this disease.
Pathogenesis:
The pathogenesis of MCN remains unclear and is generally thought to be related to immune mechanisms, but other factors may also be involved. It has been suggested that circulating glomerular toxic lymphokines produced by abnormal T-lymphocyte populations cause MCN. Because MCN patients can be relieved after suffering from measles. Patients are prone to streptococcal infections and are sensitive to cyclophosphamide and glucocorticoid treatment.
Prevention
Minimally diseased kidney disease prevention
The key to the prevention of this disease is to strengthen exercise, enhance physical fitness, improve the body's immunity, children should pay attention to reduce to public places, avoid cross-infection, if there is infection, timely use effective, sensitive and less nephrotoxic antibiotic treatment, if any Obvious infection should be removed to prevent infection from spreading. At the same time, it is necessary to avoid exposure to various toxic and harmful substances and reduce the occurrence of allergic diseases. Patients already suffering from the disease should actively treat the primary disease and control the occurrence and development of complications. Complications that have occurred should be treated aggressively, and efforts should be made to reverse or slow down the disease.
Complication
Minimal lesion nephropathy complications Complications, malnutrition, thrombosis, hypokalemia, peritonitis, pleurisy, venous thrombosis, renal failure, hyperlipidemia, coronary heart disease, arteriosclerosis, acute renal failure, renal glucosuria
Long-term hypoproteinemia, patients with malnutrition, secondary infections; hypercoagulable state can lead to thrombosis; inappropriate diuretic and forbidden salt can occur low sodium or hypokalemia.
Infection
Before the advent of antibiotics, infection is a common cause of death in this disease, especially in pediatric patients. The pathogens are mainly pneumococci, hemolytic streptococcus and other causes of peritonitis, pleurisy, subcutaneous infection, respiratory infections, etc., can also cause urinary tract infections, especially In patients receiving corticosteroids and/or immunosuppressive drugs, bacterial infections are often aggravated, and the sensitivity to viral infections is also increased. For example, herpes virus and measles virus are susceptible, and the disease is prone to infection: 1 in urine Loss of large amount of IgG; 2 immune abnormalities: the disease may have abnormalities of humoral immunity and cellular immune function, lymphocyte synthesis of IgG decreased, T cell-mediated IgM conversion synthesis of IgG decreased, B factor (complement replacement pathway component) lack of immune Abnormal conditioning, T cell activity is inhibited; 3 malnutrition; 4 low transferrin and hypozincemia: There are tests to prove that transferrin carries zinc plays an important role in lymphocyte function, and hypozincemia can cause zinc dependence Insufficient production of thymus hormone can cause the body's resistance to decline.
2. Thrombosis
Embolism complications Arterial and venous thrombosis is common in patients with nephrotic syndrome, such as pulmonary thromboembolism and thrombosis, peripheral arterial and venous thrombosis, renal vein thrombosis is mostly subclinical, but severe proteinuria can also occur. Hematuria and even renal failure, femoral artery thromboembolism is one of the acute state of the disease. If it is not treated in time, it can lead to acromion necrosis. The occurrence of this disease is accompanied by low-volume blood concentration, increased blood viscosity, strong diuretics and Long-term use of a large number of glucocorticoids and other related to the hypercoagulable state.
3. Hyperlipidemia
Long-term hyperlipidemia, especially elevated LDH and decreased HDL, may cause coronary heart disease and arteriosclerosis. Studies have confirmed that low-density lipoprotein receptors are present on mesangial cells, and low-density lipoprotein receptors can cause mesangial cell proliferation. Increased mesangial matrix, thereby aggravating glomerular progressive sclerosis.
4. Renal function damage
(1) acute renal dysfunction: patients with severe blood volume decline in clinical manifestations of oliguria, no urine, decreased urinary sodium, cold limbs, decreased blood pressure, small pulse pressure, increased hematocrit and other acute renal failure The characteristic is that it is prerenal oliguria and is easily corrected by plasma or plasma protein.
Sometimes in patients with large amounts of proteinuria and no reduction in blood volume, acute renal failure can occur, with a significant decrease in glomerular filtration rate, interstitial edema compression of the renal tubules, and proteinuria-type obstruction of the renal tubules.
(2) renal tubular dysfunction: the basic diseases causing nephrotic syndrome can occur renal tubular damage, a large number of urinary protein-induced tubular atrophy and interstitial fibrosis, especially near convoluted tubule dysfunction, manifested as hypokalemia Symptoms, renal glucosuria, amino aciduria, acidosis, etc.
Symptom
Symptoms of minimally pathological nephropathy Common symptoms Ascites oliguria Proteinuria Hypertension Nitrogenemia Nephrotic syndrome Hypoproteinemia Renal tubule collapse Hypotension Urine protein
The incidence of minimally pathological nephropathy is rapid, often with edema as the initial manifestation, 50% of patients have pre-infection (more common in adults), some patients have a history of bee stings and drug allergy, patients often show nephropathy regardless of age Syndrome, especially in young children, MCN accounts for 63% to 93% of nephrotic syndrome, and about one-third of adult cases have microscopic hematuria. When blood volume is too low, it can cause acute renal failure.
Edema: obvious edema is often the first manifestation of onset. Most children have facial edema. Adults have obvious lower extremity edema, accompanied by subarachnoid edema (the white bed is white), scrotal edema, pleural effusion, and ascites are common. In the case of massive ascites or pulmonary edema, the patient has symptoms such as difficulty breathing and respiratory distress.
Proteinuria: Highly selective proteinuria, mainly albumin, urine protein can be as much as 10g per day, and urine protein electrophoresis is a selective medium molecular protein band.
Hypoproteinemia: Plasma albumin is often significantly decreased, up to 10g/L, and hypoproteinemia is closely related to protein loss. Albumin and gamma globulin are decreased by serum protein electrophoresis, and 1 globulin is normal or mild. Increased, while 2 and globulin increased, immunoglobulin IgG, IgA decreased, IgM, IgE increased, due to changes in plasma protein content and lipid changes, the patient's erythrocyte sedimentation rate was significantly accelerated (more than 70mm / h), in addition, Hypoproteinemia can cause a decrease in blood calcium, a decrease in blood albumin of 10 g/L, and a decrease in blood calcium of 8 mg/L, but rare clinical symptoms and no low phosphorus.
Hyperlipidemia: MCN patients may have disorder of lipid metabolism, plasma cholesterol and triglyceride are significantly elevated, serum may be chylomicron, patients with hyperlipidemia often have lipid urine, and pseudo-low sodium may also occur.
Hypertension, hypotension: Significant hypoproteinemia, patients with reduced circulating blood volume may have upright hypotension, weak pulse, etc., and some patients may have transient hypertension due to increased renin angiotensin activity.
Hematuria: Some patients may have microscopic hematuria (20% to 30%), mostly transient, rare gross hematuria.
Renal function: patients with normal renal function, early onset, due to increased renal blood flow, serum creatinine clearance rate increased transiently, with the increase in urine volume can quickly return to normal, edema and severe blood volume deficiency, due to kidney Increased internal urea circulation and increased protein catabolism can lead to a decrease in glomerular filtration rate (80% to 20% of normal), oliguria and pre-renal azotemia, but this phenomenon is Reversible, so does not affect the prognosis, individual patients, especially those older, may have renal insufficiency, the main reason and mandatory diuretic, severe interstitial edema leading to tubular collapse, and epithelial cell damage caused by glomerular filtration Decreased, due to blood concentration secondary to hypoproteinemia, patients with normal or increased hemoglobin and hematocrit, renal function caused by renal parenchymal lesions often accompanied by anemia.
Examine
Examination of minimally pathological nephropathy
Abnormal laboratory tests, mainly due to the loss of a large amount of protein in the urine and compensation after protein loss, is also a compensatory mechanism for complications such as hypercoagulable state secondary to loss.
Hypoproteinemia
The plasma albumin of patients with this disease is usually less than 25g / L, a few can reach below 10g / L, when the plasma albumin drops below 20g / L, the edema is more obvious, the plasma albumin concentration is the liver synthesis of albumin and albumin As a result of metabolism and loss from the gastrointestinal tract, the amount of MCN albumin is increased. It is speculated that after albumin leakage, it is reabsorbed by the proximal tubules and metabolized. Under normal circumstances, it acts as a sinusoidal colloid osmotic pressure and viscosity. In the reaction of decreased stagnation, the amount of albumin synthesized by the liver can be increased by 300%, about 12g/d, while the metabolic rate of albumin is increased, and the absolute metabolic rate is decreased. However, the rate of synthesis of albumin in the liver cannot keep up with the urine. The amount of protein lost is the sum of the kidney's metabolism of albumin, in part because of insufficient protein intake.
Serum protein electrophoresis showed increased 2 and globulin, 1 globulin was normal or increased, gamma globulin decreased or depends on primary disease, immunoglobulin IgG, IgA levels decreased significantly, IgM, IgE did not change or increased, complement C3, C1q, C8 can decrease; fibrinogen, II, VII, VIII and factor X increase, may be related to increased intrahepatic synthesis, antithrombin III (heparin-related factor) decreased, may be due to increased urine output As a result, protein C and protein S levels are normal or increased, but activity is decreased, which is related to the formation of hypercoagulable state, factors IX, XI, X II decrease, plasminogen, antiplasmin and 1 antitrypsin levels are also Decreased, urinary fibrin degradation products (FDP) mainly reflect glomerular permeability, not necessarily reflect glomerular coagulation, transport protein changes: trace metal binding protein in urine - ceruloplasmin, ferritin from urine Loss in the blood, the protein in the blood carrying important metal ions (iron, copper, zinc) decreased, the concentration of copper and iron decreased, the iron content in the red blood cells decreased, the iron deficiency small cell hypochromic anemia, 2 / 3 cycle Zinc and white eggs Combined, low albuminemia and loss of zinc from the urine can lead to a decrease in plasma zinc levels, a decrease in blood zinc, impeding growth, leading to impaired immune function and delayed wound healing, and important endocrine hormones (thyroxine, endothelin, Prostaglandin combined protein and active 25-hydroxyvitamin D3 (25-OH vitamin D3) binding protein decreased.
2. Proteinuria
For urine examination, the amount of urine protein can be roughly estimated by test strip method: + equivalent to 30 mg/dl, ( ) is equivalent to 100 mg/dl, ( ) is equivalent to 300 ml/dl, ( ) is equivalent to 1000 mg/dl, and IgG is used. The molecular weight of 170kD) and ferritin (molecular weight of 88kD) clearance ratio to determine its selectivity, the ratio <0.1 for selective proteinuria, suggesting that small molecular weight proteins are preferentially leaked, the ratio is >0.2, indicating the mitochondrial molecular barrier damage Obviously, the protein of macromolecules leaks out. Highly selective proteinuria is a characteristic of children's MCN. Adult patients overlap with other types of NS, and their value is inferior to children. In recent years, work has confirmed that protein selectivity is not positive. Clinical value, response to treatment, and judgment of prognosis have no guiding significance, so it has been used clinically. For glomerular permeability, although urinary retinal binding protein and 2 microglobulin are not specific. Sex, but in NS against hormones, the release of these two proteins in urine is higher than that of hormone-sensitive NS, and the increase in the amount of these two proteins in the urine is a sign of damage to the proximal tubules. Significant Renal parenchymal damage, which is not sensitive to the hormone, 23% of children MCN will appear microscopic hematuria.
In recent years, it has become a consensus that proteinuria, especially persistent large amount of proteinuria can aggravate kidney damage, but its pathogenesis has long been unclear. It has been emphasized that it has aggravated glomerular hyperfiltration and promoted glomerular sclerosis. It shows that it mainly accelerates the progression of renal damage by causing renal tubular-interstitial lesions. The proximal renal tubular epithelial cells can reabsorb the glomerular filtered proteins through the pinocytosis or receptor-binding pathway. Within, the complement component is activated by ammonia after it enters the cell, producing C3a, C5a and C5b-9, C3a and C5a chemokines. C5b-9 can be inserted into the membrane, stimulating the release of inflammatory mediator interleukin from proximal tubular epithelial cells. -1 and tumor necrosis factor-, and synthesize extracellular matrix fibronectin, causing tubulo-interstitial damage, filtered insulin-like growth factor-1 can enter the proximal tubular epithelial cells via receptor-mediated pathway Then, it stimulates the synthesis of extracellular matrix components collagen I and IV, which damages the tubule-interstitial. The fatty acid bound to albumin can be reabsorbed by the proximal renal tubular epithelial cells after filtration, and the lipid will be released again. In addition, the role of chemokines is exerted to damage the renal tubule-interstitial. The filtered transferrin-iron complex releases iron in the acidic environment of the proximal renal tubule, and the divalent iron ion can reduce the hydrogen peroxide to form hydroxyl free. Base, causing lipid peroxidation, damage to the tubule-interstitial, after the organelles of the proximal tubular epithelial cells and the cytoplasm reabsorbed proteins are highly filled, the proximal tubular epithelial cells are activated, thereby releasing a variety of Inflammatory mediators, such as monocyte-stimulating protein, endothelin, activated cells producing integrin V5 and osteonectin by nuclear factor-B, these factors stimulate the synthesis of matrix in proximal tubular epithelial cells, exerting chemokines and adhesion factors After aggravating tubular-interstitial damage, and a large number of filtered proteins are reabsorbed, intracellular lysosomes will release a variety of enzymes to degrade these proteins, which may damage the proximal tubular epithelial cells themselves, causing cell damage. And the basement membrane rupture, which in turn causes extravasation of the renal tubules and cell contents, causing interstitial inflammatory reactions, and various measures to reduce urinary protein will delay the progression of renal damage. Protection of renal function.
3. Hyperlipidemia and liposuction
Hyperlipidemia can occur in the recurrence of MCN. After the disease is relieved and the hormone is stopped, hyperlipidemia can continue for a period of time. A series of disorders can occur in blood lipids (Table 4). High density lipoprotein and unidentified substances are lost in the urine. And the liver venous colloid osmotic pressure decreased, so that the liver synthesis of -lipoprotein increased, leading to hyperlipidemia, MCN is always accompanied by hypercholesterolemia, plasma albumin is significantly reduced, hyperlipidemia, kidney disease often There is an increase in low-density lipoprotein (LDL) and low-density lipoprotein (VLDL), sometimes high-density lipoprotein (IDLS), high-density lipoprotein (HDL) levels are normal, but the lipids and The apolipoprotein component is also abnormal, or the activity of lecithin cholesterol acyltransferase (LCAT) is lowered due to the production of lipourea, which makes the HDLs mature. The hemolytic lecithin is generally bound to albumin, inhibits LCAT, and is also lost in urine. LCAT, thus, LCAT activity is reduced, esterification of HDLs, reduction of cholesterol transfer, increase of free cholesterol, decrease of lipoprotein lipase activity, decrease of HDL/LDL ratio, lipidation and non-lipidated cholesterol in LDL and VLDL Increased content, increased cholesterol synthesis, cholesterol plasma concentration is inversely proportional to albumin and osmotic pressure, positively correlated with renal albumin removal rate, and the rate-limiting enzyme-hydroxymethylglutaryl COA synthetase in cholesterol biosynthesis is induced Infusion of albumin and dextran can transiently increase osmotic pressure, lower cholesterol levels, cholesterol is gradually normal when MCN is relieved, not all patients have hypertriglyceridemia, apolipoprotein A, B and The synthesis of E increased. In experimental nephropathy, the mRNA content of these apolipoproteins increased, the ratio of triacylglycerol to albumin in chylomicrons and VLDL increased, and the clearance of chylomicrons, VLDLs, IDLs and LDLs decreased in peripheral tissues. The conversion of VLDLs into LDLs is impaired, and lipoprotein lipase activity is decreased due to an increase in inhibitory factors (free fatty acids) and a decrease in activators (glycosaminoglycans, ApoCII).
In the case of lipourea, a birefringent fat body appears in the urine, which may be an epithelial cell or a fat tube type containing a cholesterol component.
4. Other
Water retention can cause a decrease in blood sodium concentration. Long-term sodium or acquired adrenal insufficiency can also lead to a decrease in blood sodium concentration. Hyperlipidemia can cause pseudo-hyponatremia. After applying new experimental methods, due to hyperlipemia Pseudohyponatremia caused by the disease is rare. Because platelets can release potassium ions in vitro, thrombocytosis can also cause pseudohyperkalemia. Because of hyperparathyroidism and bone disease, some The patient's ionized calcium concentration is not proportional to hypoalbuminemia. The transport of 25(OH) vitamin D3 can be normal or decreased. MCN bone disease occurs or not, with vitamin D3-parathyroid (PTH) axis, age of onset, The length of the disease, the frequency of recurrence and the use of hormones, adult NS patients with plasma thyroid binding protein (FBG), thyroxine (throixine, T4), triiodolyroninoline (T3), thyroid stimulating hormone (FSH) is generally normal Children with TBG and T3 lost more than adults, plasma TBG and T4 levels decreased, TSH concentration increased, but hypothyroidism did not occur, and one third of children developed transient blood urea nitrogen and creatinine High, blood Reducing the amount of content, can cause increased hematocrit, leukocyte classification and normal platelets slightly elevated glomerular filtration rate (GFR) slightly decreased, typically by 20% to 30% higher than normal.
Kidney biopsy:
Light mirror
Under light microscopy, there are few morphological changes in the glomerulus. The capillary lumen can be enlarged, but there is no cell proliferation. Repeated episodes may have a slight increase in mesangial cells and matrix. Occasionally, individual glomeruli are discarded. Without significant tubular atrophy, the interstitial or vascular changes were not obvious. Double-folded fat droplets were seen in the renal tubular epithelial cells, and vacuolar-like changes were observed in the proximal tubular epithelial cells.
Electron microscope
Under electron microscopy, the epithelial cells of the visceral layer are swollen, and the foot processes lose their original scattered grid shape, which is fused into a sheet, the pores are occluded, with vacuolar degeneration of epithelial cells, microvilli morphology, protein absorption drops and lysosomes increase. It is not unique to this disease, and the remission period can be completely restored to normal. Studies have confirmed that the disappearance or sudden fusion of cutaneous cell foot processes is the only glomerular pathological change of this disease, which is caused by a large amount of protein filtration, such as Animals injected a large amount of protein that can pass through the basement membrane, which can also produce the same foot process changes. Other types of kidney diseases such as large amounts of proteinuria can also be seen.
3. Immunofluorescence
Immunofluorescence was mostly negative, occasionally IgG and / or IgM, IgA, C3 deposition, more common in a few mesangial expansion, and clinically shown to be hormone-dependent patients.
Diagnosis
Diagnosis and diagnosis of minimally pathological nephropathy
diagnosis
The main clinical features of this disease are small age of onset, acute onset, clinical manifestations of typical nephrotic syndrome, namely a large amount of urinary protein (3.5g/d), high edema, hyperlipidemia, and low plasma proteinemia ( 30g / L), generally no hypertension, hematuria and renal dysfunction, proteinuria is highly selective, sensitive to glucocorticoid therapy, but easy to recurrent, according to the above characteristics combined with laboratory tests can make a diagnosis, individual case diagnosis Insufficient conditions, if there is excessive hypoproteinemia, the amount of urine protein may not reach the diagnostic criteria of nephrotic syndrome, and renal biopsy pathological examination can confirm the diagnosis.
Differential diagnosis
Children aged 1 to 6 years old are given experimental treatment first, but not renal biopsy. Cases that are not sensitive to sufficient glucocorticoids, especially adults, need to be diagnosed and identified by kidney biopsy when considering other kidney diseases, especially with Focal segmental sclerosis and early differentiation of membranous nephropathy, early FSGS, lesions are mostly confined to the junction of the skin and the marrow, renal biopsy often difficult to identify because of the site can not be identified, if necessary, repeat renal biopsy, serial biopsy It can improve the diagnosis rate. In addition, the diagnosis of MCN must exclude the secondary cause, and it should be differentiated from renal damage caused by lupus nephritis, purpuric nephritis, diabetic nephropathy, amyloidosis and constrictive pericarditis. Patients should be excluded from lymphoma and other solid tumors. In some cases, MCN and even the earliest signs of lymphoma should be identified.
