Gouty nephropathy

The term gouty nephropathy includes various forms of kidney damage caused by disturbances in purine metabolism and other metabolic and vascular changes characteristic of gout.

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Epidemiology

Gout affects 1-2% of the population, mostly men, with kidney damage developing in 30-50% of gout patients. With persistent asymptomatic increase in blood uric acid levels over 8 mg/dl, the risk of developing chronic renal failure increases by 3-10 times. Every 4th gout patient develops terminal chronic renal failure.

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Pathogenesis

The main pathogenetic mechanisms of gouty nephropathy are associated with increased 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. Hyperproduction of uric acid is caused by a deficiency of hypoxanthine-guanine phosphoribosyltransferase. The latter is controlled by genes localized in the X chromosome, which explains why gout predominantly affects males. Complete deficiency of hypoxanthine-guanine phosphoribosyltransferase leads to Lesch-Nyhan syndrome, characterized by an early and especially severe course of gout. Hyperuricemia is also caused by increased intracellular destruction of ATP - a defect characteristic of glycogenosis (I, III, V types), congenital fructose intolerance, chronic alcoholism.

At the same time, most patients with primary gout are diagnosed with renal tubular dysfunction: decreased secretion, increased various phases of reabsorption. An important role in pathogenesis is played by the defect of tubular acidogenesis, which promotes the crystallization of urates in urine, leading to the formation of urine with a persistently acidic reaction (pH <5) in gout.

The renal-damaging effect of hyperuricosuria leads to urate nephrolithiasis with secondary pyelonephritis, urate damage to the renal interstitial tissue with the development of chronic tubulointerstitial nephritis (CTIN), and renal acute renal failure due to intratubular obstruction by uric acid crystals (acute uric acid nephropathy). Hyperuricemia, due to the activation of renal RAAS and cyclooxygenase-2, increases the production of renin, thromboxane, and vascular smooth muscle cell proliferation factor. As a result, afferent arteriolopathy develops with renal hypertension and subsequent glomerulosclerosis. The abdominal type of obesity, hyperlipidemia with insulin resistance, and hyperphosphatemia characteristic of gout contribute to the development of severe atherosclerosis of the renal arteries with renovascular hypertension, the formation of bilateral medullary renal cysts, and the addition of urate calcium nephrolithiasis.

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Symptoms gouty nephropathy

Symptoms of gouty nephropathy include the development of acute arthritis against the background of clear signs of metabolic syndrome. Clinically, the diagnosis of "gouty nephropathy" is most likely in the presence of signs of alimentary obesity of the abdominal type in combination with volume-dependent hypertension, atherogenic hyperlipidemia, hyperinsulinemia, and microalbuminuria.

Urate nephrolithiasis is usually characterized by bilateral lesions, frequent relapses of stone formation, and sometimes coral nephrolithiasis. Urate stones are radiolucent and are better visualized by echography. Outside of an attack, changes in urine analysis are often absent. In renal colic, hematuria and urate crystalluria are detected. In prolonged renal colic, nephrolithiasis sometimes leads to an attack of secondary pyelonephritis, postrenal acute renal failure; in a long-term course, to hydronephrotic transformation of the kidney, pyonephrosis.

Chronic tubulointerstitial nephritis is characterized by persistent urinary syndrome, often combined with arterial hypertension. Proteinuria not exceeding 2 g/l is accompanied by microhematuria in more than half of the patients. Stones are usually not detected, but episodes of macrohematuria with transient oliguria and azotemia, provoked by dehydration, respiratory diseases, are noted. Bilateral medullary cysts (0.5-3 cm in diameter) are detected in 1/3 of patients. Early addition of hyposthenuria and nocturia, as well as hypertension with glomerulosclerosis are typical. Arterial hypertension is usually controlled. The development of difficult-to-control hypertension indicates the progression of glomerulosclerosis and nephroangiosclerosis or the formation of atherosclerotic stenosis of the renal artery.

Acute uric acid nephropathy manifests itself suddenly with oliguria, dull pain in the lower back with dysuria and macrohematuria, often combined with an attack of gouty arthritis, hypertensive crisis, 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, the excretion of sodium with urine is not increased. Subsequently, oliguria quickly turns into anuria. With the aggravation of intratubular obstruction by the formation of numerous urate stones in the urinary tract and in the bladder, azotemia increases at a particularly high rate, which makes this variant an urgent form of suddenly occurring gouty nephropathy.

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Forms

Gouty nephropathy is divided into the following clinical forms:

• urate nephrolithiasis;
• chronic tubulointerstitial nephritis;
• acute uric acid nephropathy.

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Diagnostics gouty nephropathy

Often, patients with gout suffer from abdominal obesity.

Laboratory diagnostics of gouty nephropathy

Laboratory diagnostics of gouty nephropathy is based on the diagnostics of uric acid metabolism disorders: detection of hyperuricemia (>7 mg/dl), hyperuricosuria (>1100 mg/day), intracellular uric acid crystals in the synovial fluid.

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Instrumental diagnostics of gouty nephropathy

Uric acid crystals are detected in the contents of tophi using polarization microscopy.

Differential diagnosis of gouty nephropathy

It is necessary to differentiate between gout and secondary hyperuricemia. The following diseases are known, often accompanied by disturbances of purine metabolism:

• chronic lead intoxication (lead nephropathy);
• chronic alcohol abuse;
• analgesic nephropathy;
• widespread psoriasis;
• sarcoidosis;
• berylliosis;
• hypothyroidism;
• myeloproliferative diseases;
• polycystic disease;
• cystinosis.

Drug-induced secondary hyperuricemia also needs to be differentiated from primary gout. Drugs that retain uric acid in the kidneys include:

• thiazide and loop diuretics;
• salicylates;
• NSAIDs;
• nicotinic acid;
• ethambutol;
• cyclosporine;
• cytostatics;
• antibiotics.

Particular importance is attached to the diagnosis of chronic renal failure (gouty “mask” of uremia), which sharply disrupts the renal elimination of uric acid.

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Treatment gouty nephropathy

Treatment of gouty nephropathy (acute form) is carried out in accordance with the principles of treatment of acute renal failure caused by acute intratubular obstruction (see acute renal failure ). In the absence of anuria and signs of ureteral obstruction by urates (postrenal acute renal failure), conservative treatment is used. Continuous intensive infusion therapy (400-600 ml/h) is used, including:

• isotonic sodium chloride solution;
• 4% sodium bicarbonate solution;
• 5% dextrose solution;
• 10% mannitol solution (3-5 ml/kg/h);
• furosemide (up to 1.5-2 g/day, in divided doses).

In this case, it is necessary to maintain diuresis at a level of 100-200 ml/h, and urine pH - more than 6.5, which ensures the dissolution of urates and the excretion of uric acid. At the same time, allopurinol is prescribed at a dosage of 8 mg/(kg x day). If there is no effect from the indicated therapy within 60 hours, the patient is transferred to acute hemodialysis.

Treatment of gouty nephropathy (chronic form) is complex and involves solving the following problems:

• correction of purine metabolism disorders;
• correction of metabolic acidosis and urine pH;
• normalization of blood pressure;
• correction of hyperlipidemia and hyperphosphatemia;
• treatment of complications (primarily chronic pyelonephritis).

The diet is low-purine, low-calorie; it should be combined with plenty of alkaline drinks. 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 to normalize body weight, blood lipid and phosphate levels, as well as metabolic acidosis. In gouty nephropathy at the stage of chronic renal failure, a low-protein diet should be used.

Allopurinol reduces urate production and blood uric acid levels by inhibiting the enzyme xanthine oxidase. It promotes the dissolution of urates. In addition to controlling purine metabolism, xanthine oxidase leads to the formation of free radicals that damage the vascular endothelium. 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 use of allopurinol:

• asymptomatic hyperuricemia combined with hyperuricosuria more than 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 (200 to 600 mg/day) depends on the severity of hyperuricemia. Due to the possibility of exacerbation of gouty arthritis, it is advisable to start treatment with allopurinol in a hospital and combine the drug with NSAIDs 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 urine (magurlite, potassium sodium hydrogen citrate, potassium bicarbonate, acetazolamide). In chronic tubulointerstitial nephritis, the dose of allopurinol is reduced as the CF decreases, and it is contraindicated in severe chronic renal failure. Allopurinol enhances the effect of indirect anticoagulants.

Uricosuric drugs correct hyperuricemia by increasing the excretion of uric acid in the urine. They are used for asymptomatic hyperuricemia, gouty chronic tubulointerstitial nephritis. These drugs are contraindicated in hyperuricosuria, urate nephrolithiasis, chronic renal failure. Probenecid (initial dose 0.5 g/day), sulfinpyrazone (0.1 g/day), benzobromarone (0.1 g/day) are most often used. A combination of allopurinol with benzobromarone or sulfinpyrazone is possible. Losartan also has a uricosuric effect.

Citrate mixtures (potassium-sodium-hydrogen citrate, magurlit, blemaren) correct metabolic acidosis, increase urine pH to 6.5-7 and thereby dissolve small urate stones. They are indicated for urate nephrolithiasis. Potassium-sodium-hydrogen citrate or magurlit are taken before meals 3-4 times a day (daily dosage 6-18 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, active pyelonephritis, and should be used with caution in hypertension (they contain a lot of sodium). Citrate mixtures are ineffective for large stones, when remote lithotripsy or pyelolithotomy is indicated.

Antihypertensive drugs

The tasks of hypotensive therapy in gouty nephropathy include ensuring a nephroprotective and cardioprotective effect. In the treatment, drugs that retain uric acid (thiazide and loop diuretics) and aggravate hyperlipidemia (non-selective beta-blockers) should not be used. The drugs of choice are ACE inhibitors, angiotensin II receptor blockers and calcium channel blockers.

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Hypolipidemic drugs

Statins (lovastatin, fluvastatin, pravastatin) are used in patients with gout with LDL levels > 130 mg/dl. When statins are combined with ACE inhibitors, the hypolipidemic and hypotensive effects are enhanced, and the risk of mortality from acute myocardial infarction is reduced by reducing the concentration of C-reactive protein in the blood and slowing left ventricular hypertrophy. The nephroprotective effect of statins also increases when combined with ACE inhibitors, reducing proteinuria and stabilizing CF.

Forecast

Urate nephrolithiasis and gouty chronic tubulointerstitial nephritis usually occur at one of the stages of a long-term course of chronic tophaceous gout with attacks of gouty arthritis and are characterized by a long course. In 30-40% of cases, nephropathy is the first sign of the renal "mask" of gout or develops against the background of an atypical articular syndrome for gout (lesions of large joints, polyarthritis, arthralgia). Urate nephrolithiasis is often characterized by a recurrent course with repeated episodes of postrenal acute renal failure. Acute uric acid nephropathy is characterized by a reversible cyclic course, typical of acute renal failure caused by acute intratubular obstruction. Gouty chronic tubulointerstitial nephritis is typically latent or subclinical. Risk factors for the development of chronic renal failure in gout include:

• persistent arterial hypertension;
• proteinuria more than 1 g/l;
• addition of chronic pyelonephritis;
• old age of a patient with gout.

Gouty nephropathy often develops into chronic renal failure. The average period of this transition is 12 years.

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