RU2580314C1 - Method for treatment and prevention of glomerular and tubulointerstitial kidney disease in children, associated with toxic effect of cadmium, lead, chromium and phenol of technogenic origin - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention is intended for treating and preventing glomerular and tubulointerstitial renal diseases in children living in zone of influence of industrial enterprises during contamination of atmospheric air with cadmium, lead, chromium and phenol. At first stage is prescribed receiving multivitamins with micro-and macro-elements from series of “Vitrum” orally in 21 day course by 1 tablet 1 time a day after meals: “Vitrum-kids” is for children aged 7 years; “Vitrum-junior” for children older than 7 years old and preparation “Dimephosphone” orally in 10 days course: children aged 7-8 years in single dose of 10 ml 3 times a day or in daily dose of 30-50 mg/kg; children aged over 8 years in single dose of 15 ml 3 times a day or in daily dose of 30-50 mg/kg. At second stage is prescribed “Xydiphone” within course of 10 days for children aged 7-10 years old 1 dessertspoon 0.2 g 2-3 times a day; and for children aged 10 years old 1 table spoon 0.3 g 2-3 times a day.

EFFECT: method provides higher clinical effectiveness of toxic glomerular and tubulointerstitial renal diseases in children associated with combined action of cadmium, lead, chrome and phenol.

4 cl, 5 tbl, 2 ex

Description

The invention relates to medicine, namely to pediatrics, and can be used for the treatment and prevention of glomerular and tubulo-interstitial kidney diseases in children living in the influence zone of industrial enterprises in conditions of atmospheric air pollution with cadmium, lead, chromium and phenol.

The toxic effect of cadmium, lead, chromium and phenol is manifested in the form of kidney diseases, namely glomerular and tubulointerstitial diseases (according to the International Classification of Diseases of the 10th revision - ICD-10: “Glomerular and tubulointerstitial kidney diseases”: N00-N15).

The kidneys are the main organ that secretes toxins absorbed by the body. A large number of nephrons provides an extensive surface of glomerular endothelial cells and tubule epithelium for contact with them. In addition, in the atmosphere, most xenobiotics are able to form aerosols that settle on the hair and skin and are absorbed directly into the blood.

In general, glomerular and tubulointerstitial kidney diseases (ICD-10: N00-N15; N14.3 - nephropathy caused by heavy metals; N15.8 - other specified tubulointerstitial kidney lesions) - there is a pathology of the glomerular or tubular apparatus and interstitial tissue of the kidneys of various origins diagnosed on the basis of identifying almost identical typical clinical and laboratory signs of the disease (the presence of predisposing factors in the form of hereditary burden in nephropathology, small developmental anomalies organs of the urinary system, perinatal risk factors; the presence of urinary excretion, hypoisostenuria, laboratory signs of decreased tubular reabsorption during the period of remission (decrease in the amplitude of change in the specific gravity of urine during the day below 0.006 cu, a decrease in tubular reabsorption below 90%) aggravated during an exacerbation by polyuria, lower back heaviness, intoxication symptoms, sometimes arterial hypertension, the presence of β2-microglobulin in urine, microhematuria, proteinuria, abacteri leukocyturia, oxalaturia, phosphaturia, rarely glucosuria) (Pediatric Nephrology: A Guide for Physicians / Ed. M.S. Ignatova - 3rd ed., Rev. and add. - M .: Medical Information Agency LLC, 2011 - 696 p.: Ill.).

In recent years, the problem of the occurrence of these kidney diseases in children is increasingly being considered in connection with the influence of environmental chemical factors of technogenic origin.

A number of technical solutions are known from the prior art that are relevant to the proposed method, which can be attributed to methods of treating intoxication with heavy metals and to methods of treating and preventing kidney diseases caused by ecopathology.

The following methods can be attributed to the first group.

- A method for the treatment and prevention of heavy metal intoxication in animals (RF Patent No. 2366415), which includes the administration of the Helavit drug for treatment in a daily dose of 0.6-0.8 ml per 10 kg of live weight for a month. The drug reduces the content of lead and cadmium in the blood, milk and hair of animals, removes signs of intoxication. Disadvantages: the recommended drug belongs to the group of veterinary drugs from the group of feed additives. For treatment and prevention in humans is not applicable.

- A method for the prevention of cadmium nephropathy in experimental animals with chronic poisoning (RF Patent No. 2366459), which consists in administering to the experimental animals once a day “Acyzole” at a dose of 30 mg / kg simultaneously with a daily injection of a solution of cadmium sulfate subcutaneously at a dose of 0.1 mg / kg The method provides the prevention of the toxic effects of cadmium in chronic poisoning of experimental animals. Disadvantages: “Acizole” is a highly effective antidote against acute poisoning with lethal doses of carbon monoxide, as well as an effective antihypoxant for oxygen deficiency. The pathogenetic mechanism of the antitoxic effect of the drug does not stop all the mechanisms of the negative effects of the combined effects of cadmium, lead, chromium and phenol, does not increase the activity of mitochondrial respiration, does not stabilize the cell’s calcium homeostasis, and therefore is an extremely ineffective drug for the treatment of glomerular and tubulointerstitial diseases.

- A method for the treatment of chronic intoxication with heavy metals (RF Patent No. 2285523). The treatment is carried out in 2 stages, and at the first stage, the Xidifon drug is administered at a rate of 10-20 mg per kg of body weight per day for a continuous course for 21-30 days, and at the second stage, a complexing pharmaceutical preparation with a stability constant of 15 is administered in therapeutic doses -20 - Succimer, Tetacin, Pentacin, Penicillamine, fractional course for 2-7 days. This invention helps to remove salts of heavy metals from the body, and also provides a membrane-stabilizing effect on renal tissue. Disadvantages: the method is used for acute and chronic poisoning, i.e. at higher initial concentrations of chemical compounds; drugs are antidotes and require intravenous administration, which is traumatic for children; the method is effective against metals, but not tested with respect to their combination with phenol.

From the RF Patent No. 2376035, methods and compositions for preventing and treating kidney disease in cats are known by adopting an animal vitamin composition that contains vitamin E, vitamin C and carotenoid, taken in certain quantities and in certain ratios to each other. In a preferred embodiment, the composition is mixed with one or more food ingredients to produce a food composition suitable for preventing or treating kidney disease in cats. The disadvantage of this method of treatment is that the proposed complex of drugs does not have an anti-inflammatory effect, does not interfere with the crystal formation characteristic of glomerular and tubulointerstitial kidney diseases in children associated with the toxic effect of cadmium, lead, chromium and phenol of technogenic origin, does not enhance the elimination of toxicants from the body .

Also, from the same RF patent No. 2376035, a method is known for treating glomerular and tubulo-interstitial injuries by taking drugs such as Enalapril (Anacard, Vazotek) in therapeutic doses. Studies in the patent have shown that these drugs limit glomerular and systemic hypertension, proteinuria, and glomerular and tubulointerstitial diseases. However, their disadvantage is that these drugs have a pronounced hypotensive effect and are used mainly in adults.

Closest to the proposed technical solution is a Method for the treatment of chronic intoxication with heavy metal salts in children (RF Patent No. 2089192), according to which treatment with Xidifon is proposed by taking it internally in therapeutic doses, which accelerates the excretion of heavy metal ions. Moreover, the patent says that this drug is used to treat econephropathy (which may include glomerular and tubulointerstitial kidney disease) in children from ecologically unfavorable areas with a high content of heavy metal salts in the environment.

"Xidiphon" - monopotassium, monosodium salt of hydroxyethylidene diphosphonic acid, refers to complexing compounds of the phosphonic series, diphosphonates. Diphosphonates are synthetic analogues of natural regulators of calcium metabolism in the body, that is, inorganic pyrophosphates. The latter contain a P-O-P-bond, which leads to their rapid destruction in the body and the inability to use as a therapeutic agent. The diphosphonates (Xidiphon) contain a P-C-P bond, which makes their molecule resistant to spontaneous and enzymatic hydrolysis. "Xidifon" is excreted mainly by the kidneys, regulates calcium metabolism, without exerting a toxic effect on the body. It is used as an aqueous 2% solution inside and is effective in microdoses (4-10 μM / l of urine).

The disadvantage of this known method is the lack of effectiveness in the treatment of toxic toxic glomerular and tubulointerstitial kidney diseases in children associated with the combined effects of cadmium, lead, chromium and phenol, because Xydifon monotherapy under the following conditions: toxic glomerular and tubulointerstitial kidney disease due to the combined effects of cadmium, lead, chromium and phenol, does not reduce the activity of lipid peroxidation and increase the antioxidant protection of cells, increase the activity of mitochondrial respiration, which means it is ineffective.

The technical result achieved by the present invention is to provide effective treatment and prevention in children of toxic glomerular and tubulointerstitial kidney diseases associated with the combined effects of cadmium, lead, chromium and phenol due to the high degree of restoration of antioxidant defense activity, calcium homeostasis and energy metabolism the level of nephron cells and increase the body's resistance to these heavy metals and phenol and to improve the medical care provided Coy assistance to children living in areas with prolonged by environmental exposure to cadmium, lead, chromium and phenol technogenic origin.

The specified technical result is achieved by the proposed Method for the treatment and prevention of glomerular and tubulointerstitial kidney diseases in children associated with the toxic effects of cadmium, lead, chromium and phenol of technogenic origin, by prescribing the drug "Xidifon", while the new is that the treatment is carried out in two stage, and at the first stage, children use the following drugs in combination: multivitamins with micro and macro elements from the Vitrum series, oral But the course of 21 days and 1 tablet 1 time a day after meals, "Vitrum-Kids" - children under the age of 7; Vitrum Junior - children over 7 years of age and Dimephosphone drug orally for 10 days: children aged 7-8 years in a single dose of 10 ml 3 times a day or in a daily dose of 30-50 mg / kg; children over 8 years of age in a single dose of 15 ml 3 times a day or in a daily dose of 30-50 mg / kg, and in the second stage, after completion of the administration of "Dimephosphon", they are introduced into the treatment regimen in therapeutic doses of "Xidiphon" course 10 days for children aged 7-10 years - 1 dessert spoon 0.2 g 2-3 times a day; and for children over 10 years old - 1 tablespoon 0.3 g 2-3 times a day.

The course of treatment and prevention is carried out once a year, if after its completion more than 80% of the criteria for the effectiveness of the specialized treatment and prevention program are achieved; twice a year, if after its completion the achievement of 60-80% of the criteria for the effectiveness of the specialized treatment and prevention program is achieved, and three times a year, if after it is completed, less than 60% of the criteria for the effectiveness of the specialized treatment and prevention program are achieved.

As criteria for the effectiveness of a specialized treatment-and-prophylactic program, a 40% reduction in the frequency and duration of disease relapse is taken; restoration of the circadian rhythm of urine output; lack of complaints of heaviness in the lower back and polyuria; lack of symptoms of intoxication; stable physiological level of blood pressure; restoration of the amplitude of the change in the specific gravity of urine during the day (≥0.006 cu); recovery of tubular reabsorption (above 90%); lack of microhematuria, abacterial leukocyturia, proteinuria, glucosuria, hyperuricuria, phosphaturia, oxalaturia, calcium crystalluria; restoration of blood flow in the subcapsular zone of the kidneys; restoration of spectrogram parameters (blood flow velocity, resistance index - above 0.6 cu, pulsation index - above 1.1 cu, systolodiastolic index, resistance index from trunk to peripheral arteries - below 0.04-0.05 c.u); decrease in increased echogenicity of the renal parenchyma (ultrasound data); normalization of the total antioxidant activity of the blood, the content of superoxide dismutase, glutathione peroxidase, lipid hydroperoxides, catalase and malondialdehyde; normalization of indicators of phagocytic blood activity; a decrease in the content of cadmium, chromium, lead and phenol in the blood below 1.5 reference.

In the treatment and prevention of glomerular and tubulointerstitial kidney diseases in children, along with medications, diet therapy and water elimination therapy are additionally prescribed.

The technical result is achieved due to the following.

To understand the essence of the issue, it should be clarified that the problem of assessing the impact of industrial environmental pollution on the health of the child population is relevant for many countries of the world, including Russia. The children's population is a high-risk group, since children have a number of physiological characteristics, are characterized by the presence of critical periods of development, and greater sensitivity to the influence of toxic substances.

Due to the functional and anatomical features, the kidneys are one of the main organs - targets for the action of xenobiotics, especially heavy metals. Metals such as cadmium, mercury, lead, chromium, arsenic, iron, bismuth, boron, lithium possess high nephrotoxicity, which is associated with their ability to be deposited in parenchymal organs, especially in the cortical substance of the kidney. There is evidence that the influence of heavy metals leads to the formation of nephropathies, phenotypically manifested in the form of various symptom complexes: dysmetabolic nephropathy, tubulointerstitial nephritis, pyelonephritis, urolithiasis, Fanconi syndrome (Studenikin M.Ya., Efimova A.A. Ecology and child health Moscow, Medicine, 1998, p. 384). Environmental pressure associated with the accumulation of salts of heavy metals (strontium, chromium, lead, cadmium) is the most important factor in the formation of nephropathy under high loads of heavy metals (Veltishchev Yu.E., Fokeeva VV Ecology and children's health. Chemical ecopathology, Moscow, 1996, p. 57; Osmanov I.M., Clinical and pathogenetic features and tactics of treating kidney lesions in children in ecologically disadvantaged regions // Abstract of thesis, Doctor of Medical Sciences, Moscow, 1996, 48 pp.).

However, as it turned out, in children living in ecologically unfavorable territories, the occurrence of glomerular / tubulointerstitial kidney disease is possible not only of a toxic nature, due to exposure to xenobiotics - heavy metals and phenol, but also the occurrence of this disease of non-toxic nature. Therefore, it is very important to differentiate the nature of this disease for the purpose of subsequent specialized treatment, because different nature implies different approaches to treatment.

One of the priority pollutants in industrialized megacities are such heavy metals as Cd, Pb, Cr and others, as well as phenol. Their accumulation in the body has a toxic effect, creating a metabolic and structural basis for reducing the body's resistance with the subsequent development of various diseases and their chronicity.

In the early stages of the development of kidney diseases (ICD-10: N00-N15; nephropathy caused by heavy metals - N14.3; other specified tubulointerstitial lesions of the kidneys - N15.8) a pathological process in the kidneys associated with exposure to cadmium, lead, chromium and phenol , occurs in children latently with minimal manifestations of dysmetabolic nephropathy, which then during the accumulation of xenobiotics in the body passes to another stage - glomerular or tubulointerstitial nephropathy (kidney disease).

The nephrotoxicity of cadmium, lead, chromium and phenol is associated with their direct cytotoxic effect on the kidney apparatus. The cytotoxic effect is due to three interrelated mechanisms:

- increased lipid peroxidation, both due to a decrease in the antioxidant protection of the cell (blockade of superoxide dismutase, glutathione transferase, catalase), and due to the direct prooxidant activity of cadmium, lead, chromium and phenol;

- inhibition of mitochondrial respiration due to changes in the membrane potential of mitochondria and impaired activity of the respiratory chain and Krebs cycle enzymes (inhibition of citrate synthetase, succinate dehydrogenase, cytochrome C oxidase, proline accumulation, decreased macroerg production, decreased ATP / ADP (ATP, adenosintrif ratio) - adenosine diphosphate) a decrease in the activity of ATP-dependent enzyme systems, and especially K-Na-ATPase and Ca-Mg-ATPase);

- violation of calcium homeostasis of the cell due to changes in intracellular calcium flow, calcium replacement at specific receptors, followed by activation of calcium-dependent enzymes.

Due to the combined use of drugs and their phased administration recommended by the proposed method, the treatment and prevention of toxic glomerular and tubulointerstitial kidney diseases associated with the combined effects of cadmium, lead, chromium and phenol in children is highly effective due to the high degree of restoration of antioxidant activity, calcium homeostasis and energy metabolism at the level of nephron cells and increase the body's resistance to these severe M is a metal and phenol.

Moreover, in the proposed method, it is recommended to use the following drugs in combination:

Multivitamins with macro- and microelements from the Vitrum series: Vitrum Kids, Vitrum Junior ATX Code: A11AA04.

Vitrum Kids - 22 components: retinol acetate (vit. A) 2500ME (0.86 mg), α-tocopherol acetate (vit. Ε) 15ME (15 mg), colecalciferol (vit. D3) 400ME (10 μg), ascorbic acid (vit. C) 60 mg, thiamine mononitrate (vit. B1) 1.05 mg, riboflavin (vit. B2) 1.2 mg, calcium pantothenate (vit. B5) 5 mg, pyridoxine hydrochloride (vit. B6) 1.05 mg, folic acid ( Vit. Sun) 300 μg, cyanocobalamin (Vit. B12) 4.5 μg, Nicotinamide (Vit. PP) 13.5 mg, Biotin (Vit. H) 20 μg, Calcium (in the form of carbonate) 100 mg, Magnesium (in the form of phosphate) 40 mg, phosphorus (in the form of magnesium phosphate) 50 mg, iron (in the form of fumarate) 15 mg, copper (in ph PME oxide) 1 mg, zinc (in the form of oxide) 10 mg, manganese (in the form of citrate) 1 mg, iodine (in the form of potassium iodide) 150 μg, selenium (in the form of sodium selenate) 25 μg, chromium (in the form of chromium aminoate ) 20 mcg.

Vitrum Junior - 23 components: retinol (in the form of acetate) (vit. A) 5000 IU, tocopherol (vit. E) (in the form of acetate) 30 IU, colecalciferol (vit. D3) 400 IU, phytomenadion (vit. K1) 10 μg, ascorbic acid (vit. C) 300 mg, thiamine (vit. B1) 1.5 mg, riboflavin (vit. B2) 1.7 mg, calcium pantothenate (vit. B5) 10 mg, pyridoxine (vit. B6) 2 mg, folic acid (vit. BC) 400 μg, cyanocobalamin (vit. B12) bmkg, nicotinamide (vit. PP) 20 mg, biotin (vit. H) 45 μg, calcium 160 mg, magnesium 40 mg, phosphorus 50 mg, iron 18 mg, copper 2 mg, zinc 15 mg, manganese 1 mg, iodine 150 μg, molybdenum 20 μg, chromium 20 μg. The properties are determined by a complex of vitamins, minerals, trace elements.

Dimephosphone »Code ATX: V03AX: An antiacidic agent that normalizes the acid-base state (CBS) by activating the metabolic mechanisms of its regulation (especially renal and pulmonary), enhancing intraorgan blood flow and tissue metabolism. It has a membrane stabilizing, immunomodulating, antihypoxic effect, stimulates tissue regeneration. Dose-dependently reduces the intensity of lipid peroxidation, inhibits spontaneous and ADP-induced aggregation, increases the antioxidant activity of platelets and reduces the content of lipid peroxidation products in them, prevents the activation of lipid peroxidation, increases the activity of antioxidant enzymes.

"Xidiphon" Code ATX: M05 BA01 - monopotassium, monosodium salt of hydroxyethylidene diphosphonic acid, refers to complexing compounds of the phosphonic series, diphosphonates. The drug prevents crystallization, as well as the growth and aggregation of crystals of calcium salts in the urine, has a moderate anti-inflammatory effect with interstitial nephritis. "Xidiphon", like other complexones, has the ability to accelerate the excretion of heavy metals. Does not upset the balance of trace elements.

It was experimentally established that only the use of the integrated scheme for the use of the above drugs in two stages provides synergies in achieving the technical result due to improved processes of antioxidant protection, restoration of calcium homeostasis and energy metabolism at the level of nephron cells.

Studies have shown that using these drugs alone or with a two-drug regimen does not cure toxic glomerular disease and tubulointerstitial nephritis in children associated with the combined effects of cadmium, lead, chromium and phenol.

When implementing the proposed method, the following operations are carried out in the following sequence:

- choose an ecologically unfavorable territory for a high load of chemical environmental factors, namely, characterized mainly by the presence of chronic aerogenic exposure to cadmium at a concentration of more than 0.000010 mg / m ³ , lead - 0.000015 mg / m ³ or more, chromium - 0 , 000015 mg / m ³ or more and phenol - 0.0012 mg / m or more, which form an unacceptable level of risk (H1> 1.0) for the development of kidney diseases for the child population;

- Further, the child is diagnosed with toxic glomerular or tubulointerstitial kidney disease associated with exposure to cadmium, lead, chromium and phenol, as follows:

a) through traditional anamnestic, clinical, laboratory and instrumental examinations, children with glomerular and tubulointerstitial kidney diseases are identified. Currently, traditional anamnestic, clinical, laboratory and instrumental examinations for the establishment of glomerular and tubulointerstitial kidney diseases in children include: the presence of predisposing factors in the form of hereditary complications in nephropathology, small anomalies in the development of the organs of the urinary system, perinatal risk factors; the presence in the period of remission of circadian rhythm disturbances of urine excretion, hypoisostenuria, laboratory signs of decreased tubular reabsorption (a decrease in the amplitude of the change in the specific gravity of the urine during the day is below 0.006 cu, a decrease in tubular reabsorption below 90%), aggravated by an exacerbation of polyuria, severity in the lower back, symptoms of intoxication, sometimes arterial hypertension, the presence of β2-microglobulin in the urine, microhematuria, proteinuria, abacterial leukocyturia, oxalaturia, phosphaturia, less often glu ozuria (Pediatric Nephrology: A Guide for Doctors / Edited by M.S. Ignatova - 3rd ed., revised and revised. - M.: Medical Information Agency LLC, 2011 - 696 pp., ill. ) Moreover, in these traditional examinations common to these two diseases, a glomerular or tubulointerstitial disease is separated by analyzing urine indices, and for glomerular disease distinct proteinuria, hematuria, leukocyturia, cylindruria are characteristic, in severe cases oliguria, a decrease in glomerular filtration rate, the presence of p2- microglobulin in urine against arterial hypertension, and for tubulointerstitial disease, the presence of circadian rhythm disturbances during remission urine division, hypoisostenuria, laboratory signs of a decrease in tubular reabsorption (a decrease in the amplitude of change in the specific gravity of urine during the day is below 0.006 cu, a decrease in the tubular reabsorption index is below 90%), exacerbated during an exacerbation of polyuria, lower back pain, symptoms of intoxication, microhematuria , abacterial leukocyturia, oxalaturia, phosphaturia, rarely glucosuria (Pediatric Nephrology: A Guide for Doctors / Edited by M.S. Ignatova - 3rd ed., Rev. and add. - M .: Medical Information Agency LLC, 2011 - 696 p.: Ill.).

b) then, a venous blood sample is taken from each child and the content of cadmium, lead, chromium and phenol is established in it; and when the cadmium content in the blood is more than 2.0 times; lead more than 1.5 times; chromium more than 1.7 times; phenol more than 4.0 times higher than the reference / background, carry out a genetic study of the polymorphism of the CYPOX, RCYT 450, SULTA1 genes in a child;

c) in the presence of polymorphism according to the homozygous and heterozygous variant of the CYPOX, RCYT 450, SULTA1 genes, an ultrasound examination of the child's blood flow state in the subcapsular zone of the kidneys is performed in the color Doppler mapping mode;

d) and further, when the depletion of blood flow is established in the color Doppler mapping mode in the subcapsular zone of the kidneys, deviations from the standard values of the spectrogram parameters in the pulse-wave Doppler mode (resistance index is above 0.7 cu, the pulsation index is above 1.5 cu, increasing the range of resistance index values from the trunk to the peripheral arteries more than 0.03-0.07 cu) and increasing the echogenicity of the renal parenchyma, carry out an additional examination of the child by establishing the following clinical and lab -valued parameters: the level of total antioxidant activity in blood serum (CCA), the level of Cu / Zn-dependent superoxide dismutase (Cu / Zn-SOD), glutathione peroxidase levels (GlPO), catalase, lipid hydroperoxides and malondialdehyde MDA absolute index of phagocytosis and phagocytic number,

e) and when the condition is met: excess or decrease relative to the physiological age norm of the OSA level by 35-50% or 20-25%, respectively, the level of Cu / Zn-SOD by 30-50% or 15-20%, respectively, 30-50% or 15-20%, respectively; excess of catalase by 30-35%, lipid hydroperoxides by 30-35%, MDA by 30-35%; and a decrease in absolute phagocytosis and phagocytic number by 1.2 and 1.3 times, respectively, and at the same time, the child is found to have at least 65% or more of these altered indicated clinical and laboratory parameters, the child is diagnosed with the presence of glomerular / tubulointerstitial kidney disease associated with with the toxic effects of cadmium, lead, chromium and phenol of technogenic origin.

In the absence of the above indicators, the child is diagnosed with the presence of glomerular / tubulointerstitial kidney disease of non-toxic nature.

When a diagnostic examination of the proposed method use the equipment specified in table 1.

The physiological levels are used as criteria for assessing deviations of clinical and laboratory parameters, and reference levels are used for cadmium, lead, chromium, and background levels for phenol (N. Tits, 2003).

- carry out complex treatment of children with toxic glomerular / tubulointerstitial kidney disease identified in this way, due to the combined effects of cadmium, lead, chromium and phenol, through the combined use of the following drugs by children: at the first stage, the children use the following drugs: multivitamins with micro- and macronutrients from the Vitrum series orally for 21 days, 1 tablet 1 time per day after meals: Vitrum Kids - children aged 7 years; Vitrum-junior - children over 7 years of age and the Dimephosphone drug orally for 10 days: children aged 7-8 years in a single dose of 10 ml (1 dess. Spoon) 3 times a day or in a daily dose of 30-50 mg / kg; children over 8 years of age in a single dose of 15 ml (1 tbsp.spoon) 3 times a day or in a daily dose of 30-50 mg / kg, and in the second stage, after taking Dimephosphone, they are introduced into the treatment regimen in therapeutic doses of "Xidifon" course of 10 days for children aged 7-10 years - 1 dessert spoon (0.2 g) 2-3 times a day; and for children over 10 years old - 1 tablespoon (0.3) 2-3 times a day.

In the treatment and prevention of toxic glomerular and tubulointerstitial kidney disease, along with medications, diet therapy and water elimination therapy can be additionally prescribed.

Diet therapy to some extent provides the elimination of cadmium, chromium and lead through the gastrointestinal tract, an increase in the rate of phenol metabolism, a decrease in the activity of peroxidation processes, an increase in the functional activity of antioxidant defense systems, and a cytoprotective effect. It may be recommended to include in the diet foods with pronounced antioxidant properties, rich in fiber and pectins, as well as products with cytoprotective properties.

For example, the basis of the diet for this diet therapy can be a potato and cabbage diet, the inclusion of low-fat varieties of fish and meat, pasta, cereals, fresh, boiled and stewed vegetables, berries, butter and vegetable oil, jelly and stewed plums, raisins, dried apricots , pears, apples. Excluded from the diet are foods rich in ascorbic acid, oxalates (strong tea, cocoa, chocolate, beets, spinach, sorrel, parsley, rhubarb, tomatoes, currants, gooseberries, rosehips), extractive meat dishes, as well as products that irritate the tubular apparatus of the kidney : obligate allergens, spices, marinades, smoked meats, herbs with an acute taste (garlic, onions, cilantro, etc.).

Water-elimination therapy provides increased activity of the microcirculation processes in the kidneys, enhances renal plasma flow and urine filtration in the renal glomeruli, which can increase the efficiency of the renal mechanism of elimination of cadmium, chromium, lead, phenol and its metabolites from the body.

The daily amount of fluid consumed is determined from the calculation: 50-60 ml per 1 kg of the child's weight; the daily volume of mineral water is determined from the calculation: 3-5 ml / kg / day in 3 doses; 200-400 ml of warm mineral water (depending on age) is recommended for a child at night. To organize water elimination therapy, it is recommended to use mineral waters: Borjomi, Slavyanovskaya, Smirnovskaya, table mineral waters.

- the proposed course of treatment and prevention of toxic glomerular / tubulointerstitial kidney disease is carried out once a year, if after its completion more than 80% of the criteria for the effectiveness of the specialized treatment and prevention program are met; twice a year, if after its completion the achievement of 60-80% of the criteria for the effectiveness of the specialized treatment and prevention program is achieved, and three times a year, if after it is completed, less than 60% of the criteria for the effectiveness of the specialized treatment and prevention program are achieved.

At the same time, as a criterion for the effectiveness of a specialized treatment and prevention program, they take a 40% reduction in the frequency and duration of disease recurrence; restoration of the circadian rhythm of urine output; lack of complaints of heaviness in the lower back and polyuria; lack of symptoms of intoxication; stable physiological level of blood pressure; restoration of the amplitude of the change in the specific gravity of urine during the day (≥0.006 cu); recovery of tubular reabsorption (above 90%); lack of microhematuria, abacterial leukocyturia, proteinuria, glucosuria, hyperuricuria, phosphaturia, oxalaturia, calcium crystalluria; restoration of blood flow in the subcapsular zone of the kidneys; restoration of spectrogram parameters (blood flow velocity, resistance index above 0.6 cu, pulsation index above 1.1 cu, systolodiastolic index, resistance index from trunk to peripheral arteries below 0.04-0.05 cu ); decrease in increased echogenicity of the renal parenchyma (ultrasound data); normalization of the total antioxidant activity of the blood, the content of superoxide dismutase, glutathione peroxidase, lipid hydroperoxides, catalase and malondialdehyde; normalization of indicators of phagocytic blood activity; a decrease in the content of cadmium, chromium, lead and phenol in the blood below 1.5 RL.

An example of the implementation of the proposed method for the treatment of children suffering from toxic glomerular / tubulointerstitial kidney disease due to the combined environmental effects of cadmium, lead, chromium and phenol of technogenic origin.

1. Choose an ecologically unfavorable territory for a high load of chemical environmental factors. The city of Perm, the city of Berezniki, the city of Gubakh of the Perm Territory, characterized by the presence of chronic aerogenic effects on the population of cadmium, lead, chromium, phenol, was chosen as such territory. It was found that in the indicated territory with atmospheric air pollution cadmium (0.000010-0.000050 mg / m ³ ), lead (0.000015-0.000043 mg / m ³ ), chromium (0.000015-0 , 000047 mg / m ³ ) and phenol (0.0012-0.0073 mg / m ³ ) under chronic inhalation exposure, the risk (HI) of developing kidney diseases in the population reaches 1.1-4.03 (at that time as an acceptable level should be HI≤1.0). The level of registered incidence of kidneys in the territories of these industrial cities of the Perm Territory is 2.0-2.5 times higher than that of children in rural areas (2011-2013: - 32.4% -36.4% versus 16.2% - 14.5%).

2. Using the above diagnostic methods, a group of children with the diseases “toxic glomerular or tubulointerstitial kidney disease” is selected. As a result, 26 students of the school were selected with this disease, including 38 boys (51.3% of the number of selected children), 36 girls (49.7% of the number of selected children) - a follow-up group. The age of the examined children was 7-14 years.

A comparison group was also formed of 48 children, also aged 7-14 years, who also lived in the contaminated area and who were also recorded according to traditional anamnestic, clinical, laboratory and instrumental examinations (the presence of predisposing factors in the form of hereditary burden by nephropathology, small abnormalities of the development of the organs of the urinary system, perinatal risk factors; the presence of urinary excretion, hypoisostenuria, laboratory signs with tubular reabsorption (decrease in the amplitude of changes in the specific gravity of urine during the day below 0.006 cu, a decrease in tubular reabsorption below 90%), aggravated by an exacerbation of polyuria, heaviness in the lower back, symptoms of intoxication, sometimes arterial hypertension, the presence of β2-microglobulin in urine, microhematuria, proteinuria, abacterial leukocyturia, oxalaturia, phosphaturia, less often glucosuria) glomerular or tubulointerstitial kidney disease, but not of a toxic but somatic nature (for evidence of "non-toxicity" used the above diagnostic criteria, which confirmed this disease of non-toxic nature).

Data on the content of cadmium, lead, chromium and phenol in the blood of children of the observation group and the comparison group are shown in table 2.

Further, children from both groups underwent treatment by the proposed method (table 3).

Data on the effectiveness of the treatment of the proposed method for children with a diagnosis of toxic glomerular or tubulointerstitial kidney disease associated with the combined effects of cadmium, lead, chromium and phenol of technogenic origin are shown in table 4.

The data shown in table 4 show that after the treatment by the proposed method there was an improvement in all types of indicators in children suffering from toxic glomerular or tubulo-interstitial kidney disease under the influence of cadmium, lead, chromium and phenol: both indicators of instrumental examinations, and clinical and laboratory indicators . In this case, after the indicated treatment in children of the observation group, the following indicators improved:

- reduction in the frequency and duration of relapse of the disease by 40%;

- restoration of the circadian rhythm of urine output in 83.3%;

- the absence of complaints of heaviness in the lower back and polyuria in 100%;

- the absence of symptoms of intoxication in 100%;

- Stable physiological level of blood pressure at 100%;

- restoration of the amplitude of changes in the specific gravity of urine during the day (≥≤0.006 cu) in 92.3%;

- recovery of tubular reabsorption (above 90%) in 87.5%;

- the absence of microhematuria, abacterial leukocyturia, proteinuria, glucosuria, hyperuricuria, phosphaturia, oxalaturia, calcium crystalluria in 80.8%;

- restoration of blood flow in the subcapsular zone of the kidneys; restoration of spectrogram parameters (blood flow velocity, resistance index above 0.6 cu, pulsation index above 1.1 cu, systolodiastolic index, resistance index from trunk to peripheral arteries below 0.04-0.05 cu ); decrease in increased echogenicity of the renal parenchyma (ultrasound data) in 80%;

- normalization of the total antioxidant activity of the blood, the content of superoxide dismutase, glutathione peroxidase, lipid hydroperoxides, catalase and malondialdehyde in 53.8-96.2%;

- normalization of indicators of phagocytic blood activity in 88.5%;

- the content of cadmium, chromium, lead and phenol in the blood is below 1.5 RL in 100%.

In the comparison group, no significant dynamics of the studied indicators were established and the following data were obtained:

- reduction in the frequency and duration of relapse of the disease by 7-9%;

- restoration of the circadian rhythm of urine excretion in 25%;

- the absence of complaints of heaviness in the lower back and polyuria in 22.9%;

- lack of symptoms of intoxication in 10.4%;

- stable physiological level of blood pressure in 37.5%;

- restoration of the amplitude of changes in the specific gravity of urine during the day (≥0.006 cu) in 14.6%;

- restoration of tubular reabsorption (above 90%) in 16.7%;

- the absence of microhematuria, abacterial leukocyturia, proteinuria, glucosuria, hyperuricuria, phosphaturia, oxalaturia, calcium crystalluria in 8.3%;

- restoration of blood flow in the subcapsular zone of the kidneys; restoration of spectrogram parameters (blood flow velocity, resistance index above 0.6 cu, pulsation index above 1.1 cu, systolodiastolic index, resistance index from trunk to peripheral arteries below 0.04-0.05 cu ); a decrease in increased echogenicity of the renal parenchyma (ultrasound data) in 10.4%;

- normalization of the total antioxidant activity of the blood, the content of superoxide dismutase, glutathione peroxidase, lipid hydroperoxides, catalase and malondialdehyde in 29.2%;

- normalization of indicators of phagocytic blood activity in 22.9%;

- the content of cadmium, chromium, lead and phenol in the blood is below 1.5 RL in 100%.

After treatment, the resistance of the body of children with toxic glomerular or tubulointerstitial disease to the accumulation of cadmium, lead, chromium and phenol increased (reduction of cadmium content after 12 months by 58.6 ± 4.9%; lead by 63.7 ± 6.4%; chromium by 68.2 ± 8.1%; phenol by 84.7 ± 10.8%, despite the fact that the children who underwent treatment continued to live under the environmental conditions of the above toxicants).

The data obtained during the studies showed that the proposed method of drug treatment and prevention in children of toxic glomerular or tubulointerstitial kidney disease due to chronic exposure to cadmium, lead, chromium and phenol, combined with the use of the proposed drugs in two stages, is pathogenetically substantiated and shows high efficiency in in relation to the clinical manifestations of the disease, indicators of antioxidant and immunological protection, functional recovery th activity of various departments of the nephron, reducing the level of toxicant load.

To prove the synergism of the impact in the claimed method of exactly the three proposed drugs in the indicated dosage and for a special staged use, we present below Table 5, which reflects the clinical efficacy in history (after 12 months) with various drug regimens for the treatment and prevention of toxic glomerular or tubulointerstitial kidney disease in children exposed to chronic long-term exposure to cadmium, lead, chromium and phenol in the territory of residence.

As studies and data shown in table 5 showed, the effect of the proposed method is not a consequence of the simple action of the drugs used, but there is a pronounced positive synergy of drugs for the treatment and prevention of toxic glomerular or tubulointerstitial kidney disease (the sum of the effects of individual drugs in the same doses gives the effect is significantly less pronounced than with the combined use of the three drugs recommended in the present method).

The complex of specialized medical and preventive care for children with toxic glomerular / tubulointerstitial kidney disease associated with the environmental effects of these metals of technogenic origin and phenol extends standard treatment approaches, includes an additional set of medical measures based on a pathogenetically based combination of multivitamins and multi-minerals, antacidotic means and drug that normalizes calcium metabolism.

Thus, the proposed method for the treatment and prevention of toxic glomerular or tubulointerstitial kidney disease in children associated with the environmental effects of cadmium, lead, chromium and phenol of technogenic origin has a pronounced clinical effect and helps to restore the antioxidant and immunological defense, functional activity of various departments of the nephron , reducing the level of toxicant load, and can be recommended for the treatment of children with such a disease, tionary living in industrialized areas and with elevated levels in biological media of cadmium, lead, chromium and phenol.

April 08, 2015

Claims (4)

1. A method for the treatment and prevention of glomerular and tubulo-interstitial kidney diseases in children associated with the toxic effects of cadmium, lead, chromium and phenol of technogenic origin, by prescribing Xidifon, characterized in that the treatment is carried out in two stages, and at the first stage carry out the combined use by children of the following medicines: multivitamins with micro- and macrocells from the Vitrum series orally, 21 days a day, 1 tablet 1 time per day after meals: Vitrum Kids - de ty at the age of 7 years; Vitrum Junior - children over 7 years of age and Dimephosphone drug orally for 10 days: children aged 7-8 years in a single dose of 10 ml 3 times a day or in a daily dose of 30-50 mg / kg; children over 8 years of age in a single dose of 15 ml 3 times a day or in a daily dose of 30-50 mg / kg, and in the second stage, after completion of the administration of "Dimephosphon", they are introduced into the treatment regimen in therapeutic doses of "Xidiphon" course 10 days for children aged 7-10 years - 1 dessert spoon 0.2 g 2-3 times a day; and for children over 10 years old - 1 tablespoon 0.3 g 2-3 times a day. 2. The method according to p. 1, characterized in that the course of treatment and prevention is carried out once a year, if after its completion more than 80% of the criteria for the effectiveness of the specialized treatment and prevention program are achieved; twice a year, if after its completion the achievement of 60-80% of the criteria for the effectiveness of the specialized treatment and prevention program is achieved, and three times a year, if after it is completed, less than 60% of the criteria for the effectiveness of the specialized treatment and prevention program are achieved. 3. The method according to p. 2, characterized in that as a criterion for the effectiveness of the specialized treatment and prevention programs take a decrease in the frequency and duration of relapse of the disease by 40%; restoration of the circadian rhythm of urine output; lack of complaints of heaviness in the lower back and polyuria; lack of symptoms of intoxication; stable physiological level of blood pressure; restoration of the amplitude of the change in the specific gravity of urine during the day (≥0.006 cu); recovery of tubular reabsorption (above 90%); lack of microhematuria, abacterial leukocyturia, proteinuria, glucosuria, hyperuricuria, phosphaturia, oxalaturia, calcium crystalluria; restoration of blood flow in the subcapsular zone of the kidneys; restoration of spectrogram parameters (blood flow velocity, resistance index - above 0.6 cu, pulsation index - above 1.1 cu, systolodiastolic index, resistance index from trunk to peripheral arteries - below 0.04-0.05 c.u); decrease in increased echogenicity of the renal parenchyma (ultrasound data); normalization of the total antioxidant activity of the blood, the content of superoxide dismutase, glutathione peroxidase, lipid hydroperoxides, catalase and malondialdehyde; normalization of indicators of phagocytic blood activity; a decrease in the content of cadmium, chromium, lead and phenol in the blood below 1.5 reference. 4. The method according to p. 1, characterized in that in the treatment and prevention of glomerular and tubulo-interstitial kidney diseases in children, along with drugs, diet therapy and water elimination therapy are additionally prescribed.