Hereditary Nephropathy

What is Hereditary Nephropathy?

Nephropathy is a general definition of acute and chronic bilateral kidney damage, which should be distinguished from the concept of “nephropathy in pregnant women.” The term “membranous nephropathy” is used with a special variant of glomerulonephritis, which often develops within the framework of the paraneoplastic syndrome with its diverse manifestations, including kidney damage. In each particular observation, it is necessary to use the term corresponding to the nosological form — nephritis, amyloidosis, etc .; Do not use the term “nephropathy” as a diagnostic. With all the conventions of this concept (like the terms “cardiopathy”, “hepatopathy”, etc.), the term is convenient, which allows it to be used in practice.

Hereditary nephropathy – kidney disease associated with the mutation of one (monogenic pathology) or several (polygenic inheritance) genes. Not all hereditary nephropathies are congenital in clinical understanding.

Causes of Hereditary Nephropathy

Hereditary nephropathy can be divided into 3 groups:

  1. Monogenically inherited, in which the manifestation of a gene mutation does not depend on environmental factors. The influence of the environment affects only the severity of symptoms of the disease. This group includes hereditary nephritis, including Alport syndrome, various types of renal tubulopathy (Fanconi syndrome, phosphate diabetes, primary oxaluria), hereditary anomalies of the urinary system, polycystic disease.
  2. Hereditary diseases of the kidneys, where the mutation remains an etiological factor, however, for the penetrance of the pathology, adverse effects of the external environment are necessary. These may include dysmetabolic nephropathies associated with the pathology of oxalic acid, purines, tryptophan metabolism, etc. They develop with improper diet, fluid restriction, repeated infectious diseases, toxic and allergic effects.
  3. Diseases, where etiological factors are external influences (microbes, viruses, toxins), but the realization of their impact occurs in individuals with a genetic predisposition. Glomerulonephritis in a family where there are immunodeficiency states can be regarded as a pathology that develops with a predisposition.

A special group of kidney diseases are nephro- and uropathies, which develop in chromosomal diseases associated with a chromosomal or genomic mutation. Chromosomal diseases, as a rule, are not inherited by inheritance and are characterized by multiple defects of various organs, including the urinary system. Hereditary nephropathy does not always have a family character. This is due to the possibility of a primary mutation in this individual, as well as the difficulty of identifying similar diseases in previous generations with recessive variants of inheritance. Hereditary nephropathy is differentiated from congenital diseases of the kidneys (embryophopathy), which develop in connection with the teratogenic effects on the fetus.

From a genetic point of view, hereditary nephropathy is divided into groups depending on the type of transmission of the disease. The “adult type” of polycystic disease, the distal type of renal-tubular acidosis, hereditary anomalies of the kidneys are autosomal dominant. . Hereditary nephropathy, in which gene mutations are linked to the X chromosome, includes hereditary nephritis, phosphate diabetes.

Symptoms of Hereditary Nephropathy

For hereditary nephropathy, despite their nosological polymorphism, a number of common clinical signs are characteristic. First, the presence of similar diseases in the family, which is clearly manifested when comparing pedigrees, secondly, a long latent course, often with “isolated urinary syndrome”, which is often regarded as one of the forms of latent glomerulonephritis, if there is hematuria and proteinuria, or latent pyelonephritis with leukocyturia. Patients with hereditary nephropathy are characterized by multiple external and somatic stigmas of dizembriogenesis (minor anomalies). Finally, early decline in renal functions is noted, usually in tubular type. For some variants of the pathology (renal dysplasia, tubulopathy, renal ammloidosis), the formation of renal failure is characteristic already in childhood.

Hereditary and congenital nephropathy are characterized by pronounced clinical polymorphism, even within the same nosological form of pathology among members of one family. However, they are also characterized by common manifestations: randomness of detection, torpid flow, a tendency to progression with early decrease in renal functions of the tubular type.

The marker of hereditary and congenital diseases of various organs and systems, including kidney diseases, is the presence of stigma diesmbriogenesis of connective tissue, or minor developmental anomalies. The most common encounter is an extended nose line, an abnormal structure of the auricles, high (Gothic) sky, varus deviation of the little finger, a tendency to pterodactyls and hypertelorism of the eyes and nipples, sandalwood shelle, a tendency to syndactyly II and III toes. Among somatic stigmas, bony abnormalities and OMC abnormalities are more common: hilariness of the renal contours, anomalies of the calyxes, obstruction of the priloanny ureteric departments. There are also more rare external and somatic anomalies: additional nipples, an extra row of teeth in the jaw, etc. The number of minor anomalies exceeding 15 is most often a sign of chromosomal disease.

Lag of growth and physical development is a frequent sign of a congenital or hereditary disease OMC, although it can be observed in the chronic course of acquired nephropathy.

Intoxication syndrome: pallor, lethargy, muscular hypotonia, anorexia without obvious reasons of a different nature. These symptoms should cause nephrological vigilance precisely in view of congenital and hereditary nephropathy.

Azotemia syndrome in the form of a specific “renal pallor” in a child with anorexia, vomiting, dry skin, developmental delays even without urinary syndrome requires a nephrological examination.

Dysuric and painful abdominal syndromes should be alarming, bearing in mind the congenital anatomical abnormalities of the OMC and the neurogenic bladder.

The edematous syndrome in hereditary diseases may appear from the moment of birth of the child, which is characteristic of congenital NA of the Finnish type, but can be detected by the layering of immune changes on the hereditary or congenital defect of the renal tissue.

Hypertension syndrome is inherent in the anatomical anomalies of the renal vessels, reflux nephropathy, segmental hypoplasia, oligonephronia, in the stage of development of chronic kidney disease – hereditary nephritis and blood pressure BPPP. With autosomal recessive PBP (AR PBP), it may be the first manifestation of the disease.

Hypotension is characteristic of Fankoni nephronophthalis, hereditary nephritis to the stage of chronic renal failure, for many congenital uropathies, hypoplastic renal dysplasia.

Urinary syndrome is often not the first manifestation of the disease; When pathology develops, it may have a polymorphic character, but more often hematuria first appears, then proteinuria is added. It is necessary to investigate the presence of crystalluria, oxaluria, uraturia, aminoaciduria, ammonium and acidogenesis indices.

Diagnosis of Hereditary Nephropathy

The diagnosis is based mainly on the hereditary history, especially in the development of proteinuria, erythrocyturia, hematuria in children, the presence of neuritis of the auditory nerves during the progressing course of the disease in men and women.

With a biopsy of the kidney, the diagnosis is confirmed by the presence of foam cells during lymphological examination. Hereditary nephritis should be distinguished from acquired glomerulonephritis, the main distinguishing features of which are the lack of a family history and neuritis of the auditory nerve, the absence of extrarenal manifestations, signs of progression, benign familial hematuria, characterized by low erythrocyturia in siblings.

Treatment of Hereditary Nephropathy

The treatment has a syndromological and, to a certain extent, substitutive character. Thus, in cystinuria, a diet depleted in methionine and sulfur-containing amino acids is used, potatoes are widely used; if there is a disturbance of purine metabolism, a diet poor in purines and citric acid is shown, allopurinol is used. To stimulate the synthesis of tubular epithelium enzymes, vitamin B6 is prescribed up to 150 mg / day, ATP, cocarboxylase. In hereditary nephropathies, glucocorticoids, cytostatics are usually contraindicated, the use of metindole is undesirable.

Prevention of Hereditary Nephropathy

Prevention of hereditary nephropathy is associated with a further expansion of medical and genetic counseling. For early detection of pathology, it is advisable to use selective screening — a complete nephrological examination of family members with renal pathology, as well as individuals who simultaneously have arterial hypotension or hypertension, multiple external stigma of diesembriogenesis, and recurrent abdominal syndrome. Prevention of progression of hereditary nephropathy includes the elimination of toxic, allergenic and other adverse effects of the external environment.