Pathogenetic therapy of gouty nephropathy: emphasis on the effectiveness and safety profile of Adenuric (febuxostat)

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Diseases of the genitourinary system | Kidneys

With nephropathy (from two Greek words “kidney” and “suffering, illness”), kidney dysfunction occurs in several stages:

1. Changes in the composition of the blood passing through the kidneys daily in an amount of about two thousand liters. The causes of changes are numerous - from the effects of toxic substances to systemic pathologies.
2. Organic and functional changes in the working apparatus of the kidneys.
3. Impaired kidney function (cleansing the blood, excreting urine, synthesizing active substances, maintaining a constant internal environment of the body), affecting the functioning of the body as a whole.
4. If the destructive effect of the causative factor persists and kidney damage worsens, renal failure develops, which is an immediate threat to the life of the body.

Diabetic nephropathy

Leader among nephropathies (more than 30%). The scenario of renal disorders includes sclerosis (replacement of working tissue with connective tissue) of the renal tissue and vascular apparatus; decreased tone of the urinary tract and its infection, etc. All this sooner or later leads to a decrease in kidney function and aggravation of systemic disorders in the body (intoxication, loss of protein in the urine, high blood pressure, etc.).

Dysmetabolic nephropathy

Often found in children.

The cause of renal pathology is disturbances of mineral metabolism (calcium, phosphates, uric and oxalic acid; mixed types). They are:

• primary (congenital deficiency of specific enzymes);
• secondary - consequences of excess and/or insufficient intake of substances; disturbances in their metabolism due to a wide range of ailments (urinary system infections, blood diseases and gastrointestinal tract - anemia, myeloma, pancreatitis, Crohn's disease, biliary dyskinesia, parasitic lesions, etc.) and side effects of medications (diuretics, cytostatics, derivatives salicylic acid).

The result of metabolic disorders is an increase in the concentration of the corresponding salts in the urine (sedimentation) with subsequent damage to the working tissue of the kidneys, the possibility of stone formation and the addition of infections.

Gouty nephropathy

It is essentially a type of dismetabolic nephropathy (urate type). The name comes from a pathology leading to kidney damage - gout. It is characterized by a violation of purine metabolism and a long-term increase in the content of uric acid in the blood and urine - the main factor damaging the renal tissue (uric acid salts are deposited in the kidneys, causing stagnation and inflammation, leading to tissue destruction, stone formation and dysfunction).

It is not found in all patients suffering from gout (in about half of the cases). The likelihood of its occurrence increases: alcohol, overeating meat and legumes, obesity, insulin resistance (reduced tissue sensitivity to insulin), prolonged heavy physical activity and drug therapy (diuretics, salicylates).

Symptoms of nephropathy

In the foreground are the symptoms of an illness that leads to impaired kidney function. The kidneys are able to hide their problems for a long time. Therefore, signs of their damage, which significantly reduce the quality of life, appear already in the later stages. Much earlier it is possible to identify characteristic quantitative and qualitative changes in urine:

• the presence of protein, red blood cells, certain salts (depending on the type of metabolic nephropathy);
• change in color and density;
• appearance of sediment, etc.

Later symptoms of nephropathy are determined by the nature of the damage to the renal tissue and developing complications (type of inflammation and its location; urolithiasis, renal failure). For example, signs of urolithiasis (characteristic of dysmetabolic nephropathies) are: pain syndrome up to renal colic, urination disorder, blood in the urine, etc.

For nephropathies of all types, an increase in the amount of urine may be observed in the early and middle stages. Later, it enters the stage of delayed fluid excretion and is accompanied by characteristic renal edema (first in the facial area). Renal edema (for example, in diabetic nephropathy) is difficult to eliminate by taking diuretics. In parallel with edema, a persistent increase in blood pressure is also possible.

1.General information

For many people, the diagnosis of gout is associated primarily with joint disease. Less known is the fact that gout is almost always (more than 80% of cases) caused by an increased level of uric acid in the blood (hyperuricemia) and is accompanied by simultaneous kidney damage. Relative to the latter trend, estimates of occurrence vary widely (30–80%); some authors even estimate this connection as one hundred percent.

One way or another, gouty kidney, or urate nephropathy, which is a more precise and correct term, is a very common type of kidney pathology, given that up to 2% of the world's population suffers from gout.

It is known that gout affects men several times more often than women, and it usually begins at the age of 25-35 (in women, during menopause; in addition, occasionally a hereditary juvenile form occurs in men). And although the etiopathogenetic mechanisms of the development of gout, damage to the joints and internal organs in this serious illness remain the subject of intensive scientific research, the connection with urolithiasis, kidney dysfunction and, ultimately, with renal failure

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Treatment of nephropathy

The leading role in the prevention and treatment of all types of nephropathies is played by lifestyle: nutrition, drinking and exercise regimen, resistance to stress. Often, perseverance and consistency in following the correct (for a particular person, taking into account the identified metabolic disorders) regimen is enough for a long-term and lasting improvement in the quality of life. Drug therapy is required for people whose bodies are no longer able to independently compensate for the organic and functional changes that have arisen.

Treatment of diabetic nephropathy

Determined by the stage of the violation. In the early stages, it is sufficient to correct carbohydrate and lipid metabolism (using the above-mentioned win-win method). In the later stages, decongestant, hypotensive, and detoxification therapy is required. Up to the use of hemodialysis with a significant decrease in kidney function.

Treatment of dysmetabolic nephropathy

A priority:

• harmonization of nutrition (the goal is to reduce the intake and/or formation of specific substances - oxalates, phosphates, urates, etc.; reduce the load on the kidneys - low-protein diet);
• drinking regimen (the goal is to reduce the concentration of these substances in the urine, plus detoxification).

Taking vitamins, antioxidants, and membrane stabilizers helps strengthen the body's reserve capabilities (including increasing the resistance of its cells to damaging factors and harmonizing metabolism).

Treatment of gouty nephropathy

All of the above is relevant. To reduce the formation of uric acid in the body and/or to dissolve precipitated salts, medications are used (nicotinamide, allopurinol citrate mixtures, preparations based on lithium salts, etc.). Physiotherapeutic methods are an effective addition.

An effective way to correct metabolic disorders is herbal medicine—individual herbal preparations selected by a doctor based on diagnosis. A significant effect in preventing nephropathies and improving the quality of life if they are present is achieved by a combination of a correct lifestyle and traditional methods of treatment (homeopathy, acupuncture, osteopathy, qigong therapy).

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Purine metabolism disorders and gouty nephropathy

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, predominantly men [1]. 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 [2].

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 USA have seen a multiple increase in the incidence of gout in parallel with the epidemic of morbid obesity, nephrolithiasis and non-insulin-dependent diabetes mellitus [1, 3]. 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) [4]. Hyperuricemia is also caused by increased intracellular destruction of adenosine triphosphate (ATP): a defect characteristic of glycogenosis (types I, III, V), congenital fructose intolerance, and chronic alcoholism [1]. At the same time, the majority of patients with primary gout exhibit disturbances in the tubular function of the kidneys: 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 [2]. The defect is manifested by the formation of urine with a persistently acidic reaction (pH < 5) in gout.

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).

As a result, afferent arteriolopathy develops with renal hypertension and subsequent glomerulosclerosis and nephroangiosclerosis [5].

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 [6]. It should be emphasized the unfavorable prognostic significance of hyperuricemia in pregnancy nephropathy [7], immunoglobulin A (IgA) nephropathy [8] and alcoholism [6]. 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) [9]. 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 [2].

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 is used (400–600 ml/h) 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 nonsteroidal 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 [10].

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, blemaren) 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 [11].

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.

Literature

1. Bunchuk N.V. Gout // Rheumatic diseases / ed. V. A. Nasonova and N. V. Bunchuk. M., 1997. pp. 363–374.
2. Mukhin N. A., Balkarov I. M. Gouty kidney // Nephrology / ed. I. E. Tareeva. M., 2000. pp. 422–429.
3. Stamatelou KK , Francis ME, Jones CA Time trends is the reported prevalence of kidney stones in the US// Kidney Int. 2003; 63:1817–1823.
4. Bingham C., Ellard S. et al. Atypical familial juvenile hyperuricemic nephropathy associated with a hepatocyte nuclear factor-1 beta gene mutation // Kidney Int. 2003; 63:1645–1651.
5. Kang DH, Nakagawa T., Feng L. A role of uric acid in the progression of renal disease // J. Amer. Soc. Nephrol. 2002; 13:2888–2897.
6. Nikolaev A. Yu. Disorders of purine metabolism in alcoholism // Alcohol disease / ed. V. S. Moiseeva. M., 1990. pp. 95–99.
7. Karumanchi SA, Maynard SE, Stillman IE Preeclampsia: a renal perspective // ​​Kidney Int. 2005; 67:2101–2113.
8. Ohno T., Hosoya T., Gomi H. Serum uric acid and renal prognosis in IgA nephropathy // Nephron - 2001; 87:333–339.
9. Munter P., He J., Vupputuri S. Blood lead and CKD in the general US population: results from NHANES III. Kidney Int. 2003; 63:1044–1050.
10. Perez-Ruiz F., Gomez-Ullate P., Amenabar J. Long-term effectiveness of hyperuricaemia treatment of renal transplant patients // Nephrol. Dial. Transpl. 2003; 18: 603–606.
11. Athyros VG, Elisaf M., Papageorgiou AA Effect of statins versus untreated dyslipidemia on serum uric acid levels in patients with coronary heart disease: a subgroup analysis of the GREck Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study // Amer. J. Kidney Dis. 2004; 43:589–599.

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

Signs and symptoms of gout

This is an acute attack of arthritis, usually of one joint, most often the first metatarsophalangeal, ankle or knee. Typically, an attack of arthritis develops in the early morning or at night, in the midst of complete health. It manifests itself in the form of severe pressing pain in one or another joint. The affected joint swells, the temperature in the joint area rises, the skin turns red and begins to become shiny. Usually the pain becomes less during the day, but by night it gets worse again. The duration of a gout attack lasts from two to three days to a week, sometimes more. With a repeated attack, other joints may be involved in such inflammation. With a long course of gout, tophi form on the flexor surfaces of the joints, which can open with the release of uric acid crystals. At this moment, the patient experiences quite intense pain.

2. Reasons

Uric acid is one of the bioactive substances necessary for the body; in water it dissolves slightly and is broken down by special enzymes, and in the blood it is present in the form of salts (urates). Urate crystals, accumulating in the joints, lead to the development of gouty arthritis, the second most common joint disease after rheumatic arthritis. An increase in the concentration of uric acid compounds may be due to a congenital deficiency of the enzymes that break it down (for the production of which the “male” X chromosome is responsible, which explains gender differences in morbidity). Statistical correlations of gout with hypertension, alcoholism, congenital abnormalities of the structure and functioning of the renal tubules, certain types of cancer pathology, obesity and other factors have also been identified and confirmed.

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Forecast

The prognosis for dysmetabolic nephropathy is generally favorable.

In most cases, with the appropriate regimen, diet and drug therapy, it is possible to achieve stable normalization of the corresponding parameters in the urine.

In the absence of treatment or if it is ineffective, the most natural outcome of dysmetabolic nephropathy is urolithiasis and kidney inflammation.

The most common complication of dysmetabolic nephropathy is the development of urinary tract infections, primarily pyelonephria.

4.Treatment

Therapy for urate nephropathy is always complex. It is necessary to control and relieve exacerbations of gout as the underlying disease, treatment and prevention of hypertension, and normalization of body weight. A diet is strictly required, which the doctor develops and explains on an individual basis (however, in any case, beer, certain types of fish and a number of other products that promote the production of uric acid are excluded). Sugar consumption is also sharply reduced, since there is a direct connection between the incidence of gout and diabetes. Diuretics (diuretics) and urostatics are prescribed - drugs that suppress the secretion of uric acid. Regular observation by a doctor of the appropriate profile and monitoring of laboratory tests are mandatory.

The prognosis is generally favorable, provided that all medical prescriptions are followed, especially those related to lifestyle and bad habits. In recent decades, significant advances have been made in understanding the etiopathogenesis and, accordingly, developing strategies for effective therapeutic control of renal (renal) functions in urate nephropathy.

Treatment methods for gout

Treatment of gout consists of both pharmacological and non-pharmacological methods, and should take into account the following factors:

• uric acid concentration, number of previous arthritis attacks,
• stage of the disease (asymptomatic increase in uric acid, interictal period, acute or intermittent arthritis, chronic tophi gout,
• age, gender, obesity, hyperuricemic drugs, polypharmacy.

It should be remembered that asymptomatic hyperuricemia does not equate to gout. Currently, there is no data proving the need for drug therapy to maintain normouricemia in such patients; the main method of therapy in this case is the treatment of comorbid diseases, dietary correction and lifestyle modification.

In the treatment of gout, a combination of non-pharmacological and pharmacological treatments is more effective than monotherapy. When treating, it is necessary to take into account the phase of the disease: acute attack of arthritis, inter-attack period, chronic form, tophi form, serum uric acid concentration, number of arthritis attacks, the presence of comorbid conditions such as diabetes mellitus (DM), arterial hypertension, coronary artery disease, and risk factors for hyperuricemia.

The main aspect of therapy is teaching the patient a healthy lifestyle, weight loss, diet, and reducing alcohol intake, especially beer. Dietary restriction of purine-rich animal products and weight loss help reduce serum uric acid levels.

One of the mandatory conditions for the treatment of gout is the control of comorbid diseases - dyslipidemia, alternative hypertension, diabetes mellitus, as well as weight loss and smoking cessation.

Treatment of an acute attack of gouty arthritis

Nonsteroidal anti-inflammatory drugs (NSAIDs) and colchicine (when taken orally) are used to treat an acute attack of gout. One effective treatment is removal of synovial fluid and intra-articular injection of long-acting steroids. This treatment method is effective and safe.