The exchange of what nitrogenous bases is disturbed in gout. Violation of purine metabolism: causes, symptoms and treatment. Treatment of gouty nephropathy

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A. Yu. Nikolaev, Doctor of Medical Sciences, Professor
Yu. S. Milovanov, Candidate of Medical Sciences, Associate Professor
MMA them. I. M. Sechenov, 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, provided timely diagnosis and correction, then at the stage of tofus 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 the level of blood uric acid > 8 mg / dl, the risk of subsequent development of chronic renal failure (CRF) increases by 3-10 times. Every 4th patient with gout develops CRF.

Both acquired and hereditary factors play a role in the development of gout. The role of malnutrition in combination with physical inactivity is especially great. Over the past 20 years in Europe and the United States, there has been a multiple increase in the incidence of gout in parallel with the epidemic of morbid obesity, nephrolithiasis and non-insulin dependent diabetes mellitus. Gout is especially common in countries with a high consumption of meat products per capita.

The metabolic syndrome characteristic of gout with insulin resistance, 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 nephrolithiasis to urate.

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. The overproduction of uric acid is caused by a deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGFT). HGFT is controlled by genes located on the X chromosome. This explains the fact that almost exclusively males get sick with gout. A complete deficiency of HHFT leads to the Lesch-Nychen syndrome, characterized by an early and especially severe course of gout. Among other variants of juvenile hereditary gout are forms caused by a mutation of the Tamm-Horsfall tubular protein, hepatic nuclear factor - RCAD (renal cyst and diabetes) syndrome (combination of gout with cystic kidney dysplasia and non-insulin-dependent diabetes mellitus). Enhanced intracellular destruction of adenosine triphosphate (ATP) also leads to hyperuricemia: a defect inherent in glycogenosis (I, III, V types), congenital fructose intolerance, and chronic alcoholism. At the same time, in most patients with primary gout, violations of the tubular function of the kidneys are detected: a decrease in secretion, an increase in various phases of reabsorption. An important role in the 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 gout 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 tubulo-interstitial nephritis, as well as renal acute renal failure (ARF) due to intratubular obstruction by uric acid crystals (acute uric acid nephropathy).

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

As a result, afferent arteriolopathy develops with renal hypertension and subsequent glomerulosclerosis and nephroangiosclerosis.

Urate nephrolithiasis. It is characterized, as a rule, by a bilateral lesion, frequent relapses of stone formation, and sometimes staghorn nephrolithiasis. Urate stones are X-ray negative, better visualized on echography. Outside of an attack, changes in urine tests may be absent. Renal colic is accompanied by hematuria, 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 is manifested by persistent urinary syndrome, often combined with arterial hypertension. At the same time, proteinuria, not exceeding 2 g/l in more than half of the patients, is combined with microhematuria. Stones are usually not found, however, there are episodes of gross hematuria with transient oliguria and azotemia, provoked by dehydration. Bilateral medullary cysts (0.5-3 cm in diameter) are found in 1/3 of patients. Typically, early addition of hypostenuria 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 back pain with dysuria and macrohematuria, often combined with an attack of gouty arthritis, a hypertensive crisis, an attack of renal colic. Oliguria is accompanied by the release of urine of red-brown color (urate crystalluria). At the same time, the concentration ability of the kidneys is relatively intact, sodium excretion in the urine is not increased.

In the future, oliguria quickly turns into anuria. With the aggravation of intratubular obstruction by the formation of numerous urate calculi in the urinary tract and in the bladder, azotemia increases at an especially high rate, which makes it possible to attribute this variant to the 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 the 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 the detection of uric acid metabolism disorders: detection of hyperuricemia (> 7 mg / dl), hyperuricosuria (> 1100 mg / day), persistently acidic urine pH, proteinuria (microalbuminuria), hematuria, crystalluria. Instrumental diagnostics includes ultrasound (identification of X-ray negative urate stones), as well as (in difficult cases) a biopsy of the affected joint, tophi. At the same time, the detection of intracellular uric acid crystals in the synovial fluid and in the contents of tophi (by polarizing microscopy) is informative. Ultrasound dopplerography 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, there are known: chronic lead intoxication (lead nephropathy), chronic alcohol abuse, analgesic nephropathy, widespread psoriasis, sarcoidosis, berylliosis, hypothyroidism, myeloproliferative diseases, polycystic disease, cystinosis. Hyperuricemia in alcoholism is usually asymptomatic and is characterized by kurtosis. The unfavorable prognostic value of hyperuricemia in pregnancy nephropathy, immunoglobulin A (IgA) nephropathy and alcoholism should be emphasized. A great danger is the tumor lysis syndrome: acute uric acid nephropathy, which complicates the chemotherapy of oncological diseases. Chronic tubulointerstitial nephritis is characterized by hypertension, early anemia, and osteoporosis. It is not uncommon to end up with chronic renal failure. Diagnosis is based on the detection of an increased concentration of lead in the blood and urine after a test with complexones (EDTA - from the English. Ethylenediaminetetraacetic acid). Drug-induced secondary hyperuricemia must also be differentiated from primary gout. Drugs that cause hyperuricemia include: thiazide and (to a lesser extent) loop diuretics, salicylates, non-steroidal anti-inflammatory drugs, nicotinic acid, ethambutol, cyclosporine, antitumor cytostatics and antibiotics, ribavirin. Especially important is the diagnosis of CRF (gouty "mask" of uremia), which sharply disrupts the renal elimination of uric acid.

The course and prognosis of gouty nephropathy

Gouty nephropathy usually occurs at one of the stages of the long-term course of chronic "tofus" 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 evidenced by hypertension with circadian rhythm disturbance, the formation of a 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 diabetes mellitus. For gouty nephropathy, a latent or recurrent course with bilateral renal colic (urate nephrolithiasis), repeated episodes of reversible renal acute renal failure (acute uric acid nephropathy) is typical. From the clinical manifestation of gouty nephropathy to the onset of CRF, an average of 12 years pass.

Risk factors for the development of chronic renal failure in gout include persistent arterial hypertension, proteinuria > 1 g/l, chronic pyelonephritis, diabetes mellitus, old age of a patient with gout, juvenile forms of gout, and 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 by 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 with the use of 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 the level of 100-200 ml / h, and the pH of the urine 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) is immediately indicated along with allopurinol due to the low efficiency of conservative infusion therapy.

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

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

The diet should be low-purine, low-calorie and combined with abundant alkaline drinking (2-3 l / day). The daily quota of proteins should not exceed 1 g/kg, fat - 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), contributes to the normalization of body weight, blood lipids and phosphates, as well as a decrease in 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, due to the high content of polyunsaturated fatty acids, has a nephroprotective and cardioprotective effect in gout. Its long-term use reduces the volume of adipose tissue, proteinuria, insulin resistance, dyslipidemia, and hypertension. With gouty nephropathy in the stage of chronic renal failure, a low-protein diet (0.6-0.8 g / kg) should be used.

We list the drugs that affect purine metabolism.

• Cupping gouty arthritis: colchicine; non-steroidal anti-inflammatory drugs; glucocorticosteroids.
• Xanthine oxidase inhibitors: allopurinol (milurit); urate oxidase (rasburicase).
• Uricosuric drugs: benzbromarone, sulfinpyrazone, probenecid; angiotensin II receptor blockers (A II); statins.
• Citrate mixtures: uralite; magurlite; 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 with 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 start 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 urates in the urine (magurlite, uralite, potassium bicarbonate, diacarb). In chronic tubulo-interstitial nephritis, the dose of allopurinol is reduced as glomerular filtration decreases, and in severe chronic renal failure (serum creatinine> 500 μmol / l) it is contraindicated. Allopurinol enhances the effect of indirect anticoagulants and exacerbates 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 urinary excretion of uric acid. They are used for asymptomatic hyperuricemia, gouty chronic tubulointerstitial nephritis. Contraindicated in hyperuricosuria, with urate nephrolithiasis, with chronic renal failure. Probenecid (initial dose 0.5 g/day), sulfinpyrazone (0.1 g/day), benzobromarone (0.1 g/day) are more commonly used. A combination of allopurinol with benzobromarone or sulfinpyrazone is possible. Losartan and other receptor-II blockers also have a uricosuric effect.

Citrate mixtures (Uralite, Magurlite, Blemaren) correct metabolic acidosis, increase urine pH to 6.5-7 and thereby dissolve small urate calculi. 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, should be used with caution in hypertension (they contain a lot of sodium). Citrate mixtures are not effective for large calculi, when remote lithotripsy or pyelolithotomy is indicated.

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

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

The combination of ACE inhibitors with A II receptor blockers, statins and allopurinol is most effective in gouty nephropathy. With this combination, hypouricemic, antiproteinuric, hypolipidemic and hypotensive effects are enhanced with the restoration of the circadian rhythm of blood pressure and slowing of left ventricular myocardial remodeling, the risk of 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 disorders of cerebral circulation and outcome in CRF is reduced.

Literature

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Acetonemic 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. In the process of metabolism, they break down into acetone substances. This can provoke the appearance of 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 acetonemic syndrome in newborns whose mothers suffered from renal insufficiency during pregnancy has increased. If the urine of a pregnant woman is periodically determined, and she suffers from constant edema, then the risk of developing intrauterine acetonemic syndrome in the fetus increases many times over.

Violation of the metabolism of purine substances, which provokes the development of acetonemic 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. This is where the blood is enriched with purines. The renal 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:

• enhanced oxygen supply for their oxidation;
• increase in blood volume to reduce their concentration;
• lower blood glucose levels to utilize acetone.

All these processes form the corresponding clinical picture:

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

But the main symptom of acetonemic syndrome in children is periodic indomitable vomiting with severe pain in the abdomen. It is repeated with a certain episodic character 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 state of a baby 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 blood of a child.

Treatment of acetone syndrome and prognosis

Treatment of acetonemic 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 a crisis under the influence of acetone substances.

To relieve the crisis, prokinetics and cofactors (involved in the metabolic process) are used in combination with enzymatic 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 remission, the focus is on the diet and lifestyle of the child.

Acetonemic syndrome in children is often accompanied by increased nervous excitability, which provokes the release of purines and ketone bodies into the blood. can trigger a crisis. Attention should be paid to the reduction of stress load and the inadmissibility of critical physical exertion.

Diet for acetonemic syndrome

A permanent diet for acetonemic syndrome is the basis for successful treatment and prevention of 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 types of 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 during the day (Borjomi, Essentuki). Useful fresh juices from fruits and vegetables.

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

Purine metabolism is a complex cascade of biochemical reactions in which many enzyme systems take part. The content of purines in the body consists of their intake with food and endogenous synthesis. Most of the salts of uric acid - urates - are formed endogenously in the process of metabolism of nucleic acids, but there are other ways of biosynthesis of these substances. In all variants, the most important intermediate is inosinic acid, which then undergoes hydrolysis. The resulting hypoxanthine, under the influence of the enzyme xanthine oxidase, is converted into xanthine and uric acid. From the point of view of biochemistry, disorders of purine metabolism are different types of imbalance between the enzyme systems responsible for the synthesis and transport of uric acid and its precursors. The intake of a significant amount of purines with food is also essential.

It is believed that the body of an adult healthy person contains about 1000 mg of uric acid. With disorders of purine metabolism, this figure can increase several times. The content of uric acid in the body is not a hard parameter and does not have any diagnostic value. Even the main indicator of the state of purine metabolism - the concentration of uric acid in the blood serum does not differ in particular rigidity. The minimum and maximum values ​​​​of the norm differ by about 2.5 times - 200-450 µmol / l in men and 160-400 µmol / day in women. In healthy people, about 750 mg or 2/3 of the total volume of uric acid is excreted and re-synthesized per day. Of this amount, about 80% or 600 mg is excreted by the kidneys. The remaining 20% ​​is excreted through the gastrointestinal tract. According to P. M. Klimenko et al. (2010) uric acid clearance is normally 5.4-9.0 ml/min.

Renal excretion of urate is a complex and multi-step process. In the glomeruli, plasma urate is filtered. The urates that have entered the ultrafiltrate are almost completely reabsorbed in the proximal tubule and then secreted into the lumen of the nephron. Some of the secreted urates are reabsorbed. The process of active secretion of urates is very sensitive to various chemical agents. It is believed that the renal secretion of urates is increased by orotic acid, losartan, estrogens, tetracycline breakdown products (expired tetracyclines are highly toxic!); renal excretion of urates is reduced by ethambutol, thiazides and thiazide-like diuretics, to a lesser extent furosemide and acetazolamide. It is quite obvious that the severity of the noted effects varies greatly from drug to drug and does not always have clinical application. In particular, the uricosuric properties of estrogens are not significant. Losartan has recently been featured in treatment regimens for gouty tubulointerstitial nephritis in patients without nephrolithiasis. The tendency of thiazides and indapamide to reduce renal excretion of urates and increase their serum concentration is quite pronounced, which makes these drugs at least undesirable for articular gout and, especially, for gouty nephropathy.

Clinical variants of kidney damage due to impaired purine metabolism

Diseases associated with disorders of purine metabolism are relatively common, which makes the issues related to their treatment relevant. Urologists, as well as most general practitioners, are well aware of the features of urate nephrolithiasis. At the same time, these specialists often do not have any idea about the existence of other, sometimes more serious diseases caused by disorders of purine metabolism. Meanwhile, they all occur with different frequency in hospitals, as well as in the provision of outpatient medical care.

The most significant consequence of disorders of purine metabolism is an increase in the level of uric acid in the blood - hyperuricemia, which is the main etiological factor in various pathological conditions. Depending on the etiology, hyperuricemia is divided into primary (without an obvious cause) and secondary to any disease.

The clinical consequence of primary hyperuricemia is gout in the broad sense of the term. This includes classic acute microcrystalline arthritis, and various variants of gouty nephropathy, one of which is urate nephrolithiasis, and tophi of various localization, and complications of all these conditions.

In the group of diseases associated with primary hyperuricemia, genetically determined disorders of purine metabolism stand somewhat apart. Among them are the Lesch-Nychen syndrome, Gierke's disease, various variants of hereditary defects in the transport systems of the renal tubules, and others. Distinctive features of hyperuricemia inherited according to a monogenic type (that is, associated with a defect in a specific gene that determines the development of the entire symptom complex) are manifestation in early childhood, high hyperproduction of uric acid, rapid, sometimes even "malignant" progression of the disease up to the formation of terminal renal failure. , often very moderate effectiveness of therapeutic measures, despite the most active therapy.

Clinical diagnosis of disorders of purine metabolism, inherited according to the polygenic type, is currently difficult. The manifestations and nature of the course of the disease in this case vary greatly depending on external factors, and the biological effect of a significant part of the genes is still not completely clear.

In nephrological and general therapeutic practice, to determine kidney damage due to hyperuricemia, several decades ago, the concept of "gouty kidney" was introduced, which in modern medicine was transformed into "gouty nephropathy". Given the experimentally proven damaging effect of uric acid salts on renal structures, the term "urate nephropathy" was also proposed. All these concepts are generalizing and combine several processes that are quite different in their pathogenesis: acute uric acid nephropathy, urate nephrolithiasis and chronic tubulointerstitial nephritis. Some authors also note the possibility of immunocomplex glomerulonephritis, the triggering factor of which is the hyperproduction of uric acid.

In urological practice, patients with urate nephrolithiasis are most common. Up to 80% of these patients had an episode of acute arthritis at least once in their lives, and it is not necessarily the classical localization - I metatarsophalangeal joint. Recently, atypical variants of gouty arthritis, for example, drives, are more and more common. In addition, the widespread and uncontrolled use of non-steroidal anti-inflammatory drugs often blurs the clinical picture, increasing the proportion of arthritis with less inflammatory activity. It can be noted that the combination of arthritis and urate nephrolithiasis is not mandatory, but rather characteristic.

The clinical picture of the calculus of the kidney, ureter is well known, so once again it makes no sense to describe it in detail. The only thing worth noting is that in the most severe, “malignant” course, along with the formation of urate stones in the lumen of the urinary tract, the deposition of urate crystals in the renal interstitium is also possible, which is called “nephrocalcinosis”. Unlike nephrolithiasis, nephrocalcinosis in gout is always bilateral. Nephrocalcinosis does not have any specific symptoms. Clinical manifestations are reduced to the progression of renal failure due to nephrosclerosis. Nephrocalcinosis in most cases is detected by ultrasound scanning and requires specific therapy.

Chronic tubulointerstitial nephritis is a characteristic and common variant of gouty nephropathy. However, due to the less vivid clinical picture, it is known mainly to nephrologists and rheumatologists.

In the initial stages of tubulointerstitial nephritis, the pathological process mainly affects the tubules and renal interstitium, so the leading symptom is a violation of the concentration function of the kidneys - polyuria with low urine density (hypostenuria). Proteinuria does not exceed 1 g / day or is completely absent - it is associated with a violation of protein reabsorption by the tubules. Gouty interstitial nephritis is characterized by persistent uraturia, as well as persistent or episodic microhematuria, especially after a respiratory viral infection.

The level of blood urate is also naturally elevated, but it must be remembered that the very fact of the presence of chronic renal failure is also a cause of hyperuricemia. With an obvious clinical picture of chronic tubulointerstitial nephritis, its relationship with purine metabolism disorders is beyond doubt with the following ratios of blood urate and creatinine levels: respectively > 536 μmol / l and< 132 мкмоль/л; >595 µmol/l and 132-176 µmol/l; > 714 µmol/l and > 176 µmol/l.

Immunohistochemical study of renal biopsy specimens in some patients with a clinical picture of gouty tubulointerstitial nephritis showed a luminescence of the C3 fraction of complement and IgG, which is typical for immunocomplex glomerulonephritis. This made it possible to isolate chronic glomerulonephritis as a separate variant of gouty nephropathy.

With the progression of gouty tubulointerstitial nephritis, the development of arterial hypertension and nephrosclerosis is natural.

Acute uric acid nephropathy (acute gouty kidney) is basically an obstruction of the renal tubules by urate crystals, leading to acute renal failure. The disease begins with oliguria. Some patients simultaneously complain of pain syndrome like renal colic, gross hematuria, which can be explained by the migration of large urate crystals along the ureter. High uraturia is pathognomonic, which is not characteristic of acute renal failure of another etiology, as well as a significant increase in the level of uric acid in the blood (above 850-900 μmol / l). In modern nephrological practice, it is believed that the diagnosis of acute uric acid nephropathy is beyond doubt when the ratio of blood levels of urate and creatinine (in mg)> 1.

The assumption of acute uric acid nephropathy is based on a combination of three clinical signs - highly active arthritis with a characteristic localization, a sharp decrease in diuresis, and brick-brown urine. The diagnosis is all the more likely if the patient indicates hypohydration of any genesis that has taken place - from visiting a bathhouse and physical work at high air temperature to inadequate infusion therapy and an overdose of diuretics, as well as the use of a significant amount of meat products and / or alcohol. In the natural course of the disease, oliguria almost always progresses to anuria with a developed clinical picture of acute renal failure.

The problem of acute uric acid nephropathy is closely related to secondary hyperuricemia. The reasons for the increase in the level of uric acid in the blood serum are quite numerous and varied. Among them: chronic renal failure, regardless of etiology, obesity, especially high degrees, poorly compensated diabetes mellitus, acromegaly, hypothyroidism, hypoparathyroidism, pregnancy toxicosis, myeloproliferative diseases, sarcoidosis, chronic lead intoxication, chronic alcoholism. There is a clear association between an increased risk of urate nephrolithiasis and the presence of severe psoriasis in a patient, especially articular psoriasis. In most cases, the severity of hyperuricemia in these diseases is small, rarely moderate. Thus, disorders of purine metabolism rarely significantly affect the clinical picture of the disease.

The most striking and clinically significant variant of secondary hyperuricemia is the “tumor lysis syndrome” (“tumor decay syndrome”), which develops during chemotherapy and radiotherapy of lymphoproliferative diseases, less often tumors of other localization. A key component of this syndrome, along with hyperphosphatemia and hyperkalemia, is the overproduction of uric acid, leading to the development of acute uric acid nephropathy, often in intact kidneys. However, severe hyperuricemia due to genetic disorders rarely leads to acute uric acid nephropathy.

Drug therapy of kidney diseases caused by disorders of purine metabolism

Conservative therapy of any variant of gouty nephropathy basically has a decrease in the level of hyperuricemia, and consequently, hyperuricuria, as well as an increase in the solubility of urate in the urine.

All patients are prescribed a mandatory diet, the purpose of which is to reduce the intake of purines in the body with food. This is achieved by the complete exclusion from the diet of the meat of young animals, offal, meat broths, sausages, etc., meat of full-aged animals, fish are allowed to a limited extent. Patients are recommended mainly a vegetable table, plentiful alkaline drinking, citrus fruits and drinks based on them, as well as complete abstinence from alcohol.

In the presence of renal failure, arterial hypertension, circulatory failure, obesity, additional restrictions are introduced. First of all, it is recommended to reduce the consumption of salt, since the effectiveness of ACE inhibitors, especially indicated for nephropathies complicated by arterial hypertension, and indeed of all antihypertensive therapy, directly depends on the volume of sodium entering the body. With a pronounced deficiency in filtration, it becomes necessary to limit protein intake. With obesity, reduce the total caloric content of the diet.

In a number of patients, for example, with rarely recurrent urate nephrolithiasis without renal failure, with sufficient motivation on the part of the patient, it is generally possible to confine oneself to correcting the diet and drinking regimen without resorting to prescribing drugs.

Medicines used for the pathogenetic treatment of gouty nephropathy are divided into:

• drugs that affect the metabolism of purines (allopurinol, febuxostat);
• drugs that increase the renal excretion of purines (probenecid, benzbromarone);
• drugs that increase the solubility of uric acid and its salts (citric acid and its salts - citrates).

The basic drug that affects the metabolism of purines is allopurinol, which is an inhibitor of the enzyme xanthine oxidase. Under the action of this enzyme, the last step in the synthesis of uric acid occurs. The urate precursors xanthine and hypoxanthine have almost 10 times higher water solubility than uric acid. Stopping the metabolism of purines at this stage reduces the risk of crystal formation, and hence microcrystalline arthritis, and nephropathy to almost zero.

Allopurinol is indicated for gouty tubulointerstitial nephritis, acute uric acid nephropathy, urate nephrolithiasis in combination with hyperuricemia, as well as for chemotherapy of malignant neoplasms to prevent the development of secondary hyperuricemia and acute renal failure. The minimum effective dosage is 200 mg / day, the average therapeutic dose is 300-400 mg / day. In chemotherapy of malignant neoplasms, high, close to maximum, dosages of allopurinol are required - 600-900 mg / day.

Allopurinol tends to cause dyspeptic disorders and skin rashes, which are observed in almost every fifth patient. Side effects of this drug are often unpleasant, but not dangerous, and due to the almost complete (up until recently) lack of alternatives to this drug, most patients still continue treatment.

Recently, a new xanthine oxidase inhibitor febuxostat has appeared on the domestic market, which differs from allopurinol in higher selectivity. Domestic experience with the use of febuxostat is still extremely limited, however, foreign researchers note its higher efficiency in relation to hyperuricemia. However, it can already be noted that this drug is a full-fledged replacement for allopurinol in conditions of its intolerance, allergies, etc.

In conclusion, it should be noted that xanthine oxidase inhibitors are contraindicated in patients receiving azathioprine and 6-mercaptopurine, since this enzyme is involved in their metabolism. With a joint appointment, the risk of toxicity, primarily bone marrow, increases sharply.

Recombinant urate oxidase, rasburicase, is also used abroad. The drug is significantly more effective than allopurinol in reducing hyperuricemia and is mainly used in hematological practice for the prevention of acute urate nephropathy.

Drugs that increase the renal excretion of purines - uricosuric drugs - inhibit the process of reabsorption of urate from the lumen of the renal tubules. In modern clinical practice, this group of drugs is used very limitedly. Not all patients demonstrate sufficient effectiveness. In addition, the result of a direct pharmacological effect - an increase in renal excretion of urate - is an increased risk of nephrolithiasis. The most famous uricosuric drug, probenecid, is currently practically absent on the domestic market. Benzbromarone is registered in Russia, but is available only in very small quantities. All uricosuric agents in the body undergo hepatic metabolism and have some hepatotoxicity. Another feature of these drugs is a huge number of drug interactions, which makes it difficult to use them in multicomponent regimens.

Citrate therapy is an integral part of the medical treatment of gouty nephropathy. The effect of citric acid salts on the process of crystal formation in the urine is multifaceted. The solubility of uric acid varies considerably depending on the reaction of the medium. In an acidic environment, urates have very poor solubility and easily pass into the solid phase - they crystallize. With a neutral or alkaline reaction, the solubility of these salts increases. The main effect of citrates is the ability to alkalinize urine, which prevents urate crystallization and creates conditions for the dissolution of already formed crystals. Litholytic therapy is based on this. However, with an alkaline reaction of the medium, the solubility of phosphates decreases. The layering of a phosphate film on a urate stone makes the process of further litholysis practically unpromising. This dictates the need for careful monitoring of the reaction of urine throughout the course of treatment. In modern conditions, the empirical use of plant materials rich in citric acid and its salts has been replaced by drugs that include chemically pure citrate and a set of test strips for monitoring the reaction of urine.

Research in the 1980s-90s demonstrated the efficiency of litholysis of urate stones using citrate mixtures in the monotherapy mode of the order of 75-80%. At present, as a result of improving the technique, the efficiency of litholysis has been increased to 85-90%, depending on the characteristics of the chemical composition of stones.

In recent years, studies have appeared that testify to the advisability of including citrate preparations in multicomponent therapy regimens. In particular, in case of uric ureteral stones, especially in its distal third, combined therapy, including citrate and tamsulosin, led to the independent discharge of 84.8% of stones, which significantly differs from the groups of patients who received monotherapy with these drugs (68.8% and 58. 8% respectively), as well as from patients who received placebo (26.1%).

There is strong evidence for the efficacy of the combination of allopurinol and citrate in gouty interstitial nephritis. A 12-week course of combination therapy, including citrate 3 g/day and allopurinol 100-200 mg/day, resulted in an increase in glomerular filtration rate by an average of 15 ml/min compared with the control group. The clearance of uric acid also increased significantly. Note the low dosage of allopurinol. 200 mg/day is considered minimally effective, and 100 mg/day is generally a subclinical dosage, however, it turned out to be effective. It can be assumed that the effects of allopurinol and citrate may be potentiated. An additional positive consequence should be a decrease in the frequency of side effects of allopurinol, which is a significant limiting factor in the medical treatment of gouty nephropathy. Unfortunately, the authors did not focus on this.

A more pronounced effect of citrate on renal function has been noted in the treatment of chronic interstitial nephritis due to hyperuricemia in obese patients.

The mechanism of action of citrate is not limited to alkalization of urine. Citrate is one of the physiological inhibitors of crystal formation. Since urine is normally a supersaturated saline solution, the presence of crystal formation inhibitors in it is a necessary condition for the adequate functioning of the entire urinary system. Hypocitraturia is one of the factors contributing to stone formation. This may explain the effectiveness of citrate mixtures not only in urate, but also in calcium oxalate nephrolithiasis.

Along with the above mechanisms of action, citric acid salts additionally have antiseptic, cytoprotective and metabolic effects, which can also be used in clinical practice. In particular, C. Strassner and A. Friesen report the disappearance of candiduria in 16 out of 18 patients during therapy with citrate mixtures, which is probably due to a change in the urine reaction. The conclusion about the cytoprotective effect of citrate was made on the basis of successful attempts by P. Bruhl et al. use it to prevent chemical injury to the bladder mucosa during therapy with drugs from the oxazaphosphorine group - cyclophosphamide and ifosfamide (in modern oncological and nephrological practice, a drug from the group of mucolytics, mesna, is used for this purpose, which practically does not affect the acid-base state). In addition, the use of citrate to correct acidosis due to ureterosigmostomy has been reported.

The main difficulty in citrate therapy of urate nephrolithiasis is the selection of an adequate dosage of the drug. N. K. Dzeranov, who has been studying and developing this aspect for many years, recommends starting with a diet and assessing the reaction of urine for 5 days at a strictly defined time of day. Based on the obtained average values ​​of the pH level of urine, the initial dose of the drug is determined and, most importantly, its distribution during the day. After 5 days of treatment, the average indicators of the urine reaction are again determined at a strictly similar time of day and, if necessary, the dosage of the drug is adjusted. "Interactive", that is, in real time, changing the dosage of citrate is inefficient and even unsafe, as it leads to pH jumps, which can cause phosphate crystallization.

Due to the fact that citrate is normally present in the body, drugs based on it are practically devoid of toxicity. However, there are clinical situations where the use of these drugs requires caution. The use of citrate mixtures is undesirable in acute uric acid nephropathy and in general in acute renal failure of any etiology. The limiting factor here is not citrate ion, but potassium, the excretion of which is difficult in this clinical situation. In acute uric acid nephropathy, it is advisable to administer a 4% solution of sodium bicarbonate, saline, etc., in combination with loop diuretics. It is necessary to maintain diuresis at a level of at least 100-150 ml / hour, urine pH not lower than 6.5. If possible, xanthioxidase inhibitors are prescribed. Citrate mixtures are useful when restoring diuresis and achieving a glomerular filtration rate of 25-30 ml / min, when there is practically no risk of hyperkalemia.

In severe circulatory failure, the limiting factor is the increased intake of sodium, also contained in citrate mixtures. Sometimes acetazolamide is preferred in this situation. This drug from the group of diuretics - inhibitors of carbonic anhydrase strongly, and most importantly, uncontrollably alkalinizes urine, which makes it uncompetitive compared to citrate in the drug therapy of urate nephrolithiasis. However, acetazolamide is practically the only way to increase the pH of urine without resorting to the introduction of salts, which is highly undesirable in conditions of severe heart failure.

Thus, drug treatment of patients with kidney diseases caused by disorders of purine metabolism, despite the very limited choice of drugs and the apparent simplicity of their choice, is a complex and multifaceted problem that requires an interdisciplinary approach.

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S. K. Yarovoy 1 , Doctor of Medical Sciences
R. R. Maksudov

Federal State Budgetary Institution Research Institute of Urology, Ministry of Health of the Russian Federation, Moscow

The most common disorder of purine metabolism is increased production of uric acid with the development of hyperuricemia. The peculiarity is that the solubility of uric acid salts (urates) in blood plasma is low and when the solubility threshold in plasma (about 0.7 mmol / l) is exceeded, they crystallize in peripheral zones with low temperatures.

Depending on duration and severity hyperuricemia manifests itself:

1. The appearance of tophi (gr. tophus- porous stone, tuff) - the deposition of urate crystals in the skin and subcutaneous layers, in the small joints of the legs and arms, in tendons, cartilage, bones and muscles.
2. Nephropathy as a result of crystallization of uric acid with damage to the renal tubules and urolithiasis disease.
3. Gout is a disease of small joints.

To diagnose disorders, the determination of the concentration of uric acid in the blood and urine is used.

Purine metabolism disorders

Gout

When hyperuricemia becomes chronic, they speak of the development of gout (Gr. poclos- leg, agra- capture, literally - "foot in a trap").

Uric acid is found in the blood in the form of its salts. sodium urates. Due to the low solubility, urates are able to settle in areas with low temperatures, for example, in the small joints of the feet and toes. The urates accumulating in the intercellular substance are phagocytosed for some time, but phagocytes are not able to destroy the purine ring. As a result, this leads to the death of the phagocytes themselves, to the release of lysosomal enzymes, activation of free radical oxidation and the development of an acute inflammatory reaction - develops gouty arthritis. In 50-75% of cases, the first symptom of the disease is excruciating night pain in the big toes.

For a long time, gout was considered a "gourmet disease", but then the attention of researchers shifted to a hereditary change in the activity of purine metabolism enzymes:

• increase in activity FRDF-synthetases- leads to excessive synthesis of purines,
• decrease in activity - because of this, FRDF is not used to recycle purine bases, but participates in the first reaction of their synthesis. As a result, the amount of purines that are destroyed increases and at the same time their formation increases.

Both enzymatic disorders are recessive and linked to the X chromosome. Gout affects 0.3-1.7% of the adult population of the world, the ratio of affected men and women is 20: 1.

Fundamentals of treatment

Diet - reducing the intake of uric acid precursors with food and reducing its formation in the body. For this, foods containing a lot of purine bases are excluded from the diet - beer, coffee, tea, chocolate, meat products, liver, red wine. Preference is given to a vegetarian diet clean at least 2 liters of water per day.

To medicines treatment of gout include allopurinol, which is similar in structure to hypoxanthine. Xanthine oxidase oxidizes allopurinol to alloxanthin, and the latter remains firmly bound to the active site of the enzyme and inhibits it. The enzyme performs, figuratively speaking, suicidal catalysis. As a consequence, xanthine is not converted to uric acid, and because hypoxanthine and xanthine are more water soluble, they are more easily excreted in the urine.

Urolithiasis disease

Urolithiasis is the formation salt crystals(stones) of different nature in the urinary tract. directly education uric acid stones accounts for about 15% of all cases of this disease. Uric acid stones in the urinary tract are deposited in about half sick gout.

Most often, such stones are present in the distal tubules and collecting ducts. Cause of deposition uric acid crystals is hyperuricemia and increased excretion of sodium urates in the urine. The main provoking factor of crystallization is increased acidity of urine. When the pH of urine drops below 5.75, urates (enol form) become less soluble keto form and crystallize in the renal tubules.

Acidification of urine (normally 5.5-6.5) occurs for various reasons. This may be an excess supply of meat products containing a large amount of nucleic acids. acids, amino acids and inorganic acids, which makes such food "acidic" and lowers the pH of the urine. The acidity of the urine also increases with acidosis different origin (Acid-base state).

Fundamentals of treatment

Just like with gout, treatment is reduced to purine-free diet and the use of allopurinol. In addition, it is recommended plant based diet, leading to alkalization of urine, which increases the proportion of more water-soluble in primary urine salts of uric acid- urates. At the same time, already existing uric acid crystals (as well as oxalates) are able to dissolve when the urine is alkalized.

Drug treatment must necessarily be accompanied by purine-free diet With lots of clean water, otherwise the appearance of xanthine crystals in tissues and xanthine stones in the kidneys.

Lesch-Nyhan syndrome

Disease L e sha-n and khana (frequency 1:300000) is a complete congenital lack of activity hypoxanthine-guanine-phosphoribosyl-transferases, an enzyme responsible for the recycling of purine bases. The trait is recessive and linked to the X chromosome. It was first described in 1964 in the United States by medical student Michael Lesh and pediatrician William Nyhan.

Children are born clinically normal, only by 4-6 months developmental abnormalities are detected, namely, a lag in physical development (it is difficult to hold their head), irritability, vomiting, and periodic fever. The release of uric acid can be detected even earlier by the orange color of the diapers. By the end of the first year of life, the symptoms increase, a violation of coordination of movements, choreoathetosis, cortical paralysis, spasm of the muscles of the legs develop. The most characteristic sign of the disease manifests itself in the 2-3rd year of life - auto-aggression or self-mutilation - an irresistible desire of children to bite their lips, tongue, knuckles of fingers and toes.

Protein foods contain high concentrations of purines. These organic substances are the "building material" of human genes, representatives of the animal and plant world. With an imbalance of purines, it is necessary to adjust the daily menu so that the food ingredients replenish their supply, maintain overall health, especially for people at risk. To avoid serious pathologies of the body, it is important to respond in a timely manner to the first signs of the disease, not to start the pathological process.

What are purines and uric acid

Purines are chemical compounds that are the basis of nucleic acids and are directly involved in the formation and structure of DNA and RNA molecules. According to their pharmacological properties, purines help to absorb vitamins and micro / macro elements, stabilize and support metabolism. Such medical concepts as "purines and gout" are closely related, it remains only to focus on the so-called "intermediate link in this chain" - uric acid (Acidum uricum).

When cells die, the process of breaking down purines to uric acid predominates. This is the natural state of the body, where the last component acts as a natural antioxidant, which reliably protects blood vessels from destruction. If the level of uric acid rises rapidly, we are talking about a progressive pathology associated with chronic kidney dysfunction. As a result of this, the concentration of Acidum uricum rises above the norm in the tendons, joints, internal organs, and the disease is called gouty arthritis or gout.

Purine exchange

This is a set of processes for the synthesis and decay of purine nucleotides, where the latter are dominated by residues of a nitrogenous purine base and phosphate acid, ribose (deoxyribose) carbohydrates. Such a harmonious composition is necessary to maintain lipid metabolism, in violation of which body weight increases, a jump in blood pressure predominates, and pronounced symptoms of cardiovascular diseases that are prone to a chronic course progress.

Purine compounds are represented by such derivatives of the heterocyclic nitrogenous base of purine as adenine, guanine and hypoxanthine, which underlie the acceptable level of renewal of nucleic acids and proteins in the body, the constancy of energy metabolism. Inhibition of the synthesis of purine nucleotides slows down tissue growth, and the concentration of uric acid may pathologically increase. To achieve a balance, it is important to determine where and what purine bases in food will be restrained, how their use affects health.

Purine intake

The recommended daily dose of this ingredient in the body should vary between 700-1,000 mg. The main source of purines should be plant foods in the daily diet. If you eat more meat products, the risk of gout is especially high for patients at risk. When the concentration of uric acid exceeds the allowable norm, it is necessary to reduce the volume of food ingredients with a capacious content of purines, reduce the daily norm of nucleotides to 100–150 mg. Otherwise, relapse cannot be avoided.

Purines in food - table

If this indicator is not controlled, chronic diseases prone to recurrence develop in the body of a sick person. Purines in food are important components, therefore, with an imbalance of them, it is necessary to introduce certain changes into the usual daily menu, adhere to a therapeutic diet of diet table number 6. Below is a table according to which you can find out the concentration of organic compounds per 100 g of product:

Diet in violation of purine metabolism

The patient begins to be interested in the content of purines in food products with an imbalance of nucleic acids in his own body. In such a clinical picture, the doctor recommends adhering to a therapeutic diet in order to exclude another recurrence of gout. Such a recommendation is also appropriate for other diseases, including urolithiasis, acute or chronic nephritis, uric acid diathesis, renal failure, cystinuria, hyperuricemia, oxaluria. Here are some valuable expert tips:

1. It is important to avoid a long or short-term hunger strike, because in this case the concentration of uric acid in the body grows pathologically, which can provoke a relapse of the underlying disease.
2. When choosing meat products, it is important not to forget that the concentration of purine in muscle tissues is directly proportional to the intensity of their functionality in the body. Fatty meats are best left in the past, and preference is given to rabbit, chicken, turkey.
3. A purine diet for gout should limit the consumption of drinks that speed up the process of removing fluid from the body, such as coffee, soda, strong tea for breakfast. But fresh juices on the menu are only welcome, they additionally enrich the body with vitamins.
4. With an exacerbation of gout, it is important to temporarily exclude vegetable broths and soups, meat and fish dishes of high fat content from the therapeutic diet, and give preference to vegetarian soups.
5. It is necessary to give up bad habits, lead a proper lifestyle, control the daily diet and avoid one form of obesity.
6. It is necessary to use only the right fats, among which corn, olive, sunflower oil is welcome. In addition, the intake of vitamins P2, PP, C is welcome.

Low purine

The main goal is to reduce the rate of uric acid and its salts, which are formed after the metabolism of purines and changes in the reaction of urine towards an alkaline environment. Doctors recommend following dietary table 6, which includes limiting purines, reducing daily doses of sodium chloride and completely eliminating oxalic acid. Proteins must be reduced to 70 - 80 g, fats - up to 80 - 90 g, carbohydrates - up to 400 g. Drinking regimen - up to 2 liters or more. The energy value of the daily diet varies between 2,700-3,000 kcal.

Alkalinization of urine increases the solubility of urates, accelerates the excretion of Acidum uricum from the body, and disrupts the process of their formation. Everyday nutrition is negotiated with a specialist, and it is important not to violate such rules. Below are the foods allowed on the hypopurine diet for every day:

• vegetables: eggplant, zucchini, potatoes, tomatoes, cucumbers;
• fruits: apples, apricots, apples;
• dairy products: milk, kefir, yogurt;
• poultry: turkey, chicken;
• meat products: rabbit.

Purines such as caffeine, theophylline and theobromine contained in cocoa, coffee, tea and chocolate do not pose a significant danger, but their acceptable doses in the daily menu should be minimal. But the strictly prohibited foods with a low-purine diet are presented below, completely excluded from the daily diet of patients:

• legumes, lentils, sorrel;
• sausage products;
• confectionery;
• Fish and seafood;
• alcoholic and carbonated drinks.

Antipurine

In this case, it is necessary to eat up to 4-5 times a day, while it is important to limit the consumption of refractory fats. Foods rich in purines and oxalic acid also remain banned. Salt, spices adversely affect the concentration of Acidum uricum, so certain restrictions are required. If you eat right, maintaining an acceptable concentration of purines in the blood, you can extend the period of remission, forget about unpleasant attacks.

Sitting on an antipurine diet, it is desirable to control the daily doses of proteins within 70 - 80 g, fats - up to 80 - 90 g, carbohydrates - up to 400 g. You can not limit the drinking regimen to 2 liters of water, supplement it with green tea, natural juices and medicinal decoctions . The energy value of the daily diet varies between 2200 - 2500 kcal. With regard to daily nutrition, the following food ingredients should be highlighted from prohibited foods.