Chronic glomerulonephritis in children

Chronic glomerulonephritis in children is a group of kidney diseases with a predominant lesion of 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 features can also occur in many systemic diseases.

[1], [2], [3], [4], [5], [6]

Epidemiology

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

FSSS in children with nephrotic syndrome revealed in 7-10% of all renal biopsies produced in connection with proteinuria. Nephrotic syndrome is more common in Asia than in Europe.

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

IGNA is quite rare in children - 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 in 2-7 years. Disease in boys occurs in 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 the ratio of 2: 1 (in Japan) and 6: 1 (in northern Europe and the United States). Family cases are observed in 10-50% of patients depending on the region of residence.

The frequency of the PGNN has not been established to date, which is due to the rarity of the pathology, especially in children. Most of the studies of the BNGN are descriptive and conducted in small groups of patients.

Causes of the chronic glomerulonephritis

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

Sometimes the persistence of viruses (hepatitis B, C, herpes, Epstein-Barr virus) is found. The aggravation of the process can be caused by the transferred intercurrent diseases (ARVI, exacerbation of tonsillitis, childhood infections). However, the genetically determined immune response of this individual to the antigenic effect plays a significant role in the development of the chronic process.

Progression of glomerulonephritis is characterized by cellular proliferation, accumulation of extracellular matrix with subsequent sclerosis and shrinkage of the kidneys. Non-immune mechanisms play a leading role in this, such as systemic and intra-cerebral arterial hypertension, prolonged proteinuria, and 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 to the proliferation of mesangial cells, followed by the development of fibrosis and sclerosis.

According to the morphology:

• proliferative GH: mesangioproliferative GN (MSPGN), mesangiocapillary, or membranoproliferative GN (MPGH), extracapillary with semilunium (PGGN);
• non-proliferative GN: minimal changes (NSME), membranous GN, focal-segmental glomerulosclerosis (FSGS).

What causes chronic glomerulonephritis?

[7], [8], [9], [10], [11], [12], [13], [14]

Symptoms of the chronic glomerulonephritis

Chronic glomerulonephritis is a disease, usually with a progressive course leading to the development of chronic glomerulonephritis in most morphological variants already in childhood. In pediatric nephrology, chronic glomerulonephritis ranks second in the structure of the 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 or spontaneous remissions of varying duration. A persistent variant is characterized by a continuous activity of the process with a preserved function of the kidneys in the early stages. However, after several years, the outcome of CRF occurs. With a progressive course, the faster development of chronic glomerulonephritis in children is noted - in 2-5 years from the onset of the disease. The prognosis of chronic glomerulonephritis depends on the clinical and morphological variant and on timely adequate therapy.

Nephrotic form of chronic glomerulonephritis or idiopathic nephrotic syndrome.

Ill children aged from 3 to 7 years old, in the anamnesis - a previously acute acute first episode. Subsequent exacerbations with proper monitoring 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 a small pastosity of the eyelids. In the analysis of urine, an increase in the protein content is determined. In rare cases, with bad observation, pronounced edema is formed. At laboratory researches find all deviations, typical for НС.

The most frequent (85-90%) morphological variant is the disease of minimal changes (NSME). This term is due to the fact that with light microscopy, the glomeruli are not changed. With electron microscopy, one can see the "melting" of the small legs of podocytes. Most patients in this group report a high sensitivity to glucocorticoid therapy. Focal-segmental glomerulosclerosis (FSGS) occurs less frequently (10-15%). With light microscopy, the glomeruli look unchanged or a small proliferation of mesangial cells is seen. Electron microscopy reveals a thickening of the podocytes, but a characteristic feature is the presence of segmental mesangial sclerosis in the part of the glomeruli. There is also atrophy of tubular epithelium, infiltration and fibrosis interstitium.

For the clinical picture of the disease in FSHS characterized by adherence to nephrotic syndrome of hypertension and hematuria, as well as the development of hormone resistance. In this case it is necessary to carry out a biopsy of the kidneys to clarify the morphological picture of the disease in order to decide the question of the tactics of further treatment.

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

• often recurrent course (at least 4 relapses per year or 2 relapses in 6 months);
• rarely recurrent course (less than two relapses in 6 months). The prognosis in most patients with NSME is favorable.

Relapses of HC are reduced after 5 years from the onset of the disease. Progression of the disease in the main group with NSMI does not occur, the kidney function is not impaired. A small group may continue to recurrence of exacerbations, usually manifested only by proteinuria. If the NS is represented by a morphological variant - FSSS, the forecast is unfavorable. The majority of patients are resistant to therapy, they have a gradual decrease in kidney function, progression of hypertension and development of CRF for 1-20 years.

The hematuric form of chronic glomerulonephritis in children

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

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

In the pathogenesis of the hematuric form, the main role is played by immunocomplex mechanisms. If the composition of the IC is IgA, then this option is called IgA-nephropathy, or Berger's disease.

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

Clinically, the following variants of the course are distinguished:

• recurrent macrohematuria, which provokes ARVI. The duration of episodes of macromeduction can range from a few weeks to several years. Between the episodes, urinalysis can remain normal;
• the only episode of macrohematuria with the subsequent persistence of microhematuria.

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

[15], [16], [17], [18], [19], [20], [21], [22], [23]

Mixed form of chronic glomerulonephritis

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

The most frequent 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 basal membrane of the glomerulus and endothelial cells, which leads to thickening and two-contouring of the basal membranes.

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

The course of the disease is progressive with persistent AH, severe persistent proteinuria and early impairment of renal function with development of CRF for 10 years from the onset of the disease. In some cases, it is possible to achieve clinical remission. Relapse of the disease can develop even in a transplanted kidney.

Forms

Currently, there is no single clinical classification of glomerulonephritis, reflecting the view of the disease as a single clinical and morphological nosological unit. The most common national classification of chronic glomerulonephritis is based on clinical and laboratory syndromes.

• Form of chronic glomerulonephritis.
  • Nephrotic.
  • Mixed.
  • The hematuric.
• Renal process activity.
  • Period of exacerbation.
  • Period of partial remission.
  • Period of complete clinical and laboratory remission.
• The state of kidney function.
  • Without infringement.
  • With violation.
  • Chronic renal failure.

Currently, the morphological classification of chronic glomerulonephritis is widely used, which distinguishes 7 basic morphological variants:

• • minimum changes;
  • membranous glomerulonephritis;
  • membrane-proliferative glomerulonephritis (IGOS);
  • mesangioproliferative glomerulonephritis (MIPGN);
  • focal segmental glomerulosclerosis (FSGS);
  • fibroplastic glomerulonephritis;
  • rapidly progressive glomerulonephritis (extracapillary with semilunar) (BNGN).

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

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

• nonimmune glomerulopathies:
  • minimum changes;
  • FSSS;
  • membranous nephropathy;
• immunoinflammatory proliferative glomerulonephritis:
  • MZPGN;
  • IGOS;
  • diffuse extracapillary glomerulonephritis (with half-moon);
  • focal glomerulonephritis.

Adverse chronic glomerulonephritis can be:

• recurrent (spontaneous or remission medications occur periodically);
• persistent (observe the constant activity of glomerulonephritis with long-term preservation of normal kidney function);
• progressive (glomerulonephritis activity is constant, but with a gradual decrease in GFR and the formation of chronic renal failure);
• fast-progressing (the formation of chronic kidney failure occurs within a few months).

As a variant of the persistent flow, it is possible to distinguish latent (torpid) hetic - with low activity and malosymptomatic manifestations of chronic glomerulonephritis. Depending on the sensitivity to glucocorticoids, the following variants of nephrotic syndrome are distinguished.

• Steroid-sensitive nephrotic syndrome (SSHNS) is characterized by the development of complete clinical and laboratory remission of the disease with taking prednisolone by mouth at a dose of 2 mg / kg per day (60 mg / day) for 6-8 weeks.
• SRNS - proteinuria persists after a prednisolone oral dose at a dose of 2 mg / kg daily (<60 mg / day) for  6-8  weeks and subsequent 3 intravenous injections of methylprednisolone at a dose of 20-30 mg / kg, but not more than 1 g per introduction.
• Often relapsing nephrotic syndrome (CHRNS) 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 (provided that the course of glucocorticoid therapy with the use of recommended doses and treatment terms).
• Steroid-dependent nephrotic syndrome (SNSN) is characterized by the development of relapses of the disease with a decrease in the dose of prednisolone or within 2 weeks after its withdrawal (provided the recommended course of glucocorticoid therapy).

According to ICD-10, chronic glomerulonephritis can refer to the following sections, depending on the clinical manifestations and the morphological variant of the course.

Classification of various clinical and morphological variants of chronic glomerulonephritis in accordance with 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 mesangihopillary 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 refined morphological lesion	Isolated proteinuria with refined 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

[24]

Diagnostics of the chronic glomerulonephritis

Clinical diagnosis is based on a typical clinical picture (nephrotic syndrome, proteinuria, hematuria, arterial hypertension), laboratory data allowing to establish the activity of glomerulonephritis and assess the functional state of the kidneys. Only carrying out a histological examination of the kidney tissue allows us to establish a morphological variant of glomerulonephritis. At the same time, it is necessary to evaluate the presence of indications for a kidney biopsy, the results of which may determine the choice of a further method of treatment and the prognosis of the disease.

[25], [26], [27], [28], [29], [30], [31]

Treatment of the chronic glomerulonephritis

Therapeutic tactics for chronic glomerulonephritis in children include pathogenetic treatment using glucocorticosteroids and, according to indications, immunosuppressants, as well as symptomatic therapy with diuretics, antihypertensive drugs, 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 timely detection and treatment of latent, latent forms of chronic glomerulonephritis.

Strengthening the child's organism: hardening, physical culture, hygiene measures are also important preventive measures.

[32], [33], [34], [35], [36], [37], [38], [39]

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, which occurs with isolated hematuria in the form of MZPGN, or with SSHC without renal dysfunction and without hypertension, the prognosis is favorable. For chronic glomerulonephritis with SRNS is characterized by a progressive course of the disease with the development of chronic insufficiency for 5-10 years in more than half of the patients.

[40], [41], [42], [43], [44], [45]