Hereditary nephritis

Among all hereditary glomerulopathies, the most studied and relevant to date is hereditary nephritis, including Alport syndrome. This disease is very common in most regions of the world and has a description among representatives of different nationalities.

Hereditary nephritis, submitted to the nephrological department of the Research Institute of Pediatrics and Pediatric Surgery of the RF Ministry of Health, for many years of observation is in different years 6-8% of the total number of patients with kidney pathology.

In the light of modern medicine, hereditary nephritis is a genetically determined non-immune glomerulopathy, characterized by the release of blood with urine( hematuria) and protein excretions in the urine, taking a tendency to progress until the development of chronic renal failure. This pathology is often combined with diseases of hearing and sight.

The disease manifests itself both genetically and clinically diverse. According to the presence of certain signs in the clinical picture of the disease, the hereditary nephritis with hearing loss( called Alport syndrome) and hereditary nephritis without pathology of the hearing function are isolated

.There are also other classifications in which the term "Alport syndrome" is understood as clinical variants of the course of the disease in the absence of deafness in patients.

One of the most complete versions of the classification of hereditary nephritis can be considered a clinical and pathological classification, presented at the XXII Congress of Pediatric Nephrologists in Europe.

According to this classification, the following are distinguished:

1) Alport syndrome, which is characterized by a combination of progressive hematuric nephritis, neurogenic type of hearing loss and visual impairment. Clinical variants are possible, including combinations of nephritis with blood pathology( thrombocytopenia);

2) hereditary nephritis without hearing loss is a progressive disease in its development. In the electron microscope study of renal biopsy is characterized by an isolated thinning of the basal membranes;

3) the so-called family benign essential gematuria, in which renal failure does not develop. Immunological examination of basal membranes reveals a decrease in their antigenic characteristics.

Genetic Aspects of the

Disease There are several hypotheses about the inheritance features of the Alport Syndrome. The following assumptions are possible:

1) dominant inheritance with partial coherence with the floor;

2) preferential segregation( autosomes with a mutant gene with an X-chromosome);

3) dominant, sex-linked inheritance( in some families, the transmission of the disease from the father to the son);

4) the effect of the modifier gene( autosomal dominant inheritance with a dominant modifier gene on the X chromosome);

5) autosomal dominant inheritance with limited penetrance of the gene among the male offspring of the sick fathers.

From the genetic point of view, 4 signs were analyzed:

1) presence in the family of hematuria and chronic renal insufficiency;

2) presence on the electronograms of the kidneys of typical thin membranes;

3) severity of ophthalmic changes;

4) presence of high-tonal hearing loss.

It is proven that if there are 3 signs in a family of 4, the disease is transmitted dominantly, linked to the X chromosome. This option is considered classic. In a sick father, sons are healthy, and daughters are carriers of a mutant gene.

With Alport syndrome, most patients have no Goodpasture antigen present, but this feature is secondary. This phenomenon of antigenic structures is characterized by the possibility of developing autoimmune glomerulonephritis in transplanted kidneys.

The frequency of Alport syndrome in the population is not exactly established. Despite the fact that the mutant gene of the Alport syndrome is identified, the mechanism of its manifestation remains unclear.

Clinical picture of the disease

It should be noted that the disease occurs much more easily in women who are ill than men. Also in women, hereditary nephritis is less often combined with deafness. It should be noted that the disease presents a sufficiently serious danger during pregnancy. In most cases, a woman suffering from this pathology, pregnancy proceeds with toxicosis, spontaneous abortions, stillbirths are often noted.

Clinical manifestations of the disease can occur at any age. With the timely and rational examination of families burdened with submitted pathology, the discharge of blood in the urine is often detected already in the first months of the child's life. The disease proceeds secretly, isolated urinary syndrome, more often in the form of the appearance of red blood cells and a small amount of protein in the urine( erythrocyturia and microproteinemia, respectively).Often there is a non-bacterial leukocyturia( the appearance of leukocytes in the urine).Most children have several external and somatic small developmental anomalies. Characteristic symptoms of intoxication and hypotension. The latter is to some extent associated with a violation of the function of the adrenal cortex.

The clinical difference between Alport syndrome and another variant of hereditary nephritis is the presence of the neuritis of the auditory nerve, however, its presence can be detected by audiometric examination no earlier than 7-8 years of age of the child. Pathology of the organ of vision, a variety of cataracts are found in one fifth of people suffering from this disease. A pronounced syndrome of thrombocytopenia( a decrease in the number of platelets in the blood) in children observed in the clinic was not detected, but it occurred in some of them. In cases of closely related marriage, children may have gross developmental defects: "wolf mouth", "hare lip", congenital heart defects. It is in such families that a combination of hereditary nephritis with another, including genetically determined, pathology - pituitary nanism( dwarfism), thalassemia, hemolytic anemia of unknown origin can be noted. As a rule, with hereditary nephritis, there are some neurological symptoms and signs of vegetovascular dystonia.

The decline in the functional state of the kidneys in Alport syndrome occurs already at preschool age. In prepubertal and especially pubertal age( puberty period), homeostatic disorders can occur, which can be regarded as an early stage of chronic renal failure. The earliest and characteristic signs are metabolic acidosis( shifting the pH of the blood to the acidic side) and disturbance of the balance of electrolytes in the body( diselectrolyte).Development of the full complex of symptoms of chronic renal failure is typical for people who have reached adulthood. Before the use of replacement therapy and kidney transplantation, the lethal outcome usually occurred in the 4th decade of life.

Treatment. There are no specific therapies for hereditary nephritis. The use of corticosteroids, immunosuppressants, indomethacin is contraindicated.

Improvement of well-being, decrease in signs of intoxication, some decrease in hematuria is evident in children treated with ATP, cocarboxylase, vitamin B6.In some cases, a similar result was obtained with the use of retabolil in age-related doses.

Symptomatic therapy, prevention of concomitant diseases are recommended. Renal transplantation of patients with hereditary nephritis in the stage of chronic renal failure can be performed without previous chronic hemodialysis.