What Is Nephrotic Syndrome?

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

Basic Information

English name

nephrotic syndrome, NS

Visiting department

Nephrology

Multiple groups

child

Common causes

Caused by infection, genetics, immunity, etc.

Common symptoms

Massive proteinuria, hypoproteinemia, edema, and hypercholesterolemia

Causes of nephrotic syndrome

Divided into three categories of primary, secondary and hereditary, primary NS belongs to primary glomerular disease, which has a variety of pathological types.

classification	child	teens	Middle-aged and elderly
Primary	Minimally diseased nephropathy	Mesangial proliferative glomerulonephritis Minimally diseased nephropathy Focal segmental glomerulosclerosis Mesangial capillary glomerulonephritis	Membranous nephropathy
Secondary	Allergic purpura nephritis Hepatitis B virus-associated nephritis Systemic lupus erythematosus nephritis	Systemic lupus erythematosus nephritis Allergic purpura nephritis Hepatitis B virus-associated nephritis	Diabetic nephropathy Renal amyloidosis Myeloma nephritis Lymphoma or solid tumor nephropathy

Clinical manifestations of nephrotic syndrome

The most basic features of NS are massive proteinuria, hypoalbuminemia, (high) edema, and hyperlipidemia, a group of clinical syndromes characterized by the so-called "three highs and one low" and other metabolic disorders.

Large amount of proteinuria

A large number of proteinuria is the most important clinical manifestation of NS patients and the most basic pathophysiological mechanism of nephrotic syndrome. Large amount of proteinuria refers to the urine protein excretion of adults> 3.5g / d. Under normal physiological conditions, the glomerular filtration membrane has a molecular barrier and a charge barrier, which results in an increase in the protein content of the raw urine. When the absorption capacity of the proximal tubule is far exceeded, a large amount of proteinuria is formed. On this basis, all factors that increase the pressure in the glomeruli and cause high perfusion and high filtration (such as hypertension, high protein diet or large infusion of plasma protein) can increase the excretion of urine protein.

2. Hypoproteinemia

Plasma albumin decreased to <30g / L. A large amount of albumin is lost from urine during NS, which promotes the liver's compensatory synthesis of albumin and an increase in renal tubular breakdown. Hypoalbuminemia occurs when the increase in liver albumin synthesis is not sufficient to overcome loss and breakdown. In addition, patients with NS due to gastrointestinal mucosal edema leading to reduced diet, insufficient protein intake, malabsorption or loss are also the causes of exacerbation of hypoalbuminemia.

In addition to the decrease in plasma albumin, certain immunoglobulins (such as IgG) and complement components, anticoagulant and fibrinolytic factors, metal-binding proteins and endocrin-binding proteins in plasma can also be reduced, especially a large amount of proteinuria, Severe pathological damage and non-selective proteinuria are more pronounced. Patients are prone to complications such as infection, hypercoagulability, lack of trace elements, endocrine disorders, and low immune function.

3. Edema

Hypoalbuminemia and plasma colloid osmotic pressure decrease during NS, which causes water to enter the interstitial space from the blood vessel cavity, which is the basic cause of NS edema. Studies in recent years have shown that approximately 50% of patients have normal or increased blood volume and normal or decreased plasma renin levels, suggesting that some primary sodium and water retention factors may play a role in the mechanism of NS edema.

4. Hyperlipidemia

The cause of NS combined with hyperlipidemia has not yet been fully elucidated. Hypercholesterol and / or hypertriglyceridemia, serum LDL, VLDL and lipoprotein () concentrations increase, often coexisting with hypoproteinemia. Hypercholesterolemia is mainly due to an increase in the production of lipoproteins by the liver, but a decrease in decomposition in the peripheral circulation also plays a part. Hypertriglyceridemia is mainly due to catabolic disorders, and increased liver synthesis is a secondary factor.

Diagnosis of nephrotic syndrome

1. The diagnostic criteria for nephrotic syndrome (NS) is

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

(2) Plasma albumin is less than 30g / L;

(3) Edema;

(4) Hyperlipidemia. Two of them are necessary for diagnosis.

2.NS diagnosis should include three aspects

(1) Diagnosis of NS.

(2) Confirmation of etiology: First, secondary and hereditary diseases should be excluded before the diagnosis of primary NS can be confirmed; renal biopsy is best to make pathological diagnosis.

(3) Determine whether there are complications.

Differential diagnosis of nephrotic syndrome

Allergic purpura nephritis

Occurs in adolescents with typical skin purpura, often symmetrically distributed on the distal extremities, more than hematuria and / or proteinuria 1 to 4 weeks after the rash.

2. Systemic lupus erythematosus nephritis

Occurs in middle-aged women and adolescents. Immunological examination shows a variety of autoantibodies and multiple systemic injuries, which can be diagnosed clearly.

3. Hepatitis B virus-related nephritis

More common in children and adolescents, clinical manifestations are mainly proteinuria or NS, and the common pathological type is membranous nephropathy. Diagnosis basis: serum HBV antigen is positive; suffering from glomerulonephritis and excluding secondary glomerulonephritis; kidney biopsy section found HBV antigen.

4. Diabetic nephropathy

Occurs in middle-aged and elderly people, and is commonly seen in patients with diabetes for more than 10 years. Early urine microalbumin excretion can be found to increase, and gradually develop into a large amount of proteinuria, NS. A history of diabetes and characteristic fundus changes can help with differential diagnosis.

5. Renal amyloidosis

Occurs in middle-aged and elderly people. Renal amyloidosis is part of multiple organ involvement throughout the body. Primary amyloidosis mainly affects the heart, kidney, digestive tract (including tongue), skin, and nerves; secondary amyloidosis is often secondary to diseases such as chronic suppurative infection, tuberculosis, and malignant tumors, mainly affecting the kidneys and liver And spleen and other organs. Renal involvement increases in volume, often NS. Renal amyloidosis often requires a renal biopsy.

6. Myeloma nephropathy

Occurs in middle-aged and elderly people, which are more common in men. Patients may have the characteristic clinical manifestations of multiple myeloma, such as bone pain, increased serum monoclonal globulin, protein electrophoresis M-band, and urine protein positive this week. Bone marrow shows plasma cells. Abnormal hyperplasia (occupies more than 15% of nuclear cells) and is accompanied by qualitative changes. NS can occur in multiple myeloma involving the glomeruli. The above-mentioned characteristic manifestations of myeloma are conducive to differential diagnosis.

Nephrotic syndrome complications

Complications of NS are important factors affecting the long-term prognosis of patients and should be actively prevented.

Infection

Generally, antibiotics are not required to prevent infection during hormone treatment, otherwise not only the prevention purpose will not be achieved, but fungal double infection may be induced. Once an infection is found, antibiotics that are sensitive to pathogenic bacteria, potent and non-nephrotic should be selected for active treatment in time, and those with a clear infection should be removed as soon as possible. When severe infections are difficult to control, the reduction or withdrawal of hormones should be considered, but it depends on the specific circumstances of the patient.

2. Thrombosis and embolism complications

It is generally believed that when plasma albumin is less than 20 g / L (idiopathic membranous nephropathy is less than 25 g / L), anticoagulant therapy can be given by subcutaneous injection of sodium heparin (also can choose low molecular weight heparin) or oral warfarin. Anticoagulation can be supplemented with antiplatelet drugs such as dipyridamole or aspirin. For those who have developed thrombosis and embolism, they should be administered systemic or local thrombolytic therapy with urokinase or streptokinase as early as possible (the effect is best within 6 hours, but it is still expected to be effective within 3 days). More than six months. Anticoagulant and thrombolytic therapy should avoid excessive drug bleeding.

3. Acute renal failure

NS associated with acute renal failure can be life-threatening if improperly handled, and most patients are expected to recover if given promptly and correctly. The following measures can be taken:

(1) Diarrhea diuretics Those who are still effective should be given a larger dose to wash away the obstructed renal tubular cast;

(2) Hemodialysis Diuretic is ineffective, and those who have reached the dialysis indication should be hemodialyzed to maintain life and properly dehydrated after supplementation with plasma products to reduce renal interstitial edema;

(3) Primary disease treatment Because its pathological type is mostly minimally pathological nephropathy, it should be actively treated;

(4) Alkalized urine Sodium bicarbonate can be used to alkalinize urine to reduce cast formation.

4. Disorders of protein and fat metabolism

It is often difficult to completely correct metabolic disorders before NS relief, but the amount and structure of protein and fat in the diet should be adjusted in an effort to minimize the effects of metabolic disorders. At present, many drugs can be used to treat protein and fat metabolism disorders. For example, both ACEI and angiotensin receptor antagonists can reduce urinary protein. Studies have suggested that traditional Chinese medicine Astragalus can promote liver albumin synthesis, and may have the effect of reducing hyperlipidemia. Lipid-lowering drugs can be selected from cholesterol-lowering hydroxyglutarate coenzyme A (HMG-CoA) reductase inhibitors, such as statins such as lovastatin; or triglyceride-based clobetin Class, such as fenofibrate, etc. Hyperlipidemia can be naturally relieved after NS remission, and no further medication is required.

Nephrotic Syndrome Treatment

(A) general treatment

Those with severe edema and hypoproteinemia need bed rest. After the edema disappears and the general condition improves, you can get up and move.

A normal amount of 0.8 to 1.0 g / (kg · d) of high-quality protein (mainly rich in essential amino acid animal protein) diet was given. Ensuring sufficient calories, daily weight should not be less than 30 ~ 35kcal. Although patients lose a large amount of urinary protein, high protein diets increase glomerular hyperfiltration, which can aggravate proteinuria and promote the progression of renal disease, so it is generally no longer recommended.

Edema should be reduced to a salt (<3g / d) diet. To reduce hyperlipidemia, eat less diet rich in saturated fatty acids (animal fats) and eat more diets rich in polyunsaturated fatty acids (such as vegetable oils and fish oils) and soluble fiber (such as beans).

(Two) symptomatic treatment

Diuretic swelling

(1) Thiazine diuretics Mainly act on the thick-walled section of the ascending branch of the myelin and the anterior segment of the distal tubule, diuretic by inhibiting sodium and chlorine reabsorption and increasing potassium excretion. Long-term use should prevent hypokalemia and hyponatremia.

(2) Rhenium potassium diuretics Mainly acts on the posterior segment of the distal tubule, and excrete sodium and chlorine, but Rhenium potassium is suitable for patients with hypokalemia. Diuretic effect is not significant when used alone, and can be combined with thiazide diuretics. Commonly used ampicillin or aldosterone antagonist spironolactone. Long-term use needs to prevent hyperkalemia, and patients with renal insufficiency should be used with caution.

(3) Diuretics Mainly act on the ascending branch of the myelin, and have a strong inhibitory effect on the reabsorption of sodium, chlorine and potassium. Furosemide (fast urine) or bumetanide (buturamine) are commonly used (the effect is 40 times stronger than furosemide at the same dose), orally or intravenously. The effect is better when the osmotic diuretic is applied immediately after application. Be careful of hyponatremia and hypokalemia and hypochloremic alkalosis when using diuretics.

(4) Osmotic diuretics By temporarily increasing the plasma colloid osmotic pressure, water in the tissue can be absorbed back into the blood. In addition, they are filtered through the glomerulus, causing a hypertonic state of the renal tubule fluid, reducing the reabsorption of water and sodium and diuretic. Dextran 40 (low-molecular dextran) or starch-based plasma (706-generation plasma) (both molecular weights are 25,000 to 45,000) without sodium are commonly used intravenously. Subsequent addition of urinary diuretics can enhance the diuretic effect. But for patients with oliguria (urine volume <400ml / d), such drugs should be used with caution, because it is easy to form casts with the Tamm-Horsfall protein secreted by the renal tubules and the albumin filtered by the glomeruli. And due to its hypertonic effect, renal tubular epithelial cells degeneration and necrosis, induce "osmotic nephropathy", and lead to acute renal failure.

(5) Increasing plasma colloid osmotic pressure Plasma or plasma albumin and other intravenous infusions can increase plasma colloid osmotic pressure, promote water absorption and diuresis in tissues, such as slow intravenous infusion of furosemide in glucose solution, Sometimes a good diuretic effect can be obtained. However, since the input protein will be excreted from the urine within 24 to 48 hours, it can cause high glomerular filtration and high tubular metabolism, cause damage to the glomerular layer and tubular epithelial cells, and promote renal interstitial fibers. The milder affects the efficacy of glucocorticoids, delays the remission of the disease, and severely damages renal function. Therefore, the indications should be strictly controlled. NS patients with severe hypoproteinemia, high edema, and oliguria (urinary volume <400ml / d) should be considered when diuresis is necessary, but excessive frequency should be avoided. . Patients with heart failure should be used with caution.

The principle of diuretic treatment for NS patients is not to be too fast or too fierce, so as not to cause insufficient blood volume, aggravate the tendency of high blood coagulation, and induce complications of thrombosis and embolism.

2. Reduce urine protein

Sustained large amount of proteinuria itself can cause high glomerular filtration, aggravate tubulo-interstitial damage, and promote glomerulosclerosis, which are important factors affecting the prognosis of glomerulopathy. Decreased urinary protein has been shown to delay the deterioration of renal function.

Angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor antagonist (ARB), in addition to effectively controlling hypertension, can reduce the glomerular pressure and directly affect the glomerular basement membrane. The permeability of the molecule has a urinary protein-reducing effect that does not depend on lowering systemic blood pressure. When ACEI or ARB is used to lower urinary protein, the dosage should generally be larger than the conventional antihypertensive dose in order to obtain good results.

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

Glucocorticoid therapy

Glucocorticoids (hereinafter referred to as hormones) are used in kidney diseases, mainly for their anti-inflammatory effects. It can reduce the exudation during acute inflammation, stabilize the lysosomal membrane, reduce fibrin deposition, reduce capillary permeability and reduce urine protein leakage; in addition, it can also inhibit the proliferative response in chronic inflammation and reduce fibroblasts Activity to reduce fibrosis caused by tissue repair. The response of glucocorticoids to the disease depends to a large extent on its pathological type, and the effect of small lesions is the most rapid and certain. The principles and schemes of use are generally: Initial sufficient dose: Prednisone is commonly used for 8 weeks orally, and can be extended to 12 weeks if necessary; Slow drug reduction; reduce the original dosage every 2 to 3 weeks after adequate treatment 10%, when it is reduced to about 20mg / d, the symptoms are easy to repeat, and it should be reduced more slowly; Long-term maintenance: last for a few months to half a year with the minimum effective dose. Hormones can be taken in full daily doses or once every other day in two days during the maintenance period to reduce the side effects of hormones. When the edema is severe, liver function is impaired, or prednisone is ineffective, it can be replaced with prednisone orally or intravenously.

According to the patient's response to glucocorticoid treatment, it can be divided into "hormonal sensitive" (NS remission within 8 to 12 weeks of treatment), "hormone dependent" (hormonal relapse to a certain extent, that is, relapse) and "hormonal resistance There are three types of "type" (ineffective hormone therapy), and their further treatments are different.

Patients with long-term use of hormones may have side effects such as infection, drug-induced diabetes, and osteoporosis. A few cases may also occur aseptic ischemic necrosis of the femoral head, which needs to be strengthened for monitoring and timely treatment.

2. Cytotoxic drugs

Hormonal therapy is ineffective, or hormone-dependent or recurrent, and can be assisted with cytotoxic drugs. Because these drugs are mostly gonadotoxic, liver damage, and large doses can cause the risk of tumors, they should be carefully mastered in the indications and course of treatment. Among such drugs, cyclophosphamide (CTX) and phenylbutyric acid nitrogen mediation (CB1348) have more clinical applications.

3. Immunosuppressive

At present, the commonly used immunosuppressants in clinical practice are cyclosporine A, tacrolimus (FK506), mycophenolate mofetil and leflunomide.

In the past, immunosuppressants were often used in combination with glucocorticoids to treat many different pathological types of nephrotic syndrome. In recent years, some patients have been recommended due to relative contraindication or intolerance to glucocorticoids (such as uncontrolled diabetes, mental factors, severe Osteoporosis), and some patients are unwilling to receive glucocorticoid treatment regimens or patients with contraindications can be treated with immunosuppressants alone (including as an initial regimen) for certain pathological types of nephrotic syndrome, such as focal segments Glomerulosclerosis, membranous nephropathy, micropathy nephropathy, etc.

There are many options for the treatment of NS with glucocorticoids and immunosuppressants (including cytotoxic drugs). In principle, it is advisable to enhance the efficacy and minimize the side effects. The use of hormone therapy, the length of treatment, and the use and selection of immunosuppressants (cytotoxic drugs) should be based on the pathological type, age, renal function, and relative contraindications of the patient's glomerulopathy. Different treatment, based on the target of the role of immunosuppressive agents, to develop individualized treatment plans. In recent years, according to the results of evidence-based medicine research, corresponding treatment plans have been proposed for different pathological types.

Prognosis of nephrotic syndrome

Individual prognosis for NS varies widely. The main factors determining prognosis include:

Pathological type

In general, the prognosis for micropathic nephropathy and mild mesangial proliferative glomerulonephritis is good. Some patients with minimally pathological nephropathy can resolve spontaneously, and the remission rate is high, but it is easy to relapse after remission. Early membranous nephropathy still has a high rate of treatment remission. Although it is difficult to achieve treatment remission in the later stage, most of the disease progresses slowly and renal failure occurs later. Mesangial capillary glomerulonephritis and severe mesangial proliferative glomerulonephritis are not effective, have a poor prognosis, and quickly enter chronic renal failure. The most important factors affecting the prognosis of focal segmental glomerulosclerosis are the degree of urinary protein and response to treatment. The 10-year renal survival rate of non-NS patients in natural course is 90%, and 50% in NS patients; The 10-year renal survival rate of remission patients was over 90%, and those who did not respond were only 40%.

2. Clinical factors

A large amount of proteinuria, hypertension and hyperlipidemia can promote glomerulosclerosis. If the above factors are not controlled for a long time, they will become important factors for poor prognosis.

3. Recurrence of infection and complications of thromboembolism often affect prognosis.