Tubulopathies in children - clinical guidelines. Common causes of tubulopathies

May 28, 2018 Vrach

Tubulopathy is a group of pathologies characterized by persistent dysfunction of the renal tubules. With this pathology, the process of regular “transfer” of vital nutrients to the internal organ is disrupted in the renal tubules. Tubulopathy is diagnosed in adults and children different ages. The nature of the course of the disease is always different, which carries the risk of manifestation in patients of certain negative consequences that adversely affect the general physical state health.

Causes

Tubulopathies are subdivided into primary as well as secondary forms of education. Primary tubulopathy is characterized by the following root causes of development:

violation of the structural part of the membranes that are "carriers" of protein compounds;
lack of substances involved in the transport of vital important trace elements, as well as nutritional components to the kidneys and other organs of the urinary system;
reduced sensitivity of membranes, as well as tubules to the effects of hormones;
violation structural structure membrane cells.

The main reason for the development of the second type of tubulopathy is hereditary factor when, due to the genetic characteristics of the organism, the transport tubules are damaged. In addition, diseases such as dysplasia or inflammation of the kidney tissues often become provocateurs for the development of pathology. The cause of tubulopathy is also acquired diseases that develop due to impaired metabolic functions.

Types of disease

Tubulopathy is characterized by damage to different parts of the renal tubules, so doctors have established the following classification of the disease:

The defeat of the proximal renal tubules - the development of Tony-Debre-Fanconi syndrome, cystinuria, renal tubular acidosis, glycosuria, galactosemia or oxaluria. These diseases require qualified diagnostics and subsequent timely therapy. Diseases are treated in stationary conditions.
The defeat of the distal convoluted renal tubules - tubulopathy develops. The root cause is the following pathologies Key words: pyelonephritis, renal diabetes insipidus, tubular renal acidosis. The nature of the lesion internal organs- hereditary. The patient needs to control own food(refuse salt) and regularly undergo examinations (urinalysis).

Tubulopathy in children can be classified into other types. For example, Fanconi nephronophthisis, Liddle's syndrome, and Bartter's syndrome.

In people diagnosed kidney failure the risk of developing tubulopathy increases dramatically. With the development of the disease, a destructive process of the tubular renal apparatus will be observed. This condition poses a huge danger to the health and life of the patient.

Clinical picture

At the beginning of the development of the disease, the patient has no pathological symptoms. As a rule, the pathology is "disguised" as other diseases. A vivid clinical picture begins to emerge already with severe renal failure.

Symptoms of tubulopathy include:

renal colic;
glycinuria;
cystinuria;
iminoglycinuria;
tyrosinemia;
Lesch-Nyhan syndrome;
nephrolithiasis;
kidney failure;
changes in the structure of the skeleton (rickets).

Tubular renal acidosis may also be a sign of tubulopathy. The disease is characterized by symptoms such as paralysis, great weakness in the muscles.

The development of the disease is difficult to diagnose on early stages, since the clinical picture in the patient is always absent. If one or more of the above signs of tubulopathy are found, it is important to urgently consult a doctor.

Diagnostics

As diagnostic methods the patient is given:

delivery of urine and blood tests (general, biochemical);
x-ray examination of the kidneys;
Ultrasound procedure;
Magnetic Resonance Imaging;
kidney biopsy;
additional studies (immunological, physical);
x-ray study of the structure of the skeleton.

For comprehensive examination the patient is referred by the attending physician for a consultation with an ophthalmologist, surgeon, cardiologist, traumatologist.

Treatment Methods

The method of treatment of tubulopathy depends on the localization of the disease and the provoking factor. The disease is treated by a nephrologist. In most cases, the doctor prescribes conservative treatment, but with severe course the patient is indicated for surgical intervention.

Conservative therapy

Appointment medicines with tubulopathy, the doctor deals individually with each patient. basis conservative therapy is balanced therapeutic diet and taking medication.

Medications

Choice medicines depends on the form of the disease, the cause of its development and physiological features patient. At pain syndrome The patient is prescribed painkillers. Necessity of appointment antibacterial agents determined by the doctor.

The dosage and duration of treatment is determined only by the doctor. The effectiveness of therapy depends on the accuracy of patient compliance with medical recommendations. Basic correct therapy is the treatment menu. The patient is advised to consume foods enriched with calcium and phosphorus. It is important to abandon foods and alcohol that are “harmful” to the kidneys.

Surgical intervention

According to the indications, the patient may be prescribed surgery. As a rule, indications for surgery are inefficiency conservative treatment, secondary pathologies or the presence of kidney stones in the patient.

Methods surgical intervention with tubulopathy:

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Lithotripsy. The method of surgical intervention is prescribed for patients who are diagnosed with kidney stones. Before performing lithotripsy on a patient using ultrasound or shock wave therapy remove kidney stones. The operation is classified as a minimally invasive method of therapy.

The choice of the method of surgical intervention depends on many factors. Before the operation, the patient undergoes a complete medical research body, where the doctor establishes the presence of indications for surgery and contraindications. Treatment is carried out in stationary conditions. After being discharged home, the patient should carefully follow all the recommendations of the doctor.

Alternative therapy for the treatment of tubulopathy is not used. It's important to know that wrong treatment can harm the health of the patient. Treatment of the disease is carried out only under the supervision of a qualified doctor, taking into account all the physiological characteristics of the patient's body, as well as the nature of the pathology.

Prevention

The main prevention of the development of the disease is an attentive attitude to one's own health. Especially this recommendation refers to people who have a genetic predisposition to develop pathology. In this case, regular medical examinations are required, which will help to detect pathogenic changes in the body in the early stages and begin appropriate treatment.

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1. Proximal tubulopathies

1.1 Hypophosphatemic rickets

Hypophosphatemic rickets (phosphate-diabetes) is a disease associated with a defect in the reabsorption of phosphates in the proximal tubules, which manifests itself in children with phosphaturia, hypophosphatemia and severe rachitic changes resistant to usual doses vitamin D.

Several hereditary forms diseases occurring with an isolated violation of proximal phosphate reabsorption in the kidneys:

Hypophosphatemic rickets, X-linked dominant (OMIM 307800);

Hypophosphatemic rickets, autosomal dominant (OMIM 193100);

Hypophosphatemic rickets, autosomal recessive (OMIM 241520; OMIM 613312);

Hereditary hypophosphatemic rickets with hypercalciuria (OMIM 241530).

Normally, phosphate transport across the luminal membrane of the proximal tubule is carried out by sodium-phosphate co-transporters (sodium-phosphate transporter 2a, 2c - NPT2a, NPT2c), the expression of which is modified by fibroblast growth factor-23 (fibroblast growth factor 23 - FGF23) and parathyroid hormone.

FGF23 contributes to the development of phosphaturia by inhibiting phosphate reabsorption, due to the reduction of NPT2a, NPT2c and suppression of 1-α-hydroxylase expression, followed by suppression of circulating 1,25(OH)2D.

Parathyroid hormone also inhibits phosphate reabsorption in the proximal tubules by inactivating sodium phosphate cotransporters, but unlike FGF23, it simultaneously induces transcription of 1-α-hydroxylase, stimulating the synthesis of 1,25(OH)2D in the proximal tubules, which leads to an increase in NPT2b-dependent intestinal absorption of phosphates and suppression of transcription of parathyroid hormone genes.

At X-linked dominant hypophosphatemic rickets Mutations in the gene for phosphate-regulating endopeptidase homologous endopeptidase at the Xp22.1 locus (PHEX - phosphate-regulating endopeptidase homolog, X-linked) lead to disruption of enzyme systems that carry out FGF23 proteolysis. An excess of FGF23 causes a violation of phosphate reabsorption in the proximal tubules of the kidneys, which forms a characteristic biochemical phenotype, manifested by phosphaturia, hypophosphatemia, low or normal, but inadequately reduced relative to hypophosphatemia, the level of 1,25(OH)2D3. Despite the fact that more than 170 mutations of the PHEX gene (missense, nonsense, deletions, splice site mutations) have been described to date, distinct genotype-phenotypic correlations are not described.

Cause autosomal dominant hypophosphatemic rickets is the direct occurrence of mutations in the FGF23 gene on chromosome 12p13.3, which form the resistance of the factor to proteolytic cleavage.

emergence autosomal recessive hypophosphatemic rickets promote mutations in the gene dentin matrix protein 1 (dentin matrix protein 1 - DMP1) on chromosome 4q21 or the ectonucleoid pyrophosphatase / phosphodiesterase 1 gene (endonucleotide pyrophosphatase / phosphodiesterase 1 - ENPP1) on chromosome 6q22-q23, also contributing to an increase in FGF23 concentrations.

Autosomal recessive hereditary hypophosphatemic rickets with hypercalciuria develops due to mutations in the SLC4A3 gene on chromosome 9q34, which directly encodes the sodium phosphate cotransporter (NPT2c) of the luminal membrane of the proximal tubules.

1.2. Proximal renal tubular acidosis

Proximal RTA (type II) (OMIM 179830) is a disease characterized by impaired reabsorption of bicarbonates (HCO3-) in the proximal tubules.

Primary proximal RTA (isolated) :

. autosomal dominant;

. autosomal recessive with eye pathology and lag in mental development, mutation of the SLC4A4 gene (chromosome 4q21), disruption of the structure of the sodium bicarbonate cotransporter-1 (Na + -CO3-cotransporter - NBC-1) of the basolateral membrane of the proximal tubule (OMIM 604278);

. Sporadic

Transient (children's), immaturity of the sodium-hydrogen antiporter-3 (Na + -H + exchanger - NHE-3) of the apical membrane of the proximal tubule;

Persistent (adult).

Secondary proximal PTA is caused by a number of diseases: cystinosis, galactosemia, glycogenosis (type I), tyrosinemia, Wilson's disease, hyperparathyroidism, medullary cystic disease, vitamin D-deficient and dependent rickets, idiopathic hypercalciuria, primary hyperoxaluria, Lowe's syndrome, Sjögren's syndrome, multiple myeloma. It can also be called toxic damage proximal tubules with salts heavy metals, some drugs.

Normally, up to 90% of filtered bicarbonates are reabsorbed in the proximal tubules. Due to a violation of the reabsorption of bicarbonates in the proximal tubule, bicarbonaturia develops at a normal concentration of bicarbonates in the blood plasma. This leads to metabolic acidosis in the absence of acidification of the urine, despite intact mechanisms for distal secretion of H+ ions. Once the plasma bicarbonate concentration falls below the threshold value (in most cases less than 15 mmol/l, in the absence of treatment), the filtered bicarbonates begin to be completely reabsorbed, the reaction of the urine becomes acidic.

1.3 Fanconi syndrome

Fanconi syndrome (de Toni-Debre) is a disease caused by generalized dysfunction of the proximal tubules, leading to impaired reabsorption of amino acids, glucose, potassium, sodium, water, phosphates, bicarbonates, uric acid.

There are two forms of the disease:

. primary idiopathic Fanconi syndrome, in most cases sporadic; isolated cases may be hereditary (autosomal recessive, autosomal dominant inheritance);

. secondary Fanconi syndrome due to genetic diseases(cystinosis, galactosemia, hereditary fructose intolerance, tyrosinemia (type I), glycogenosis (type I), Wilson-Konovalov disease, mitochondrial cytopathies, Dent's disease, Lowe's syndrome), toxic effect drugs (gentamicin, tetracycline, antiretroviral drugs), salts of heavy metals, or developing as a result of primary amyloidosis, multiple myeloma and some other diseases.

Most common cause Fanconi syndrome in children is cystinosis (OMIM 219800), a rare autosomal recessive disorder characterized by the accumulation of cystine crystals within lysosomes and is accompanied by progressive

Defeat interstitial tissue kidneys with an outcome in chronic renal failure; frequency of occurrence ~1:200,000 newborns (Europe, USA).

The defect in the lysosomal cystine transporter, cystinosine, is caused by various mutations in the CTNS gene (chromosome 17p13). The most frequently detected large deletion of the CTNS gene completely disrupts its function.

Violation of cystine transport across the lysosomal membrane leads to the accumulation of cystine in the lysosome, a decrease in cystine and cysteine in the cytosol, which leads to an increase in the production of reactive oxygen radicals, causes ATP depletion, and stimulates apoptosis.

1.4 Renal glucosuria

Renal glucosuria is a disease caused by a violation of glucose transport in the proximal tubules of the kidneys, with a normal level of glucose in the blood.

. Autosomal dominant inheritance (type A)(OMIM 233100) - mutation of the sodium glucose cotransporter-2 (SGLT2) gene SLC5A2, chromosome 16p11.2;

. Autosomal recessive inheritance (type B)(OMIM 606824) - mutation of the sodium glucose cotransporter-1 (SGLT1) gene SLC5A1, chromosome 22q12.3.

Under physiological conditions, glucose is completely reabsorbed in the proximal tubules. Reabsorption of the bulk of glucose occurs in the S1 and S2 segments with the participation of the kidney-specific sodium-glucose transporter-2 of the luminal membrane. The rest of the glucose is removed from the filtrate in the S3 segment via the sodium-glucose transporter-1. This transporter is also present in small intestine. Like other membrane transport systems, glucose transporters have a saturation limit. Renal glucosuria occurs when the renal threshold for glucose falls despite normal blood sugar levels.

2. Loop tubulopathies

2.1 Bartter syndrome

Bartter's syndrome is an autosomal recessive disease caused by a defect in the reabsorption of sodium and chlorides in the thick ascending knee of the loop of Henle, which is characterized by the development of hypokalemia, hypochloremia, metabolic alkalosis and hyperreninemic hyperaldosteronism.

. Neonatal Bartter syndrome (type I)(OMIM 601678) - mutation of the NKCC2 gene (locus SLC12A1, chromosome 15q21.1), a primary defect in the sodium/potassium chloride cotransporter (Na-K-2CL) of the thick ascending limb of the loop of Henle;

. Neonatal Bartter syndrome (type II)(OMIM 241200) - mutation of the ROMK gene (locus KCNJ1, chromosome 11q24.3), dysfunction of the ROMK channel (ATP-sensitive rectifying potassium channel) of the thick ascending knee of the loop of Henle;

. Classic Syndrome Bartter ( type III) (OMIM 607364) - mutation of the CLCNKB gene (1p36.13), defect in the structure of the CLC-Kb channel (kidney-specific chloride channel) of the thick ascending limb of the loop of Henle;

. Neonatal Bartter syndrome associated with sensorineural hearing loss (type IV)(OMIM 602522) - mutation of the BSND gene (1p32.3), disruption of the structure of the membrane-bound subunit of chloride channels ClC-K (ClC-Ka, ClC-Kb).

In type I neonatal variant a primary defect in the Na+-K+-2Cl- cotransporter results in impaired sodium reabsorption in the thick ascending limb of the loop of Henle. Loss of sodium leads to a decrease in intravascular volume, activation of renin and aldosterone production, an increase in fractional potassium excretion, followed by hypokalemia and metabolic alkalosis.

In type 2 neonatal variant dysfunction of the ROMK channel prevents the return of reabsorbed potassium into the lumen of the thick ascending limb of the loop of Henle, which reduces the function of the Na+-K+-2Cl- -cotransporter.

With neonatal variant Bartter syndrome develops hypercalciuria and nephrocalcinosis.

The classic variant (type III) is accompanied by impaired transport of chlorides across the basolateral membrane back into circulation, which leads to hypovolemia and subsequent activation of the renin-angiotensin system with the development of hypokalemic metabolic alkalosis.

Nephrocalcinosis is absent.

3. Distal tubulopathies

3.1 Gitelman syndrome

Gitelman syndrome (OMIM 263800), familial hypokalemic hypomagnesemia, a salt-losing tubulopathy characterized by hypomagnesemia, hypocalciuria, and secondary aldosteronism, which leads to the development of hypokalemia and metabolic alkalosis.

An autosomal recessive type of transmission is characteristic - a gene mutation at the SLC12A3 locus on chromosome 16q13. The gene encodes a thiazide-sensitive Na + -Cl cotransporter (NCCT) of the distal convoluted tubules.

A defect in the Na+-Cl--cotransporter leads to a decrease in NaCl transport in the distal convoluted tubules, followed by the development of hypovolemia and stimulation of the renin-aldosterone system. Hypokalemia, hypomagnesemia, and metabolic alkalosis occur.

3.2 Distal renal tubular acidosis (type I)

Distal RTA (type I) (OMIM 179800, OMIM 602722) is a disease characterized by severe hyperchloremic metabolic acidosis due to impaired excretion of hydrogen ions in the distal nephron.

Primary distal RTA:

. autosomal dominant, mutation of the SLC4A1 gene (chromosome 17q21-22), disruption of the structure of the chloride-bicarbonate antiporter-1 (AE-1 - anion exchager 1) of the basolateral membrane of the cortical collecting ducts;

. Autosomal recessive with hearing loss, mutation of the ATP6V1B1 gene (chromosome 2p13), violation of the structure of the B1 subunit of the hydrogen ATPase of the intercalated cells of the population A of the apical membrane of the cortical collecting ducts;

. Autosomal recessive without hearing loss, mutation of the ATP6V0A4 gene (chromosome 7q33-34), encoding the alpha-4 subunit of the hydrogen ATPase of the intercalated cells of population A of the apical membrane of the cortical collecting ducts.

Along with familial forms of the disease, there are also sporadic cases.

Secondary (acquired) forms of distal RTA have been described in many pathological conditions caused by disorders of calcium metabolism with nephrocalcinosis and hypercalciuria, primary hyperparathyroidism, drug and toxic damage, other renal diseases, including medullary cystic disease and spongy kidney, autoimmune diseases (hypergammaglobulinemia, Sjögren's syndrome, autoimmune hepatitis, thyroiditis, fibrosing alveolitis, systemic lupus erythematosus, periarteritis nodosa).

Violation of ammonium excretion in all variants is secondary. Bicarbonate reabsorption is quantitatively normal, but, consistent with the increase in urine pH, some degree of bicarbonaturia is necessarily present (less than 5% of the filtered amount).

In severe chronic metabolic acidosis, the bone provides up to 40% of the buffer capacity of the blood; neutralization of hydrogen ions by bone carbonate causes the release of calcium from the bone into the extracellular fluid, which leads to a violation of its normal structure and various bone deformities.

Excretion of citrate in the proximal tubule is reduced, which is the basis for the formation of nephrocalcinosis.

3.3 Pseudohypoaldosteronism

Pseudohypoaldosteronism is a heterogeneous group of clinical forms arising from the inability of aldosterone to carry out its main physiological effects to ensure the excretion of potassium and hydrogen ions.

Pseudohypoaldosteronism, type I

- Autosomal dominant renal form(OMIM 600983) - mutations in the MLR gene (NR3C2, 4q31.1) of the mineralocorticoid receptors of the main cells of the collecting ducts.

A transient syndrome of hyperkalemia and metabolic acidosis without salt loss has been described in infants and is considered a variant of type I renal pseudohypoaldosteronism.

The ability to acidify the urine after acid loading in disease is preserved, but acid excretion by the kidneys is reduced due to very low ammonium excretion. Although the decrease in ammonium production is due to hyperkalemia itself, aldosterone deficiency or renal tubular resistance to it plays a key role in the development of this form.

- Autosomal recessive multiple organ form(OMIM 600228, OMIM 600760, OMIM 600761) - mutations in genes encoding α, β, γ subunits of sodium epithelial channels (ENaC) of collecting ducts (SCNN1A, SCNN1B, SCNN1G, 12p13, 6p13). Defect of sodium transport in many organs containing epithelial sodium channels - in the kidneys, lungs, intestines, exocrine glands.

Pseudohypoaldosteronism, type II (Gordon's syndrome - Gordon's syndrome)

- Autosomal dominant inheritance(OMIM 601844, OMIM 605232, OMIM 605775, OMIM 603136) - mutations in the WNK4, WNK1, KLHL3, CUL3 genes encoding kinases responsible for trans- and paracellular

The movement of chlorine, which secondarily leads to damage to the secretion of potassium and hydrogen.

Increased reabsorption of sodium chloride in the thick ascending knee of the loop of Henle, which leads to a violation of the secretion of potassium and hydrogen in the cortical collecting ducts.

- Acquired forms of pseudohypoaldosteronism described in obstructive uropathy, tubulointerstitial nephritis, severe pyelonephritis, sickle cell nephropathy, systemic lupus erythematosus, amyloidosis, multiple myeloma, neonatal medullary necrosis, unilateral renal vein thrombosis.

3.4 Nephrogenic diabetes insipidus

Nephrogenic diabetes insipidus - rare hereditary disease, characterized by the lack of permeability of the collecting ducts for water and resistance to the action of antidiuretic hormone with its adequate secretion.

X-linked recessive form(OMIM 304800) - mutations in the AVPR2 gene (Xq28 locus), encoding the arginine vasopressin receptor (V2R) in collecting duct cells.

Activated by binding to vasopressin, the V2 receptor causes an increase in cAMP. This leads to the movement towards the apical membrane of intracellular vesicles containing water channels of aquaporin-2 (AQ-2), which increases the permeability of the tubules for water. A genetic defect that includes different quantity mutations in the V2 receptor gene leads to a decrease in the binding of vasopressin to the receptor, a decrease in synthesis, or an increase in degradation of the receptor itself. As a result, the antidiuretic action of antidiuretic hormone (ADH) is blocked. Various mutations are associated with variable ADH resistance. The X-linked variant of inheritance implies the presence of severe polyuria in boys; in asymptomatic females most of the time, polyuria may occur during pregnancy when secretion of placental vasopressinase leads to increased clearance of endogenous ADH.

Autosomal recessive form(OMIM 125800) is caused by mutations in the aquaporin-2 gene (AQP2, locus 12q13). Both boys and girls are affected.

The post-receptor defect consists in a violation of the movement and subsequent fusion with the luminal membrane of ADH-sensitive aquaporin-2 water channels localized in the cytosol of the main cells of the collecting ducts, which prevents passive diffusion water.

The existence of an autosomal dominant form of inheritance of the disease is disputed, but isolated cases have been described.

In addition to genetically determined, there are also sporadic cases of the disease.

3.5 Liddle syndrome

Liddle's syndrome (pseudoaldosteronism) (OMIM 177200) is a hereditary disease characterized by the early onset of severe arterial hypertension, in conjunction with low levels plasma renin and aldosterone activity, hypokalemia and metabolic alkalosis.

Autosomal dominant type of inheritance - mutations in the SCNN1B, SCNN1G genes (locus 16p12.2), which lead to disruption of the structure of β and γ subunits of amiloride-sensitive epithelial sodium channels (ENaC) of the connecting tubules and main cells of the cortical collecting ducts.

Deceleration of ENaC degradation is manifested by excess sodium reabsorption and loss of potassium. Excess sodium reabsorption leads to arterial hypertension due to an increase in circulating blood volume, which suppresses the secretion of renin and aldosterone.

The term "Tubulopathy" refers to more than one individual disease, but a heterogeneous group of various diseases urinary system. It is characterized by changes in the processes of reabsorption of the tubules of the kidneys. Clinical manifestations are varied.

Tubulopathy affects people of all ages, including young children. The causes of the disease are various, but mostly people with genetic defects. Treatment is mainly conservative, in severe cases - surgical. The prognosis of the disease depends on the cause of development, the complications caused, the timeliness of treatment.

Features of tubulopathy, predisposing factors

Although tubulopathies are considered pathologies of the renal tubules, some of the diseases in this group arise on the basis of a violation of the structure of carrier proteins. The urgency of this disease is very high. The fact is that tubulopathies are often confused with rickets, the clinical manifestations and symptoms are so similar, and therefore true reason diseases are sometimes established late, when the disease has passed into a severe stage - chronic renal failure. This disease complete healing practically unsustainable.

Another reason for the relevance of tubulopathies lies in the fact that many causes of primary pathologies still remain poorly understood. Because of this factor, only maintenance therapy is possible, and complete treatment and healing is not available.

Predisposing factors may include inflammation of the kidneys, sharp violation in metabolism, changes in transportation systems.

Attention! Damage to the transport of the renal tubules results in serious violations in the urinary system general well-being person, which can lead to lethal outcome.

Classification

Tubulopathy has many varieties. Research was carried out long time, its types and subtypes were determined, but in the end, scientists settled on the division according to the localization of the defect and the main (leading) syndrome.

Tubulopathies are divided into primary and secondary.

Primary. Often this is the main diagnosis. The cause of the disease lies in the violation of the transport of substances in the membranes of the renal tubules.
Secondary. This is a complication of the underlying disease. The tubules are damaged due to metabolic pathology or diseases of various renal areas, for example, glomeruli.

There are 2 more groups of tubulopathies, these are chronic (myeloma or gouty kidney, amyloidosis, pyelonephritis) and acute (a deadly condition, as it requires immediate replacement of the kidney due to complete blockage of the lumen of the tubules; uremic condition occurs).

The main manifestations of tubulopathies

Violation of water-electrolyte metabolism (electrolyte deficiency, dehydration of the body).
Violation of the acid-base state.
Damage to the interstitial renal tissue.
Changes in the glomerular apparatus.
development of chronic renal failure.

Required differential diagnosis With various types hypophosphatemic rickets, osteopathies, tubular acidosis, cystinosis, phosphate diabetes. It is important to periodically conduct Sulkovich's test.

Common causes of tubulopathies

Genes that encode the synthesis of proteins that transport substances across the tubular cell membrane can undergo various mutations. A mutation occurs at the gene level, which means it can be inherited. That is, the main cause of tubulopathies is considered to be a genetic factor.

In addition, there are other reasons, these are:

defect in the development of receptors for certain hormones;
Tony-Debre-Fanconi disease;
renal dysplastic changes (changes in tubulocytes);
change in the process of reabsorption of certain trace elements or compounds (from primary urine);
poisoning of the body (salts of heavy metals, poor-quality food, drugs);
last degree burns;
renal glucosuria;
Bartter or Liddle syndrome;
hyperaldosteronism;
blood diseases.

The development of tubulopathies can provoke any serious condition at which there is a change in the function of the renal tubules.

Clinical manifestations, symptoms of tubulopathy

Clinical manifestations depend on those compounds that were subject to violation, damage:

Lack of calcium in the body (excreted in the urine in some forms of diabetes).
Lack of sodium chloride (displayed with pseudohypoaldosteronism).
Severe rickets-like disorders (with de Toni-Debre-Fanconi disease, with tubulopathy combined with multiple bone changes and pathologies, diseases of other organs, for example, eyes or blood vessels).
Lack of glucose in the body (polyuria, polydyspia).
Decreased potassium reabsorption (hypokalemia is formed, causes paralysis, hypotension).
Lack of amino acids (cystinuria, renal colic).

This group of tubulopathies - Hartnap's disease, cystinuria, pellagra and others, can lead to nephrolithiasis (deposition of stones in the kidneys).

Tubulopathy affects adults and children differently, but the nature of the course of the disease is different.

If a person has already been initially diagnosed with " Kidney failure", The risk of tubulopathies is very high. it dangerous state for the life of the patient, so it is necessary Special attention by doctors.

Diagnostics

For staging accurate diagnosis a comprehensive examination of the patient is necessary. It is especially important to study the work of the urinary system and the urine of a sick person.

Appointed following methods diagnostics:

test for the presence of glucose in the urine;
urinalysis for the detection of amino acids (chromatography), sodium chloride, calcium, potassium;
analysis for thyroid hormones;
radiographic examination;
ultrasound procedure;
molecular genetic methods (possibly not always);
blood chemistry;
analysis of adrenal hormones;
MRI and/or CT.

In each individual case, certain methods for diagnosing are selected. Often, consultations of such highly specialized specialists as an endocrinologist, gastroenterologist, and neuropathologist are important.

Tubulopathy treatment

Therapy of the disease is always different, depending on the localization of the pathology, the leading syndrome, age, the presence of complications, the presence of other chronic diseases, a number of other factors.

A strict diet is very important for tubulopathy (mainly with the rejection of salt and fat), with a predominance of fresh vegetables and fruits, foods rich in calcium, potassium, and phosphorus. The basis of the diet should be lactic acid products, bananas, carrots, tomatoes, kiwi, grapes, dried fruits, apricots.

Reception medications the doctor writes for each patient individually. If there are any complications, it is also important to eliminate and treat them, which is done in parallel with the treatment of tubulopathy.

Prevention

To prevent the occurrence of any complications, including diseases urinary tract, it is important to visit the doctor regularly and undergo clinical examination, hand over laboratory tests(at least once a year to undergo ultrasound diagnostics).

Galina Vladimirovna

Tubulopathy is not individual disease, and a group of pathologies.

They are characterized by a malfunction of one or more protein enzymes that control the reabsorption of substances.

Diseases have a separate classification, and the symptoms are not pronounced, as a result of which they are easily confused with manifestations of other diseases.

general information

Tubulopathies - group certain diseases kidneys with a similar developmental mechanism do not differ clinical manifestations and method of therapy.

In medicine, several types of tubulopathies are distinguished depending on the cause of their occurrence and the period of occurrence.

Tubulopathies occur mainly due to a violation of the formation of the fetus or under the influence various factors affecting the structure of the kidneys.

Symptoms are nonspecific and a thorough diagnosis is required to establish an accurate diagnosis.

Causes

It is customary to distinguish between primary and secondary tubulopathies. The causes of the development of the first type of diseases are:

violation of the structure of protein-transporting membranes;
insufficient amount of enzymes that are involved in transportation nutrients and trace elements in the organs of the urinary system, including the kidneys;
low sensitivity of tubules and membranes to the effects of hormones;
violation of the structure of cell membranes.

Secondary tubulopathy most often occurs as a result of damage to the transport tubules against the background of a genetic predisposition. Also provoke the development of diseases can:

inflammatory process affecting the tissues of the kidney;
dysplasia.

The cause of tubulopathy is also acquired pathologies characterized by metabolic disorders.

Classification and types

There are several classifications of diseases. There are both primary and secondary. The first type includes:

phosphate-diabetes;
renal glucosoria;
glucosamine diabetes;
Hartnap's disease and others.

Secondary pathologies occur against the background of already existing developmental anomalies or as a result of inflammatory processes. The main ones are:

congenital fructose intolerance;
cystinosis;
Wilson-Konovalov disease;
celiac disease and others.

Depending on the predominant symptom, there are:

. It can also be primary or secondary. These include pathologies such as pyelonephritis, renal diabetes insipidus.
BUT nomalia of the skeleton. Occurs when structure is changed bone tissue. Also called renal osteopathy.
. Stones begin to form in the kidneys, it is observed.

Establishing the type of tubulopathy is based on the results diagnostic measures. A treatment regimen is also selected.

proximal tubule disorder

These diseases include renal glycosuria, diabetes phosphate, and aminoaciduria. All pathologies have a favorable prognosis, but therapy should take place under the strict supervision of a physician.

Secondary disorders of the distal tubules include glycogenesis, Lowe's syndrome, and cystinosis. The prognosis is ambiguous and depends on many factors. Treatment is also carried out under the supervision of specialists.

distal tubules

Only congenital diseases are observed. The patient should control the volume of urine and follow a special diet.

It is impossible to completely cure the disease, but thanks to modern medicine can improve the prognosis and return the person to normal life. Most often, when establishing diseases belonging to this category, disability is established.

Development of the disease

Against the background of tubulopathy, the process of transporting nutrients, trace elements and oxygen to the kidney is disrupted. This disrupts their work and negatively affects the general condition.

The pathological process affects not only the tubules, but also neighboring tissues of the organ. Violation of working capacity occurs as a result of a lack of necessary substances.

Tubulopathy in children occurs for the same reasons as in adults. But some symptoms are different. The risk of developing diseases increases in cases where the patient has already suffered kidney failure. Already in the background past illness there is a violation of the tubules.

Clinical picture

Clinical manifestations of diseases are diverse and depend on which element of the urinary system was affected.

In some cases, excretion a large number calcium along with urine. Rickets-like disorders are combined with deformation of the eyes, blood vessels, heart, ears, nose. There are also signs of dehydration.

At not enough glucose, the following symptoms occur:

hunger;
weakness;
limb numbness.

These signs often resemble diabetes mellitus, as a result of which many patients look for the cause of their appearance in the wrong area.

Symptoms in children

Manifestations of tubulopathy in children differ slightly from the clinical picture in adults. With the development of pathology, there is a loss of appetite, weakness, constant drowsiness.

The process of urination is also disturbed. Depending on the area of localization of the pathological process, there may be a decrease in urine volume, incontinence or retention.

Diagnostic Measures

First of all, if symptoms occur, you should contact your therapist or. The specialist will establish the presence of symptoms, conduct an examination and prescribe a number of diagnostic tests.

The main diagnostic method is urine analysis. Laboratory research allows you to set the level of calcium, sodium, potassium in urine. It is also required to pass an analysis to determine the amount of glucose.

Chromatography is used to identify amino acids. All are carefully examined with a microscope or determined during an X-ray examination.

In order to confirm the anomalies in the development of the kidneys, ultrasound of the ureters and other organs of the urinary system is prescribed. If possible, a molecular genetic study may be prescribed.

Patients are prescribed a blood test, since in most cases the presence of various trace elements or an increase in their level is observed. Biochemical analysis Allows you to set your glucose level.

AT without fail a determination of the amount of hormones is also carried out, which allows you to evaluate the work endocrine system. Based on the results obtained, the doctor establishes a diagnosis and prescribes a course of therapy.

Methods of therapy

The method of treatment depends on the type of disease. Most often used drug therapy but in severe cases surgery is used.

conservative method

The basis of treatment for tubulopathy is the appointment of a diet. The patient should take vitamin complexes to replenish the level of calcium, phosphorus and other trace elements.

Medicines are selected individually, depending on the disease, the degree of its development and the patient's condition. In the presence of pain painkillers are indicated, antibiotics may be prescribed.

All drugs should be taken only as prescribed by a doctor and in the indicated dosages. The effectiveness of treatment depends on the correct observance of the recommendations of a specialist.

Surgical intervention

In the presence of kidney stones or other diseases, the treatment of which cannot be carried out with the help of drugs, an operation is prescribed. The main methods are:

Method surgical intervention depends on many factors. First of all, the operation is carried out in cases where other methods are ineffective. Before the procedure, the patient should undergo a series of examinations to establish the presence of indications and contraindications.

Traditional medicine recipes

It is strictly forbidden to use traditional medicine methods for tubulopathy. This is due to the diversity of diseases included in this complex.

The use of traditional medicine recipes can cause serious complications.

Complications and consequences

The main complication of tubulopathy is acute renal failure. There is also a risk of developing necrosis of the cortical substance of the organ.

The causes of their development are metabolic disorders and renal ischemia. To avoid complications, you should follow all the recommendations of a specialist.

Forecast and prevention

The prognosis directly depends on the disease and the cause of its development. In some cases, there is an improvement in the condition and full recovery. But in case of severe disorders and the impossibility of performing an operation, patients are shown supportive therapy, and disability is established.

There are no specific preventive measures to reduce the risk of developing tubulopathy. Specialists recommend medical genetic counseling to future parents.

Tubulopathy is a complex of various diseases that are characterized by a violation of the metabolic process in the kidneys. Symptoms and method of therapy depend on the type of pathology. In some cases, recovery is possible. But for this you should follow all the recommendations of the doctor.

Tubulopathy in children occurs due to disruption of the tubules of the kidneys. As a result of the development of pathology, the transport of nutrients to the organs is suspended. People with a burdened heredity are most susceptible to this disease. On the early stage kidney tubulopathy occurs under the guise of rickets, so the disease is diagnosed later, when severe chronic renal failure is already developing.

The disease is extremely difficult, it is important not to miss the moment and start treatment in a timely manner. Future parents are advised to consult a doctor in order to somehow protect the unborn child from pathology.

The etiology of the development of pathology includes a congenital (primary) and acquired (secondary) factor.

The formation of primary tubulopathy can occur against the background of:

transformations of the structure of membranes;
development of enzymopathy (insufficiency of enzymes);
violations of the sensitivity of tubule receptors to hormones;
dysplasia (violations of the structure of the membranes).

The formation of acquired tubulopathy occurs due to:

violations of transportation within the tubules;
failure of metabolic processes;
inflammation in the kidneys;

The tubules are constantly delivering useful material to the kidneys. Their malfunction or blockage leads to severe pathology. It is impossible to ignore tubulopathies in children and adults, otherwise the consequences can be deplorable, even fatal.

Attention! Classification of the disease involves dividing it on the basis of the leading symptoms and localization.

Diagnostics

Pathology is diagnosed using laboratory and instrumental methods research.

These include conducting:

radiography of the kidneys;
ultrasound examination of an organ (ultrasound);
skeletal radiography;
kidney biopsy;
OAM and UAC;
biochemical blood tests.

Also for complete examination the patient needs to be examined by specialists:

ophthalmologist;
trauma surgeon;
cardiologist.

Only on the basis of the results of the examination, a diagnosis is established and an appointment is made. complex treatment. Therapy is carried out exclusively in a hospital under the strict supervision of a doctor.

Symptoms

At the beginning of the disease, it is very difficult to diagnose pathology by symptoms. Clinical picture blurred, often the disease is disguised as comorbidities. Therefore, it is already detected in severe renal failure.

Treatment

Symptoms and treatment of tubulopathy depend on the location of the lesion and the underlying disease. Basically, treatment includes:

vitamin therapy;
diet, eating foods rich in calcium and phosphorus;
drug therapy.

After completion of hospital treatment, the patient for a long time must be registered with a pediatrician and nephrologist. Self-treatment at home with folk remedies prohibited. All procedures performed must be reported to the attending physician.

Prevention

Tubulopathy is an unpredictable disease. Preventive measures aimed at maintaining healthy lifestyle child's life. It is necessary to strengthen the immune system in every possible way. People with a burdened heredity need to regularly undergo medical examinations, which will allow timely detection of violations in the work of the kidneys. In case of any suspicion and symptoms, you should immediately consult a doctor.

Attention! In children, the disease often occurs in the form of rickets syndrome. The patient has obvious and hidden deformations of the skeleton. Early detection any changes in the kidney will avoid complications. it important point, which affects the further recovery of the patient.

The result of the disease

The prognosis is not always positive, depending on the etiology of the onset of the disease. The formation of renal diabetes insipidus in babies leads to rapid death. There is dehydration of the body, which causes death. And with de Toni-Debre-Fanconi syndrome, renal failure occurs, in which it is important to carry out replacement therapy.

Most tubulopathies that occur against the background of a failure in the membrane transport of amino acids can be treated. But some diseases causing appearance such deviations are asymptomatic, so it is important to conduct a regular examination of the child to identify violations in the functioning of the organs.

According to statistics, primary tubulopathies are more severe, the prognosis for cure is unfavorable, pathology often leads to death than secondary ones. This is due to the impossibility of conducting etiotropic therapy, which helps to eliminate the cause of the development of the disease.