Purine diseases. Purine base metabolism disorder

Along with other diseases, disorder of purine metabolism is also an important disease, the treatment of which should be given special attention. First of all, it is a violation of the metabolism of useful substances in the body and the metabolism of proteins, which in turn can be expressed in several diseases, such as: renal failure, nephropathy, gout. In most cases, a disorder of purine metabolism is a childhood disease, but very often it can occur in adults.

Symptoms of the disease.

The symptoms of the disease are very similar to those with metabolic disorders (metabolism of nutrients in the body and their absorption) - metabolic myopathy. The disease is characterized by elevated levels of creatinine kinase (in most cases). Other, nonspecific symptoms of the disease can be determined using an electromyographic study.
In patients who have a disorder of purine metabolism, ammonia production is very low, and performance and appetite also decrease. Patients feel lethargic, sometimes developing very great weakness in the body. Children who suffer from metabolic disorders for a long time often remain mentally undeveloped and have a tendency to develop autism. In rare cases, children (and sometimes adults) experience seizures, convulsions, and the psychomotor development of the individual is greatly inhibited.
Diagnostics cannot give a 100% result in determining the correctness of the disease, since it has many similar indicators with other disorders in the homeostasis of the body, but in general terms and with long-term observation of the patient’s tests, a disorder of purine metabolism can be determined. The diagnosis is based, first of all, on the complete absence of enzyme activity in the kidneys, liver and skeletal muscles. Using a number of tests, partial deficiency can be determined in fibroblasts and lymphocytes. Specific treatment that would be focused on achieving results in the treatment of dysfunction of these enzymes has not yet been developed and can only rely on the generally accepted comprehensive methodology.

Purine base exchange

The optimal level of protein synthesis and the creation of new ones is the basis for the correct, systematic exchange of purine bases, since they are the most important component of the proper functioning of the body and contribute to the release of a sufficient number of enzymes. The correct exchange of purine bases will ensure stability in metabolism and the balance of energy that is released during the exchange of useful substances.
You should carefully monitor the metabolism in the body, as this will affect not only excess weight (as many people who have heard about the causes of excess weight believe), but also directly on the proper development of all body tissues. A deficiency or slowdown in the metabolism of important substances will slow down tissue development. The synthesis of puric acids is the main catalyst for all division processes in human tissues, since these are protein formations that are supervised by the beneficial components that are delivered to the tissue thanks to these processes. Another symptom that can be detected when diagnosing metabolic disorders is an increased ratio of metabolic products in uric acid, in which they accumulate during the breakdown of purine nucleotides.
Disorders of purine metabolism, symptoms and treatment of purine metabolism in the body, diagnostics of software are actions that should be carried out systematically, especially in children and young men, in whom the disease manifests itself most often.
Where do these purine bases come from?
Purine bases enter the body directly with food, or can be synthesized in the cells themselves. The process of synthesis of purine bases is a rather complex, multi-stage process that largely takes place in the liver tissue. The synthesis of purine bases can be carried out in a variety of ways, in which adenine in the nucleotides and ordinary, free adenine are broken down, converted into other components, which are further converted into xathin and, as a consequence, further converted into uric acid. In primates and humans, this particular product is the final product of the process of synthesis of purine bases and, being unnecessary for the body, is excreted from it in the urine.
Violation of purine bases and their synthesis leads to the formation of uric acid more than the prescribed norm and its accumulation in the form of urates. As a result, uric acid is poorly absorbed and enters the blood, exceeding the permissible, accepted norm of 360-415 µmol/l. This state of the body, as well as the amount of substances allowed, may vary depending on the person’s age, overall weight, gender, proper kidney function and alcohol consumption.
As this disease progresses, hyperuricemia may occur—an increased amount of urate in the blood plasma. If this disease is not treated, then soon there is a possibility of gout. This is a type of disorder of purine metabolism in the body, which is accompanied by a disorder of fat metabolism. As a consequence of this - excess weight, atherosclerosis and the possible development of coronary heart disease, high blood pressure.

Treatment of the disease.

Metabolic disorders (the treatment of which is described below) implies complex treatment, which is based primarily on strict diets containing foods with a reduced amount of purine bases (meat, vegetables), but medicinal methods of treatment can also be used:

Balancing and stabilizing purine metabolism through fortification.
Establishment of metabolic acidosis and regulation of the acidic environment of urine.
Monitoring and stabilization of the patient’s blood pressure throughout the day.
Establishment and maintenance of hyperlipidemia norms.
Complex treatment of possible complications of purine metabolism in the body (treatment of pyelonephritis)

Treatment of PO in the body can be carried out either in a hospital or independently after consultation with a doctor.

Acetone syndrome in children is a dysfunction of the metabolic system. The condition of a sick child is characterized by a high content of ketone bodies in the blood. During metabolism, they break down into acetone substances. This can trigger episodic attacks with abdominal pain. In severe cases, the child develops a coma.

Acetonemic syndrome can be secondary when the disease develops against the background of other disorders of carbohydrate, fat or protein metabolism. Primary idiopathic acetonemic syndrome also occurs in children. In this case, the main provoking mechanism is the hereditary factor. Recently, the incidence of acetone syndrome in newborns whose mothers suffered from insufficient renal function during pregnancy has increased. If the urine of a pregnant woman is periodically detected, and she suffers from constant edema, then the risk of developing intrauterine acetonemic syndrome in the fetus increases many times over.

The metabolic disorder of purine substances, which provokes the development of acetone syndrome, may be associated with the use of drugs containing artificial purines.

Symptoms of acetone syndrome in children

The mechanism of pathological changes in biochemical reactions begins in the renal structures. Blood enriched with purines enters here. The glomeruli are unable to adequately process large amounts of purine substances. With the blood flow, they return to the bloodstream in the form of ketone bodies. In the future, these substances require:

increased oxygen supply for their oxidation;
increasing blood volume to reduce their concentration;
reducing blood glucose levels to utilize acetone.

All these processes form the corresponding clinical picture:

develops - increased ventilation of the lungs;
the child's breathing quickens;
heart rate increases;
against the background of all this, the child becomes lethargic and apathetic;
An acetone coma may develop under the narcotic influence of acetone and ketone bodies on brain structures.

But the main symptom of acetone syndrome in children is periodic uncontrollable vomiting with severe pain in the abdominal area. It is repeated with a certain frequency and is distinguished by the constancy of such parameters as duration, amount of vomit and the condition of the child.

Acetonemic syndrome in children is a typical alternation of periods of absolute well-being in the child’s condition with attacks of acetonemic crises. Their clinical picture is described above. The reasons for their occurrence are the accumulation of a critical amount of ketone bodies in the child’s blood.

Treatment of acetone syndrome and prognosis

Treatment of acetone syndrome in children comes down to two aspects:

relief of acetone crisis;
prolongation of the remission period, in which there is a tendency to reduce the incidence of crisis cases under the influence of acetone substances.

To relieve a crisis, prokinetics and cofactors (involved in the metabolic process) are used in combination with enzyme replacement therapy. In severe cases, intravenous infusion therapy is prescribed. Thus, the electrolyte composition of the blood is restored, fluid losses are replenished, and the level of ketone bodies is reduced. For intravenous infusion, drugs with an alkaline reaction are used. During the remission period, the focus is on the child's diet and lifestyle.

Acetonemic syndrome in children is often accompanied by increased nervous excitability, which provokes the release of purines and ketone bodies into the blood. may provoke a crisis. Attention should be paid to reducing stress load and avoiding critical physical activity.

Diet for acetone syndrome

A constant diet for acetone syndrome is the basis for successful treatment and preventing the risk of developing crises. Foods that are sources of large amounts of purines should be excluded from the child’s diet. These are meat products, rice, offal, mushrooms, beans, peas, fatty fish.

Introduce easily digestible foods into your child's diet. These are eggs, dairy products, vegetables and fruits. Be sure to let your child drink at least 2 glasses of mineral water with a weak alkaline reaction (Borjomi, Essentuki) during the day. Fresh juices from fruits and vegetables are beneficial.

If necessary, you can use enzyme preparations to improve digestion processes. But this can only be done after consulting with your doctor.

Over the past decades, the spread of uricosuria and uricosemia has increased in both children and adults. Kidney pathology caused by disorders of purine metabolism can be diagnosed in 2.4% of the child population. You will learn from the article how dysmetabolic nephropathy occurs in children, how it is diagnosed and treated.

Dysmetabolic kidney nephropathy - what is it?

According to screening studies [Mukhin N.A., 1994], increased uricosuria occurs in 19.2% of adults. This increase in disorders of the metabolism of purine bases is explained by environmental reasons: the products of gasoline engines that saturate the air of large cities significantly affect purine metabolism.

The term "econephropathy" arose. It is practically important to take into account that maternal hyperuricemia is dangerous for the fetus due to its teratogenic effect and the possibility of the formation of congenital nephropathies - anatomical and histological. Uric acid and its salts have a direct nephrotoxic effect.

Types of hyperuricemia

In the pathogenesis of hyperuricemia, it is important to determine its type: metabolic, renal or mixed.

The metabolic type involves increased synthesis of uric acid, a high level of uricosuria with normal or increased clearance of uric acid.
The renal type is diagnosed when the secretion of uric acid is impaired and, accordingly, when these parameters decrease.
A combination of metabolic and renal, or mixed type, is a condition in which uraturia does not exceed normal or is reduced, and uric acid clearance is not changed.

Violation of purine metabolism in children

Since disorders of purine metabolism are hereditarily determined, in most patients with this pathology the main markers of hereditary nephropathies can be found: the presence in the pedigree of people with kidney diseases, frequently recurring abdominal syndrome, a large number of small stigmas of disembryogenesis, a tendency to arterial hypo- or hypertension. The range of diseases in the pedigree of a proband with dysmetabolic nephropathy based on the type of purine metabolism disorders is wide: pathology of the digestive tract, joints, endocrine disorders.

The development of pathology of uric acid metabolism can be traced in stages. Metabolic disorders without clinical manifestations have a toxic effect on the tubulointerstitial structures of the kidneys, as a result of which interstitial nephritis of dysmetabolic origin develops. When a bacterial infection occurs, secondary pyelonephritis occurs. When the mechanisms of lithogenesis are triggered, the formation of urolithiasis is possible. The participation of uric acid and its salts in the immunological restructuring of the body is allowed. Children with impaired purine metabolism are often diagnosed with a hypoimmune condition. The development of glomerulonephritis cannot be excluded.

What are the signs of dysmetabolic nephropathy?

Intestinal manifestations of an uncomplicated form of purine metabolism disorder are nonspecific. In younger children (1-8 years old), the most common symptoms are abdominal pain, constipation, dysuria, myalgia and arthralgia, excessive sweating, nocturnal enuresis, tics, and logoneurosis. The most common manifestations in older children and adolescents are excess body weight, itching in the urethra, biliary dyskinesia and lower back pain. Moderate signs of intoxication and asthenia are possible.

In children with disorders of purine metabolism, one can usually find a large number of external stigmas of disembryogenesis (up to 12) and abnormalities in the structure of internal organs ("minor" heart defects, that is, valve prolapse, additional chordae, structural anomalies of the kidneys and gall bladder). In 90% of cases, chronic pathology of the digestive tract is diagnosed.

Main signs of dismetabolic kidney nephropathy

Signs of metabolic disorders in the myocardium occur almost as often - in 80 - 82%. More than half of these children have arterial hypotension, and 1/4 of the patients have a tendency towards arterial hypertension, which increases with the age of the child. Most children drink little and have low urine output (“opsiuria”). Urinary syndrome is typical for tubulointerstitial disorders: crystalluria, hematuria, less often – leukocyturia (mainly lymphocyturia) and cylindruria, unstable proteinuria. Obviously, there is a close connection between purine metabolism and oxalate metabolism. Crystalluria can be of mixed composition. In 80% of cases, disturbances in the circadian rhythm of urination can be detected - the predominance of nighttime diuresis over daytime. As interstitial nephritis progresses, the daily excretion of ammonium ions decreases.

Treatment of dysmetabolic nephropathy in children

Treatment of patients with disorders of purine metabolism is based on dietary restrictions on foods rich in purine bases or that provoke increased synthesis (strong tea, coffee, fatty fish, dishes containing gelatin) and increased fluid intake. Alkaline reaction mineral waters (Borjomi) are recommended; a citrate mixture is prescribed in courses of 10 to 14 days or Magurlit.

Medicines for the treatment of dysmetabolic nephropathy

For the metabolic type of purine metabolism disorder, uricose depressants are indicated: allopurinol at a dose of 150 mg/day for children under 6 years of age, 300 mg/day for children aged 6 to 10 years, and up to 600 mg/day for older schoolchildren. The drug is prescribed in full dose for 2 - 3 weeks. after meals with a transition to half the maintenance dose for a long course of up to 6 months. Additionally, orotic acid is prescribed (potassium orotate at a dose of 10 - 20 mg/kg per day for 2 - 3 doses).
In the renal type, uricosuric drugs are prescribed - aspirin, etamide, urodan, anturan - which inhibit the reabsorption of uric acid by the renal tubules.
In case of mixed type, a combination of uricose depressors with uricosuric drugs is applicable. Both drugs are prescribed at half the dose each.

It is necessary to monitor the reaction of urine with mandatory alkalization. For long-term use in outpatient settings, the drug allomaron containing 50 mg of allopurinol and 20 mg of benzobromarone is recommended. Senior schoolchildren and adults are prescribed 1 tablet per day.

Prognosis of dysmetabolic nephropathy with impaired purine metabolism

In rare cases, extreme situations are possible when hyperuricemia leads to acute occlusion of the tubular system of the kidneys and urinary tract with the development of acute renal failure (“acute uric acid crisis”). Glomerulonephritis against the background of disorders of purine metabolism usually occurs in the hematuric form with episodes of reversible decline in renal function with the prospect of developing chronic renal failure within 5 to 15 years. As a rule, secondary pyelonephritis occurs latently.

The doctor’s task is to diagnose disorders of purine metabolism at the preclinical stage, that is, to identify patients at risk and give recommendations regarding lifestyle and nutrition that will help slow down the development of pathology and prevent complications.

Now you know what dysmetabolic nephropathy in children is. Health to your child!

", sanatorium.

A. Yu. Nikolaev, Doctor of Medical Sciences, Professor
Yu. S. Milovanov, Candidate of Medical Sciences, Associate Professor
MMA im. I. M. Sechenova, Moscow

The concept of “gouty nephropathy” includes various forms of kidney damage caused by disorders of purine metabolism and other metabolic and vascular changes characteristic of gout. Gout affects 1-2% of the population, mostly men. If early asymptomatic disorders of purine metabolism are potentially reversible with timely diagnosis and correction, then at the stage of tophi gout with damage to blood vessels and target organs (heart, brain, kidneys), the prognosis of the disease is unfavorable. Kidney damage develops in 30-50% of patients with gout. With a persistent increase in blood uric acid levels > 8 mg/dL, the risk of subsequent development of chronic renal failure (CRF) increases by 3-10 times. Every 4th patient with gout develops chronic renal failure.

Both acquired and hereditary factors play a role in the development of gout. The role of malnutrition in combination with physical inactivity is especially important. Over the past 20 years, Europe and the United States have seen a manifold increase in the incidence of gout in parallel with an epidemic of morbid obesity, nephrolithiasis and non-insulin-dependent diabetes mellitus. Gout develops especially often in countries with high per capita consumption of meat products.

The metabolic syndrome with insulin resistance characteristic of gout, as well as hyperphosphatemia, contribute to the formation of severe atherosclerosis of the renal and coronary arteries with the development of coronary heart disease, renovascular hypertension, and the addition of calcium urate nephrolithiasis.

The leading pathogenetic mechanisms of gouty nephropathy are associated with an increase in the synthesis of uric acid in the body, as well as with the development of an imbalance between the processes of tubular secretion and reabsorption of urates. Overproduction of uric acid is caused by deficiency of hypoxanthine-guanine phosphoribosyltransferase (GGPT). GGPT is controlled by genes located on the X chromosome. This explains the fact that gout affects almost exclusively males. Complete deficiency of GGPT leads to Lesch-Nychen syndrome, characterized by early and especially severe gout. Other variants of juvenile hereditary gout include forms caused by a mutation of the Tamm-Horsfall tubular protein, nuclear liver factor - RCAD (renal cyst and diabetes) syndrome (a combination of gout with cystic renal dysplasia and non-insulin-dependent diabetes mellitus). Hyperuricemia is also caused by increased intracellular destruction of adenosine triphosphate (ATP): a defect characteristic of glycogenosis (type I, III, V), congenital fructose intolerance, chronic alcoholism. At the same time, in the majority of patients with primary gout, disturbances in the tubular function of the kidneys are detected: decreased secretion, increased various phases of reabsorption. An important role in pathogenesis is played by the defect of tubular acidogenesis, which contributes to the crystallization of urates in the urine. The defect is manifested by the formation of urine with a persistently acidic reaction (pH< 5).

The kidney-damaging effect of hyperuricosuria leads to urate nephrolithiasis with secondary pyelonephritis, urate damage to the interstitial tissue of the kidneys with the development of chronic tubulointerstitial nephritis, as well as renal acute renal failure (ARF) due to intratubular obstruction by uric acid crystals (acute uric acid nephropathy).

Hyperuricemia, due to activation of the renal reninangiotensin system and cyclooxygenase-2, increases the production of renin, thromboxane and vascular smooth muscle cell proliferation factor, and also induces atherogenic modification of very low density lipoproteins (VLDL).

The result is afferent arteriolopathy with renal hypertension and subsequent glomerulosclerosis and nephroangiosclerosis.

Urate nephrolithiasis. It is characterized, as a rule, by bilateral lesions, frequent relapses of stone formation, and sometimes coral nephrolithiasis. Urate stones are X-ray negative and are better visualized on echography. Outside of an attack, changes in urine tests may be absent. Renal colic is accompanied by hematuria and urate crystalluria. With prolonged renal colic, nephrolithiasis can be complicated by an attack of secondary pyelonephritis, postrenal acute renal failure. With a long course it leads to hydronephrotic transformation of the kidney, pyonephrosis.

Chronic tubulointerstitial nephritis. It manifests itself as persistent urinary syndrome, often combined with arterial hypertension. In this case, proteinuria, not exceeding 2 g/l in more than half of the patients, is combined with microhematuria. No stones are usually found, but episodes of gross hematuria with transient oliguria and azotemia, provoked by dehydration, are observed. In 1/3 of patients, bilateral medullary cysts (0.5-3 cm in diameter) are found. Typically, the early development of hyposthenuria and nocturia, as well as hypertension with glomerulosclerosis. Arterial hypertension is usually controlled. The appearance of difficult-to-control hypertension indicates the progression of glomerulosclerosis and nephroangiosclerosis or the formation of atherosclerotic stenosis of the renal arteries.

Acute uric acid nephropathy. It manifests suddenly with oliguria, dull pain in the lower back with dysuria and gross hematuria, often combined with an attack of gouty arthritis, hypertensive crisis, and an attack of renal colic. Oliguria is accompanied by the release of red-brown urine (urate crystalluria). At the same time, the concentrating ability of the kidneys is relatively preserved, and urinary sodium excretion is not increased.

In the future, oliguria quickly turns into anuria. With the aggravation of intratubular obstruction by the formation of numerous urate stones in the urinary tract and bladder, azotemia increases at a particularly high rate, which makes it possible to classify this option as an urgent form of sudden onset gouty nephropathy.

Diagnosis and differential diagnosis

Clinically, the diagnosis of gout is most likely in the development of acute arthritis against the background of manifestations of metabolic syndrome - alimentary obesity of the abdominal type in combination with volume-sodium-dependent hypertension, hyperlipidemia, hyperinsulinemia, microalbuminuria. Laboratory diagnosis of gout is based on identifying disorders of uric acid metabolism: detection of hyperuricemia (> 7 mg/dl), hyperuricosuria (> 1100 mg/day), persistently acidic urine pH, proteinuria (microalbuminuria), hematuria, crystalluria. Instrumental diagnostics include ultrasound examination (identification of X-ray negative urate stones), as well as (in difficult cases) biopsy of the affected joint, tophi. In this case, the detection of intracellular crystals of uric acid in the synovial fluid and in the contents of tophi (by polarization microscopy) is informative. Doppler ultrasound is performed for difficult-to-control hypertension in patients with gout in order to exclude atherosclerotic stenosis of the renal arteries.

The second stage of diagnosis is the distinction between gout and secondary hyperuricemia. Among the diseases often accompanied by disorders of purine metabolism are: chronic lead intoxication (lead nephropathy), chronic alcohol abuse, analgesic nephropathy, common psoriasis, sarcoidosis, berylliosis, hypothyroidism, myeloproliferative diseases, polycystic disease, cystinosis. Hyperuricemia in alcoholism, as a rule, is asymptomatic and is characterized by excess dependence. It should be emphasized the unfavorable prognostic significance of hyperuricemia in pregnancy nephropathy, immunoglobulin A (IgA) nephropathy and alcoholism. Tumor lysis syndrome is a great danger: acute uric acid nephropathy, complicating chemotherapy for cancer. Chronic tubulointerstitial nephritis is characterized by hypertension, early anemia, and osteoporosis. The outcome in chronic renal failure is not uncommon. Diagnosis is based on the detection of increased concentrations of lead in the blood and urine after a test with complexones (EDTA - from the English ethylenediaminetetraacetic acid). Drug-induced secondary hyperuricemia also needs to be differentiated from primary gout. Drugs that cause hyperuricemia include: thiazide and (to a lesser extent) loop diuretics, salicylates, nonsteroidal anti-inflammatory drugs, nicotinic acid, ethambutol, cyclosporine, antitumor cytostatics and antibiotics, ribavirin. Particularly important is the diagnosis of chronic renal failure (gouty “mask” of uremia), which sharply impairs the renal elimination of uric acid.

Course and prognosis of gouty nephropathy

Gouty nephropathy usually occurs at one of the stages of the long-term course of chronic “tophus” gout with attacks of gouty arthritis. At the same time, in 30-40% of cases, nephropathy is the first manifestation - a renal “mask” - of gout or develops against the background of an articular syndrome atypical for gout (damage to large joints, polyarthritis, arthralgia).

Advanced gout with a risk of target organ damage is indicated by hypertension with circadian rhythm disturbances, the formation of metabolic syndrome, microalbuminuria, a significant increase in lipids (low-density lipoprotein cholesterol > 130 mg%), C-reactive protein. Among the early signs of target organ damage in gout: persistent proteinuria, a moderate decrease in glomerular filtration (up to 60-80 ml/min), left ventricular hypertrophy, and the addition of diabetes mellitus. Gouty nephropathy typically has a latent or recurrent course with bilateral renal colic (urate nephrolithiasis), repeated episodes of reversible renal acute renal failure (acute uric acid nephropathy). On average, 12 years pass from the clinical manifestation of gouty nephropathy to the appearance of chronic renal failure.

Risk factors for the development of chronic renal failure in gout include persistent arterial hypertension, proteinuria > 1 g/l, the addition of chronic pyelonephritis, diabetes mellitus, old age of the patient with gout, juvenile forms of gout, chronic alcoholism.

Treatment of gouty nephropathy

Treatment of acute uric acid nephropathy is carried out in accordance with the principles of treatment of acute renal failure caused by acute intratubular obstruction. In the absence of anuria, signs of ureteral obstruction with urates (postrenal acute renal failure) or bilateral atherosclerotic stenosis of the renal arteries (ischemic kidney disease), conservative treatment is used. Continuous intensive infusion therapy (400-600 ml/h) is used using isotonic sodium chloride solution, 4% sodium bicarbonate solution and 5% glucose, 10% mannitol solution (3-5 ml/kg/h), furosemide (up to 1. 5-2 g/day, in fractional doses). In this case, diuresis should be maintained at a level of 100-200 ml/h, and the urine pH should reach a value of 6.5, which ensures the dissolution of urates and the excretion of uric acid. At the same time, allopurinol is prescribed at a dose of 8 mg/kg/day or urate oxidase (0.2 mg/kg/day, intravenously). If there is no effect from this therapy within 60 hours, the patient is transferred to acute hemodialysis. In the event that acute uric acid nephropathy has developed as a complication of tumor chemotherapy (hemoblastosis) as part of secondary hyperuricemia - with tumor lysis syndrome, emergency hemodialysis (hemodiafiltration) together with allopurinol is immediately indicated due to the low effectiveness of conservative infusion therapy.

Treatment of chronic forms of gouty nephropathy should be comprehensive and include solving the following problems:

correction of purine metabolism disorders;
correction of metabolic acidosis and urine pH;
normalization of the value and daily (circadian) rhythm of blood pressure (BP);
correction of hyperlipidemia and hyperphosphatemia;
treatment of complications (primarily chronic pyelonephritis).

The diet should be low-purine, low-calorie and combined with plenty of alkaline drinking (2-3 l/day). The daily quota of proteins should not exceed 1 g/kg, fats - 1 g/kg. Long-term adherence to such a diet reduces the level of uric acid in the blood by 10% (uricosuria - by 200-400 mg/day), helps normalize body weight, blood lipids and phosphates, as well as reduce metabolic acidosis. It is advisable to enrich the diet with potassium citrate or potassium bicarbonate, as well as fish oil. Eicosapentaenoic acid, the active principle of fish oil, has a nephroprotective and cardioprotective effect in gout due to its high content of polyunsaturated fatty acids. Its long-term use reduces the volume of adipose tissue, proteinuria, insulin resistance, dyslipidemia, and hypertension. For gouty nephropathy in the stage of chronic renal failure, a low-protein diet (0.6-0.8 g/kg) should be used.

Let us list the drugs that affect purine metabolism.

Relieving gouty arthritis: colchicine; non-steroidal anti-inflammatory drugs; glucocorticosteroids.
Xanthine oxidase inhibitors: allopurinol (milurite); urate oxidase (rasburicase).
Uricosuric drugs: benzbromarone, sulfinpyrazone, probenecid; angiotensin II (A II) receptor blockers; statins.
Citrate mixtures: uralite; magurlit; lemaren.

Drugs that control hypertension in gout include:

angiotensin-converting enzyme (ACE) inhibitors;
A II receptor blockers;
calcium antagonists;
selective β-blockers;
loop diuretics;
statins;
fibrates.

Allopurinol (milurite) reduces the production and level of uric acid in the blood by inhibiting the enzyme xanthine oxidase. Promotes the dissolution of urates. The hypouricemic effect of allopurinol correlates with its nephroprotective effect associated with a decrease in proteinuria, renin production, free radicals, as well as a slowdown in glomerulosclerosis and nephroangiosclerosis. Indications for the use of allopurinol: asymptomatic hyperuricemia in combination with hyperuricosuria > 1100 mg/day, gouty chronic tubulointerstitial nephritis, urate nephrolithiasis, prevention of acute uric acid nephropathy in cancer patients and its treatment.

The daily dose of allopurinol (from 200 to 600 mg/day) depends on the severity of hyperuricemia. In view of the possibility of exacerbation of gouty arthritis, it is advisable to begin treatment with allopurinol in a hospital and combine the drug with non-steroidal anti-inflammatory drugs or colchicine (1.5 mg/day) for 7-10 days. In the first weeks of treatment of urate nephrolithiasis with allopurinol, it is advisable to combine it with drugs that increase the solubility of urate in urine (magurlit, uralit, potassium bicarbonate, diacarb). In chronic tubulointerstitial nephritis, the dose of allopurinol is reduced as glomerular filtration rate decreases, and in cases of severe chronic renal failure (serum creatinine > 500 μmol/l), it is contraindicated. Allopurinol enhances the effect of indirect anticoagulants and aggravates the toxic effect of azathioprine on the bone marrow. If hyperuricemia (gout) is detected in a recipient after transplantation, it is necessary to reduce the dose of cyclosporine and saluretics. If there is no effect, replace azathioprine with mycophenolate mofetil and only then add allopurinol.

Uricosuric drugs correct hyperuricemia by increasing uric acid excretion in the urine. Used for asymptomatic hyperuricemia, gouty chronic tubulointerstitial nephritis. Contraindicated in hyperuricosuria, urate nephrolithiasis, and chronic renal failure. The most commonly used are probenecid (initial dose 0.5 g/day), sulfinpyrazone (0.1 g/day), and benzobromarone (0.1 g/day). A combination of allopurinol with benzobromarone or sulfinpyrazone is possible. Losartan and other II receptor blockers also have a uricosuric effect.

Citrate mixtures (uralit, magurlit, blemarene) correct metabolic acidosis, increase urine pH to 6.5-7 and thereby dissolve small urate stones. Indicated for urate nephrolithiasis. Uralite or Magurlit is taken before meals 3-4 times a day in a daily dose of 6-10 g. During treatment, constant monitoring of urine pH is necessary, since its sharp alkalization can lead to crystallization of phosphates. Citrate mixtures are contraindicated in chronic renal failure, with active pyelonephritis, and should be used with caution in hypertension (contain a lot of sodium). Citrate mixtures are not effective for large stones when extracorporeal lithotripsy or pyelolithotomy is indicated.

The objectives of antihypertensive therapy for gouty nephropathy include ensuring nephroprotective and cardioprotective effects. Drugs that retain uric acid (thiazide diuretics) and aggravate hyperlipidemia (non-selective β-blockers) should not be used. The drugs of choice are ACE inhibitors, A II receptor blockers, calcium antagonists, and selective β-blockers.

Statins (lovastatin, fluvastatin, pravastatin) are used in patients with gout with low-density lipoprotein cholesterol levels > 130 mg%. III generation statins (atorvastatin) have an independent hypouricemic effect.

The most effective treatment for gouty nephropathy is a combination of ACE inhibitors with A II receptor blockers, statins and allopurinol. With this combination, hypouricemic, antiproteinuric, hypolipidemic and hypotensive effects are enhanced with restoration of the circadian rhythm of blood pressure and slowing down the remodeling of the left ventricular myocardium, the risk of developing metabolic syndrome and diabetes mellitus is reduced, and the concentration of C-reactive protein in the blood decreases. As a result, the risk of developing acute myocardial infarction, acute cerebrovascular accidents and outcome in chronic renal failure is reduced.

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The invention relates to the field of medicine, namely to the physical analysis of liquid biological materials, and can be used to diagnose disorders of purine metabolism in children. Morphological studies of urine are carried out by studying the texture of its liquid crystal structure in dynamics in a bright field and in polarized light. A drop of urine is applied to the surface of the slide and covered with a coverslip. Keeping the environmental conditions constant, the preparation is kept until pronounced typical structures appear on the slide. The drug is examined by examining the entire surface. If single typical crystals of uric acid and in small quantities round yellow non-birefringent crystals, birefringent hexagonal or rosette-shaped small crystals, small skeletal dendrites are simultaneously observed on a glass slide, then the absence of a disorder in purine metabolism is diagnosed. If a large number of atypical uric acid crystals of various shapes, birefringent needle-shaped crystals, atypical birefringent and non-birefringent crystals, as well as large numbers of cholesterol crystals and large skeletal dendrites in combination or separately are simultaneously observed on a glass slide, then a disorder of purine metabolism is diagnosed. . The technical result is to increase the sensitivity and accuracy of diagnosis.

The invention relates to medicine, in particular to the physical analysis of liquid biological materials, and can be used as an additional test for the rapid diagnosis of kidney disease in children in the early stages and rapid assessment of the effectiveness of therapy.

There is a known method for diagnosing pathology of kidney function, including in children, according to which a general examination of urine is carried out (Kamyshev V.S. \Clinical laboratory tests from A to Z, their diagnostic profiles\, reference manual, Minsk: Belaruskaya Navuka, 1999, p. .229).

The disadvantage of this known method is that it allows one to identify only the fact of the presence of impaired renal function and does not allow one to ascertain the presence of a specific disease, in particular a disorder of purine metabolism.

Thus, the known method for diagnosing pathology of renal function does not ensure the achievement of a technical result, which consists in the possibility of diagnosing disorders of purine metabolism.

The closest to the proposed method is a method for diagnosing disorders of purine metabolism, including in children, according to which a morphological examination of urine is carried out, namely: the level of uric acid in the urine is determined and, if it deviates from the norm, a disorder of purine metabolism is diagnosed. (Kamyshev V.S. \Clinical laboratory tests from A to Z and their diagnostic profiles\, reference manual, Minsk: Belaruskaya Navuka, 1999, p. 233-235).

The disadvantage of this known method is, first of all, that it determines only the amount of uric acid in the urine and does not allow determining the form of uric acid, namely, identifying the presence of its atypical form, which is characterized by the presence of sodium urates in the urine - monosodium salt of uric acid. The latter is a characteristic sign of a disorder of purine metabolism. This reduces the reliability of diagnosis. The presence of certain normal limits for the quantitative content of uric acid in urine makes it possible to state the presence of pathology only when they are exceeded, i.e. already at the stage of the disease. This reduces the sensitivity of the known method and does not allow diagnosing the pathology at earlier stages, when the disease has not yet developed, and preventing its chronicity. For the same reason, the known method makes it possible to evaluate the effectiveness of therapy only when there is a noticeable improvement in the patient’s condition. The presence of a tolerance for deviation from the norm, which is the result of averaging the individual characteristics of the patient’s body, does not allow the diagnosis to directly take into account the individual characteristics of a particular patient, which also reduces the reliability of the diagnostic results. In addition, the known method is complex to implement and requires highly qualified personnel to obtain reliable diagnostics. The dependence of diagnostic results on the personal qualities of the laboratory assistant reduces their reliability.

Thus, the known method for diagnosing disorders of purine metabolism, including in children, identified as a result of a patent search, when implemented, does not allow achieving the technical result of increasing the reliability of diagnosis, increasing the sensitivity of the method, or simplifying the diagnostic method.

The present invention solves the problem of creating a method for diagnosing disorders of purine metabolism in children, the implementation of which allows one to achieve a technical result consisting in increasing the reliability of diagnosis, increasing the sensitivity of the method, and simplifying the diagnostic method.

The essence of the invention is that in the method for diagnosing disorders of purine metabolism in children, including a morphological examination of urine, analysis of the results and a statement of the absence or presence of a disorder of purine metabolism, morphological studies are carried out by studying the texture of the liquid crystal structure of urine in dynamics in a bright field and in a polarized light, for which a drop of urine is applied to the surface of the slide, then, maintaining environmental conditions constant, the preparation is kept until pronounced typical textures appear on the slide, after which the preparation is examined by examining the entire surface of the sample in a bright field, and then polarization is performed optical examination of the drug, the results of the examination are recorded, and if single typical crystals of uric acid in small quantities are simultaneously observed on the glass slide: round yellow non-birefringent crystals, birefringent hexagonal or rosette-shaped small crystals, small skeletal dendrites, then the absence of a violation of purine metabolism is diagnosed if On a glass slide, large quantities of uric acid crystals of various shapes, birefringent needle-shaped crystals, atypical birefringent and non-birefringent crystals, as well as large quantities of cholesterol crystals and large skeletal dendrites in combination or separately are simultaneously observed, then the presence of a disorder of purine metabolism is diagnosed.

The technical result is achieved as follows. Many liquid biological media of the human body are capable of crystallizing and, under certain conditions, transforming into an intermediate liquid crystalline state. In the liquid crystalline state, the medium, while maintaining fluidity, displays specific crystalline patterns - textures - in polarized light. It is known that biological fluids are multicomponent systems, most of which exhibit structural heterogeneity (heterogeneity) and are highly sensitive to the composition and form of existence of the components. The composition of biofluids adequately reflects the physiological state of the human body, as well as the functional usefulness of its individual organs and systems. For example, regulatory mechanisms and pharmacological factors influence the quantitative content of protein and calcium salts in the urine, the ratio of saturated and unsaturated lipids in the blood serum, the nature of aggregation of the lipid complex of bile, the amount of phospholipids, derivatives of cholesterol and its esters that exhibit liquid crystalline properties. These changes at the fine molecular level are manifested, in particular, in the features of aggregation of biological fluids at the microstructure level. The morphology of the textures of the liquid crystalline phase correlates with the state of the body and changes in the presence of pathology, which makes it possible to observe this in dynamics in a bright field and in polarized light with conventional optical magnifications (AS USSR No. 1209168, A 61 V 10/00, 07.02. 86; A.S. USSR No. 1486932, G 01 N 33/92, 06.15.89; A.S. USSR No. 1723527, G 01 N 33/92, 03.30.92; RF patent No. 2173462, G 01 N 33/ 48, 33/68, 09/10/2001; RF patent No. 2170432, G 01 N 33/48, 33/68, 07/10/2001).

In the proposed method, to diagnose purine metabolism disorders in children, a morphological study of the biological environment, namely urine, is used. Biological fluid - urine - is a product of the kidneys and its composition adequately reflects their functional state. Due to the fact that urine is capable of crystallizing, passing through an intermediate liquid crystalline state, it is possible to morphologically study urine by studying the texture of the liquid crystalline structure of urine in dynamics in a bright field and in polarized light by examining the entire surface of the sample.

In the proposed method, a drug is prepared from urine for research, for which a drop of urine is applied to a glass slide. Due to the fact that the preparation remains open, it is possible for the liquid medium to evaporate from it and form a crystalline pattern - texture - on the glass slide. Maintaining constant environmental conditions during aging of the drug ensures the reliability of the research results. The formation of pronounced typical base textures on the glass slide means the end of the aggregation process. This makes it impractical to further increase the exposure time of the drug and determines the start time of texture research.

After this, the preparation is examined by examining the entire surface of the sample in a bright field, and then a polarization optical examination of the preparation is performed, and the inspection results are recorded. Since the surface of the preparation is examined twice: in a bright field and in polarized light, this makes it possible to reliably identify texture crystals. This is explained by the fact that, for example, uric acid crystals in an atypical form are similar to oxalate crystals, but unlike them, uric acid crystals are not visible in polarized light. Sodium urate crystals have a common needle-like shape, but unlike others, they are birefringent in polarized light.

If on a glass slide, after studying the texture of the liquid crystalline structure of urine in a bright field and in polarized light, single typical crystals of uric acid, round yellow non-birefringent crystals in small quantities, birefringent hexagonal or rosette-shaped small crystals, small skeletal dendrites are simultaneously observed, then the absence of a purine disorder is diagnosed exchange. This is explained as follows. A sign of a disorder in purine metabolism is the presence of an atypical form of uric acid, namely when uric acid in the urine is in the form of sodium urate. It has been experimentally proven that the round yellow non-birefringent crystals are crystals of ordinary urates; birefringent hexagonal or rosette-shaped small crystals - calcium oxalate crystals; small skeletal dendrites - crystals of protein-lipid-salt complexes. The presence in the texture of the small crystals listed above of the test drop of urine in combination with single typical crystals of uric acid, with the simultaneous absence of crystals indicating the presence of sodium urates in the test drop of urine, indicates compliance with the norm of the qualitative and quantitative composition of the test urine. Moreover, the presence of precisely small birefringent hexagonal or rosette-shaped crystals and small crystals of skeletal dendrites indicates the presence of calcium oxalates and crystals of protein-lipid-salt complexes in a small amount in the test drop of urine. This is additional information confirming the absence of renal dysfunction and increases the reliability of diagnosis using the proposed method.

If a large number of atypical uric acid crystals of various shapes, birefringent needle-shaped crystals, atypical birefringent and non-birefringent crystals, as well as cholesterol crystals and large skeletal dendrites in combination or separately are observed on a glass slide, then a disorder of purine metabolism is diagnosed.

The presence of atypical uric acid crystals of various shapes indicates a qualitative change in the composition of urine, which is not typical for the composition of normal urine. The presence of sodium urate crystals indicates that their concentration in uric acid is increased and exceeds the solubility of sodium urate in urine. The presence in the urine of both atypical uric acid crystals and sodium urate crystals - birefringent needle-shaped crystals - makes it possible to reliably diagnose a disorder of purine metabolism.

The presence in the texture of the test drop of urine, in combination or separately, of cholesterol crystals and large skeletal dendrites, provides additional supporting information for the diagnosis of purine metabolism disorders, which increases its reliability. This is explained by the fact that the presence of cholesterol crystals in the urine indicates the activation of lipid peroxidation and instability of the cell membranes of the kidneys, and the presence of large skeletal dendrites in the urine indicates the presence of protein-lipid-salt complexes in large quantities in the urine. The presence of atypical birefringent and non-birefringent crystals confirms the atypical form of uric acid.

Thus, the texture of the liquid crystal structure of the liquid under study - urine - gives us a complete picture of its qualitative and quantitative composition, and examination of the texture of the test drop of urine on a glass slide by studying the texture of the liquid crystal structure of urine in dynamics in a bright field and in polarized light allows us to obtain complete information about the morphology of the examined drop of urine, both in terms of qualitative and quantitative content, which makes it possible to increase the reliability of the diagnosis of purine metabolism disorders. In this case, a highly qualified laboratory technician is not required, since the research results are the result of a visual review of the drug and do not require additional processing of the research results. This also improves diagnostic results. The comparative simplicity of the method also increases its reliability, as it reduces the likelihood of error.

In addition, it is known that the quantitative ratio of uric acid and urate in the urine depends on the acidity of the urine. In a slightly acidic environment with a urine pH below 5.75, sodium urate in the urine is represented by uric acid. At a urine pH of 5.75, uric acid and its monosodium salt are equimolar. When urine pH is above 5.75, i.e. When the pH of the environment changes to the alkaline side, sodium urates become the dominant form of uric acid. This once again confirms that the presence and quantity of sodium urate crystals in the test drop of urine can be used to judge the acidity of urine, which is reliable information for diagnosing disorders of purine metabolism and increases the reliability of diagnosis.

The proposed method, unlike the prototype, makes it possible to diagnose the disease at an early stage. This is explained by the fact that in the prototype method there is a tolerance for the normal level of uric acid in the urine. As a result, this does not allow us to take into account that in the initial stage of a disorder of purine metabolism, the acidity of urine is heterogeneous, and both uric acid in a typical form and crystals of sodium urate may be present in the urine at the same time. The claimed method, in contrast to the prototype, allows one to obtain a complete true picture of the morphological composition of urine at a given time, which makes it possible to detect the presence of sodium urate crystals in the urine at an early stage of the disease in the absence of visible signs of the disease. As a result, the sensitivity of the method increases.

Since the method uses the character of textures (crystalline pattern) as an evaluation criterion, which corresponds to a very specific composition of the biological fluid being studied, the proposed method, when diagnosing, automatically takes into account the physiological corridor, which makes it possible to take into account the individual characteristics of the body of a particular patient, which increases the information content and reliability of the method .

In addition, the proposed method for diagnosing disorders of purine metabolism in children, in comparison with the prototype, achieves an additional technical result, which consists in the possibility of using the method for rapid assessment of the effectiveness of therapy used in the treatment of disorders of purine metabolism. The achievement of an additional technical result is ensured due to the adequacy of the change in the nature of the texture of the test drop of urine when the qualitative or quantitative composition of urine changes or when they change together in combination with the ability to obtain a complete true picture of the morphological composition of urine in the form of its texture at a given point in time, i.e. combined with the increased sensitivity of the proposed method.

Thus, the claimed method for disrupting purine metabolism in children, when implemented, ensures the achievement of a technical result consisting in increasing the reliability of diagnosis, increasing the sensitivity of the method, simplifying the diagnostic method, and also allows, in comparison with the prototype, to obtain an additional technical result consisting in the possibility of using the claimed a method for rapid assessment of the effectiveness of therapy used in the treatment of purine metabolism disorders.

A method for diagnosing purine metabolism disorders in children is carried out as follows. Morphological studies of urine are carried out by studying the texture of its liquid crystal structure in dynamics in a bright field and in polarized light. Why is a drop of urine applied to the surface of a glass slide? Then, keeping the environmental conditions constant, the preparation is kept until pronounced typical textures appear on the slide. After that, the preparation is examined by examining the entire surface of the sample in a bright field, and then a polarization optical examination of the preparation is performed. The results of the inspection are recorded. Moreover, if single typical crystals of uric acid are simultaneously observed on a glass slide in small quantities: round yellow non-birefringent crystals, birefringent hexagonal or rosette-shaped small crystals, small skeletal dendrites, then the absence of a disorder in purine metabolism is diagnosed. If a large number of atypical uric acid crystals of various shapes, birefringent needle-shaped crystals, atypical birefringent and non-birefringent crystals, as well as large numbers of cholesterol crystals and large skeletal dendrites in combination or separately are simultaneously observed on a glass slide, then a disorder of purine metabolism is diagnosed. .

In all examples of the method, pre-treated glass slides were taken to prepare preparations from urine. Pay attention to the quality of the glass slide processing to avoid artifacts during research. The slide is washed with distilled water, then degreased by immersion in 96% medical alcohol and wiped dry in one direction with a dry sterile cloth.

The formation of textures occurs due to evaporation from the edges of the preparation and, first of all, appears in the peripheral areas, so viewing began from the peripheral areas. Then the central areas were examined.

An insignificant (or small) number of crystals was taken when crystals occupy no more than 20% of the area of the field of view at 150x magnification and in no more than 2 out of five...seven fields of view.

The small size of crystals was taken to be the case when the crystal is located in 1/4 of the field of view and occupies less than 0.1 of it.

Viewing in a bright field was carried out with diluted nicols at a magnification of ×150...×250. The entire surface of the sample was examined by longitudinal transverse scanning with a step equal to the field of view.

Viewing in polarized light was carried out with crossed nicols at a magnification of ×150...×250. The entire surface of the sample was examined by longitudinal transverse scanning with a step equal to the field of view.

All detected features were recorded. Microscopes of the BIOLAM (with polarized filters), POLAM, and MBI series can be used for research. Example

1. Patient A., 6 years old, examination. Express diagnostics were previously carried out in accordance with the stated method.

When examining an open drop of urine in a bright field and in polarized light, the following were simultaneously observed on a glass slide: single crystals of uric acid of a typical shape, non-birefringent, round yellow non-birefringent crystals mainly along the edge of the drop, birefringent hexagonal or rosette-shaped small crystals in small quantities, small non-birefringent skeletal dendrites along in the center of the drop in a small amount.

Diagnosis: no disorders of purine metabolism.

2. Patient D., 7 years old, examination. Express diagnostics were previously carried out in accordance with the stated method.

When examining an open drop of urine in a bright field and in polarized light, atypical crystals of uric acid, birefringent needle-shaped crystals of sodium urate, atypical birefringent and non-birefringent crystals, as well as a large number of cholesterol crystals in combination over the entire surface of the drop were simultaneously observed on a glass slide. and large skeletal dendrites.

Diagnosis: disorders of purine metabolism.

In both cases, the diagnosis was confirmed by standard laboratory tests.

A method for diagnosing disorders of purine metabolism in children, including a morphological examination of urine, analysis of the results and a statement of the absence or presence of a disorder of purine metabolism, characterized in that morphological studies are carried out by studying the texture of the liquid crystal structure of urine in dynamics in a bright field and in polarized light, for which a drop of urine is applied to the surface of the slide, then, maintaining the environmental conditions constant, the preparation is kept until pronounced typical textures appear on the slide, after which the preparation is examined by examining the entire surface of the sample in a bright field, and then a polarization optical examination of the preparation is performed, the results of the examination are recorded, and if single typical crystals of uric acid and in small quantities round yellow non-birefringent crystals, birefringent hexagonal or rosette-shaped small crystals, small skeletal dendrites are simultaneously observed on the slide glass, then the absence of a disorder of purine metabolism is diagnosed if on the slide glass at the same time If atypical uric acid crystals of various shapes, birefringent needle-shaped crystals, atypical birefringent and non-birefringent crystals are observed in large quantities, as well as cholesterol crystals and large skeletal dendrites in large quantities in combination or separately, then a disorder of purine metabolism is diagnosed.

The invention relates to the field of medicine, namely to the physical analysis of liquid biological materials, and can be used to diagnose disorders of purine metabolism in children