Nephrotic syndrome (NS) can be caused by a variety of etiologies, with increased glomerular basement membrane permeability, characterized by a large group of proteinuria, hypoproteinemia, high edema, hyperlipidemia, and a group of clinical syndromes
The basic features of NS are massive proteinuria, hypoproteinemia, edema, and hyperlipidemia, a group of clinical syndromes characterized by the so-called "three highs and one low" and other metabolic disorders
1. massive proteinuria
A large number of proteinuria is the main clinical manifestations of NS patients with nephrotic syndrome, is also the most basic pathophysiology. Proteinuria refers to adult urinary protein excretion of >3.5g/d. in normal physiological conditions, glomerular filtration membrane with molecular barrier and charge barrier, resulting in the urine protein content increased, when more than proximal tubular back absorption, the formation of proteinuria. On this basis, an increase in glomerular pressure and lead to high perfusion, high filtration factors (such as hypertension, high protein diet or a large infusion of plasma protein) may increase urinary protein excretion.
Plasma albumin to <30g/L.NS the albumin in the urine loss, promote albumin synthesis by the liver and renal tubular decomposition increased. When the liver albumin increased synthesis is not sufficient to overcome the loss and decomposition, appeared hypoalbuminemia. In addition, NS patients due to gastrointestinal mucosal edema in diet decreased, insufficient protein intake, malabsorption or loss the reason is also aggravated, hypoalbuminemia.
Besides the reduction of plasma albumin, some plasma immunoglobulin and complement components (such as IgG), anticoagulation and fibrinolytic factors, metal binding proteins and endocrine hormone binding protein can also be reduced, especially the large amount of proteinuria, glomerular pathological damage and non selective proteinuria is more significant. Patients prone to infection, high coagulation, trace element deficiency, endocrine disorders and immune dysfunction and other complications.
NS, hypoproteinemia, decrease of plasma colloid osmotic pressure, the water from the lumen into the interstitial space, is the basic cause of NS edema. Recent studies show that about 50% of patients with normal or increased blood volume, plasma renin levels decreased or normal, suggesting that some primary renal sodium and water retention factors play a role in the pathogenesis of NS edema.
The reason of hyperlipidemia in NS has not been fully elucidated. (or) high cholesterol and triglyceride, serum LDL, VLDL and lipoprotein (a) concentration increase, often with hypoproteinemia coexist. Hypercholesterolemia is mainly due to the increase in hepatic lipoprotein synthesis, but in the peripheral circulation decomposition also reduced part. Hypertriglyceridemia is mainly caused by the decomposition of metabolic disorders, increased hepatic synthesis are the secondary factors.
1. diagnostic criteria for nephrotic syndrome (NS) are
(1) urinary protein is greater than 3.5g/d;
(2) plasma albumin was lower than 30g/L;
(4) hyperlipidemia. Among them, two are necessary for diagnosis
The diagnosis of 2.NS should include three aspects
(1) diagnose NS.;
(2) confirm the cause of the disease: first of all, exclude secondary and hereditary diseases, can be diagnosed as primary NS; it is better to do renal biopsy and make a pathological diagnosis
(3) to judge whether there is any complication
1. Henoch Schonlein purpura nephritis
It is common in adolescents and has typical skin purpura. It is usually symmetrical in the distal extremities, more than 1~4 days after the rash, and hematuria and / or proteinuria
2. systemic lupus erythematosus nephritis
It is common in middle-aged women and adolescents, and multiple autoantibodies and multisystem damage can be identified by immunological examination
3. hepatitis B virus associated glomerulonephritis
More common in children and adolescents, the main clinical manifestations of proteinuria or NS, common pathological types of membranous nephropathy. Diagnosis: serum HBV antigen positive; the patients with glomerulonephritis, and eliminate secondary glomerulonephritis; the renal biopsy found HBV antigen.
4. diabetic nephropathy
Good hair in the elderly, common in more than 10 years duration of diabetes. Early urinary albumin excretion increased, then gradually developed into a large number of proteinuria, NS. diabetes history and characteristics of the fundus is helpful for differential diagnosis.
5. renal amyloidosis
Good hair in the elderly, renal amyloidosis is a systemic multi organ involvement. Mainly involving the heart, primary amyloidosis kidney, digestive tract (including the tongue), skin and nerve; secondary amyloidosis often secondary to chronic suppurative infection, tuberculosis, cancer and other diseases, mainly involving the kidney, liver and spleen. Increasing the volume of kidney involvement, usually with NS. renal amyloidosis often require renal biopsy.
6. myeloma nephropathy
Good hair in the elderly, male, patients may have characteristics of multiple myeloma clinical manifestations, such as pain, serum monoclonal immunoglobulin increased, protein electrophoresis band M and urine protein positive this week, showed bone marrow plasma cells (more than 15% nucleated cells), and accompanied by quality change. NS. the myeloma features for differential diagnosis of multiple myeloma with renal glomerulus.
The complication of NS is an important factor affecting the long-term prognosis of patients, and should be actively prevented and treated
Usually in hormone therapy without the use of antibiotics to prevent infection, otherwise not only reach the purpose of prevention, but may cause fungal superinfection. Once found infection, should be timely selection of sensitive to pathogens, potent and non nephrotoxic antibiotic treatment, there is a clear focus of infection should be removed as soon as possible. Serious infection should be difficult to control consider reducing or discontinuing hormone, but depending on the specific situation of patients.
2. thrombosis and embolism complications
Generally, when the plasma albumin was lower than that of 20g/L (idiopathic membranous nephropathy below 25g/L) when anticoagulation therapy can be given heparin sodium (also used low molecular weight heparin) subcutaneous injection or oral warfarin anticoagulation. At the same time can be supplemented with antiplatelet drugs such as aspirin, dipyridamole or oral administration. On thrombosis and embolism (as soon as possible 6 hours is best, but 3 days is still expected to be effective) treated with urokinase or streptokinase systemic or local thrombolysis, combined with anticoagulation, anticoagulation should be continued for more than half a year. The general application of anticoagulation and thrombolysis treatment should avoid drug overdose leading to bleeding.
3. acute renal failure
NS complicated with acute renal failure, such as improper treatment can be life-threatening, if the correct treatment in a timely manner, most patients are expected to recover:
(1) loop diuretics remain in effect for loop diuretics should be larger dose to scour blocking renal tubule type;
(2) hemodialysis is diuretic and ineffective and has reached dialysis indications. Hemodialysis should be given to maintain life and appropriate dehydration after supplementation of plasma products to reduce renal interstitial edema;
(3) primary disease treatment should be treated with active treatment because of its pathological type, mostly small change nephropathy;
(4) alkaline urine can be orally injected with sodium bicarbonate to clear urine, so as to reduce the formation of tube type
4. protein and fat metabolism disorder
In the NS before remission is often difficult to completely correct metabolic disorders, but should adjust the amount and structure of protein and fat in the diet, and strive to reduce the impact of metabolic disturbance to a minimum. At present, many drugs can be used for the treatment of protein and fat metabolism disorder. Such as: ACEI and angiotensin II receptor antagonists can reduce urinary protein; it has been suggested that Astragalus can promote liver function and albumin synthesis, both may reduce hyperlipidemia. Lipid-lowering drugs can choose cholesterol based hydroxymethylglutaryl coenzyme A reductase inhibitors (HMG-CoA), such as lovastatin and other statins; or triglyceride lowering mainly clofibrate, such as fenofibrate.NS after remission of hyperlipidemia spontaneous remission, there is no need to continue medication.
(I) general treatment
All patients with severe edema and hypoproteinemia need to stay in bed. Edema disappeared and after general improvement, they can get up
Give a normal amount of 0.8 ~ 1.0g/ (kg - D) (high quality protein rich in essential amino acids of animal protein diet). To ensure sufficient heat, per kg body weight per day should not be less than 30 ~ 35kcal. despite the loss of a large number of patients with urinary protein, but due to the high protein diet increased glomerular hyperfiltration, can aggravate proteinuria and promote kidney the progression of the lesion, generally no longer stands for application.
Edema should be low salt (<3g/d) diet. To alleviate hyperlipidemia, should be less rich in saturated fat (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.
(two) symptomatic treatment;
1. diuresis detumescence
(1) a thiazide diuretic major role in the thick ascending limb of Henle segment and distal tubule segment, through reabsorption inhibition of sodium and chlorine, increased potassium excretion and diuresis. Long term use should prevent hypokalemia, hyponatremia.
(2) retention of potassium sparing diuretics a major role in the distal tubule segment, the excretion of sodium, chloride removing, but the retention of potassium, suitable for patients with hypokalemia. When used alone the diuretic effect is not significant, can be used in combination with thiazide diuretics. Triamterene or aldosterone antagonists spironolactone. Long term use to prevent high hyperkalemia, renal insufficiency patients should be used with caution.
(3) the main effect of loop diuretics in the ascending limb of Henle, sodium, potassium and chloride reabsorption has potent inhibitory activities. Furosemide (Lasix) or bumetanide (Ding Niaoan) (the same dose effect of furosemide is 40 times stronger), graded oral or intravenous administration. Then, in osmotic diuresis effect is better after drug application. Application of diuretics should beware of hyponatremia and hypokalemia, hypochloremia alkalosis occurred.
(4) osmotic diuretic through a transient increase in plasma colloid osmotic pressure, can be absorbed into the blood water back into the organization. In addition, they went through the glomerular filtration caused by renal tubular fluid in the hypertonic state, reduce water and sodium reabsorption and diuresis. Commonly used sodium dextran 40 (low molecular dextran) or hetastarch (706 generation plasma) (molecular weight ranged from 2.5 to 45 thousand). Then combined with intravenous diuretics can enhance diuresis effect. But less urine (urine <400ml/d) in patients with these drugs should be used with caution, because Tamm-Horsfall protein and glomerular filtration and tubular secretion of the albumin together tube type, tubular obstruction, and because of its high osmotic pressure and cause renal tubular epithelial cell degeneration, necrosis, infiltration induced nephropathy, resulting in acute renal failure.
(5) increase the plasma colloid osmotic pressure of plasma albumin or plasma infusion can increase plasma colloid osmotic pressure, moisture absorption and to promote the organization such as diuretic, and furosemide on glucose solution for intravenous drip can sometimes get a good diuretic effect. But because of the input protein were in 24 ~ 48 hours by urine, can cause glomerular hyperfiltration and high metabolism in renal tubules, resulting in visceral glomerular damage and renal tubular epithelial cells, promote renal interstitial fibrosis, it may affect the efficacy of glucocorticoids, delayed remission, severe cases can damage renal function. The indications should be strictly controlled, for severe hypoproteinemia the height, edema and less urine (urine <400ml/d) NS patients under the diuretic must consider the use, but also to avoid excessive frequency. Heart failure patients should be used with caution.
The principle of diuretic treatment for NS patients should not be too fast or too severe, so as to avoid insufficient blood volume, aggravate the tendency of hypercoagulability, induce thrombosis and embolism complications
2. reduce proteinuria
Persistent proteinuria itself can cause glomerular hyperfiltration, aggravate tubulointerstitial injury, promote glomerular sclerosis, is an important factor affecting the prognosis of glomerular disease has been confirmed. The deterioration of reducing urinary protein can effectively retard renal function.
Angiotensin converting enzyme (ACEI) inhibitors or angiotensin II receptor antagonist (ARB), in addition to effectively control hypertension, can reduce the glomerular pressure and directly affect the permeability of the glomerular basement membrane of macromolecules, is not dependent on the decrease of systemic blood pressure reducing urinary protein reducing urine protein with ACEI. Or ARB, the dosage of the general than conventional antihypertensive dose, to achieve the good results.
(three) main treatment (suppression of immune and inflammatory reaction);
1. glucocorticoid therapy
Glucocorticoid (the hormone) for kidney disease, mainly its anti-inflammatory effect. It can reduce the acute inflammation exudation, lysosomal membrane stability, reduce the deposition of fibrin, reduce capillary permeability and reduce urinary protein leakage; in addition, can inhibit the proliferation of chronic inflammatory reaction in the reduced fibroblast activity. Reduce tissue repair and fibrosis. The effect of corticosteroid response to disease depends on the pathological type, clinical lesions most quickly and surely. The principles and schemes are generally sufficient: Starting: commonly used drugs for oral prednisone, 8 weeks, when necessary, may be extended to 12 weeks; the slow reduction of drug; 10% every 2 to 3 weeks Jianyuan dosage sufficient after treatment, when reduced to about 20mg/d symptoms should be more easily repeated, slow reduction; the long-term maintenance: at the minimum effective dose again For a few months to half a year. The hormone can take the full amount or meal served in the maintenance of medication during the two days the amount of every one ton service, to reduce the side effects of hormone. Edema, liver function damage or poor efficacy of prednisone, prednisolone can replace oral or intravenous drip. According to the treatment of patients with response to glucocorticoid the hormone, which can be pided into "hormone sensitive" (after 8 ~ 12 weeks, NS response) "hormone dependent type" (hormone drug reduction to a certain extent that recurrence and steroid resistant) "(hormone therapy invalid) three, differ further respectively. Long term steroid treatment the drug can occur in patients with infection, diabetes, osteoporosis and other side effects, may also occur in a few cases of femoral head aseptic necrosis, the need to strengthen monitoring, timely treatment. 2. ineffective cytotoxic drugs or hormone therapy, hormone dependent or recurrent For the type of cytotoxic drugs, can assist the treatment. Because such drugs have gonadal toxicity, liver damage and large dose can be dangerous, so in the induction of tumors, the indications of drug use and treatment should be carefully mastered. At present this kind of drug, cyclophosphamide (CTX) and phenylbutyric acid mediated (CB1348) clinical application of 3.. Immunosuppressant clinically used immunosuppressive agent cyclosporin A, tacrolimus (FK506), mycophenolate mofetil and leflunomide. Previous immunosuppressive drugs often combined with glucocorticoid treatment of various pathological types of nephrotic syndrome, in recent years also recommended some patients with relative contraindications to the glucocorticoid hormone or intolerance (osteoporosis without diabetes control, mental factors, serious), and some patients not receiving glucocorticoid treatment or in patients who have contraindications, can only use of immunosuppressant treatment (such as the initial treatment regimen) some pathological types of nephrotic syndrome, such as focal segmental glomerulosclerosis, membranous nephropathy, minimal change nephrotic syndrome.
The application of corticosteroid 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. Whether hormone therapy, treatment length, and should use and choice of immunosuppressive agents (cytotoxic drugs) should be combined with patients with glomerular pathologic type, age, renal function and whether there are relative contraindications so different, based on the role of target of immunosuppressive agents, inpidualized treatment in recent years. According to the results of evidence-based medicine, for different types of Pathology, put forward the corresponding treatment plan. Inpidual differences in prognosis of NS patients greatly the main factors affecting prognosis. Including: 1. pathological types
In general, the prognosis of minimalchange nephropathy and mild mesangial proliferative glomerulonephritis. Minimalchange nephrotic patients spontaneous remission, with high remission rate, but reduce recurrence. Early membranous nephropathy is still high remission rate, although it is difficult to reach the advanced treatment, but the disease most progress slowly, renal failure occurred late. Mesangiocapillary glomerulonephritis and severe clinical department of membranoproliferative glomerulonephritis is poor, poor prognosis, quickly into chronic renal failure. The main influence for focal segmental glomerulosclerosis is prognosis of urine protein level and the response to treatment in the natural history of 10 non NS patients renal survival rate was 90%, 50% in NS; and NS on hormone therapy remission 10 year renal survival rate was above 90%, is only 40%. 2. clinical factors of proteinuria, hypertension and hyperlipidemia can promote kidney The factors such as glomerular sclerosis, not long-term control, has become an important factor of poor prognosis. 3. had recurrent infections and thromboembolic complications often affect the prognosis.