Pediatric Primary Nephrotic Syndrome

Introduction to primary nephrotic syndrome in children Nephrotic syndrome (NS) is a common pediatric kidney disease. It is a clinical syndrome in which the permeability of the glomerular basement membrane is increased due to various causes, and a large amount of protein is lost from the urine. The main feature is a large amount of proteinuria. , low albuminemia, severe edema and hypercholesterolemia, according to its clinical manifestations are divided into three types: simple nephropathy, nephritic nephropathy and congenital nephropathy. In children under 5 years old, the pathological types of nephrotic syndrome are mostly small lesions, while the pathological types of older children are mostly non-minor lesions (including mesangial proliferative nephritis, focal segmental sclerosis, etc.). basic knowledge The proportion of illness: 0.002%-0.005% Susceptible people: young children Mode of infection: non-infectious Complications: edema, brain edema

Causes of primary nephrotic syndrome in children

(1) Causes of the disease

Nephrotic syndrome can be divided into primary, secondary and congenital according to the etiology. Primary nephrotic syndrome accounts for more than 90%, followed by various secondary nephrotic syndrome. Congenital nephrotic syndrome is extremely rare. .

The etiology of primary nephrotic syndrome is unclear, and its onset is often triggered by respiratory infections, allergic reactions, etc. The causes of secondary nephrotic syndrome are mainly infections, drugs, poisoning, etc. or secondary to tumors, genetic and metabolic diseases. And after systemic systemic disease.

(two) pathogenesis

1. Pathogenesis The pathogenesis of this disease is not fully understood. It is generally believed that proteinuria is caused by the destruction of the wall of the glomerular capillaries and/or the barrier of the sieve. The normal glomerular filtration membrane is negatively charged. The charge barrier consists of a fixed anion site on the basement membrane (mainly heparin sulfate) and the endothelium, a polyanion on the surface of the epithelial cells (mainly citrate protein), and the sieve barrier is filtered by the endothelial cell window inside the membrane. a basement membrane and an epithelial cell fissure membrane composition, wherein the basement membrane plays a major role.

(1) Non-small lesion nephrotic syndrome: through the immune response, activation of complement and coagulation, fibrinolytic system, and matrix metalloproteinases damage the basement membrane, leading to the destruction of the sieve barrier, the emergence of non-selective proteinuria, and, also Proteinuria can occur through non-immune mechanisms such as increased blood pressure, increased blood glucose, or destruction of the screen barrier due to structural defects in the basement membrane.

(2) Minimal lesion nephrotic syndrome:

1 Cellular immune disorder: may be related to cellular immune disorders, especially T cell immune dysfunction, based on:

There is no immunoglobulin and complement deposition in A.MCN kidney tissue.

The number of BT cells decreased, the ratio of CD4+/CD8+ was imbalanced, the activity of Ts was increased, the conversion rate of lymphocytes was decreased, and the pHA skin test reaction was decreased.

C. Inhibition of viral infection of T cells can induce remission of the disease.

D. Diseases with abnormal T cell function such as Hodgkin's disease can cause MCN.

E. Corticosteroids and immunosuppressive agents that inhibit T cells can induce remission of the disease.

Although blood biochemical and endocrine changes may also induce immunosuppressive status in kidney disease, these changes are mainly seen in MCN, but are rare in non-microscopic nephrotic syndrome, suggesting that this immune disorder is more likely to be a cause than a kidney disease. The result of the state.

How 2MCN immune disorders lead to the production of proteinuria has been found:

A. Lymphocytes produce a 29 kd polypeptide that causes a decrease in glomerular filtration membrane polyanion and proteinuria.

B. Concanavalin (conA)-stimulated lymphocytes can produce 60-160kd glomerular permeability factor (GPF), which can directly cause proteinuria.

C. Lymphocytes can also cause proteinuria by secreting 12-18 kd of soluble immune response suppressors (SIRS).

2. Pathology Although some renal interstitial tubule diseases involve a large amount of protein after reaching the glomerulus and reach the standard of nephrotic syndrome, most of the primary or secondary nephrotic syndrome is mainly glomerular lesions, and Pathological classification according to glomerular lesions under light microscopy, there are five pathological types: minimal change nephropathy (MCN), mesangial proliferative glomerulonephritis (MSPGN), focal section Focal segmental glomerulous sclerosis (FSGS), membranous nephropathy (MN) and membranoproliferative glomerulonephritis (MPGN).

Children with nephrotic syndrome are most common with MCN. Glassoek reports that MCN accounts for 66% of 1066 children with kidney disease, while only 21% of adult cases. In 1996, China reported 699 children with nephrotic syndrome kidney living tissue in 20 hospitals nationwide. In the examination, MCN accounted for 18.7%, MSPGN accounted for 37.8%, FSGS accounted for 11.6%, MN was 6.0%, MPGN was 5.5%, and the rest were other types of mild lesions, but these proportions were affected by patient sources and were non-selective. Kidney biopsy, it is difficult to accurately reflect its actual distribution, foreign people have 566 cases of non-selective children with nephrotic syndrome pathological examination found that MCN accounted for 77.8%, MSPGN 2.7%, FSGS 6.7%, MN 1.3%, MPCN 6.7%, so MCN is the most important pathological type of childhood nephropathy.

3. Pathophysiology

(1) A large amount of proteinuria: the most fundamental pathophysiological change, which is also the root cause of the other three major characteristics of the intrinsic, because the glomerular filtration membrane is damaged by immunity or other causes, the charge barrier and/or molecular sieve The barrier effect is weakened, and a large amount of plasma protein leaks into the urine. In recent years, the loss of other protein components has also been noted, and the corresponding consequences, such as:

1 carrier proteins of various trace elements, such as loss of transferrin to small cell hypochromic anemia, zinc-binding protein loss caused by zinc deficiency in vivo.

2 A variety of hormone binding proteins, such as 25-hydroxycalciferol-binding protein, are caused by loss of calcium metabolism in the urine, and loss of thyroxine-binding protein leads to a decrease in T3 and T4.

3 immunoglobulin IgG, IgA and B factors, the loss of complement components caused a decrease in anti-infective power.

4 thrombin III, X, XI factors and loss of prostaglandin binding protein lead to hypercoagulability and thrombosis.

In addition, glomerular epithelial cells and proximal tubular epithelial cells can secrete albumin and degrade it. If protein overload can lead to impaired function of glomerular epithelial cells and tubular epithelial cells, this may be associated with disease progression and therapeutic response. related.

(2) hypoalbuminemia: the loss of a large amount of plasma albumin from the urine is the main cause of hypoalbuminemia. The increase of protein breakdown is a secondary cause, and hypoalbuminemia is a key link in pathophysiological changes. The stability of the body environment (especially osmotic pressure and blood volume) and the metabolism of various substances can have various effects. When the albumin is lower than 25g/L, edema can occur, and at the same time, due to the decrease of blood volume, there is a large amount of concomitant Hypovolemic shock is easily induced when body fluids are lost, and hypoalbuminemia can also affect lipid metabolism.

(3) hypercholesterolemia: may increase liver compensatory albumin synthesis due to hypoproteinemia, some lipoprotein and albumin synthesis through the synthesis of synthetic pathways, coupled with decreased lipoprotein lipase activity and other factors Hyperlipidemia occurs, generally plasma albumin <30g / L, that is, increased blood cholesterol, such as albumin further reduced, the triacylglycerol is also increased.

(4) Edema: The mechanism of edema in nephrotic syndrome has not been fully elucidated. Possible mechanisms:

1 Due to the decrease of plasma albumin, the plasma colloid osmotic pressure is reduced, and the water in the plasma is transferred from the blood vessel into the interstitial space to form edema directly.

2 water extravasation caused by decreased blood volume, through the volume and pressure receptors to change the body's neurohumoral factors (such as antidiuretic hormone, aldosterone, natriuretic factors, etc.), causing water and sodium retention resulting in systemic edema.

3 low blood volume makes the sympathetic nerve excitability increased, the proximal tubule reabsorbs sodium increased, and the water and sodium retention is aggravated.

4 other intrarenal causes lead to increased renal absorption in the renal proximal tubules.

Therefore, edema of primary nephrotic syndrome may be the result of a combination of these factors, and may vary from patient to patient in different stages.

Prevention of primary nephrotic syndrome in children

Active prevention and treatment of infection is an important part of reducing the mortality rate and recurrence rate. In addition to bacterial infection, it is necessary to raise awareness of the infection of conditional pathogens and make timely diagnosis and treatment.

Take care to ensure that the patient's diet, adequate calories and rationalized structure are compared to supplement the necessary vitamins and elements to prevent complications.

Pediatric primary nephrotic syndrome complications Complications edema cerebral edema

1, infection

It is the most common complication and the main cause of death; according to the International Childhood Kidney Disease Research Organization (ISKDC) in 1984, 70% of deaths due to infection directly or indirectly due to infection are often repeated. / or increase the incentives and leads, and can affect the efficacy of hormones.

The causes of infection are intrinsic: 1 low humoral immune function (immunoglobulin loss from urine, reduced synthesis, increased catabolism); 2 often accompanied by cellular immune function and insufficient complement system function; 3 protein malnutrition, edema Cause local circulatory disorders; 4 commonly used corticosteroids, immunosuppressive agents.

Bacterial infections have been dominated by pneumococcal infections in recent years. In recent years, infections caused by bacilli have also increased (such as E. coli). Common respiratory infections, urinary tract infections, skin erysipelas and primary peritonitis generally do not advocate preventive. The use of antibiotics, because the effect is not reliable, and easily lead to the proliferation of drug-resistant strains and dysbacteriosis; but in the event of infection should be promptly active treatment.

Children are also more sensitive to viral infections, especially in the process of receiving corticosteroids and immunosuppressive agents, complicated with varicella, measles, and herpes zoster. The condition is often heavier than the average child; for those with a history of exposure, hormones and immunosuppression The agent can be temporarily reduced, and the injection of -gamma globulin is given, and there are individual reports of temporary relief of nephropathy after infection with measles.

2, hypercoagulable state and thromboembolic complications

(1) Changes in coagulation and fibrinolysis system: The coagulation and fibrinolysis system in the kidney can have the following changes:

1 increased fibrinogen;

2 The increase of V, VII coagulation factor in plasma;

3 antithrombin III decreased;

4 plasma plasminogen activity decreased;

5 The number of platelets can be increased, and the adhesion and aggregation are increased. The result is a hypercoagulable state and thromboembolism can occur.

(2) Renal vein thrombosis: Among them, renal vein thrombosis is the most clinically important.

1 acute renal vein thrombosis: manifested as sudden onset of gross hematuria and abdominal pain, examination of spinal rib angle tenderness and renal lumps, bilateral acute renal dysfunction.

2 chronic renal vein thrombosis: chronic renal vein thrombosis clinical symptoms are not obvious, often only edema aggravated, proteinuria is not relieved, X-ray examination of kidney enlargement, ureteral notch, B-mode can sometimes be detected, if necessary Renal venography was used to confirm the diagnosis.

(3) other parts of the thrombus: in addition to the renal vein, other parts of the vein or artery can also occur in such complications, such as femoral vein, femoral artery, pulmonary artery, mesenteric artery, coronary artery and intracranial artery, and cause the corresponding symptoms .

3, calcium and vitamin D metabolic disorders

In kidney disease, vitamin D-binding protein (VDBP, molecular weight 59000) is lost from the urine, vitamin D deficiency in the body, affecting intestinal calcium absorption, and feedback leads to hyperparathyroidism, clinical manifestations of hypocalcemia, vitamin D in circulation Insufficient, poor bone calcification, these changes are particularly prominent in children in the growing season.

4, low blood volume

Due to the low plasma albumin, the plasma colloid osmotic pressure is reduced, and the intrinsic blood volume is often insufficient. Some children have long-term inappropriate salt avoidance, when there is a sharp loss of body fluids (such as spit, diarrhea, high-dose diuretic application, a large number of Ascites, etc. can occur with varying degrees of hypovolemia, such as orthostatic hypotension, pre-renal azotemia, and even shock.

5, acute renal failure

It is not uncommon to have temporary mild azotemia at the onset of the disease. Acute renal failure can occur during the course of the disease. The reasons are:

(1) low blood volume, inappropriately large amount of diuretic caused by renal blood perfusion, and even can cause tubular necrosis.

(2) severe renal interstitial edema, renal tubules are blocked by protein tube type, resulting in increased hydrostatic pressure in the renal capsule and proximal convoluted tubules, and decreased glomerular filtration.

(3) tubulointerstitial lesions caused by drugs.

(4) complicated bilateral renal vein thrombosis.

(5) glomerular severe proliferative lesions.

6, renal tubular dysfunction

Can be expressed as diabetes, amino acid urine, potassium loss of phosphorus in the urine, lack of concentration and so on.

7, atherosclerosis

Children with persistent hyperlipidemia can occur occasionally, and may have chest tightness, angina pectoris, electrocardiogram changes, and even sudden death when the coronary artery is involved.

8, children with occasional headache, convulsions, visual impairment and other neurological symptoms, may be caused by hypertensive encephalopathy, cerebral edema, dilute hyponatremia, hypocalcemia, hypomagnesemia and other reasons.

9, adrenal cortical crisis

Seen in the sudden withdrawal of corticosteroids or infection stress, endogenous corticosteroid levels are insufficient, manifested as apathy, vomiting, blood pressure reduction and even shock.

Symptoms of primary nephrotic syndrome in children Common symptoms Powerless skin dry edema pale pale hypoproteinemia urine protein azotemia proteinuria hypertension low complement syndrome

Diagnosis of nephrotic syndrome is mainly based on clinical manifestations, where there is a large amount of proteinuria (24h urine protein quantitation >0.1g/kg, or >3.5g/kg), high edema, hypercholesterolemia (>5.7mmol/L, <220mg%) ), hypoalbuminemia (<30g / L, <3Gg%) can be diagnosed as nephrotic syndrome, typical cases of serum protein electrophoresis more suggestive of 2, and , some children may have low complementemia, Microscopic or gross hematuria, azotemia or hypertension, preschool children >1610.6kPa (120/80mmHg), school age >17.3/12kPa (130/90mmHg), is nephritic nephropathy, resistant to hormones (sufficient hormones) 8 weeks of ineffective or partial effect), frequent recurrence or recurrence (years 2 times, 1 year 3 times) and hormone-dependent nephropathy, called refractory nephropathy, refractory nephropathy is one of the indications for renal biopsy, The pathological type can be clarified, the severity of renal disease can be used to guide the treatment, the prothrombin time is shortened, the plasma fibrinogen level is increased, the platelet count is higher than normal, and the hormone treatment process appears. Low back pain with hematuria, elevated blood pressure, increased edema or worsening renal function, suggesting renal vein thrombosis, In addition, the analysis of the primary disease treatment helps, in which a large number of proteinuria and hypoalbuminemia as a prerequisite for diagnosis.

The age and sex of onset were the peak of preschool age. The age of simple onset was small, and the degree of tightness was too long. There were more men than women, and males were about 1.5 to 3.7:1.

Edema is the most common clinical manifestation, often found by parents, starting from the eyelids, face, gradually and limbs, edema is concave, there may be serous effusion such as pleural effusion, ascites, boys often have significant scrotum Edema, body weight can be increased by 30% to 50%, children with severe edema can be seen in the thighs and upper arm inner and abdominal wall skin white or purple lines, the severity of edema usually has nothing to do with the prognosis, edema often with reduced urine output.

In addition to edema, children may suffer from protein malnutrition due to long-term protein loss. The performance is pale, dry skin, dry and sallow hair, white horizontal stripes on the nails, weak ear shells and nasal cartilage, mental weakness, fatigue and weakness. Loss of appetite, sometimes diarrhea, may be related to intestinal mucosal edema and or associated with infection, long-term or recurrent episodes of the author's developmental backwardness, nephritis children may have increased blood pressure and hematuria.

Examination of primary nephrotic syndrome in children

Urine routine

(1) Proteinuria: A large amount of proteinuria is a prerequisite for nephrotic syndrome, and its criteria are:

A. 2 weeks consecutive qualitative (+++).

B. 24h urine protein quantification 50 ~ 100mg / (kg · d).

C. International Society for Pediatric Nephrology (ISKDC) recommends >40mg/(m2·h).

D. Infants and young children are difficult to collect 24h urine, Mendoza recommends any time urine protein / creatinine > 2.0.

Simple nephrotic syndrome is selective proteinuria with a selection index (SPI) > 0.2.

(2) urinary fibrinogen degradation products (FDP): Determination of urinary FDP contributes to the classification of glomerular disease. Urine FDP is measured several times a day, such as FDP<1.25g/ml, then primary glomerular nephropathy (small Pathological nephropathy is likely to be large. If the urinary FDP continues to increase, it is mostly proliferative, membrane proliferative or rapidly progressive crescentic nephritis.

(3) Others: visible transparent tube type or granular tube type, hematuria can be seen in nephritic nephropathy (centrifugal urinary red blood cells > 10 / Hp).

2. Hypoalbuminemia

Total plasma protein decreased, white/globulin was inverted, plasma albumin was <30.0 g/L, and infants were <25.0 g/L.

3. Hyperlipidemia

Mainly for hypercholesterolemia and hypertriglyceridemia, blood cholesterol 5.7mmol / L, infants 5.2mmol / L, triacylglycerol > 1.2mmol / L.

4. Renal function

Generally normal, the urea nitrogen in the oliguria period is slightly elevated.

5. Protein electrophoresis

The 2-globulin is markedly increased, and the -globulin is lowered.

6. Other

Erythrocyte sedimentation rate increased, and continued low complementarity, urinary FDP in some nephritis can be greater than 1.25mg / L (1.25g / ml).

Regular X-ray examination, B-ultrasound and electrocardiogram examination.

Chronic renal vein thrombosis X-ray examination can be found that the kidney is enlarged, the ureter has a notch, B-ultrasound can sometimes be detected, if necessary, renal venography to confirm the diagnosis, in addition to the renal vein, other parts of the vein or artery can also occur Comorbidities, such as the femoral vein, femoral artery, pulmonary artery, mesenteric artery, coronary artery and intracranial artery, etc., and cause the corresponding symptoms, clinically selected according to the performance of the examination site and method.

Diagnosis and diagnosis of primary nephrotic syndrome in children

Diagnostic criteria

Diagnosis can be based on medical history, clinical symptoms, and laboratory findings.

1. Diagnostic criteria for nephrotic syndrome

(1) A large amount of proteinuria: urinary protein ~ lasts for more than 2 weeks, and 24h urine protein is more than 0.1g/kg.

(2) Hypoproteinemia: plasma albumin is less than 30g/L.

(3) Hypercholesterolemia: cholesterol is greater than 5.7 mmol/L (220 mg/dl).

(4) edema: edema can be light and heavy, a large number of proteinuria and hypoproteinemia are essential.

2. Diagnostic criteria for nephritic nephrotic syndrome

On the basis of the four characteristics of nephrotic syndrome, one or more of the following four items can be diagnosed as nephritic nephrotic syndrome.

(1) Hematuria: More than 10 urinary red blood cells/Hp (refer to three or more centrifugation tests performed within 2 weeks).

(2) Persistent or recurrent hypertension: preschool children over 16.0/10.6 kPa (120/80 mmHg), school-age children over 17.33/12.0 kPa (130/90 mmHg), and excluded due to adrenocortical hormone.

(3) persistent azotemia: urea nitrogen (BUN) exceeded 10.7 mmol / L (30 mg / dl), and excluded due to insufficient blood volume.

(4) Serum total complement (CH50) or C3 is continuously or repeatedly decreased.

Differential diagnosis

1. Simple nephrotic syndrome, which meets the above four criteria is simple nephrotic syndrome.

2, nephritic nephrotic syndrome, in addition to the above four items, one or more of the following four can be diagnosed as nephritic nephrotic syndrome, (1) uroscopy red blood cells more than 10 / HP, ( 2) Repeated hypertensive patients, school-age children greater than 130/90 mm Hg, preschool children greater than 120/80 mm Hg, (3) persistent azotemia, urea nitrogen greater than 10.7 mmol per liter, (4) blood Complement C3 is repeatedly lowered.

In addition, primary nephrotic syndrome must be differentiated from secondary or primary nephritis with symptoms of nephrotic syndrome, such as lupus nephritis, purpuric nephritis, nephritis after streptococcal infection, and acute nephritis.

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