Nephrology for the Family Physician - O.I. Bakaliuk 2003

Pediatric Nephrology
Hereditary and Congenital Nephropathies

For the timely Diagnosis of hereditary and congenital nephropathies, M.S. Ignatova et al. (1989) proposed selective screening based on 5 criteria: a family history of renal pathology, the presence of five or more minor Connective Tissue anomalies (stigmata of dysembriogenesis), recurrent abdominal syndrome, and hypo- or Hypertension in the child. Identifying 2 out of these 5 criteria contributes to the accurate preclinical diagnosis of these pathological forms in 90% of examined patients.

These disorders are divided into several groups (M.S. Ignatova, 1995).

The first group includes so-called monogenic nephropathies, which are rooted in Gene Mutations. The specific loci of gene defects in these pathological forms are currently under active investigation.

Monogenic nephropathies with an Autosomal dominant inheritance pattern include Urinary System anomalies, adult-type Polycystic Kidney Disease, hypoplastic Dysplasia, and distal Renal Tubular Acidosis; autosomal recessive forms include Infantile Polycystic Kidney disease, Fanconi nephronophthisis, De Toni-Debré-Fanconi Syndrome, familial Mediterranean fever with amyloidosis, and glucosuria; X-linked forms include Fabry disease, Phosphate Diabetes, nephrogenic diabetes insipidus, and hereditary nephritis.

The second group is represented by multifactorial nephropathies, in which the mutation manifests under METABOLISM/18.html">The Influence of adverse environmental factors (lupus nephritis, oxaluria, uraturia); the third group comprises diseases where The impact of viral, bacterial, protozoan, or drug Antigens occurs against a Background of genetic predisposition (e.g., Glomerulonephritis in the presence of HLA system antigens B12 and B35).

The fourth group includes conditions where the child's genotype and phenotype do not play a decisive role in their onset (trauma, hypothermia, poisoning, Burns, etc.).

Genetically determined pathology also encompasses kidney DISEASES ASSOCIATED WITH Chromosomal aberrations. In such cases, other developmental anomalies are observed, and the frequency of renal involvement depends on the specific type of aberration.

The most significant renal lesions are observed in trisomy D (Hydronephrosis, polycystic kidney disease).

Congenital nephropathies are forms of renal impairment that exist from the moment of a child's birth, regardless of when they are detected. They can be hereditary or non-hereditary, although not all Hereditary Nephropathies are congenital. For instance, multifactorial nephropathies develop only under the influence of adverse environmental factors, which can be avoided by changing, for example, one's place of residence or diet.

Perinatal Pathology of the Urinary System is also distinguished, which includes the Finnish type of congenital Nephrotic Syndrome, renal vascular dysembriogenesis with hypertensive syndrome, familial non-Finnish nephrotic syndrome, and the autosomal recessive variant of polycystic kidney disease.

The Clinical presentation of such nephropathies is diverse. They are all united by a latent course, the prolonged presence of an isolated urinary syndrome, and tubular dysfunctions. However, one should still highlight the syndromes of vascular hypotonia, endogenous intoxication, abdominal and dysuric syndromes, and occasionally renal failure, which may be combined with stigmata of dysembriogenesis.

For instance, a gothic palate, a widened nasal bridge, varus deviation of the fifth fingers, and a tendency toward Syndactyly of the second and third toes are more characteristic of hereditary nephritis; Anomalies of the auricles, epicanthus, and a gothic palate are more typical of renal dysplasias, and so forth.

Among monogenic forms of pathology, a prominent place is occupied by variants of hereditary nephritis—genetically determined non-immune glomerulopathies manifested by Hematuria and/or proteinuria, with or without associated visual and auditory impairments (M.S. Ignatova, 1995). According to V.V. Fokeeva (1989), hereditary nephritis occurs in 15% of children and 0.2% of adults.

As early as 1985, L. Menlove et al., and subsequently H. Brunner et al. (1988), established that the gene for one of the clinical variants of hereditary nephritis—Alport syndrome (COL4A5)—is located in the region q22 of the long arm of the X chromosome. At the same time, an inherited Impairment of the antigenic Structure of type IV Collagen in the glomerular basement membrane was demonstrated, as well as analogous structures in ocular basement membranes (lens capsule, Descemet's membrane, cornea, retina) and cochlear basement membranes (N.D. Savenkova et al., 1988).

In this syndrome, the alpha-5 chain is absent in type IV collagen and is replaced by embryonically immature alpha-1 and alpha-2 chains. Overall, based on the inheritance pattern, dominant X-linked (COL4A5 gene mutation), autosomal dominant (COL4A3 and COL4A4 gene mutations on chromosome 2), and autosomal recessive (COL4A3 or COL4A4 gene mutations) variants are distinguished. According to R. Torra et al. (1999), Alport syndrome also includes a variant clinically characterized by diffuse leiomyomatosis combined with thrombocytopenia (XL subtype).

The most common variants of hereditary nephritis include classic Alport syndrome (a combination of progressive nephritis with hematuria and Hearing or Vision impairment), hereditary nephritis without hearing impairment, and familial benign hematuria. The classic inheritance pattern is one in which the sons of a father with hereditary nephritis are healthy, while his daughters are carriers of the pathological gene, with the disease running a relatively milder course in them. Thus, affected men can transmit the disease only to their daughters, whereas affected women can transmit it to both daughters and sons. However, the reasons for the lower penetrance or expressivity of the mutant gene in females and the phenotypic polymorphism of the pathology among members of the same family remain a subject of debate today. It is hypothesized that an autosomal dominant type of inheritance regarding phenotypic polymorphism and genetic heterogeneity also exists (V.V. Fokeeva et al., 1988). Clinically, Alport syndrome is closely related to the Goyer-Reynolds-Burk-Burkholder syndrome.

The clinical picture of hereditary nephritis is characterized by persistent hematuria emerging as early as the first months of a child's life. Exacerbations of hematuria are noted following respiratory tract infections, physical exertion, and vaccinations (!). Proteinuria is typically moderate, with a predominance of the tubular type of renal involvement (acidosis, dyselektrolytemia). Subsequently, symptoms of endogenous intoxication develop, and partial renal Functions deteriorate. Deafness most frequently appears at the age of 7–8 years; ocular involvement (decreased visual acuity, spherophakia, anterior lenticonus, perimacular changes, cataracts) is observed in 20–67% of cases. Among connective tissue stigmata, ocular hypertelorism, a high palate, bite anomalies, abnormal auricle shape, and clinodactyly of the fifth finger are frequently noted. The diagnosis of Alport syndrome is considered reliable if a child presents with three of the four typical features: a family history of a patient with hematuria and chronic renal failure, sensorineural hearing loss, ocular pathology, and Changes in the glomerular capillary basement membrane (M.S. Ignatova, 1996). Differential diagnosis for hematuria is primarily performed with the hematuric variant of acquired glomerulonephritis, oxaluria, hypoplastic dysplasia, and benign familial hematuria.

There are no specific treatments for Alport syndrome, and a fatal outcome most often occurs at the age of 30–40 years. Management includes limiting physical activity, prescribing A balanced diet, and sanitizing foci of infection. Medications used include ATP, cocarboxylase, pyridoxine, dimephosphon, and hemostatic herbs; corticosteroids and cytostatics are ineffective.

Polycystic kidney disease is a disorder inherited in both autosomal recessive and autosomal dominant manners.

When inherited in an autosomal recessive manner (1:10,000–40,000 newborns), cysts develop primarily from the proximal tubules; with the autosomal dominant type, they arise from any part of the nephron. In the latter variant, involvement of other Organs (Liver, Pancreas) is also frequently observed.

The clinical presentation of polycystic kidney disease in the Autosomal Recessive Inheritance type depends on the number of affected tubules (life expectancy ranges from a few hours when 90% of the tubules are affected to 45–50 years or more when 5%–10% of the tubules are affected).

The autosomal dominant inheritance type is more common (1:500–1,000 newborns) and manifests in two variants: neonatal and adult.

The neonatal variant is characterized by bilateral enlargement of the Kidneys, other developmental anomalies (Heart defects), and the rapid development of arterial hypertension and renal failure; the adult variant presents with onset in adolescence, a more favorable course, and quite frequently an asymmetrical enlargement of one kidney (H. Ishikawa et al., 2000).

In infancy, the initial sign of polycystic kidney disease may be enlarged kidneys. In some cases, hepatosplenomegaly is detected. Renal function impairment develops in a tubular pattern and is characterized by acidosis. Urinary changes are minimal. The Development of multiple small cysts (microcysts) in the kidneys is also characteristic of Gruber, Meckel-Gruber, Jeune, Krause-Rieger, Zellweger, Saldino-Noonan, and Ullrich syndromes.

The Clinical Features of polycystic kidney disease are described in the section "Congenital Tubulopathies and Nephropathies."

Diagnosis is based on clinical findings, renal ultrasound, computed tomography, angiography, and needle biopsy.

Fanconi nephronophthisis (medullary cystic kidney disease) is characterized by The formation of cysts within the renal medulla. This condition is inherited in an autosomal recessive manner. Several variants of nephronophthisis are distinguished: juvenile Fanconi nephronophthisis without retinal involvement, juvenile nephronophthisis with tapetoretinal degeneration (Senior-Løken syndrome), renal dysplasia, and adult-onset medullary cystic kidney disease. The disorder typically manifests during school age, regardless of sex.

Clinical features include polyuria, polydipsia, hyponatremia, hypokalemia, hypocalcemia, anemia, seizures, growth retardation, bone pain (ostalgia), paresthesia, and Muscle weakness. Edema is absent, and Blood pressure is not elevated; hyposthenuria is observed along with transient glucosuria, phosphaturia, uricosuria, and Aminoaciduria. Proteinuria reaches up to 1 g/day.

The diagnosis is established based on clinical observations, ultrasound and angiographic imaging (revealing small cysts in the renal medulla), and renal needle biopsy. There are no specific treatments for Fanconi nephronophthisis.

Parenchymal renal structural anomalies without cystic degeneration include oligomeganephronia and segmental hypoplasia (Ask-Upmark kidney). These two nephropathy variants must be mentioned because they are the most common causes of severe, progressive hypertension leading to rapid end-stage renal disease in children.

Diagnosis relies primarily on the aforementioned instrumental techniques; the prognosis is unfavorable without renal transplantation.

Nephrotic syndrome in children is a frequent clinical symptom complex manifested by proteinuria with a diagnostic threshold of 1 g/m²/day or 40 mg/m²/h, hypoalbuminemia down to 25 g/L, hyperlipidemia of types IIa, IIb, and less frequently type IV, lipiduria, and varying degrees of edema (S.I. Ryabov, 1992; S.P. Savenkova, 1996).

According to G.C. Arneil (1984), nephrotic syndrome is classified into congenital, primary, and secondary types.

Congenital nephrotic syndrome manifests During the first year of life. Its onset is most commonly associated with intrauterine infection, renal vein thrombosis, or structural renal damage. At this age, it is customary to distinguish between true congenital NS and infantile NS. True congenital NS presents from birth up to 3 months of age, whereas infantile NS develops between 4 and 12 months (A.V. Papayan et al., 1994). The Pathogenesis of this form of renal pathology remains unclear, although a certain role is attributed to impaired activity of several Enzymes, such as elevated blood levels of alpha-fetoprotein.

According to literature data (N.D. Savenkova, 1996; V. Amin, 1989), clinical and morphological variants of congenital and infantile nephrotic syndrome are divided into Primary and secondary.

Primary variants include congenital nephrotic syndrome of the Finnish type; congenital nephrotic syndrome of the French type with diffuse mesangial sclerosis; congenital and infantile nephrotic syndrome with minimal changes; congenital and infantile nephrotic syndrome with mesangioproliferative glomerulonephritis; and congenital and infantile nephrotic syndrome with focal segmental glomerulosclerosis. Secondary variants include congenital nephrotic syndrome associated with hypothyroidism, hypoadrenocorticism; neonatal Insulin-dependent Diabetes Mellitus, autoimmune enteropathy, dermatitis; bilateral cataracts; congenital microcephaly; cystic pulmonary hypoplasia, microgyria; renal vein thrombosis; nephrotic syndrome in Toxoplasmosis, cytomegalovirus infection, congenital Viral Hepatitis, congenital Syphilis, hemolytic-uremic syndrome, nephroblastoma, AIDS, Lowe syndrome, nail-Patella syndrome, and renal dysplasia. Familial occurrence of this syndrome (2.5–15% of cases) is diagnosed when a sibling of the proband is similarly affected, following an autosomal recessive or X-linked inheritance pattern.

Clinical symptoms are apparent at birth, and fatal outcomes occur rapidly upon the onset of infection and septic complications.

The method of Treatment is kidney transplantation once the child reaches a body weight of 10 kg or more.

Symptomatic therapy involves managing individual symptoms, treating concurrent renal failure, and utilizing prolonged hemodialysis. Tubular Function can be improved to some extent by ATP, cocarboxylase, and membrane stabilizers, notably vitamin E, retinol, and B-group Vitamins.

Primary nephrotic syndrome develops in glomerulonephritis with minimal glomerular changes (synonyms: lipoid nephrosis, nephrotic form of glomerulonephritis). It is characterized by a pure nephrotic syndrome symptom complex—absence of hematuria, hypertension, or renal impairment—with a prompt response to glucocorticoid therapy (by days 10–11), an acute course with remission in 20–30% of cases, a relapsing or frequently relapsing course in 70–80%, and a favorable prognosis leading to Clinical Recovery in 85–95% (N.A. Korovina, 1990). The diagnosis is established based on typical clinical and laboratory changes and a rapid response to Pathogenetic Therapy, with patient survival approaching 98–100% (N.D. Savenkova, 1998).

Secondary nephrotic syndrome in children is encountered less frequently than in adults. The group of underlying conditions is diverse: systemic connective tissue diseases (systemic lupus erythematosus, scleroderma spectrum disorders, dermatomyositis, rheumatoid Arthritis), systemic vasculitides (polyarteritis nodosa, hemorrhagic vasculitis), rheumatic fever, Goodpasture and Wegener syndromes, renal dysembriogenesis (dysplasia, hypoplasia, hypoplastic dysplasia, focal segmental glomerulosclerosis), vesicoureteral reflux and reflux nephropathy, Metabolic Disorders (diabetes mellitus, autoimmune thyroiditis), chronic infections (viral hepatitis, enterovirus and cytomegalovirus infections, AIDS, syphilis, bacterial endocarditis, tuberculosis, diphtheria, protozoal and helminthic infestations), dermatoses (psoriasis, ichthyosis), tumors and hemoblastoses (Wilms Tumor, leukemias, lymphosarcoma, Hodgkin lymphoma), hemoglobinopathies (Sickle Cell anemia, thalassemia), renal vein thrombosis, poisonings, drug-induced renal injury, vaccine administration, and hemolytic-uremic syndrome (N.D. Savenkova, 1996).

Secondary nephrotic syndrome is characterized by a polymorphism of clinical manifestations and a less favorable life prognosis.

Hypercoagulation and pronounced hyperlipidemia as manifestations of nephrotic syndrome create Prerequisites for the rapid development of glomerulosclerosis and chronic renal failure, which necessitates the correction of these metabolic disorders. Recently, the heparinoid sulodexide (trade name: Vessel Due F, Alfa Wassermann S.p.a.) has been used for this purpose due to its antithrombotic effect and favorable impact on Lipid Metabolism (S.A. Loskutova et al., 2000).

In pediatric nephrotic syndrome, immunomodulators are also employed (G.A. Makovetskaya et al., 2000): dibazol (1 mg/day per year of life, in the morning, for 3 weeks), thymogen (a synthetic analogue of thymic factors, 0.01% solution as nasal drops once daily for 5 days), sodium nucleinate (0.01–0.05 g/day, after meals, for 10–20 days), licopid (a synthetic analogue of bacterial membrane fractions, 1 mg 1–4 times daily for 10 days with repeated courses after 1 month), Rhodiola rosea extract (2–5 drops sublingually, twice daily, for 10–12 days), and immunonephrophyt (decoction 30–50 mL/day for 30–40 days).

Multifactorial (dysmetabolic) nephropathies are characterized by metabolic disorders that promote structural lesions at the nephron level.

Among the most common are oxaluria and uricosuria.

Primary hyperoxaluria comprises two pathological forms: a monogenic hereditary disorder characterized by enhanced oxalate Biosynthesis, and a polygenic hereditary disorder associated with the potential renal formation of oxalate and phosphate precursors, with which calcium forms insoluble salts. In both cases, the disease is characterized by recurrent calcium oxalate Nephrolithiasis combined with chronic dyspepsia, flatulence, biliary dyskinesia, occasionally cholelithiasis, intestinal anomalies (Loeper syndrome, M.R. Loeper), frequent secondary infections, and the development of progressive renal failure as early as childhood. The condition is inherited in an autosomal recessive manner, affecting boys more frequently than girls.

Initial symptoms appear during the first year of life: typical Renal Colic attacks and hematuria. Urine specific gravity is high, and urinary sediment shows proteinuria, hematuria, and A large number of aggregated oxalate and phosphate crystals.

M.S. Ignatova et al. (1982) cite the following frequencies of the main clinical signs of hyperoxaluria: abdominal pain (100%), oxaluria (100%), hypercholesterolemia and hyper-alpha₂-globulinemia (83.2%), aminoaciduria (83.2%), allergic diathesis (72%), cholecystopathy (58.8%), proteinuria (56%), and leukocyturia (50%).

Diagnosis is based on clinical data, ultrasound, and radiopaque imaging Methods (detecting renal stones).

The mainstay of treatment for oxaluria is diet therapy combined with agents that stabilize cell membranes and influence oxalate metabolism or binding processes, such as membrane stabilizers, antioxidants (especially vitamin E), B vitamins, and potassium and magnesium salts.

Here are foods that, while retaining acceptable palatability (which is important for a child!), positively influence the course of oxaluria: buckwheat, wheat, and oatmeal porridges, white bread with butter, rye bread, vegetarian soup, stewed potatoes with meat, potato cutlets, pancakes with sour cream, fresh lightly salted lard, meat cutlets with potatoes, boiled or baked potatoes, cabbage casserole, stuffed cabbage rolls with meat and rice, watermelons, bananas, and compotes made from apricots, apples, pears, dried apricots, and prunes. Vegetable oil should be included in the menu, and meat is best served boiled. To increase diuresis, patients are prescribed a high fluid intake (2 L per 1.73 m² of body surface area), preferably In the second half of the day.

Primary uricosuria develops As a result of purine metabolism disorders, where renal damage occurs due to a high influx of urates into the kidneys from the blood. It is rooted in enzymatic defects (glucose-6-phosphate dehydrogenase deficiency, hypoxanthine-guanine phosphoribosyltransferase deficiency, and excessive activation of phosphoribosyl pyrophosphate synthetase), which manifest under the influence of certain environmental factors (such as dietary habits).

Signs of kidney damage appear quite early (abdominal pain, renal colic, tubular dysfunctions without joint involvement (!)). The relative urine density is high, and the reaction is acidic (pH 5.5–5.7). The urinary syndrome is characterized by moderate proteinuria, leukocyturia, microhematuria, and a high content of urate crystals.

The mainstay of treatment for primary uricosuria is also diet therapy, combined with medications that reduce uric acid synthesis in the body. These issues are covered in the chapter «Dysmetabolic Nephropathies».

Hereditary and congenital tubulopathies are a common form of pathology in children.

They are based on impaired membrane Transport of substances in the tubules due to a lack of specific enzymes or receptor defects that ensure the action of these BIOLOGICALLY ACTIVE SUBSTANCES (systemic and local Hormones, Transmitters). This is accompanied by the predominant loss of function in the proximal tubules (de Toni-Debré-Fanconi syndrome, glucosuria, phosphate diabetes, Hartnup disease, cystinuria, glycinuria, proximal renal tubular acidosis), distal tubules (nephrogenic diabetes insipidus, distal renal tubular acidosis, pseudohypoaldosteronism (renal salt-wasting diabetes)), or both proximal and distal convoluted tubules simultaneously (Fanconi nephronophthisis).

The most severe form of proximal tubulopathy is de Toni-Debré-Fanconi syndrome. Tubule dysfunction (decreased reabsorption of Water, phosphates, sodium, potassium, calcium, bicarbonate, glucose, Amino Acids) in this case is combined with impaired glomerular function (proteinuria).

The disease is inherited in an autosomal recessive or autosomal dominant manner and begins to manifest during the first year of life. Symptoms include delayed physical and mental development, Rickets-like skeletal changes, vulnerability to infections, polyuria, thirst, muscle weakness, hyporeflexia, hypotonia, seizures, bone pain, fractures, and signs of metabolic acidosis (lethargy, irritability).

Laboratory tests reveal glucosuria without hyperglycemia, hyperaminoaciduria, phosphaturia, calciuria, kaliuresis, natriuresis, bicarbonaturia, and a shift in urine pH toward the acidic side.

There is also a de Toni-Debré-Fanconi syndrome variant with similar clinical features, most commonly caused by cystinosis—an inherited disorder of cystine metabolism characterized by the accumulation of cystine in the Cells of many Internal Organs, particularly in renal tubular cells.

Cystinosis, one of the manifestations of which is cystinuria, is inherited in an autosomal recessive manner. Cystinuria manifests as the formation of cystine kidney stones (2% of all stone types), impaired urine flow, and early-onset infection. Clinical signs characteristic of urolithiasis and secondary Pyelonephritis can appear at any age.

Diagnosis is based on detecting significant cystinuria using specialized tests.

The cornerstone of treatment for de Toni-Debré-Fanconi syndrome is diet therapy, aimed at limiting the intake of Sulfur-Containing Amino Acids while ensuring an adequate supply of phosphorus-containing and alkalinizing foods.

These requirements are best met by a potato and cabbage diet combined with alkaline mineral waters, dried fruits, carrots, vitamin D supplementation (up to 10,000–15,000 IU/day), and anabolic Steroids.

A medicinal mixture is prescribed (up to 50–60 mL/day), prepared from 2 g of citric acid, 3 g of sodium citrate, and 3.3 g of potassium citrate per 100 mL of water (I.E. Tareyeva et al., 1995).

In cystinuria, urine alkalinization is essential using alkaline mineral waters, oral administration of sodium hydrogen carbonate or sodium bicarbonate (up to 6–10 g/day), and a high fluid intake (over 3 L/day), with up to 1 liter of fluid consumed in the second half of the day and at night; unithiol and cuprenil are added to the treatment regimen.

Glucosuria may be isolated. Clinical symptoms are mild and mostly observed when there are significant urinary sugar losses (weakness, hunger, polyuria leading to dehydration and hypokalemia). Other types of -urias (phosphaturia, aminoaciduria) are not detected in these cases.

Diagnosis of glucosuria takes into account the following criteria: glucosuria without hyperglycemia, glucosuria in all urine portions, and a normal blood sugar curve during a glucose tolerance test. The prognosis is favorable, and this type of tubulopathy requires no special treatment.

Phosphate diabetes, a disease with a dominant inheritance pattern, is caused by decreased renal phosphate reabsorption, leading to hypophosphatemia and the clinical features of hypophosphatemic (vitamin D-resistant) rickets. Male carriers of the mutant gene can transmit it only to their daughters, whereas the probability of inheriting the mutant gene from a mother is roughly equal for sons and daughters.

The disease typically manifests at 1–2 years of age with growth retardation, Varus deformity of the legs, and bone pain. Laboratory findings include hypophosphatemia with normal blood calcium levels, and hyperphosphaturia.

Phosphate diabetes should be suspected when treating rickets with standard doses of vitamin D yields no clinical response.

Treatment involves ergocalciferol or calciferol (vitamin D₂) at a daily dose of 40,000–120,000 IU, or oxidevit (a synthetic metabolite of vitamin D₃).

To replenish phosphate levels, Albright's solution is recommended: citric acid 24 g, sodium citrate 40 g, distilled water 400 mL; take 1 tablespoon 4–5 times a day.

Proximal renal tubular acidosis (type II acidosis) is caused by impaired bicarbonate reabsorption in the proximal tubules while the distal tubules retain their ability to acidify urine. The result of these disorders is marked bicarbonaturia, alkaline urine, and metabolic acidosis. Rickets-like bone changes appear early, and nephrocalcinosis may develop. Diagnosis is based on identifying the aforementioned clinical and laboratory findings.

Treatment involves administering large doses of bicarbonate (up to 1 g/kg of body weight per day) combined with prolonged use of hypothiazide (6.25–12.5 mg/day) against the background of a low-sodium diet, along with the correction of hypokalemia and hypocalcemia. Regular oral intake of citrate mixtures is also recommended (dissolve 140 g of citric acid and 98 g of crystalline sodium citrate in 1 L of water and take 50–100 mL three times a day).

A characteristic feature of distal renal tubular acidosis (Lightwood-Butler-Albright syndrome) is the loss of the renal tubules' ability to lower urine pH in response to the intake or endogenous production of excess hydrogen ions. Notably, under any conditions, even during systemic acidosis or ammonium chloride loading, the urine remains persistently alkaline (urine pH does not drop below 6.0), although bicarbonate reabsorption in the proximal tubules is not impaired.

The inheritance pattern of the disease is autosomal dominant.

Clinical signs usually manifest in the 2nd–3rd year of life, although prior to this, growth retardation, anorexia, occasional vomiting, constipation, and polyuria are already detectable. Pronounced clinical symptoms include rickets-like bone changes, dehydration crises, nephrocalcinosis, and urolithiasis accompanied by interstitial nephritis or renal failure. The clinical picture is further complemented by hypokalemia (muscle hypotonia, hyporeflexia, arterial hypotension, corresponding ECG changes) and hypocalcemia (convulsions, bone pain).

Differential diagnosis between proximal and distal renal tubular acidosis is performed using the ammonium chloride loading test.

The management of distal renal tubular acidosis involves prescribing small doses of bicarbonates (0.2 g/kg of body weight per day).

Nephrogenic diabetes insipidus (vasopressin-resistant diabetes insipidus) is a type of tubulopathy associated with the kidneys' inability to concentrate urine due to an inadequate response of the distal tubular epithelial cells to antidiuretic hormone.

Two Types of inheritance are considered possible: X-linked recessive and autosomal dominant. The mutant gene is transmitted from father to son, and boys are affected more frequently.

Signs of tubulopathy appear immediately after birth—polyuria, polydipsia, dehydration (fever, convulsions, vomiting, lethargy) combined with hyposthenuria. Dehydration is the primary complication of the disease, while the development of hydronephrosis and bladder hypertrophy is considered a secondary manifestation.

To confirm the diagnosis, a vasopressin test is used: in nephrogenic diabetes insipidus, unlike central (pituitary) diabetes insipidus, parenteral administration of vasopressin is not accompanied by a decrease in daily urine output or an increase in its specific gravity.

Treatment for nephrogenic diabetes insipidus consists of the continuous intake of large amounts of fluid combined with the administration of thiazide Diuretics (hypothiazide) and potassium supplements in doses adjusted for clinical efficacy.

Reduced sensitivity of tubular epithelial receptors to aldosterone—and consequently, to adequate sodium reabsorption—is the cause of a tubulopathy known as "pseudohypoaldosteronism." Along with sodium, the body loses large amounts of fluid, leading to dehydration, salt depletion, and dystrophy. Hyponatremia and hypovolemia serve as triggers for aldosterone hypersecretion, yet sodium reabsorption remains impaired in the presence of hyponatremia.

Treatment consists of the continuous oral and parenteral administration of sodium chloride in accordance with daily losses.

Finally, we will discuss reflux nephropathy.

In 1960, C.J. Hodson and D. Edwards first drew attention to the direct link between chronic atrophic pyelonephritis and vesicoureteral reflux. In 1973, R.R. Bailey, and in 1976, L.R. King reported that conditions such as chronic atrophic pyelonephritis, segmental Renal Hypoplasia, focal segmental glomerulosclerosis (Ask-Upmark kidney), and the secondarily shrunken kidney are pathogenetically caused by vesicoureteral reflux. Consequently, the authors grouped these pathological forms together under the term "reflux nephropathy."

Reflux nephropathy is a frequent cause (5–25%) of chronic renal failure and arterial hypertension in children (L.T. Tebloeva, 1997); furthermore, a hereditary predisposition to this condition has been identified, linked to the A9, B12, and W15 loci of the Major Histocompatibility Complex.

The pathogenesis of this disease can be represented as follows (A.L. Cheskis et al., 1994; M. Monga et al., 1995).

In vesicoureteral reflux, the kidney experiences the damaging effects of both the retrograde backflow of infected urine and the increased hydrostatic pressure that occurs when urine from the bladder enters the renal pelvis. As a result, dilation of the collecting ducts and pyelorenal reflux occur, facilitating the invasion of microbial agents into the renal parenchyma, where an inflammatory focus develops. Additionally, the reflux disrupts renal blood flow, leading to tissue ischemia.

Depending on the body's reactivity and the virulence of the pathogen, the process can take an aggressive course, especially against the background of immature or dysplastic renal parenchyma. The leading role of Bacteria from the Enterobacteriaceae family has been established in this regard (S.N. Zorkin, 1998).

Inflammation primarily occurs in the area of the renal poles, where flat and curved papillae are localized, making them most vulnerable to the damaging effects of infected urine. The consequence of the inflammatory process is the sclerosis of renal tissue with scar formation, predominantly in the upper pole region. The Vessels of the renal parenchyma, glomerular capillaries, and Lymphatic vessels also undergo sclerotic changes.

In parallel, The Mechanism of hyperfiltration and compensatory hypertrophy of functioning nephrons in both kidneys is activated, and the process culminates in segmental glomerulosclerosis.

The most severe forms of reflux nephropathy are predominantly diagnosed in early childhood, although in some cases, renal damage occurs prenatally.

Radiological signs of renal damage (ectasia and deformation of the calyces with a reduction in renal parenchymal thickness and scarring) are so characteristic that excretory urography allows for the diagnosis of reflux nephropathy even in the absence of reflux on cystourethrograms.

It is also worth noting the certain significance of Marion's disease (H. Marion) in the development of reflux nephropathy.

Timely diagnosis and appropriate antibacterial therapy can largely prevent the development of severe renal complications (36–86% of cases), whereas surgical or endoscopic correction of reflux remains the method of choice for a subset of children (20–30%) (N.V. Markov, 1995).