Gouty Nephropathy

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

[1], [2], [3], [4], [5], [6]

Epidemiology

Podgra suffer 1-2% of the population, mostly men, with kidney damage developing in 30-50% of patients with gout. With persistent asymptomatic increase in uric acid level of blood more than 8 mg / dL, the risk of developing chronic renal failure is increased 3-10 times. Each fourth patient with gout develops terminal chronic renal failure.

[7], [8], [9], [10], [11], [12]

Pathogenesis

The main 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 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 the gout is predominantly male. A complete deficiency of hypoxanthine-guanine phosphoribosyltransferase leads to Lesch-Naikhan syndrome characterized by early and especially severe gout. Hyperuricemia is also associated with increased intracellular destruction of ATP, a defect typical of glycogenesis (I, III, V type), congenital intolerance to fructose, chronic alcoholism.

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

The kidney-damaging effect of hyperuricosuria leads to urate nephrolithiasis with secondary pyelonephritis, urate damage to interstitial kidney tissue with the development of chronic tubulointerstitial nephritis (CTIH), and renal acute renal failure due to intracanular obstruction by uric acid crystals (acute urinary nephropathy). Hyperuricemia due to the activation of renal RAAS and cyclooxygenase-2 enhances the production of renin, thromboxane and proliferation factor of smooth muscle cells of blood vessels. As a result, afferent arteriolopathy develops with renal hypertension and subsequent glomerulosclerosis. The characteristic gout abdominal type of obesity, hyperlipidemia with insulin resistance, hyperphosphatemia promote the development of pronounced arteriosclerosis of the renal arteries with renovascular hypertension, the formation of bilateral medullary renal cysts, and adherence to urate calcium nephrolithiasis.

[13], [14], [15], [16], [17], [18], [19], [20], [21]

Symptoms of the gouty nephropathy

Symptoms of gouty nephropathy consist in the development of acute arthritis against the background of vivid 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, microalbuminuria.

Urinary nephrolithiasis is characterized, as a rule, by bilateral lesions, frequent recurrences of stone formation, sometimes coral nephrolithiasis. Uranium stones are X-ray negative, better visualized on ultrasound. Outside the attack, changes in urine tests are often absent. With renal colic they detect hematuria, urate crystalluria. With prolonged renal colic nephrolithiasis sometimes leads to attack secondary pyelonephritis, postrenal acute renal failure; with a long course - to hydronephrosis transformation of the kidney, pionephrosis.

Chronic tubulo-interstitial nephritis is characterized by persistent urinary syndrome, often combined with hypertension. At the same time, proteinuria, not exceeding 2 g / l, is accompanied by microhematuria in more than half of the patients. Concrements usually do not show, however, there are episodes of macrohematuria with transient oliguria and azotemia, provoked by dehydration, respiratory diseases. In one third of patients, bilateral medullary cysts (0.5-3 cm in diameter) are detected. Typically, the early addition of hypostenuria and nocturia, as well as hypertension with glomerulosclerosis. Arterial hypertension is usually of a controlled nature. 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 uricemia nephropathy manifests suddenly oliguria, blunt low back pain with dysuria and macrogematuria, often combined with an attack of gouty arthritis, 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 preserved, the excretion of sodium in the urine is not increased. Later oliguria quickly turns into anuria. With aggravation of the intracanular obstruction with the formation of numerous urate calculi in the urinary tract and in the bladder, azotemia is growing at a particularly high rate, which makes this variant the urgent form of a sudden onset gouty nephropathy.

[22], [23], [24], [25], [26], [27], [28]

Forms

Gouty nephropathy is divided into the following clinical forms:

• urate nephrolithiasis;
• chronic tubulointerstitial nephritis;
• acute urinary nephropathy.

[29], [30], [31], [32], [33], [34]

Diagnostics of the gouty nephropathy

Often, patients with gout suffer from obesity of the abdominal type.

Laboratory Diagnosis of Gouty Nephropathy

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

[35], [36], [37]

Instrumental diagnosis of gouty nephropathy

Uric acid crystals are detected in the contents of tofusov by the method of 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 impaired purine metabolism:

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

Drug-induced secondary hyperuricemia also needs to be differentiated from primary gout. To medicines, which retain uric acid by 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 violates renal elimination of uric acid.

[38], [39], [40], [41], [42]

Treatment of the 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 intracanulent obstruction (see acute renal failure ). In the absence of anuria and signs of ureteral obstruction urate (postrenal acute renal failure) conservative treatment is used. Use continuous intensive infusion therapy (400-600 ml / h), 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).

It is necessary to maintain diuresis at the level of 100-200 ml / h, and the urine pH is more than 6.5, which ensures the dissolution of urates and excretion of uric acid. At the same time, allopurinol is administered at a dosage of 8 mg / kg kg. In the absence of the effect of this therapy for 60 hours the patient is transferred to acute hemodialysis.

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

• correction of purine metabolism disorders;
• correction of metabolic acidosis and urine pH;
• normalization of blood pressure;
• correction of hyperlipidemia and hyperphosphataemia;
• treatment of complications (in the first place - chronic pyelonephritis).

The diet is low-purple, low-calorie; it should be combined with an abundant alkaline drink. Long-term compliance with such a diet reduces the level of uric acid in the blood by 10% (uricosuria - by 200-400 mg / day), promotes normalization of body weight, lipid and blood phosphate levels, and metabolic acidosis. With gouty nephropathy in the stage of chronic kidney failure should use a low protein diet.

Allopurinol reduces urate production and uric acid level of blood, inhibiting the enzyme xanthine oxidase. Helps dissolve urates. In addition to controlling purine metabolism, xanthine oxidase results in the formation of free radicals that damage the vascular endothelium. The hypouricemic effect of allopurinol is correlated with its nephroprotective effect associated with a decrease in proteinuria, production of renin, free radicals, as well as with retardation of glomerulosclerosis and nephroangiosis.

Indications for allopurinol:

• asymptomatic hyperuricemia in combination with hyperuricosuria more than 1100 mg / day;
• gouty chronic tubulointerstitial nephritis;
• urate nephrolithiasis;
• prevention of acute urinary 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 possible exacerbation of gouty arthritis, it is advisable to start allopurinol treatment 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 desirable to combine it with drugs that increase the solubility of urate in the urine (magurlite, potassium-sodium-hydrogen-citrate, potassium bicarbonate, acetazolamide). In chronic tubulointerstitial nephritis, the dose of allopurinol is reduced with decreasing CF, and in severe chronic renal failure it is contraindicated. Allopurinol enhances the effect of indirect anticoagulants.

Urikozuric 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. More often apply probenecid (initial dose 0.5 g / day), sulfinpyrazone (0.1 g / day), benzobromarone (0.1 g / day). A combination of allopurinol with benzobromarone or sulphinpyrazone is possible. Urticazuric effect is also possessed by losartan.

Citrate mixtures (potassium-sodium-hydrogen-citrate, magurlite, blemarene) correct metabolic acidosis, increase urine pH to 6,5-7, and by this dissolve small urate calculi. Are shown with urate nephrolithiasis. Potassium-sodium-hydrogen-citrate or magurlite is taken before meals 3-4 times a day (daily dosage of 6-18 g). In the treatment, a constant urine pH control is necessary, as its sharp alkalinization can lead to the crystallization of phosphates. Citrate mixtures are contraindicated in chronic renal failure, active pyelonephritis, should be used with caution in hypertension (contain a lot of sodium). Citrate mixtures are ineffective in large calculi, when remote lithotripsy or pyelolithotomy is indicated.

Antihypertensive drugs

In the task of antihypertensive therapy for gouty nephropathy is the provision of nephroprotective and cardioprotective effect. In the treatment should not use drugs that delay uric acid (thiazide and loop diuretics), aggravating hyperlipidemia (nonselective beta-blockers). The drugs of choice are ACE inhibitors, angiotensin II receptor blockers and calcium channel blockers.

[43], [44], [45], [46], [47], [48]

Lipid-lowering drugs

Statins (lovastatin, fluvastatin, pra-vastatin) are used in patients with gout with LDL levels> 130 mg / dl. In the combination of statins with ACE inhibitors, hypolipidemic and hypotensive effects increase, as well as a reduction in the risk of death from acute myocardial infarction due to a decrease in the concentration of C-reactive protein in the blood and slowing of left ventricular hypertrophy. The nephroprotective effect of statins also increases when combined with ACE inhibitors, reducing proteinuria and stabilizing CF.

Forecast

Urinary nephrolithiasis and gouty chronic tubulointerstitial nephritis usually occur at one of the stages of perennial flow of chronic toffee gout with attacks of gouty arthritis and are characterized by a prolonged course. In 30-40% of cases, nephropathy is the first sign of the kidney "mask" of gout or develops against a background of atypical arthritic syndrome for gout (lesions of large joints, polyarthritis, arthralgia). Urinary nephrolithiasis is often characterized by a recurring course with repeated episodes of postrenal acute renal failure. Acute urinary acid nephropathy is characterized by a reversible cyclic flow, typical of acute renal failure caused by acute intracanulent obstruction. For gouty chronic tubulointerstitial nephritis, a latent or subclinical course is typical. The risk factors for the development of chronic kidney failure in gout include:

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

Gouty nephropathy often turns into chronic kidney failure. The duration of this transition is on average 12 years.

[49], [50], [51], [52], [53], [54]