Treatment of nephrotic syndrome

Treatment of nephrotic syndrome

(A) cause primary disease treatment of nephrotic syndrome

1. glucocorticoid treatment of glucocorticoids 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 nephrotic syndrome depends largely on its response to pathological type, is generally believed that only the most effective treatment of minimal change in kidney disease.

(12 to 36 hours): prednisone (5mg), prednisolone (5mg), methylprednisolone (5mg), prednisone (5mg) Long-acting (48 to 72 hours): dexamethasone (0.75mg), betamethasone (0.60mg); long-acting (4mg), fluoxetine prednisolone (4mg); Hormones can be quickly absorbed through the gastrointestinal tract, so the tablet is the most commonly used formulations. The first dose is generally prednisone 1mg / (kg · d), children 1.5 ~ 2mg / (kg · d). After 8 weeks of treatment, the effective application should be maintained, and then gradually reduce the amount, usually every 1 to 2 weeks minus the original dose of 10% to 20%, the less the dose the less the amount of decline, the slower the speed. Hormone maintenance and maintenance of time vary by case to clinical symptoms do not appear to use the minimum dose of degrees to less than 15mg / d as satisfactory. In the maintenance phase there are changes in body weight, infection, surgery and pregnancy, and so adjust the amount of hormones. More than 8 weeks of regular treatment of invalid cases, the need to rule out the factors that affect the efficacy, such as infection, edema caused by weight gain and renal vein thrombosis, should be diagnosed and treated as soon as possible. Poor response to oral hormone therapy, a high degree of edema of the gastrointestinal tract on the absorption of hormones, systemic diseases (such as systemic lupus erythematosus) caused by severe nephrotic syndrome; pathologically significant renal interstitial lesions, diffuse small ball proliferation, Crescent formation and vascular fibrinoid necrosis and other changes in patients, may be intravenous hormone therapy. The impact of the dose of methylprednisolone 0.5 ~ 1g / d, course of 3 to 5 days, but according to clinical experience, the general choice of small and medium doses of treatment, that prednisolone 240 ~ 480mg / d, 3 to 5 days, One week later, oral dose was changed. This can reduce the impact of high-dose hormones caused by infection and other side effects, clinical effects are not affected. The corresponding dose of dexamethasone 30 ~ 70mg / d, but pay attention to increase water and sodium retention and high blood pressure and other side effects.

Long-term use of hormones can produce a lot of side effects, and sometimes quite serious. Hormone-induced protein degradation state can aggravate azotemia, to promote blood uric acid increased, induced by gout and increased renal dysfunction. High-dose application can sometimes exacerbate high blood pressure, triggering heart failure. Hormonal application of infection symptoms may be obvious, especially easy to delay the diagnosis, the infection spread. Long-term use of hormones may exacerbate nephrotic syndrome, bone disease, and even produce aseptic femoral neck ischemic necrosis.

2. cytotoxic drug hormone therapy ineffective, or hormone-dependent or recurrent type, can not tolerate hormonal side effects and difficult to continue the drug treatment of nephrotic syndrome can try cytotoxic therapy. Because these drugs are more gonadal toxicity, reduce human resistance and the risk of tumor induced, therefore, indications and medication should be carefully controlled. Such as focal segmental glomerulonephritis cytotoxic drug response is poor, it should not be used. The current clinical commonly used in such drugs, cyclophosphamide (CTX) and phenylbutyrate nitrogen mediated (CB1348) the most reliable effect. CTX dose of 2 ~ 3mg / (kg · d), treatment for 8 weeks, when the cumulative total of more than 300mg / kg prone to gonadal toxicity. N-phenylbutyrate 0.1mg / (kg · d), three times orally, for 8 weeks, the cumulative total of 7 ~ 8mg / kg are prone to toxic side effects. Relapse after treatment relapse and more do not advocate for a second medication, so as to avoid poisoning. On lupus nephritis, nephrotic syndrome caused by membranous nephritis, some people advocate the use of CTX shock therapy, the dose of 12mg ~ 20mg / (kg · times), once a week, once every 5 to 6 times, after the patient's tolerance Extend the medication interval, the total dose up to 9 ~ 12g. Shock therapy aims to reduce the amount of hormones, reduce complications and improve the efficacy of infection, but should be based on glomerular filtration rate of choice or hanged.

 3. Cyclosporine A (CyA) CyA is an effective cell immunosuppressant, in recent years has been tested for a variety of autoimmune diseases. At present, clinical minor lesions, membranous nephropathy and membranoproliferative glomerulonephritis is more positive. Compared with hormones and cytotoxic drugs, CyA application of the biggest advantages is to reduce proteinuria and improve the efficacy of hypoproteinemia reliable, does not affect the growth and development and inhibition of hematopoietic cell function. But the drug also has a variety of side effects, the most serious side effects for the kidney, liver toxicity. The incidence of nephrotoxicity in 20% to 40%, long-term use can lead to interstitial fibrosis. Individual cases of recurrence after drug withdrawal. It is not appropriate long-term use of this drug treatment of nephrotic syndrome, but should not be easily as the drug of choice for this drug. CyA treatment dose of 3 ~ 5mg / (kg · d), the drug blood concentration in the valley of 75 ~ 200μg / ml (whole blood, HPLC method), usually 2 to 8 weeks after treatment onset, but individual differences , Individual patients will take more time to be effective, should be gradually reduced after the effect. Drugs appear in the process of elevated serum creatinine should be alert to the possibility of CyA poisoning. Treatment is generally 3 to 6 months, then the recurrence can still be effective.

 4. Chinese medicine comprehensive treatment of certain nephrotic syndrome due to poor response to immunosuppressive therapy, sustained loss of large amounts of protein from the urine. For these patients in addition to symptomatic treatment, you can try traditional Chinese medicine treatment. Nephrotic syndrome in accordance with traditional Chinese medicine theory, in the edema period, mainly for the spleen and kidney deficiency and water accumulation in the tissue interstitial, showing the performance of the virtual and standard real, so the treatment should be supplementation, namely Wenshenjianpi Based on diuretic swelling. Syndrome treatment as follows: ① spleen and kidney yang type, while the treatment of Wenshen spleen, and to benefit the water. Recipe can be Zhenwu Tang, Ji Sheng Shenqi pills addition and subtraction. ② spleen and kidney qi deficiency: the rule of Qi and spleen Wenshen, herbs can be real or spleen drink Fuling Decoction Shenlingbaizhu powder addition and subtraction. Â '¢ kidney yin and yang are: the rule of yin and yang double complement, prescription available Ji Sheng Shen Qi Wan, Dihuang Yinzi addition and subtraction.

(B) symptomatic treatment

1. Hypoalbuminemia treatment

(1) diet therapy: patients with nephrotic syndrome is usually negative nitrogen balance, such as intake of high-protein diet, it is possible to switch to positive nitrogen balance. However, patients with nephrotic syndrome, high protein intake can lead to increased proteinuria, increased glomerular damage, and plasma albumin levels did not increase. Therefore, the proposed daily protein intake of 1g / kg, together with the daily loss of protein in urine, each intake of 1g protein, must also intake of non-protein calorie 138kJ (33kcal). The protein supply should be high-quality protein, such as milk, eggs and fish, meat.

(2) intravenous albumin: as intravenous albumin in 1 to 2 days that is lost by the kidneys from the urine, and expensive. In addition, a large number of intravenous application of albumin immunosuppression, hepatitis C, induced heart failure, delayed remission and increase the recurrence rate and other side effects, so the application of intravenous albumin should be strictly controlled indications: severe systemic edema, and intravenous injection rate Urine can not achieve diuretic effect in patients after intravenous albumin, followed by intravenous infusion of furosemide (furosemide 120mg, adding glucose solution 100 ~ 250ml, slow infusion of 1 hour), can often make the original furosemide Ineffective who can still get a good diuretic effect. ② the use of furosemide after diuresis, the clinical manifestations of insufficient plasma volume. ③ renal interstitial edema caused by acute renal failure.

2. The treatment of edema

(1) limited sodium diet: edema itself suggests excessive sodium body, so patients with nephrotic syndrome limit salt intake is important. Normal daily salt intake of 10g (including 3.9g of sodium), but because of sodium limit after the patient often because of food tasteless and loss of appetite, affecting the intake of protein and calories. Therefore, limited sodium diet should be tolerated by patients, does not affect their appetite for the degree of low-salt diet of salt content of 3 ~ 5g / d. Chronic patients, due to long-term sodium diet, can lead to intracellular sodium deficiency, should be noted.

(2) the application of diuretics: According to different parts of the role of diuretics can be divided into: ① loop diuretics: the main mechanism of action is to inhibit the ascending branch of the medullary loop of chlorine and sodium reabsorption, such as Cyamemide (furosemide) And bumetanide (BUT) as the most potent diuretic. The dose of furosemide 20 ~ 120mg / d, butylamine 1 ~ 5mg / d. ② thiazide diuretics: the main role in the myeloid thick section of the ascending branch (cortex) and the distal distal tubule, by inhibiting the reabsorption of sodium and chlorine, increased excretion of potassium to achieve diuretic effect. Commonly used hydrochlorothiazide dose of 75 ~ 100mg / d. ③ row sodium retention potassium diuretics: the main role in the distal tubule and collecting duct, aldosterone antagonists. Spironolactone is usually used in a dose of 60 ~ 120mg / d, alone, the effect of such drugs is poor, so often combined with potassium excretion of diuretics. ④ osmotic diuretic: free glomerular filtration through the renal tubular reabsorption, thereby increasing the osmotic concentration of renal tubules, proximal tubules and distal tubules to prevent reabsorption of sodium to achieve diuretic effect. Commonly used low molecular weight dextran 500Ml / 2 ~ 3d, mannitol 250Ml / d, attention to renal function impairment with caution. Nephrotic syndrome in patients with diuretic drugs preferred furosemide, but the dose of individual differences; intravenous drug better, method: 100mg furosemide added 100Ml glucose solution or 100ml mannitol, slow intravenous infusion of 1 hour; Potassium diuretics, Guchang and spironolactone combined. Furosemide long-term application (7 to 10 days), the diuretic effect weakened, and sometimes need to increase the dose, preferably to the gap medication, that is, 3 days after the withdrawal and then. It is suggested that diuretics should be used alternately in patients with severe edema.

3. Hypercoagulable state treatment

Patients with nephrotic syndrome due to coagulation factor changes in the blood hypercoagulable state, especially when the plasma albumin below 20 ~ 25g / L, that is, venous thrombosis possible. At present, commonly used anticoagulant drugs are:

(1) heparin: mainly through the activation of antithrombin Ⅲ (AT Ⅲ) activity. Commonly used dose of 50 ~ 75mg / d intravenous infusion, the AT Ⅲ activity units in more than 90%. Heparin has been reported in the literature to reduce nephrotic syndrome, proteinuria and improve renal function, but its mechanism is unclear. It is noteworthy that heparin (MW65600) can cause platelet aggregation. There are small molecular weight heparin subcutaneous injection, once a day.

(2) urokinase (UK): direct activation of plasminogen, leading to fibrinolysis. Commonly used dose of 2 to 8 million U / d, the use of small doses from the beginning, and with heparin at the same time intravenous infusion. The time of dissolution of the euglobulin was monitored and allowed to fall between 90 and 120 minutes. UK's main side effects are allergies and bleeding.

(3) warfarin: inhibition of liver cell vitamin K dependent factors Ⅱ, Ⅶ, Ⅸ, X synthesis, commonly used dose of 2.5mg / d, oral, monitoring prothrombin time, so that in normal 50% to 70% .

(4) dipyridamole: for platelet antagonists, commonly used dose of 100 ~ 200mg / d. General hypercoagulable state of intravenous anticoagulation time of 2 to 8 weeks, later changed to warfarin or dipyridamole orally.

Patients with venous thrombosis: ① removal of thrombosis surgery. ② intervention thrombolysis. Interventional radiation in the renal artery end-injection UK24 million U to dissolve renal vein thrombosis, this method can be repeated application. Systemic venous anticoagulation. That heparin plus urokinase, treatment 2 to 3 months. ④ oral warfarin to relieve nephrotic syndrome to prevent thrombosis re-formation.

4. Hyperlipidemia treatment

Patients with nephrotic syndrome, especially in multiple relapses, the duration of hyperlipidemia is very long, even after nephrotic syndrome remission, hyperlipidemia persisted. In recent years, to recognize the impact of hyperlipidemia on the progress of kidney disease, and some treatment of nephrotic syndrome drugs such as: adrenal cortex hormones and diuretics, can increase hyperlipidemia, it is currently more advocates of nephrotic syndrome Lipidemia using lipid-lowering drugs. The choice of lipid-lowering drugs are: ① fibric acids (fibric acids): fenofibrate (fenofibrate) 3 times a day, each 100mg, gemfibrozil (gemfibrozil) 2 times a day, each 600mg, Its blood triglyceride lowering effect is stronger than cholesterol-lowering. The drug occasionally gastrointestinal discomfort and elevated serum transaminase. ②Hmg-CoA reductase inhibitors: lovastatin (US lipid-lowering), 20mgBid, simvastatin (Shu lipid-lowering), 5mg Bid; these drugs mainly to intracellular Ch decline, lower plasma LDL-Ch concentration, Cells produce VLDL and LDL. ③ angiotensin-converting enzyme inhibitor (ACEI): the main role in reducing plasma Ch and TG concentration; the plasma HDL increased, and its main apolipoprotein ApoA-Ⅰ and ApoA-Ⅱ also increased, can accelerate Clear the surrounding tissue in the Ch; reduce the infiltration of LDL on the arterial intima, protect the arterial wall. In addition ACEI can still have different degrees of proteinuria.

5. Acute renal failure treatment

Nephrotic syndrome with acute renal failure due to different causes of treatment are different. For hemodynamic factors, the main treatment principles include: the rational use of diuretics, adrenal cortex hormones, to correct low blood volume and dialysis therapy. Hemodialysis not only control azotemia, to maintain electrolyte acid-base balance, and can quickly remove the body of water retention. Due to renal interstitial edema caused by acute renal failure after the above treatment, rapid renal function recovery. Diuretics need to pay attention to: ① timely use of diuretics: nephrotic syndrome with acute renal failure who have severe hypoproteinemia, plasma protein is not added to the use of large doses of diuretics, will increase the hypoalbuminemia and low blood Capacity, renal failure worse. It should be added in the plasma albumin (daily intravenous use of 10 ~ 50g human albumin) and then to diuretics. But an excessive supplementation of plasma albumin and not with diuretics, they may lead to pulmonary edema. ② appropriate use of diuretics: due to nephrotic syndrome patients with relative hypovolemia and hypotension tendency, this time with diuretics should be daily urine output 2000 ~ 2500ml or weight daily decline in 1kg or so is appropriate. ③ patients with elevated plasma renin levels, the use of diuretics decreased blood volume after a higher plasma renin levels, diuretic therapy is not only ineffective but aggravate the condition. Such patients only correct hypoproteinemia and low blood volume before diuretic is conducive to renal function recovery.

Nephrotic syndrome with acute renal failure are generally reversible, the majority of patients in the treatment, with the increase in urine output, renal function gradually restored. A small number of patients in the course of multiple acute renal failure can also be restored. Prognosis and the etiology of acute renal failure, generally speaking, progressive glomerulonephritis, renal vein thrombosis prognosis is poor, and simple and nephrotic syndrome-related prognosis is better.