Chronic glomerulonephritis in children

Chronic glomerulonephritis in children is a group of kidney diseases with predominant damage to the glomeruli, having different etiology, pathogenesis, clinical and morphological manifestations, course and outcome.

The main clinical types of glomerulonephritis (acute, chronic and rapidly progressive) are independent nosological forms, but their characteristic signs can also be found in many systemic diseases.

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Epidemiology

The incidence of glomerulonephritis averages 33 per 10,000 children. Each year in the United States, 2 new patients with primary nephrotic syndrome are diagnosed per 100,000 children. In recent years, there has been a trend toward an increase in the incidence of steroid-resistant nephrotic syndrome (SRNS) in children and adults, primarily due to focal segmental glomerulosclerosis (FSGS).

FSGS in children with nephrotic syndrome is found in 7-10% of all renal biopsies performed due to proteinuria. Nephrotic syndrome is more common in Asia than in Europe.

Membranous nephropathy is one of the most common variants of chronic glomerulonephritis in adult patients and accounts for an average of 20-40% of all glomerulonephritis cases. In children, membranous nephropathy with nephrotic syndrome occurs in less than 1% of cases.

MPGN is quite rare in children, occurring in only 1-3% of all biopsies.

Most often, glomerulonephritis in children is detected at the age of 5 to 16 years. The manifestation of idiopathic nephrotic syndrome in most cases occurs at 2-7 years. The disease occurs in boys 2 times more often than in girls.

IgA nephropathy is one of the most common forms of primary glomerulopathies in the world: its prevalence varies from 10-15% in the USA to 50% in Asia. IgA nephropathy is more often detected in males in a ratio of 2:1 (in Japan) and 6:1 (in northern Europe and the USA). Familial cases are observed in 10-50% of patients depending on the region of residence.

The incidence of RPGN has not yet been established, which is due to the rarity of the pathology, especially in children. Most studies of RPGN are descriptive in nature and were conducted in small groups of patients.

Causes chronic glomerulonephritis

The causes of chronic glomerulonephritis in children remain largely unclear; the etiological factor can be established only in 5-10% of cases.

Sometimes persistence of viruses (hepatitis B, C, herpes, Epstein-Barr virus) is found. Exacerbation of the process may be caused by intercurrent diseases (ARI, exacerbation of tonsillitis, childhood infections). However, a significant role in the development of a chronic process is played by the genetically determined immune response of a given individual to an antigen effect.

Progression of glomerulonephritis is characterized by cellular proliferation, accumulation of extracellular matrix with subsequent sclerosis and shrinkage of the kidneys. The leading role is played by non-immune mechanisms, such as systemic and intraglomerular arterial hypertension, prolonged proteinuria, hyperlipidemia. These factors lead to stimulation of systemic and local increase in the amount of angiotensin II (AT II), which serves as a powerful stimulus for the proliferation of mesangial cells with the subsequent development of fibrosis and sclerosis.

According to morphology, the following are distinguished:

• proliferative GN: mesangioproliferative GN (MsPGN), mesangiocapillary, or membranoproliferative GN (MPGN), extracapillary with crescents (ECC);
• non-proliferative GN: minimal changes (NCM), membranous GN, focal segmental glomerulosclerosis (FSGS).

What causes chronic glomerulonephritis?

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Symptoms chronic glomerulonephritis

Chronic glomerulonephritis is a disease, as a rule, with a progressive course, leading to the development of chronic glomerulonephritis in most morphological variants already in childhood. In pediatric nephrology, chronic glomerulonephritis ranks 2nd in the structure of causes of chronic renal failure after a group of congenital and hereditary nephropathies.

The course of chronic glomerulonephritis in children can be recurrent, persistent and progressive. The recurrent course is characterized by drug-induced or spontaneous remissions of varying duration. The persistent variant is characterized by continuous activity of the process with preserved renal function in the early stages. However, after several years, the outcome in CRF occurs. With a progressive course, more rapid development of chronic glomerulonephritis in children is noted - 2-5 years after the onset of the disease. The prognosis of chronic glomerulonephritis depends on the clinical and morphological variant and timely adequate therapy.

Nephrotic form of chronic glomerulonephritis or idiopathic nephrotic syndrome.

Children aged 3 to 7 years fall ill, with a history of a previous acute first episode. Subsequent exacerbations, with proper observation of patients, are rarely accompanied by significant edema. Exacerbation of the process usually (60-70%) develops after intercurrent diseases (ARI, childhood infections) or against the background of complete health (30-40%). Parents note slight pastosity of the eyelids. Urine analysis reveals an increase in protein content. In rare cases, with poor observation, severe edema develops. Laboratory studies reveal all the deviations typical for NS.

The most common (85-90%) morphological variant is minimal change disease (MCD). This term is related to the fact that glomeruli are unchanged by light microscopy. Electron microscopy shows “melting” of the small podocyte legs. Most patients in this group have high sensitivity to glucocorticoid therapy. Focal segmental glomerulosclerosis (FSGS) is less common (10-15%). By light microscopy, glomeruli appear unchanged or show slight proliferation of mesangial cells. Electron microscopy reveals thickening of podocytes, but a characteristic feature is the presence of segmental mesangial sclerosis in some glomeruli. Atrophy of the tubular epithelium, infiltration and fibrosis of the interstitium are also noted.

The clinical picture of the disease in FSGS is characterized by the addition of hypertension and hematuria to the nephrotic syndrome, as well as the development of hormone resistance. In this case, it is necessary to perform a kidney biopsy to clarify the morphological picture of the disease to decide on the tactics of further treatment.

There are several variants of the course of chronic glomerulonephritis with nephritic syndrome:

• frequently recurring course (at least 4 relapses per year or two relapses in 6 months);
• rarely relapsing course (less than two relapses in 6 months). The prognosis for most patients with NSMI is favorable.

Relapses of NS become less frequent after 5 years from the onset of the disease. The disease does not progress in the main group with NSMI, renal function is not impaired. In a small group, relapses of exacerbations may continue, usually manifested only by proteinuria. If NS is represented by a morphological variant - FSGS, the prognosis is unfavorable. Most patients are resistant to therapy, they experience a gradual decline in renal function, progression of hypertension and development of chronic renal failure over 1-20 years.

Hematuric form of chronic glomerulonephritis in children

The hematuric form of chronic glomerulonephritis is characterized by recurrent isolated (without edema and hypertension) macro- or microhematuria in combination with proteinuria less than 1 g/day or without it, occurring 2-5 days after an acute respiratory disease. Most often, the disease is based on a specific form of GN, which is called Berger's disease, or IgA nephropathy. Currently, Berger's disease is considered one of the most common hematuric glomerulopathies in many countries of the world. Almost half of children with the hematuric form of glomerulonephritis have Berger's disease. The disease is more common in boys and children over 10 years of age.

The etiology is associated with a viral or bacterial infection of the upper respiratory tract, as well as with the carriage of the HB5 antigen. However, more often the cause remains unknown.

In the pathogenesis of the hematuric form, the main role is played by immune complex mechanisms. If the IC contains IgA, then this variant is called IgA nephropathy, or Berger's disease.

Morphologically, this is a mesangioproliferative glomerulonephritis, which is characterized by proliferation of mesangial cells, expansion of the mesangial matrix, and deposition of IC in the mesangium and subendothelium.

Clinically, the following course variants are distinguished:

• recurrent macrohematuria, which is provoked by acute respiratory viral infections. The duration of macrohematuria episodes can vary from several weeks to several years. Between episodes, urine tests may remain normal;
• a single episode of macrohematuria followed by persistence of microhematuria.

The course of the disease is recurrent or persistent with slow progression. The prognosis worsens with the addition of arterial hypertension and nephrotic syndrome.

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Mixed form of chronic glomerulonephritis

A relatively rare disease in children, more common in adolescents. The onset of the disease is associated with a previous viral infection, persistence of the hepatitis B virus. However, in most cases, the cause of occurrence and exacerbations remains unknown.

The most common morphological variant is membrane-proliferative (mesangiocapillary) glomerulonephritis. The morphological picture is characterized by diffuse mesangial proliferation and an increase in the mesangial matrix with its interposition between the glomerular basement membrane and endothelial cells, which leads to thickening and double-contour basement membranes.

Symptoms of chronic glomerulonephritis in children are manifested by a combination of nephrotic syndrome with hematuria and/or arterial hypertension. The diagnosis is confirmed by renal biopsy.

The course of the disease is progressive with persistent hypertension, severe persistent proteinuria and early renal dysfunction with the development of chronic renal failure within 10 years from the onset of the disease. In some cases, clinical remission can be achieved. Relapse of the disease can develop even in a transplanted kidney.

Forms

At present, a unified clinical classification of glomerulonephritis has not been developed, reflecting the view of the disease as a single clinical and morphological nosological unit. The most common domestic classification of chronic glomerulonephritis is based on clinical and laboratory syndromes.

• A form of chronic glomerulonephritis.
  • Nephrotic.
  • Mixed.
  • Hematuric.
• Activity of the renal process.
  • Period of exacerbation.
  • Period of partial remission.
  • Period of complete clinical and laboratory remission.
• Status of kidney function.
  • No violation.
  • With violation.
  • Chronic renal failure.

Currently, a morphological classification of chronic glomerulonephritis is widely used, which distinguishes 7 main morphological variants:

• • minimal changes;
  • membranous glomerulonephritis;
  • membranoproliferative glomerulonephritis (MPGN);
  • mesangioproliferative glomerulonephritis (MPGN);
  • focal segmental glomerulosclerosis (FSGS);
  • fibroplastic glomerulonephritis;
  • rapidly progressive glomerulonephritis (extracapillary with crescents) (RPGN).

IgA nephropathy is considered separately - a variant of MsPGN, which is characterized by persistent micro- and/or macrohematuria with predominant fixation of IgA in the mesangium.

Depending on the pathogenetic mechanisms of development, the following glomerulonephritis are distinguished:

• non-immune glomerulopathies:
  • minimal changes;
  • FSGS;
  • membranous nephropathy;
• immune-inflammatory proliferative glomerulonephritis:
  • MzPGN;
  • MPGN;
  • diffuse extracapillary glomerulonephritis (with crescents);
  • focal glomerulonephritis.

According to the course of chronic glomerulonephritis there can be:

• recurrent (spontaneous or drug-induced remissions occur periodically);
• persistent (constant activity of glomerulonephritis is observed with long-term preservation of normal renal function);
• progressive (glomerulonephritis activity is constant, but with a gradual decrease in SCF and the formation of chronic renal failure);
• rapidly progressive (the development of chronic renal failure occurs over several months).

As a variant of persistent course, latent (torpid) course can be distinguished - with low activity and low-symptom manifestations of chronic glomerulonephritis. Depending on sensitivity to glucocorticoids, the following variants of nephrotic syndrome are distinguished.

• Steroid-sensitive nephrotic syndrome (SSNS) is characterized by the development of complete clinical and laboratory remission of the disease against the background of oral administration of prednisolone at a dose of 2 mg/kg per day (60 mg/day) for 6-8 weeks.
• SRNS - proteinuria persists after a course of oral prednisolone at a dose of 2 mg/kg per day (<60 mg/day) for 6-8 weeks and subsequent 3 intravenous administrations of methylprednisolone at a dose of 20-30 mg/kg, but not more than 1 g per administration.
• Frequently relapsing nephrotic syndrome (FRNS) is characterized by the occurrence of relapses of the disease more often than 4 times a year or more than 2 times in 6 months (subject to a course of glucocorticoid therapy using the recommended doses and treatment periods).
• Steroid-dependent nephrotic syndrome (SDNS) is characterized by the development of relapses of the disease when the dose of prednisolone is reduced or within 2 weeks after its discontinuation (provided that the recommended course of glucocorticoid therapy is administered).

According to ICD-10, chronic glomerulonephritis can be classified into the following sections depending on the clinical manifestations and morphological course of the disease.

Classification of various clinical and morphological variants of chronic glomerulonephritis according to ICD-10

Syndrome	Pathological sign	ICD-10 code
Recurrent and persistent hematuria	Recurrent and persistent hematuria	N02
	Minor glomerular disorders	N02.0
	Focal and segmental glomerular lesions	N02.1
	Diffuse membranous glomerulonephritis	N02.2
	Diffuse mesangial proliferative glomerulonephritis	N02.3
	Diffuse endocapillary proliferative glomerulonephritis	N02.4
	Diffuse mesangiocapillary glomerulonephritis	N02.5
Chronic nephritic syndrome	Chronic nephritic syndrome	N03
	Minor glomerular disorders	N03.0
	Focal and segmental glomerular lesions	N03.1
	Diffuse membranous glomerulonephritis	N03.2
	Diffuse mesangial proliferative glomerulonephritis	N03.3
	Diffuse endocapillary proliferative glomerulonephritis	N03.4
	Diffuse mesangiohepatic glomerulonephritis	N03.5
	Other changes	N03.8
	Unspecified change	N03.9
Nephrotic syndrome	Nephrotic syndrome	N04
	Minor glomerular disorders	N04.0
	Focal and segmental glomerular lesions	N04.1
	Diffuse membranous glomerulonephritis	N04.2
	Diffuse mesangial proliferative glomerulonephritis	N04.3
	Diffuse endocapillary proliferative glomerulonephritis	N04.4
	Diffuse mesangiocapillary glomerulonephritis	N04.5
Isolated proteinuria with specified morphological lesion	Isolated proteinuria with specified morphological lesion	N06
	Minor glomerular disorders	N06.0
	Focal and segmental glomerular lesions	N06.1
	Diffuse membranous glomerulonephritis	N06.2
	Diffuse mesangial proliferative glomerulonephritis	N06.3
	Diffuse endocapillary proliferative glomerulonephritis	N06.4
	Diffuse mesangiocapillary glomerulonephritis	N06.5

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Diagnostics chronic glomerulonephritis

The clinical diagnosis is based on the typical clinical picture (nephrotic syndrome, proteinuria, hematuria, arterial hypertension), laboratory test data that allow to establish the activity of glomerulonephritis and assess the functional state of the kidneys. Only a histological examination of the renal tissue allows to establish the morphological variant of glomerulonephritis. In this case, it is necessary to assess the presence of indications for a kidney biopsy, the results of which may determine the choice of further treatment method and the prognosis of the disease.

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Treatment chronic glomerulonephritis

Therapeutic tactics for chronic glomerulonephritis in children include pathogenetic treatment using glucocorticosteroids and, if indicated, immunosuppressants, as well as symptomatic therapy using diuretics, antihypertensive agents, and correction of complications of the disease.

Prevention

The basis for the prevention of chronic glomerulonephritis in children is the timely detection and elimination of foci of infection in the body, regular examination of urinary sediment after intercurrent diseases, which allows for the timely detection and treatment of hidden, latently occurring forms of chronic glomerulonephritis.

Strengthening the child's body: hardening, physical education, and observing hygiene measures are also important preventive measures.

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Forecast

In children with chronic glomerulonephritis, the prognosis depends on the clinical form of the disease, the morphological variant of the pathology, the functional state of the kidneys and the effectiveness of the pathogenetic therapy. In children with chronic glomerulonephritis occurring with isolated hematuria in the form of MsPGN, or with SRNS without renal dysfunction and without arterial hypertension, the prognosis is favorable. Chronic glomerulonephritis with SRNS is characterized by a progressive course of the disease with the development of chronic insufficiency over 5-10 years in more than half of the patients.

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