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Nephrotic syndrome

  Nephrotic syndrome (NS) can be caused by a variety of causes, increased glomerular basement membrane permeability, manifested as a large number of proteinuria, hypoproteinemia, a high degree of edema, hyperlipidemia, a group of clinical syndrome.

  Etiology

  Divided into primary, secondary and genetic three categories, the primary NS is a primary glomerular disease, a variety of pathological types.

  Clinical manifestations

  NS is the most basic characteristics of a large number of proteinuria, hypoproteinemia, (high) edema and hyperlipidemia, the so-called "three high and one low", and other metabolic disorders characterized by a group of clinical syndrome.

  A large number of proteinuria

  A large number of proteinuria is the most important clinical manifestations of NS patients, nephrotic syndrome is the most basic pathophysiological mechanisms. A large number of proteinuria is adult urinary protein excretion> 3.5g / d. Under normal physiological conditions, glomerular filtration membrane with a molecular barrier and charge barrier, resulting in the original urine protein content increased, when far more than the amount of the proximal tubule absorption, the formation of large amounts of proteinuria. On this basis, any increase in glomerular pressure and lead to high perfusion, high filtration factors (such as high blood pressure, high protein diet or large infusion of plasma protein) can increase the excretion of urinary protein.

  2. Hypoproteinemia

  Plasma albumin decreased to <30g / L. NS large albumin lost from the urine, and promote the compensatory synthesis of albumin liver and renal tubular decomposition increased. Hypoalbuminemia occurs when an increase in liver albumin synthesis is not sufficient to overcome loss and breakdown. In addition, NS patients with gastrointestinal mucosal edema caused by eating loss, inadequate protein intake, malabsorption or loss, but also increase the cause of hypoalbuminemia.

  In addition to plasma albumin reduction, the plasma of certain immunoglobulin (such as IgG) and complement components, anticoagulant and fibrinolytic factors, metal binding protein and endocrine-binding protein can also be reduced, especially large amounts of proteinuria, glomerular Severe pathological damage and non-selective proteinuria is more significant. Patients prone to infection, hypercoagulability, trace element deficiency, endocrine disorders and immune dysfunction and other complications.

  3. Edema

  NS hypoalbuminemia, decreased plasma colloid osmotic pressure, so that water from the vascular cavity into the tissue space, is the basic cause of NS edema. Recent studies have shown that about 50% of patients with normal or increased blood volume, plasma renin levels normal or decreased, suggesting that some of the primary intrarenal sodium, water retention factors in NS play a role in the mechanism of edema.

  4. Hyperlipidemia

  The cause of NS with hyperlipidemia has not been fully elucidated. High cholesterol and / or hypertriglyceridemia, serum LDL, VLDL and lipoprotein (α) concentration increased, often co-exist with hypoalbuminemia. Hypercholesterolemia is mainly due to increased synthesis of lipoproteins in the liver, but in the reduction of the surrounding circulation also play a part. Hypertriglyceridemia is mainly due to catabolic disorders caused by increased liver synthesis as a secondary factor.

  diagnosis

  1. nephrotic syndrome (NS) diagnostic criteria is

  (1) urinary protein is greater than 3.5g / d;

  (2) plasma albumin less than 30g / L;

  (3) edema;

  (4) hyperlipidemia. Which ① ② two necessary for the diagnosis.

  2.NS diagnosis should include three aspects

  (1) confirmed NS.

  (2) to confirm the cause: first rule out secondary and genetic diseases, can be diagnosed as primary NS; the best biopsy, to make pathological diagnosis.

  (3) to determine whether the complications.

  Differential diagnosis

  1. Henoch-Schonlein purpura nephritis

  Occur in adolescents, with typical skin purpura, often symmetrical distribution in the distal limbs, more than 1 to 4 weeks after the rash appears hematuria and (or) proteinuria.

  2. Systemic lupus erythematosus nephritis

  Occur in the middle-aged women and adolescents, immunological examination shows a variety of autoantibodies, and multi-system injury, can confirm the diagnosis.

  3. Hepatitis B virus-associated glomerulonephritis

  More common in children and adolescents, clinical manifestations of proteinuria or NS, the common pathological type of membranous nephropathy. Diagnosis based on: ① serum HBV antigen positive; ② suffering from glomerulonephritis, and the exclusion of secondary glomerulonephritis; ③ renal biopsy section to find HBV antigens.

  4. Diabetic nephropathy

  Occur in the elderly, common in the course of more than 10 years of diabetes. Early can be found in urine microalbumin excretion increased, then gradually developed into a large number of proteinuria, NS. A history of diabetes and characteristic fundus changes can help in the differential diagnosis.

  5. Renal amyloidosis

  Occur in the elderly, renal amyloidosis is part of the body multiple organ involvement. Secondary amyloidosis often secondary to chronic suppurative infection, tuberculosis, malignancy and other diseases, mainly involving the kidneys, liver, liver and kidney disease, mainly in the liver, kidney, digestive tract (including the tongue), skin and nerve; And spleen and other organs. Involvement of renal volume increases, often showed NS. Renal amyloidosis is often diagnosed by renal biopsy.

  6. myeloma nephropathy

  Occur in the elderly, more common in men, patients with multiple myeloma may have the characteristics of clinical manifestations, such as bone pain, increased serum monoclonal globulin, protein electrophoresis M band and urine protein positive week, bone marrow showed plasma cells Abnormal proliferation (accounting for more than 15% of nucleated cells), accompanied by qualitative changes. Multiple myeloma may occur when the glomerular involvement of NS. The characteristic performance of the above-mentioned myeloma is advantageous for the differential diagnosis.

  complication

  NS complications is an important factor affecting long-term prognosis of patients, should be actively prevention and treatment.

  Infection

  Usually in the hormone treatment without the use of antibiotics to prevent infection, or not only fail to prevent the purpose, but may induce fungal double infection. Once the infection, should be used in time sensitive to pathogens, potent and no renal toxicity of antibiotics, active treatment, a clear infection foci should be removed as soon as possible. Severe infections difficult to control should be considered to reduce or disable the hormone, but depending on the specific circumstances of patients.

  2. thrombosis and embolism complications

  Generally believed that when plasma albumin below 20g / L (idiopathic membranous nephropathy less than 25g / L) when anticoagulant therapy can be given heparin (also available low molecular weight heparin) subcutaneous injection or oral warfarin. Anticoagulation can be supplemented with antiplatelet agents such as dipyridamole or aspirin. Thrombosis has occurred, embolization should be as early as possible (within 6 hours the best, but still effective within 3 days) given urokinase or streptokinase systemic or local thrombolysis, combined with anticoagulant therapy, anticoagulants should generally continue to apply More than six months. Anticoagulant and thrombolytic therapy should avoid excessive drug lead to bleeding.

  3. Acute renal failure

  NS complicated with acute renal failure, such as improper handling can be life-threatening, if given the right treatment in time, most patients are expected to recover. The following measures can be taken:

  (1) loop diuretics on loop diuretics are still effective should be a larger dose to rinse obstruction of the renal tubular;

  (2) hemodialysis diuretic invalid, and has reached the dialysis indications, should be to maintain the life of hemodialysis, and plasma products in the appropriate dehydration after supplementation to reduce renal interstitial edema;

  (3) the primary disease treatment because of its pathological type mostly small change nephropathy, should be actively treated;

  (4) alkaline urine can be oral sodium bicarbonate alkaline urine, in order to reduce the tube formation.

  4. protein and fat metabolism disorders

  It is often difficult to completely correct metabolic disorders before NS remission, but the amount and structure of protein and fat in the diet should be adjusted to minimize the effects of metabolic disorders. At present, many drugs can be used for the treatment of protein and fat metabolic disorders. Such as: ACEI and angiotensin Ⅱ receptor antagonists can reduce urinary protein; Studies have suggested that traditional Chinese medicine Astragalus can promote liver albumin synthesis, and may have both the role of reducing hyperlipidemia. Lipid-lowering drugs can choose to lower cholesterol-based hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors, such as lovastatin and other statins; or lower triglyceride-based clofibrate Class, such as fenofibrate. NS remission after hyperlipidemia can be natural remission, you do not need to continue drug treatment.

  treatment

  (A) general treatment

  Where there is severe edema, hypoproteinemia who need bed rest. Edema disappeared, the general situation improved, you can get up activities.

  The normal amount of 0.8 ~ 1.0g / (kg · d) of high-quality protein (essential amino acids rich in animal protein-based) diet. Heat to ensure adequate daily weight per kilogram should not be less than 30 ~ 35kcal. Although the patient lost a lot of urine protein, but because of high protein diet increased glomerular filtration, can aggravate proteinuria and promote kidney disease progression, it is generally no longer advocate application.

  Edema should be low salt (<3g / d) diet. To reduce hyperlipidemia, should be less into the rich in saturated fatty acids (animal fat) diet, and eat more rich in polyunsaturated fatty acids (such as vegetable oil, fish oil) and rich in soluble fiber (such as beans) diet.

  (B) symptomatic treatment

  1. Diuretic swelling

  (1) thiazide diuretics mainly role in the medullary loop ascending thick section and the distal part of the distal tubule, by inhibiting sodium and chlorine reabsorption, increased excretion of potassium and diuretic. Long-term use should be to prevent hypokalemia, hyponatremia.

  (2) retention of potassium diuretics main role in the posterior segment distal tubule, row of sodium, chlorine discharge, but the retention of potassium, suitable for patients with hypokalemia. Diuretic effect alone is not significant, with thiazide diuretics combined. Common triamterene or aldosterone antagonist spironolactone. Long-term use need to prevent hyperkalemia, renal insufficiency patients should be used with caution.

  (3) loop diuretics main role in the myeloid ascending branch, sodium, chlorine and potassium reabsorption has a strong inhibitory effect. Common furosemide (furosemide) or bumetanide (butyral amine) (equivalent to the role of 40 times stronger than furosemide), divided into oral or intravenous injection. In osmotic diuretic drugs immediately after application, the effect is better. The use of loop diuretics should beware of hyponatremia and hypokalemia, hypochloremia alkalosis occurs.

  (4) osmotic diuretics through a transient increase in plasma colloid osmotic pressure, the organization can be absorbed back into the blood of blood. In addition, they passed through the glomerular filtration, resulting in hypertonic renal tubular fluid state, reduce water and sodium reabsorption and diuretic. Commonly used sodium dextran 40 (low molecular weight dextran) or starch generation plasma (706 generation plasma) (molecular weight of 2.5 to 4.5 million) intravenous drip. Followed by the addition of loop diuretics can enhance the diuretic effect. However, oliguria (urine output <400ml / d) patients should be used with caution in such drugs, because of its easy to secrete tubular Tamm-Horsfall protein and glomerular filtration albumin together to form tube, blocking the renal tubules, And due to its role in hypertonic renal tubular epithelial cell degeneration, necrosis, induced "osmotic nephropathy", leading to acute renal failure.

  (5) to improve plasma colloid osmotic pressure plasma or plasma albumin and other intravenous infusion can improve plasma colloid osmotic pressure, and promote tissue moisture back to the absorption and diuretic, such as re-furosemide plus glucose solution in slow intravenous infusion, Sometimes a good diuretic effect can be obtained. But because of the input protein will be 24 to 48 hours from the urine, can cause glomerular filtration and renal tubular high metabolism, resulting in glomerular visceral and renal tubular epithelial cell injury, and promote renal interstitial fibrosis Of light effects of glucocorticoid efficacy, delayed disease remission, severe cases can damage renal function. It should be strictly indications, severe hypoproteinemia, highly edema and oliguria (urine output <400ml / d) of NS patients, must be considered in the case of diuretic use, but also to avoid too much frequency . Heart failure patients should be used with caution.

  The principle of diuretic therapy in patients with NS is not too fast too fast, so as to avoid blood volume, increased blood hypercoagulant tendencies, induced thrombosis, embolism complications.

  2. Reduce urinary protein

  Continuous large amounts of proteinuria itself can lead to glomerular hyperfiltration, increased renal tubular - stromal damage, and promote glomerular sclerosis, is an important factor in the prognosis of glomerular disease. Reduced urinary protein has been shown to effectively delay the deterioration of renal function.

  Angiotensin converting enzyme inhibitors (ACEI) or angiotensin Ⅱ receptor antagonist (ARB), in addition to the effective control of hypertension, can reduce the glomerular pressure and directly affect the glomerular basement membrane on the large Molecular permeability, there is no dependence on reducing systemic blood pressure to reduce urinary protein. With ACEI or ARB urinary protein, the dose should generally be larger than the conventional antihypertensive dose, in order to obtain a good effect.

  (C) the main treatment (inhibition of immune and inflammatory response)

  1. Glucocorticoid therapy

  Glucocorticoids (hereinafter referred to as hormones) for kidney disease, mainly its anti-inflammatory effect. It can reduce the exudation of acute inflammation, stable lysosomal membrane, reduce fibrin deposition, reduce capillary permeability and reduce leakage of urine protein; In addition, still inhibit the proliferation of chronic inflammation in response to lower fibroblasts Activity, reduce tissue repair caused by fibrosis. Glucocorticoid response to disease depends largely on its pathological type, the most rapid and effective treatment of small lesions and certainly. The use of principles and programs are generally: ① start enough: commonly used drugs for prednisone, oral 8 weeks, if necessary, may be extended to 12 weeks; ② slow drug reduction; adequate treatment after every 2 to 3 weeks by the amount of the original 10%, when reduced to 20mg / d when the symptoms are easy to repeated, should be more slowly reduction; ③ long-term maintenance: the last effective dose to maintain a few months to six months. Hormones can take full-day Dayton clothing or in the maintenance of medication during the two-day amount once a Dayton clothing to reduce hormone side effects. Severe edema, liver dysfunction or poor efficacy of prednisone, can be replaced by oral prednisolone or intravenous infusion.

  According to the treatment of patients with glucocorticoid response, can be divided into "hormone-sensitive" (medication 8 to 12 weeks of NS remission), "hormone-dependent" (hormone to a certain degree of relapse) and "hormone resistance Type "(hormone therapy ineffective) three categories, their respective further treatment differences.

  Long-term use of hormones in patients with infection, drug-induced diabetes, osteoporosis and other side effects, a few cases may also occur aseptic avascular necrosis of the femoral head, the need to strengthen monitoring and timely treatment.

  2. Cytotoxic drugs

  Hormone therapy ineffective, or hormone-dependent or recurrent type, can be cytotoxic drugs to help treatment. Because these drugs are more gonadal toxicity, liver damage and high-dose can cause cancer risk, therefore, indications and medication should be carefully controlled. At present, these drugs, cyclophosphamide (CTX) and phenylbutyrate nitrogen mediated (CB1348) clinical application more.

  3. Immunosuppressive agents

  Commonly used immunosuppressive agents currently available are cyclosporine A, tacrolimus (FK506), mycophenolate mofetil and leflunomide.

  Past immunosuppressive agents are often used in combination with glucocorticoid treatment of a variety of different pathological types of nephrotic syndrome, in recent years also recommended some patients due to glucocorticoid relative contraindication or intolerance (such as diabetes control, mental factors, serious Osteoporosis), and some patients are not willing to accept glucocorticoid treatment regimen or contraindication in patients with immunosuppressant therapy alone (including as the initial program) certain pathological types of nephrotic syndrome, such as focal segment Glomerular sclerosis, membranous nephropathy, minimal change nephropathy and so on.

  Application of glucocorticoids and immunosuppressive agents (including cytotoxic drugs) treatment of NS can have a variety of programs, in principle, should be to enhance the efficacy while minimizing side effects is appropriate. For the application of hormone therapy, duration of treatment, and should use and select what immunosuppressive agents (cytotoxic drugs), etc. should be combined with glomerulopathy in patients with pathological type, age, renal function and whether the relative contraindications, etc. And different treatment, based on the role of immunosuppressive target target, to develop individualized treatment. In recent years, according to the results of evidence-based medicine, for different pathological types, the corresponding treatment programs.

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