Acute poststreptococcal glomerulonephritis in children

Acute poststreptococcal glomerulonephritis (acute glomerulonephritis, acute nephritis, postinfection glomerulonephritis) is an immunocomplex disease with diffuse kidney damage, mainly of the glomeruli, which occurs 10-14 days after streptococcal infection (angina, impetigo, scarlet fever, pyoderma, etc.) and characterized by nephritic syndrome.

ICD-10 codes

• N00. Acute nephritic syndrome.
• N00.0. Acute nephritic syndrome with minor glomerular disorders.
• N04. Nephrotic syndrome.

Epidemiology of acute glomerulonephritis in children

The incidence of post-streptococcal glomerulonephritis averaged 32.4 cases per 100,000 children. Most cases of sporadic, epidemic outbreaks occur rarely. In winter and spring, the occurrence of post-streptococcal glomerulonephritis is associated with acute respiratory viral infection, in summer and in the autumn - with pyoderma. In recent decades, in developed countries, there has been a reduction in the incidence of glomerulonephritis to 10-15% of all glomerulonephritis, which is associated with an improvement in socioeconomic conditions. In developing countries, post-streptococcal glomerulonephritis is the cause of 40-70% of all glomerulonephritis. The peak incidence falls on preschool and primary school age (5-9 years), less than 5% of children suffer from glomerulonephritis before the age of 2. Post-streptococcal glomerulonephritis is 2 times more common in boys. In recent years, the incidence of acute post-streptococcal glomerulonephritis has increased in Russia, which is associated with an increase in the frequency of streptococcal infection in children due to the emergence of resistant strains to the main antibacterial drugs used in clinical practice.

[1], [2], [3], [4], [5]

Causes of acute glomerulonephritis in children

Etiological factor can be established in 80-90% of cases of acute glomerulonephritis and only 5-10% - chronic.

The main etiological factors of acute glomerulonephritis

• Infectious.
  • Bacteria: group A beta-hemolytic streptococcus, enterococci, pneumococci, staphylococcus, corynebacterium, Klebsiella, salmonella, mycoplasma, iersenia, meningococcus.
  • Viruses: hepatitis B, measles, Epstein-Barr, Coxsackie, rubella, chicken pox, cytomegalovirus, less often - herpes simplex virus.
  • Parasites: plasmodium of malaria, toxoplasma, schistosomes.
  • Mushrooms: Candida.
• Non-infectious.
• Alien proteins.
• Serums.

The most common cause of development of acute glomerulonephritis in children is a streptococcal infection, therefore in all guidelines acute acute poststreptococcal GB is isolated. Most often, 1-3 weeks before acute glomerulonephritis, children suffer angina, pharyngitis, skin infections, less often scarlet fever. These diseases cause beta-hemolytic streptococcus group A, most often M-type strains 1, 3, 4, 6, 12, 25, 49 after infections of the upper respiratory tract, as well as M-type strains 2, 49, 55 after skin infections. These types are called nephritogenic, of which the most common are strains 12 and 49.

Other bacterial antigens cause the disease less often.

Viral antigens cause the development of acute glomerulonephritis in children in a small percentage of cases. In case of puncture biopsy, antigens of viruses are found in deposits with immunofluorescence. Even less important role in the etiology of OGN is caused by diseases caused by protozoa and fungi.

Resolving factors can be: cooling, excessive insolation, physical trauma.

The peak of acute glomerulonephritis in children occurs during the autumn-winter period, at low temperatures and high humidity.

What causes acute glomerulonephritis?

[6]

Pathogenesis of acute glomerulonephritis

In the pathogenesis of acute glomerulonephritis in children, two mechanisms can be distinguished: immunocomplex and non-immunocomplex.

The majority of true glomerulonephritis are immunocomplex, while the soluble immune complexes "antigen-antibody" are deposited in the glomeruli. Immune complexes can be formed in the circulation of blood - circulating immune complexes (CIC) - or locally in the kidney tissue. At the heart of the formation of the CEC is a protective mechanism aimed at removing the antigen. In conditions of excess antigen, the production of antibodies increases, the size of the complexes increases, they activate complement and are removed from circulation by a mononuclear phagocytic system. Part of the immune complexes that have not undergone phagocytosis are put by the blood flow into the kidneys and deposited in the capillaries of the glomerulus, causing glomerulonephritis. There are other factors that lead to the deposition of the CEC:

• large endothelial surface of capillary capillaries;
• a large volume of blood passing through the glomeruli;
• positive electric charge of the antigen, since complexes with positively charged antigen are deposited on the negatively charged wall of the glomerular capillaries. Immunocomplex glomerulonephritis differs depending on the location of immune complexes (IR), the class of immunoglobulins and the presence of complement components in the kidney tissue.

Immune complexes can be formed and deposited in the kidney in different ways and in different glomerular structures:

• from the circulation (CEC), while they are located subendothelial and / or in mesangium;
• And K can be formed "in situ" by antibodies to glomer antigens or to antigens not related to the glomerular basement membrane. In this case, IK are subepithelial;
• it may be altered immunoglobulins, rather than immune complexes. For example, the deposition of polymeric forms of immunoglobulin A in mesangium.

Immune complexes attract inflammation cells (neutrophils, monocytes, platelets) that form proinflammatory cytokines (IL-1, TNF, TGF-a) into the focus of their deposits. Cytokines activate the accumulation of vasoactive substances, which leads to damage, the appearance of cracks and increased permeability of the basal membranes. The kidney responds to the damage by the proliferation of mesangial and endothelial cells. Inflammatory infiltrate develops. Damage to the endothelium of the capillaries leads to local activation of the coagulation system and parietal thrombus formation, narrowing of the lumen of the vessels. As a result of inflammation, hematuria, proteinuria and renal dysfunction occur. The picture of acute proliferative GB is developing, more often with the clinical picture of ONS.

With non-immunocomplex glomerulonephritis, cell-mediated immune responses develop. In this case, the leading role is assigned to the emergence of a pathological clone of T-lymphocytes, which stimulates the hyperproduction of lymphokines that damage the glomeruli.

A pathological clone of T-lymphocytes can exist as a primary defect or arise under the influence of such immune complexes that are not localized in the glomerulus but have the ability to activate a pathological clone of T-lymphocytes. Dysfunction of T cells promotes hyperproduction of vasoactive interleukin. The object of the action of cytokines is the glomerular epithelial cells responsible for the synthesis of negatively charged proteoglycans and sialoproteins that form part of the glomerular basal membranes. This leads to a loss of negative charge on the basal membrane (BM) and podocytes. It is also possible to directly affect the neuraminidase BM, the virotoxin. Loss of negative charge on BM and podocytes leads to selective loss of large volumes of finely dispersed proteins (mainly albumins). Pronounced proteinuria causes the development of clinical and laboratory syndrome, called nephrotic (NS).

Pathomorphology of acute glomerulonephritis

Acute poststreptococcal glomerulonephritis in children is characterized by a diffuse endocapillary proliferative process. The proliferation of mesangial and endothelial cells is expressed in the glomerulus. The loops of the capillaries in the glomeruli look swollen, with thickened walls. The lumen of the capillaries is narrowed. In the first 4 weeks of the disease on the site of the glomerular cell inflammation: neutrophils, eosinophils, lymphocytes, macrophages. Proliferation of epithelial cells is minimal. Narrowed and subcapsulated space. BM thickened or thinned, tears are found in them.

Electron microscopy reveals large deposits in the form of humpbacks (IR + C +) located on the inner or outer side of the BM and, rarely, inside it in the form of cloddy deposits.

In immunohistological examination, the components of complement, various immunoglobulins (in, M, A, E), antigens of streptococci or other antigens are determined in deposits.

The morphological variant of acute glomerulonephritis with nephrotic syndrome is most often manifested by minimal changes in children. They are called the disease of "small legs of podocytes". Light microscopy does not make it possible to detect pathology. Only the introduction of electron microscopy allowed to study changes in podocytes. Electron microscopy is used to detect severe changes in podocytes in the form of deformation, fusion and loss of small legs throughout the entire length of the capillary wall. Fusing with each other, the small legs form an uneven thickness layer that covers the BM.

The BM remains unchanged, retains its structure and thickness. In the cells of the tubular epithelium, the protein and fatty degeneration are expressed. This is due to the overload of the tubular epithelium with massive proteinuria and lipiduria. Glucocorticoid therapy results in the normalization of the structure of podocytes.

Acute glomerulonephritis with nephritic syndrome

Acute nephritic syndrome (ONS) is a classic manifestation of acute glomerulonephritis. More often children of school age from 7 to 14 fall ill. ONS develops in 1-6 weeks after the infection (more often streptococcal). In the latent period, the state of children remains satisfactory. Often they start attending school, but then the deterioration comes again: lethargy, malaise, loss of appetite.

The main criteria for the diagnosis of acute glomerulonephritis with nephrotic syndrome:

• moderate edema at a normal level of protein and albumin against a background of increased BCC;
• arterial hypertension;
• urinary syndrome in the form of macro- or microhematuria, proteinuria less than 2 g / day, non-selective nature.

The onset of the disease can be turbulent, acute, with a classic triad of symptoms: edema, arterial hypertension, macrogematuria. Children complain of malaise, headache, nausea, vomiting, a change in the color of urine, a decrease in its quantity. The degree of expression of these symptoms is different.

Less often, there is a gradual development of the disease with scant clinical and laboratory changes.

During examination, edema of the eyelids, shins, paleness of the skin due to spasm of the vessels is always found. Spasm of blood vessels is also expressed on the retina of the fundus. Patients may complain of headache and back pain, which is explained by the expansion of the capsule of the kidney due to their edema.

[7], [8], [9], [10], [11], [12]

Pathogenesis of the main symptoms in acute nephritic syndrome

Edema

Edemas - one of the main manifestations of ONS - occur in 60-80% of patients. The degree of expression can vary within wide limits: from edema of the eyelids in the mornings to the expressed puffiness of the face, shins, anterior abdominal wall. Very rarely, but can develop cavitary edema: hydrothorax, hydropericardium, ascites. During the period of swelling, patients can gain 2-5 kg in weight. Occurrence of edema occurs gradually. They are dense, sedentary.

Mechanism of edema formation:

• increase in the volume of circulating blood as a result of reduced glomerular filtration - hypervolemia;
• retention of sodium and water (hyperaldosteronism, increased secretion of ADH);
• increased vascular permeability as a result of hyaluronidase activity of streptococcus, histamine release and activation of kallikrein-kinin system.

The formation of peripheral edema can be considered as a compensatory mechanism, since some of the fluid from the vascular bed moves to the tissues, reducing hypervolemia, and this prevents the development of complications. With the deposition of fluid may also be associated with an increase in the liver and spleen. Edema is usually easily cured by prescribing a salt-free diet and diuretic medications. Duration of edema is 5-14 days.

[13], [14]

Arterial hypertension

Arterial hypertension - one of the terrible symptoms of acute glomerulonephritis (OGN) - occurs in 60-70% of patients. Patients complain of a headache, nausea, vomiting. The development of hypertension occurs quickly. With her most often associated complications: eclampsia and acute heart failure. Arterial hypertension is systolic-diastolic, but with a large increase in systolic pressure. The mechanism of arterial hypertension in the ONS:

• hypervolemia, i.e. An increase in the volume of circulating blood (BCC) occurs due to a drop in glomerular filtration, a delay in water and sodium;
• a much smaller role is played by the activation of the renin-angiotensin-aldosterone system.

Due to the fact that hypervolemia serves as the main mechanism for the development of hypertension, it can be easily treated (salt-free diet, diuretics), there is less need to prescribe antihypertensive drugs. Do not administer drugs that increase BCC. The duration of hypertension syndrome is 7-14 days.

[15], [16], [17]

Urinary Syndrome

Oliguria - a decrease in normal diuresis by 20-50% of the norm. There is an oliguria due to the decline of glomerular filtration and increased reabsorption of water and sodium, the development of "antidiureza" and increased secretion of ADH. Relative density of urine is high. Oliguria occurs in the first days of the disease and lasts 3-7 days.

Hematuria - one of the main manifestations of urinary syndrome - occurs in 100% of patients. Macrogematuria is found in the beginning of the disease in 60-80% of patients, its severity gradually decreases to the 3-4th week. In the majority of patients, hematuria completely stops by the 8th-10th week, but in some cases the microhematuria remains for 6-12 months.

Hematuria is associated with increased permeability of BM, its ruptures. In the urine appear dysmorphic erythrocytes (altered, irregular shape), which is due to their glomerular origin. Erythrocyte cylinders may also occur.

Proteinuria is one of the leading signs of kidney damage, in all cases it is necessary to establish a daily protein loss. In norm it is 100-200 mg / day. With ONS, the daily proteinuria ranges from 1 to 2.5 g / day. Protein, lost with urine, of plasma origin and contains small and large proteins, i.e. Proteinuria nonselective. The leading mechanism of proteinuria is structural changes in the basement membrane (increase in pore size, cracks) and functional changes (loss of negative charge). Proteinuria gradually decreases to the second or third week of the disease. Prolonged proteinuria up to 1.5-2 g / day is a poor prognostic sign.

Leukocyturia with ONS can occur in the first week of the disease and has an abacterial nature. It is explained by active immune inflammation with the involvement of neutrophils, lymphocytes and monocytes in the focus of inflammation in the 1-2-nd week.

Cilindrarium may be present (30-60%) in the initial period. By its structure, the cylinders are a tubular protein (tamm-Horsfall uroprotein) with the incorporation of shaped elements, epithelial cells, detritus. With OGN can appear erythrocyte, granular cylinders.

Pathogenesis of acute glomerulonephritis

Symptoms of acute glomerulonephritis in children

The course of ONS, as a rule, is cyclical, with a gradual decrease in clinical and laboratory indicators.

First of all, the disappearance of clinical symptoms, in the first week of the disease, diuresis, blood pressure, disappear edema, the concentration of urea and creatinine decreases. The normalization of the amount of complement occurs by the 6th-8th week, the disappearance of changes in the urine sediment occurs more slowly. Macrogematuria passes through 2-3 weeks, proteinuria - within 3-6 months, the disappearance of microhematuria occurs within a year.

Symptoms of acute glomerulonephritis

Classification

Clinical classification of acute glomerulonephritis

Clinical manifestations of acute poststreptococcal glomerulonephritis	Activity of the pathological process	Kidney function status
Nephritic syndrome (HC) Isolated urinary syndrome Nephritic syndrome with hematuria and arterial hypertension	The period of initial manifestations. Period of reverse development. Transition to chronic glomerulonephritis	Without impaired renal function. With impaired renal function. Acute kidney failure

[18], [19], [20], [21], [22],

Diagnosis of acute glomerulonephritis in children

To diagnose, in addition to the clinical picture, great importance is the laboratory diagnosis.

In the general analysis of blood in the first days of the disease, anemia associated with hypervolemia can be diagnosed, i. Anemia is relative. Small leukocytosis and an increase in ESR can be detected.

The aetiological role of streptococcus is confirmed by an increase in the concentration of ASL-O, as well as sowing from the throat and nose of hemolytic streptococcus.

An increase in the content of CRH and seromucoid is indicative of inflammation, and an increase in the number of CICs, immunoglobulins (G, M), and a decrease in the concentration of the complement C3 component testify to its immune character. The content of total protein and albumins can be somewhat reduced, and cholesterol - increased.

In the initial period with oliguria, an increase in the concentration of urea and creatinine is possible with a high specific gravity of urine, which is regarded as a renal failure of an acute period.

In ultrasound diagnosis, an increase in the size of the kidneys and a violation of the differentiation of structures are noted.

Diagnosis of acute glomerulonephritis

[23], [24], [25], [26], [27], [28], [29], [30]

Indications for consultation of other specialists

With persistently persisting arterial hypertension, it is necessary to consult an ophthalmologist for examination of the fundus to exclude angiopathy of the retinal vessels. Consultation of an otolaryngologist is necessary for suspected chronic tonsillitis, adenoiditis for choosing a method of treatment (conservative, surgical). If the child has carious teeth it is necessary to consult a dentist in order to sanitize the oral cavity.

Treatment of acute glomerulonephritis in children

General principles of treatment of acute poststreptococcal glomerulonephritis include compliance with diet and regimen, etiotropic and pathogenetic therapy depending on the clinical course and complications of the disease.

Indications for hospitalization

With persisting arterial hypertension, pronounced proteinuria, a decrease in the functional state of the kidneys, a prolonged macroscopic condition, it is necessary to hospitalize the child for differential diagnosis with other variants of glomerulonephritis, optimal treatment, and the determination of the functional state of the kidneys in dynamics.

Non-pharmacological treatment of acute glomerulonephritis

In acute poststreptococcal glomerulonephritis with nephritic syndrome and hypertension, it is necessary to comply with bed rest until the normalization of blood pressure (> 1 week). With improvement in well-being and lowering blood pressure, the regime is gradually expanded.

It is necessary to limit the intake of liquid, table salt and protein. The liquid is prescribed based on diuresis for the previous day, taking into account extra-renal losses (approximately 500 ml for school-age children). When normal arterial pressure is reached, the disappearance of the edematous syndrome gradually increases salt intake starting from 1 g / day. Limit the use of animal proteins (up to 0.5 g / kg per day) need no more than 2-4 weeks before the normalization of the concentration of creatinine and urea in the blood.

With an isolated urinary syndrome without extra-renal manifestations of acute poststreptococcal glomerulonephritis, there is usually no need to restrict regimen and diet. Assign table number 5 on Pevzner.

Drug treatment of acute glomerulonephritis

In patients with hypertension in children with acute poststreptococcal glomerulonephritis as antihypertensive agents, thiazide diuretics and slow calcium channel blockers are used.

Of the thiazide diuretics, furosemide is used orally (IM or IV) according to indications) 1-2 mg / kg body weight 1-2 times per day, if necessary, increase the dose to 3-5 mg / kg. Of slow calcium channel blockers, nifedipine is sublingually at a dose of 0.25-0.5 mg / kg per day, dividing the total dose by 2-3 doses, or amlodipine by 2.5-5 mg 1 time per day, until normalization of the arterial pressure. With the preservation of kidney function and the absence of hyperkalemia, as well as in the case of insufficient blockers of slow calcium channels, ACE inhibitors are prescribed: captopril orally 0.5-1.0 mg / kg per day in 3 doses or enalapril orally at 5-10 mg / kg in a day in 1-2 receptions.

As an antihypertensive drug in adolescents with acute streptococcal glomerulonephritis, it is possible to use angiotensin II receptor blockers (losartan inside 25-50 mg 1 time per day, valsartan inside 40-80 mg 1 time per day). Significantly less often in children, beta-blockers are used.

Regardless of the clinical course of the disease, it is necessary to perform antibiotic therapy taking into account the sensitivity of streptococcal flora. Most often use antibiotics penicillin series: amoxicillin inside at a dose of 30 mg / kg per day in 2-3 doses for 2 weeks or amoxicillin + clavulanic acid inside 20-40 mg / kg per day in 3 doses for 2 weeks (amoxiclav, augmentin, flemoclav soluteba). The second course is optimal to use macrolides of II or III generations:

• josamycin inside at 30-50 mg / kg per day in 3 doses for 2 weeks;
• midekamycin orally 2 times a day before meals: children under 12 years of age at 30-50 mg / kg per day, children over 12 years of 400 mg 3 times a day for 7-10 days;
• roxithromycin inside at 5-8 mg / kg per day 2 times a day for not more than 10 days.

The duration of antibiotic therapy is 4-6 weeks. Some specialists prescribe bicillin-5 intramuscularly for 4-5 months:

• children of preschool age to 600 000 units every 3 weeks;
• children from 8 years - to 1 200 000 units 1 time in 4 weeks.

At the expressed hypercoagulation with increase of fibrinogen concentration in blood more than 4 g / l use:

• antiagreganty - dipyridamole inside at 5-7 mg / kg per day in 3-4 receptions on the Snake;
• anticoagulants:
• heparin sodium at 200-250 units / kg per day 4 times a day subcutaneously;
• low-molecular heparins - calcium supraparin (subcutaneously once a day at a dose of 171 IU / kg or 0.01 ml / kg by a course of 3-4 weeks), dalaparin sodium (subcutaneously once a day at a dose of 150-200 IU / kg, single dose should not exceed 18 000 ME, the course - 3-4 weeks).

Patients with a nephrotic syndrome that persists for more than 2 weeks, a stable increase in the concentration of creatinine in the blood (without a tendency to increase and normalize), in the absence of the possibility of a biopsy of the kidneys, prednisolone should be administered orally at a dose of 1 mg / kg per day (children <3 years <2 mg / kg per day) for 2-3 weeks until the restoration of kidney function.

How is acute glomerulonephritis treated in children?

[31], [32], [33]

Surgical treatment of acute glomerulonephritis

Tonsillectomy is necessary:

• with chronic tonsillitis;
• established connection of glomerulonephritis with exacerbation of chronic tonsillitis or with angina;
• increased ASO in the blood and a positive smear from the throat to hemolytic streptococcus group A.

Tonsillectomy is performed no earlier than 8-12 weeks from the onset of acute poststreptococcal glomerulonephritis.

How to prevent acute glomerulonephritis in a child?

Timely diagnosis and treatment of streptococcal diseases. Treatment of angina at least 10 days of antibiotics. Sanitation of chronic foci of infection. The analysis of urine after acute angina and exacerbation of chronic tonsillitis at the second and third weeks after streptococcal infections for the purpose of early diagnosis of a possible disease with acute glomerulonephritis.

Prognosis for acute glomerulonephritis in children

In 90-95% of children with acute poststreptococcal glomerulonephritis, which develops with the nephritic syndrome, the manifestations of the disease gradually decrease and within 5-10 days the edematous syndrome disappears, after 2-4 weeks from the onset of the disease, blood pressure normalizes, hematuria disappears and renal function is restored . Less than 1% of patients with the disease progress to the development of chronic renal failure.

One of the main factors of progression are tubulointerstitial changes:

• decrease in the optical density of urine;
• leukocyturia;
• decrease in the function of osmotic concentration;
• increased urinary excretion of fibronectin - in focal lesions of 0.040 g / day, with a diffuse 0.250 g / day;
• Ultrasound-documented presence of hypertrophic renal pyramids;
• resistance to pathogenetic therapy.

Dispensary supervision

After discharge from the hospital, the patient is sent to a local sanatorium for patients with kidney disease. After discharge from the sanatorium, the child is supervised by a pediatrician and a nephrologist - on the first year once a month, on the second - once a quarter. Inspection ENT doctor and dentist 1 time in b months. During any intercurrent disease, it is mandatory to examine urine, measure blood pressure.

Dispensary observation is carried out for 5 years. By the end of this period, a comprehensive examination with functional renal tests in a hospital or diagnostic center is necessary. In the absence of abnormalities from the results of the study, the child can be considered recovered and removed from the dispensary record.

[34], [35]