Hyperuricemia Nephropathy

　　1. Etiology

　　The causes of uric acid nephropathy and gouty nephropathy are the increased concentration of uric acid in blood and (or) urine, and many factors can lead to a persistent increase in uric acid concentration:

　　1. Increased uric acid production

　　(1) Genetic factors: enzyme gene mutations, such as the deficiency of hypoxanthine-guanine phosphoribosyltransferase.

　　(2) Acquired factors: myelodysplastic syndrome, high purine intake, obesity, hypertriglyceridemia, high dietary fructose content, high alcohol content in beverages, and exercise.

　　2. Decreased uric acid excretion

　　(1) Genetic factors: decreased uric acid excretion or excretion fraction.

　　(2) Acquired factors: drugs such as thiazide diuretics, salicylates, metabolites such as lactic acid, ketone bodies, angiotensin and vasopressin, decreased plasma volume, hypertension, and obesity.

　　3. Excessive endogenous uric acid production Uric acid is the final product of purine metabolism.Uric acid is a trioxide of purine, mainly produced by the metabolism and decomposition of nucleic acids and other purine compounds in cells, and uric acid is produced from the decomposition of purines in food by enzymes. The most important reasons for excessive endogenous uric acid production are the decreased activity of hypoxanthine-guanine phosphoribosyltransferase (HGPRT), increased activity of phosphoribosylpyrophosphate amidotransferase (PRPP) and hypoxanthine, xanthine oxidase (XO) activity. When HGPRT is deficient, hypoxanthine and guanine cannot be converted into corresponding nucleotides, and a large amount of hypoxanthine in the body is converted into uric acid. The increased activity of PRPP synthetase can increase the intracellular PRPP, which is a key enzyme for the conversion of purines to uric acid, ultimately increasing uric acid production. XO converts hypoxanthine to xanthine and xanthine to uric acid.

　　4. Impaired uric acid excretion Uric acid has no physiological function in the body. In a physiological state, 2/3 to 3/4 of uric acid is excreted by the kidneys, and the rest is excreted by the intestines, secreted into the intestinal lumen by intestinal mucosal cells.Intestinal bacteria contain uricase, which decomposes it into water and ammonia, so uric acid is not excreted in feces. When renal function is impaired, there is a slight increase in the amount excreted from the intestines. Almost all uric acid filtered by the glomerulus is reabsorbed by the proximal renal tubules, and uric acid in urine is secreted by the renal tubular loop. It has been confirmed that the renal tubules secrete uric acid, and the renal tubules can be reabsorbed again. Kidney excretion is an important part of regulating blood uric acid concentration. The factors affecting kidney excretion of uric acid include the following:

　　(1) In the early stages of chronic renal insufficiency, there is compensation by healthy renal units, with a slight increase in uric acid concentration that is not consistent with the decrease in glomerular filtration rate (GFR).

　　(2) When blood volume decreases, such as when sodium salt intake is restricted, the use of diuretics, and polyuria, the clearance rate of uric acid decreases. When blood volume decreases and urine flow rate is below 1ml/min, uric acid can accumulate in the S3 segment of the proximal renal tubule beyond the concentration in the peritubular capillaries, leading to a back-diffusion phenomenon. Conversely, sodium salt loading and the secretion of antidiuretic hormone increase blood volume, leading to an increase in uric acid clearance.

　　(3) Organic acids can affect the excretion of uric acid by renal tubules: Organic acids need to be excreted with the help of renal tubular anion pumps, at which point they compete with uric acid; or due to the accumulation of organic acids in the proximal renal tubules, it can limit the secretion of uric acid by causing metabolic disorders. An increase in organic acids is often seen in severe metabolic disorders such as alcohol intoxication, lactic acid accumulation due to strenuous exercise, and diabetic ketoacidosis.

　　(4) Diuretics, antituberculosis drugs, aspirin, and catecholamines can all affect the excretion of uric acid: The effect of diuretics on the secretion of uric acid by renal tubules, whether it is to reduce secretion or increase reabsorption, is not yet clear. Antituberculosis drugs such as ethambutol and pyrazinamide can inhibit the secretion of uric acid by renal tubules. Aspirin can inhibit the secretion of uric acid by renal tubules at low doses, and when the dose increases to 2-3g, it can inhibit the reabsorption of uric acid by renal tubules, thus promoting the excretion of uric acid. Catecholamines affect renal blood flow, reducing the effect of uric acid.

　　(5) Lead can inhibit the secretion of uric acid by renal tubules: In chronic lead poisoning, the decrease in uric acid clearance is more pronounced than the decrease in creatinine clearance.

　　Uric acid maintains a dynamic balance within the body, with a total uric acid pool storing 1200mg, with 600-900mg exchanged daily, produced at a rate of 750mg, decomposed in the intestines by 100-365mg, and excreted in urine by 500-1000mg. Daily intake of foods containing purines or nucleotides maintains normal blood uric acid levels through excretion. If normal diet is changed to a purine-free diet, blood uric acid levels only decrease by 59.5μmol/L (1mg/dl), thus diet is not the main cause of hyperuricemia. The normal range for uric acid levels using the uricase method is 150-380/μmol/L (2.4-6.4mg/dl) for males and 100-300/μmol/L (1.6-4.8mg/dl) for females. The lower blood uric acid levels in females compared to males may be related to the level of estrogen or oral contraceptives. Post-menopausal female uric acid levels are similar to those of males. Ninety-eight percent of uric acid in body fluids exists in the form of sodium salts, with a maximum solubility of 380μmol/L (6.4mg/dl) under physiological conditions of 37℃ and pH 7.4. Therefore, regardless of gender, when serum uric acid levels exceed 416/μmol/L (7mg/dl), it is considered hyperuricemia.

　　The pathogenesis of the disease

　　Since 95% of uric acid molecules exist in the dissociated form, i.e., urate ions, at a pH of 7.4, uric acid in plasma, glomerular filtrate, or renal interstitium is in the form of urate ions. In the low pH environment of the distal tubules, the vast majority of uric acid appears in a non-dissociated form. When urine concentration and pH decrease to a certain extent, amorphous uric acid crystals precipitate in the distal tubules or collecting duct lumens. Due to the countercurrent multiplication mechanism, there is a urate gradient between the renal cortex and medulla. In the medulla with sufficient uric acid concentration, uric acid forms monosalt-hydrate or urate crystals, which are acicular in shape, causing giant cell reactions characterized by痛风 stones. X-ray studies have confirmed the existence of two types of crystals in the kidneys:

　　1. Acicular uric acid monosalt-hydrate crystals appear in the renal medulla and can cause microscopic痛风 stone reactions.

　　2. Uric acid crystals, which are amorphous substances under the microscope, appear in the tubular lumen and can cause tubular obstruction and acute renal function impairment.

　　It has been observed that tubular cells interact with uric acid or uric acid crystals, part of which is the absorption of crystals in the tubular lumen. Some experimental research results show that these crystals can actually enter the renal interstitium. According to these research results, uric acid or uric acid crystals can form foci, leading to the formation of microscopic痛风 stones.

　　Animal experiments using uricase inhibitors, oxalate, and uric acid loading have confirmed that excessive renal excretion of uric acid observed in clinical practice can lead to renal crystal deposition and cause renal damage.

　　Kidney stones are a major complication. Renal failure can occur when hypertension, arteriosclerosis, diabetes, renal cysts, and amyloidosis coexist.

　　Kidney stones refer to stones occurring in the renal pelvis, calyces, and the junction of the renal pelvis and ureter. Most are located within the renal pelvis and calyces, while renal parenchymal stones are rare. X-ray films show solitary or multiple round, oval, or obtuse triangular dense shadows in the renal area, with high and uniform density and smooth edges, but some are not smooth and appear like mulberries.

　　In the absence of antihypertensive drugs, hypertension is classified into stages 1, 2, and 3 according to blood pressure levels, with systolic pressure ≥139mmHg and/or diastolic pressure ≥89mmHg.

　　Arteriosclerosis is a non-inflammatory disease of arteries, a general term for degenerative and proliferative changes in the arterial wall, which become thickened, hardened, lose elasticity, and become narrow. Common types include atherosclerosis, arteriosclerosis of the middle layer, and small artery arteriosclerosis.

　　Diabetes is a common disease caused by the interaction of genetic and environmental factors. Clinically, it is characterized by hyperglycemia, with common symptoms including polydipsia, polyuria, polyphagia, and weight loss. Diabetes can cause damage to multiple body systems. It leads to absolute or relative deficiency in insulin secretion and reduced sensitivity of target tissue cells to insulin, causing a series of metabolic disorders including protein, fat, water, and electrolytes, with hyperglycemia as the main sign.

　　5. Renal cysts, or kidney cystic diseases, as the name implies, are a general term for cystic lesions that appear in the kidneys and are not connected to the outside world. Common renal cysts include simple renal cysts, para-renal cysts, and polycystic kidney disease, etc. With the popularization of physical examinations and the wide application of B-ultrasound and CT, the detection rate of renal cyst diseases has significantly increased and has become a relatively common kidney disease in clinical practice.

　　The serious consequences of long-term hyperuricemia are mainly gouty arthritis and kidney damage, with kidney damage ranking second to joint disease. Joint symptoms are often obvious, while kidney lesions are hidden. Renal damage may appear after repeated gout for more than 10 years. Acute hyperuricemia nephropathy is mainly acute renal failure.

　　1. Chronic hyperuricemia nephropathy:Gouty arthritis presents with acute onset, worsening at night, often triggered by stress, fatigue, banquets, excessive alcohol consumption, and infection. Minor trauma such as surgery can also trigger it. The affected joints are mostly metatarsophalangeal joints, followed by ankle, hand, wrist, knee joints, etc., especially the first metatarsophalangeal joint is the most common. Joint pain is accompanied by paresthesia within a few hours, as well as significant redness, swelling, heat, and pain. Large joints such as the shoulder and hip are less involved, but when involved, there is often effusion. With the progression of the disease, uric acid deposition in the joint gradually increases, and frequent attacks lead to joint enlargement, fibrous tissue proliferation, and joint deformity, stiffness, and limited activity.

　　Long-term untreated gout patients may develop gouty nodules (or痛风 stones) at any stage of the disease course. This is due to the high blood uric acid, which is in a supersaturated state. In addition to the central nervous system due to the blood-brain spinal cord barrier, it is seen in any part of the body, and is more significant near the joints. Nodules can be found in the synovial membrane around the joint margin, tendons, cartilage, and subcutaneous tissue of the auricle. Bone erosion can occur around cartilage or nearby, resulting in boring-like bone defects. The bone defects around the joint surface can extend outward and upward to form volcanic-like defects. Gouty stones can also break the skin and excrete white uric acid crystals, which are double-refractive sodium urate needles under the microscope. The skin can form fistulas that are difficult to heal, and because uric acid has preservative properties, infections are rare.

　　Gouty hyperuricemia nephropathy urine changes are mainly mild proteinuria and small amounts of red blood cell urine. The early changes in renal function are a decrease in concentrating function, followed by a gradual impact on glomerular filtration function. When hypertension, arteriosclerosis, diabetes, renal cysts, and amyloidosis coexist, renal failure may occur, which is also the destination of gouty nephropathy. It is reported that 40% of gouty patients with hypertension in foreign countries, and 63.1% in China, because 25% to 35% of primary hypertension is accompanied by hyperuricemia. Therefore, hyperuricemia is a risk factor for cardiovascular diseases. The high blood pressure often accompanied by hyperuricemia, obesity, and other risk factors for arteriosclerosis are prone to coronary heart disease, and may also be related to the deposition of uric acid crystals in the arterial wall, which damages the arterial intima.

　　2. Acute hyperuricemic nephropathy:When myeloproliferative diseases such as leukemia and lymphoma and malignant tumors are widely disseminated, especially when radiotherapy and chemotherapy are received, hyperuricemia occurs when a large amount of uric acid is excreted into the kidneys. Uric acid crystals abruptly deposit in the renal tubules, collecting tubules, and renal pelvis, causing an increase in intratubular pressure and intraglomerular pressure, leading to a sharp decrease in glomerular filtration rate. The clinical features are initially increased uric acid excretion, polyuria in the urine, hematuria, and small amounts of proteinuria. As the disease progresses, oliguria and anuria may occur, accompanied by symptoms such as back pain, nausea, vomiting, and somnolence. Acute hyperuricemic nephropathy shows a significant increase in both blood and urine uric acid levels. Literature reports that blood uric acid >1189μmol/L (20mg/dl) accounts for 60%; while primary gout accounts for only 14%; and 20% of patients have a 24-hour urine uric acid excretion volume >19.48μmol/L, while primary gout accounts for only 6%.

　　3. Uric acid stones:10% to 25% of gout patients have kidney stones, which are usually more than 200 times higher than the normal population. About 20% of those excreting 1000mg of uric acid per day have stones, and nearly half have stones when excreting 1100mg. Uric acid stones are also related to hyperuricemia. If the blood uric acid level is 1.37μmol/L, 50% of patients have kidney stones. There are also some diseases that do not accompany hyperuricemia and excessive uric acid excretion, but due to less urine and high urine acidity, uric acid stones can still occur. For example, in patients with ileostomy diarrhea, prostatic diseases in elderly patients, and those with reduced fluid intake due to difficulty in urination, uric acid stones can also occur.

　　The symptoms of uric acid stones mainly include local irritation of the urinary tract, obstruction of urine flow, and secondary infection, which vary due to the size, shape, location, and presence of infection of the stones. Uric acid stones are often round or oval, smooth or slightly rough, and yellow-brown in color, with a firm texture. Renal colic suggesting obstruction may occur, and a few patients may have bilateral renal colic (i.e., renal-renal reflex). After exercise, hematuria, stone passage, and symptoms such as difficulty in urination, interruption of urine flow, and sudden urinary retention (calculous urinary retention) may occur. Small stones can be excreted in the urine, and more than 80% of痛风 patients' stones are not uric acid. Pure uric acid stones are translucent and usually cannot be imaged. However, stones with a diameter of more than 2cm may be mixed stones of calcium oxalate and calcium phosphate, which can generally be imaged. Large upper urinary tract stones can deform the renal pelvis and calyces.

　　The measures to prevent gouty nephropathy are multifaceted. It is important to first clarify and as far as possible eliminate the factors causing hyperuricemia in patients. After the dietary and lifestyle factors, which are among the causes of the disease, are reasonably changed, the serum uric acid concentration can subsequently decrease, but many patients still need medication to control hyperuricemia.

　　To prevent gout nephropathy, it is almost necessary to use drugs to reduce serum uric acid concentration for a lifetime. Reducing the serum uric acid concentration to below 6.0 mg/dl (360 μmmol/L) can prevent gout attacks, and the concentration reduced to below 5.0 mg/dl (300 μmmol/L) can cause the absorption of gout stones.

　　In addition, attention should be paid to the prevention and treatment of adverse reactions during the process, such as the maximum risk of promoting uric acid excretion drug treatment is the formation of uric acid crystals in urine and the deposition of uric acid in the renal tubules, renal pelvis, and urinary tract, leading to renal colic or renal function impairment. Therefore, attention should be paid. It should start with a low dose and gradually increase the dose, and apply sodium bicarbonate to alkalinize the urine to maintain a larger urine volume to reduce the aforementioned risk. Before chemotherapy or radiotherapy in patients with malignant tumors, allopurinol should be used to prevent hyperuricemia to prevent the occurrence of uric acid nephropathy.

　　One, urine examination:When there are明显 renal tubular function disorder manifestations, polyuria, nocturia, low specific gravity urine, or decreased urine osmolality can be seen, with small amounts of proteinuria, generally 19.48 μmol/L, and polymorphic crystals in the urine, which are uric acid stones. The urine changes in gout nephropathy are mainly mild proteinuria and small amounts of red blood cell urine. The component analysis of the stones excreted can determine whether they are uric acid, but the technical requirements are high, and attention should be paid to the determination of blood and urine uric acid.

　　Two, blood examination:Serum uric acid levels are significantly elevated, with literature reports indicating that 60% of patients have serum uric acid levels greater than 1189 μmol/L (20 mg/dl) or serum uric acid reaching 1.37 μmol/L. Early renal function changes are a decrease in concentrating function, followed by a gradual impact on glomerular filtration function, with blood urea nitrogen and creatinine levels increasing, but serum uric acid levels rising more significantly than blood urea nitrogen and creatinine, with serum uric acid/blood creatinine > 2.5 (in mg/dl units).

　　Three, renal biopsy:During acute uric acid nephropathy, uric acid crystals abruptly precipitate in the renal tubules, collecting ducts, renal pelvis, and lower urinary tract, with the most deposition occurring at the renal papilla, causing intrarenal and extrarenal obstruction. In chronic uric acid nephropathy, uric acid crystals and uric acid crystals are deposited separately in the renal interstitium and renal tubules, with more deposition in the medulla, and the renal papillary deposition is more than 8 times higher than the cortex. Under light microscopy, two types of uric acid crystals can be seen:

　　Uric acid crystals are amorphous substances that appear in the interstitium and tubular lumen.

　　Needle-shaped uric acid monosalt-water compound crystals appear in the renal medulla.

　　Microscopic gout stones formed by uric acid or urate crystals as the core lesion, surrounded by lymphocytes, monocytes, and plasma cells, with tubular atrophy and变性, tubular basement membrane destruction, accompanied by interstitial scar, glomerular basement membrane thickening and fibrosis, medium and small artery sclerosis, kidney shrinkage, scarring. Gout stones can ulcerate the skin and excrete white uric acid crystals, which are needle-like sodium urate crystals under the microscope. The diagnosis of uric acid nephropathy can be confirmed by observing double refraction uric acid crystals in renal biopsy tissue under a polarized microscope.

　　Fourth, renal imaging examination:If urinary tract obstruction causes renal pelvis hydrops and ureteral dilatation, and reflux nephritis or obstructive nephritis complicated with infection, renal scans, CT scans, and radionuclide renal scans may show unequal sizes of bilateral kidneys, irregular kidney shape, dilated or blunted renal calyces.

　　X-ray shows subperiosteal cystic changes without bone infiltration, and unilateral tarsal joint lesions are visible.

　　Fifth, B-ultrasound:It shows that the bilateral kidney lesions are not equal and is helpful for the localization diagnosis of stones.

　　First, dietary recipes for gouty hyperuricemia nephritis

　　1. Radish juice:Take 500 grams of radish, wash it clean, and squeeze the juice with an appropriate amount of water.

　　Radish is slightly warm in nature and can prevent gout. Tang Dynasty Meng Xian said: Radish 'is very good for joints'. 'Herbology of Food Properties' says, radish 'promotes the flow of Qi, removes evil heat, promotes urination, and relieves constipation'. In addition, radish can prevent cancer and tumor, lower blood pressure, aid digestion, relieve cough and phlegm, and relieve asthma.

　　2. Green celery juice:Take 500 grams of fresh celery, wash it clean, and squeeze the juice with an appropriate amount of water.

　　Celery is sweet and pungent in taste, cool in nature, and has the effects of clearing heat and relieving irritability, calming the liver, and promoting diuresis and reducing edema. 'New Studies on the Composition of Herbs' says: Celery can 'treat liver yang headache, red face and eyes, dizziness, unsteady gait, and other symptoms'. Modern pharmacological studies have shown that celery can diuretic, lower blood pressure, lower blood lipids, prevent atherosclerosis, and prevent cancer and tumor.

　　3. Golden papaya juice:Take 500 grams of peeled fresh papaya and squeeze the juice with an appropriate amount of water.

　　Papaya is warm in nature, sour in taste, and has the functions of removing dampness, relieving stiffness, relaxing tendons, and promoting digestion. 'Compendium of Materia Medica' says: 'It relieves heartache, and the decoction is used to wash wind arthritis'. Modern pharmacological studies have shown that it has the effects of calcium supplementation, blood pressure reduction, anti-tumor, and antibacterial action.

　　4. White lotus root juice:Take 300 grams of fresh white lotus root, boil for 10 minutes and remove it, then add an appropriate amount of water to squeeze the juice.

　　White lotus root is warm in nature, sweet in taste, and has the effects of benefiting the stomach and spleen, invigorating qi and nourishing blood, clearing heat and promoting diuresis. Because it is rich in amino acids and a variety of trace elements, it has a certain auxiliary therapeutic effect on the treatment of gouty hyperuricemia patients.

　　Second, what is good for gouty hyperuricemia nephritis

　　1. Grains:Rice, wheat, millet, buckwheat, corn flour, refined flour, strong flour, pasta, noodles, bread, steamed buns, soda crackers, butter cookies

　　2. Vegetables:Cabbage, cauliflower, carrots, celery, cucumbers, eggplants, kale, salsify, collard greens, lettuce, green beans, pumpkins, gourds, zucchinis, tomatoes, sweet potatoes, potatoes, pickled vegetables, salted vegetables

　　3. Fruits:Various fruits. Eggs and dairy products: fresh milk, condensed milk, cheese, yogurt, malted milk drinks: soda, tea, coffee, cocoa, chocolate

　　4. Others:All kinds of oils, peanut butter, gelatin desserts, jam, dried fruits, etc.

　　Third, what foods should not be eaten for hyperuricemia nephropathy

　　1. Animal offal:Such as pancreas, liver, kidney, bone marrow, large intestine (high in purines).

　　2. Vegetables high in oxalate:Spinach, celery, radishes, and other vegetables can easily lead to a doubling of hyperoxaluria, causing a sharp increase in uric acid levels and increasing the burden on the kidneys.

　　3. Seafood, shellfish, and other aquatic products:Because these foods are rich in polysaccharides, high protein, and so on, which will increase the burden on kidney decomposition, leading to increased uric acid levels, so they should not be eaten in large quantities.

　　4. Avoid spicy foods.

　　First, treatment

　　1. General treatment:Regulating diet, limiting high-purine diet, controlling calorie intake, and avoiding obesity are important links in preventing hyperuricemia and gout. For those with hyperuricemia, maintaining sufficient urine volume and alkalinizing the urine is conducive to the excretion of uric acid.

　　2. Uric acid excretion drugs for drug treatment:Indications for lowering serum urate concentration include the inability to remove the cause of hyperuricemia; failure to correct hyperuricemia to below 7.0mg/dl (420μmmol/L) after removal; patients with 2 to 3 gout attacks or gout stones with good renal function can take etacrynic acid (lithium urate) drugs such as probenecid (carboxybenzenesulfonamide) and benzbromarone (gout relief, benzbromarone) for a long time. Increase the dose gradually starting from a low dose. And pay attention to maintain a large urine volume and apply sodium bicarbonate (1g, 3 to 4 times/d) to alkalinize the urine, which can reduce the aforementioned risks, especially in the first 3 weeks of treatment. The commonly used uricosuric agents are sulfinpyrazone, with an initial dose of 50 to 100mg, twice a day, gradually increased to 200 to 400mg, twice a day. As renal function deteriorates, the efficacy of uricosuric agents decreases, and the efficacy is very low when the creatinine clearance rate is below 50 to 60ml/min.

　　3. Inhibitors of uric acid production:Primarily allopurinol, which inhibits xanthine oxidase, thereby reducing the synthesis of xanthine and uric acid. Since allopurinol has the effect of preventing uric acid and calcium oxalate kidney stones, patients with established gout diagnosis, especially those with uric acid stones, should use this drug for treatment. This preventive measure is particularly effective in patients with renal disease, who have a poor response to drugs that promote uric acid excretion. Secondary gout and myeloproliferative diseases are also indications for allopurinol treatment. The dose of uric acid synthesis inhibitors (xanthine oxidase inhibitors) should be reduced as GFR decreases. The effective dose range of allopurinol for different individuals is from 100mg/d to 300mg/d, with a suitable dose of 100mg for individuals with a GFR of 30ml/min, 200mg for individuals with a GFR of 60ml/min, and 300mg for individuals with normal GFR. Since the inactivation of azathioprine and mercaptopurine relies on xanthine oxidase, the inhibition of this oxidase by allopurinol can increase the toxicity of the aforementioned two drugs.

　　4. Colchicine can be used for acute attacks of gouty arthritis.Colchicine is the most effective for controlling arthritis pain, with a dose of 1mg, twice a day. When the total dose reaches 4-8mg, reduce to 0.5mg per day.

　　5. Radiotherapy and chemotherapy for malignant tumors and leukemia:Prophylaxis with full hydration, alkalinization of urine, or allopurinol should be considered. The use of allopurinol before chemotherapy or radiotherapy in patients with malignant tumors can prevent hyperuricemia and the occurrence of uric acid nephropathy.

　　II. Prognosis

　　The view that gout patients need to take medication to reduce hyperuricemia for a long time recently has been questioned, but in clinical practice, there are often acute attacks of gout within 6 months after intermittent treatment with the above drugs, and gout stones appear within 3 years. Therefore, most people still believe that drugs to reduce hyperuricemia should be taken for life. In some patients, even with the correct use of reasonable medication, hyperuricemia still persists, which is partly due to the continued existence of other factors that promote hyperuricemia, especially alcohol intake, diuretic therapy, and obesity. The dependence on diuretics can often be corrected by angiotensin-converting enzyme inhibitors.

　　The most difficult clinical problem is that gout patients with kidney disease are allergic to allopurinol, and this allergy cannot be corrected. In this case, the severity of kidney disease is often mild to moderate, and is often related to the occurrence of allopurinol allergy. For such cases, treatment with high-dose potent uricosuric drugs, such as sulfinpyrazone, should be used. If the serum uric acid concentration cannot be reduced, the focus of treatment should be shifted to symptomatic treatment. This disease generally has a good prognosis with lifelong medication to reduce hyperuricemia and symptomatic treatment.