Hyperuricemic nephropathy
Introduction
Introduction to hyperuricemia nephropathy With the improvement of people's living standards and life expectancy, the population is aging, the incidence of hyperuricemia and gout is increasing rapidly. Clinically, hyperuricemia is often accompanied by hyperuricemia, regardless of hyperuricemia or high. Uricoururia can cause uric acid (salt) to cause renal damage in renal tissue deposition called uric acid nephropathy. Uric acid and urate can cause gout, acute uric acid nephropathy (acuteuric acid nephropathy), uric acid kidney stones, chronic gout nephropathy (chronic goutynephropathy), and asymptomatic hyperuricemia. basic knowledge The proportion of sickness: 0.007% Susceptible people: no specific population Mode of infection: non-infectious Complications: Kidney stones Hypertension Arteriosclerosis Diabetes Renal failure Renal cysts
Cause
Cause of hyperuricemia nephropathy
(1) Causes of the disease
The cause of uric acid nephropathy and gout nephropathy is an increase in blood and/or urinary uric acid concentration, and many factors that increase persistent uric acid concentration are:
1. Increased uric acid production
(1) Genetic factors: enzyme gene mutations, such as hypoxanthine-guanine phosphoribosyltransferase deficiency.
(2) Acquired factors: abnormal myeloid hyperplasia, sorghum intake, obesity and hypertriglyceridemia, high dietary fructose content, high alcohol content in beverages, exercise.
2. Reduced uric acid excretion
(1) Genetic factors: uric acid excretion or excretion score reduction.
(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. Endogenous uric acid production excessive uric acid is the final product of sputum metabolism. Uric acid is antimony trioxide, a nucleic acid and other terpenoids mainly decomposed by cellular metabolism. The decomposition of sputum in food produces uric acid, endogenous uric acid. The cause of excessive production is hypoxanthine, the activity of guanine ribose converting enzyme (HGPRT) is decreased, the phosphoribosyl pyrophosphate amide transferase (PRPP) and hypoxanthine, and the activity of xanthine (XO) is the most important. HGPRT lacks jaundice, guanine can not produce corresponding nucleotides, and the body's hypoxanthine is converted into uric acid. The increase of PRPP synthase activity can increase intracellular PRPP, which is a key enzyme for the conversion of sputum into uric acid. Increased uric acid production, XO converts hypoxanthine into jaundice and jaundice to produce uric acid.
4. Uric acid excretion disorder Uric acid has no physiological function in the body. Under physiological conditions, uric acid 2/3~3/4 is excreted by the kidney, and the rest is excreted by the intestine. The intestinal mucosal cells are secreted into the intestine, and the intestinal bacteria contain uricase. It is decomposed into water and ammonia, so it is not uric acid discharged from the feces. When the kidney is insufficiency, it is slightly increased from the intestine. The uric acid filtered from the glomerulus is almost completely reabsorbed by the proximal tubule, urine. The uric acid in the liquid is secreted by the renal tubules. It has been confirmed that the renal tubules secrete uric acid, and the renal tubules can be reabsorbed again. Renal excretion is an important part of regulating blood uric acid concentration. The factors affecting renal excretion of uric acid are as follows:
(1) In the early stage of chronic renal insufficiency, there is a compensation for a healthy nephron. The increase in uric acid concentration is not significant, and is inconsistent with the decrease in glomerular filtration rate. When GFR<10ml/min produces significant hyperuricemia, the primary Hypertensive patients, hyperuricemia caused by impaired treatment of sodium by proximal convoluted tubules or renal tubular uric acid excretion caused by early renal vascular disease.
(2) When the blood volume is reduced, such as limiting sodium intake, diuretic use and polyuria, the uric acid clearance rate is reduced. When the blood volume is reduced, the urine flow rate is less than 1 ml/min, so that uric acid accumulates in the proximal renal tubule S3 segment. More than the concentration in the capillaries around the renal tubules, back-diffusion can occur. On the contrary, sodium salt load, antidiuretic hormone secretion increases blood volume, and uric acid clearance increases.
(3) Organic acids affect the excretion of uric acid by renal tubules: organic acids are excreted from the body by means of a renal tubular anion pump, which competes with uric acid at this time; or because of the accumulation of organic acids in the proximal tubules, the metabolic disorder limits uric acid The secretion, increased organic acid is seen in alcoholic poisoning, severe exercise lactic acid accumulation and diabetic ketoacidosis and other serious metabolic disorders.
(4) Diuretics, anti-tuberculosis drugs, aspirin, catecholamines, etc. can affect the excretion of uric acid: diuretic drugs reduce renal tubular secretion of uric acid or increase its reabsorption, it is still unclear, anti-tuberculosis drugs such as ethambutol and pyridin The azine amide can inhibit the secretion of uric acid from the renal tubules. The small dose of aspirin inhibits the secretion of uric acid from the renal tubules. When the dose is increased to 2~3g, it can inhibit the reabsorption of uric acid by the renal tubules, and the effect of clearing uric acid. The catecholamine affects the renal blood flow and reduces The role of uric acid.
(5) Lead can inhibit the secretion of uric acid by renal tubules: chronic lead poisoning, uric acid clearance rate decreased compared with creatinine clearance rate is obvious.
The body's uric acid maintains a dynamic balance. The total uric acid pool stores 1200mg of uric acid, 600-900mg per day for exchange, 750mg per day, 100-365mg from the intestinal tract, 500-1000mg of urine, and daily intake of strontium or nucleus. Glycosylate foods, blood uric acid is maintained at a normal level through the excretion of uric acid. For example, if the normal diet is changed to a flawless diet, blood uric acid only drops by 59.5 mol/L (1 mg/dl), so the diet is not the main cause of hyperuricemia. The reason is that the current uric acid enzyme method is used to check the normal value of male 150 ~ 380 / mol / L (2.4 ~ 6.4mg / dl), female 100 ~ 300 / mol / L (1.6 ~ 4.8mg / dl), female blood uric acid level The reason for low men may be related to women's estrogen levels or oral contraceptives. Postmenopausal women's blood uric acid levels are similar to men's. 98% of uric acid in body fluids is in the form of sodium salt. At 37 ° C, pH 7.4 under physiological conditions, uric acid The maximum solubility is 380 mol/L (6.4 mg/dl), so serum uric acid value >416/mol/L (7 mg/dl) is called hyperuricemia regardless of male or female.
(two) pathogenesis
Because uric acid is present in a pH 7.4 environment, 95% of the uric acid molecules are in the form of dissociation, ie, urate ions, so the uric acid in plasma, glomerular filtration or renal interstitial is urate ion, at the distal end. In the low pH environment of the small tube, most of the uric acid appears in a non-dissociated form. When the urine concentration and pH decrease to a certain extent, amorphous uric acid crystal deposition occurs in the distal tubule or collecting duct lumen due to the countercurrent multiplication mechanism. There is a urate gradient between the renal cortex and the medulla. In the medulla with sufficient urate concentration, uric acid forms a single salt-water compound or urate crystal, which is needle-shaped, which is characterized by tophi. The giant cell response, X-ray studies have confirmed two crystals in the kidney:
1. Needle-shaped uric acid mono-salt-water compound crystallized, which appears in the renal medulla and can cause microscopic tophiite reaction.
2. Uric acid crystals, which are amorphous substances under the microscope, appear in the tubule lumen, can cause tubule obstruction and acute renal dysfunction.
It has been observed that tubule cells interact with urate or uric acid crystals, part of which is to absorb intraluminal crystals. Some experimental studies have shown that these crystals can actually enter the renal interstitial through epithelial cells. According to these findings, urine Acid or uric acid crystals can form a lesion core, resulting in the formation of microscopic tophi.
At the same time, the use of uricase inhibitors, animal experiments of oxalic acid and uric acid load, confirmed that the clinical observation of excessive renal uric acid excretion can lead to renal damage caused by intrarenal crystal deposition.
Prevention
Hyperuricemia nephropathy prevention
The measures to prevent gout nephropathy are multi-faceted. It is important to first clear and remove as much as possible the factors that cause hyperuricemia in patients. When the dietary and lifestyle factors as one of the causes are reasonably changed, the serum urate concentration can be Subsequent decline, but many patients still need medication to control hyperuricemia.
To prevent gout nephropathy, it is necessary to use a drug that lowers serum urate concentration for almost a lifetime, and the serum urate concentration is lowered to 6.0 mg/dl (360 mmol/L) or less to prevent gout attacks and the concentration is reduced to 5.0 mg/dl (300 mmol/ L) The following can make the tophi.
In addition, attention should be paid to side effects during preventive treatment. For example, the greatest risk of uric acid excretion treatment is the formation of uric acid crystals in the urine and the deposition of uric acid in the renal tubules, renal pelvis and urinary tract, leading to renal colic or renal dysfunction. Attention should be paid to gradually increase the dose from a small dose, and use sodium bicarbonate to alkalinize the urine to maintain more urine to reduce the aforementioned risks. Patients with malignant tumors should be treated with allopurinol to prevent hyperuricemia before receiving chemotherapy or radiotherapy. To prevent the occurrence of uric acid nephropathy.
Complication
Hyperuricemia nephropathy complications Complications Kidney stones Hypertension Arteriosclerosis Diabetic Renal failure Renal cysts
Mainly complicated with kidney stones, when there are hypertension, arteriosclerosis, diabetes, renal cysts and amyloidosis, etc., renal failure can occur.
Symptom
Hyperuricemia nephropathy symptoms common symptoms polyuria proteinuria nausea joint fluid white blood cells... joint deformity renal failure joint pain less urinary blood joint swelling and pain
The serious consequences of long-term hyperuricemia are mainly gouty arthritis and kidney damage. Kidney damage is second only to joint disease. Joints often have obvious symptoms, while kidney lesions are hidden. Gout has kidney damage for 10 years. Performance, acute hyperuricemia nephropathy is mainly acute renal failure.
1. Chronic hyperuricemia nephropathy: gouty arthritis is an acute attack, which is aggravated late at night, often caused by mental stress, fatigue, banquet, alcoholism and infection. Mild trauma can also be induced by surgery. The affected joints are metatarsophalangeal joints. More, followed by pickpockets, wrists, knee joints, etc., especially the first metatarsophalangeal joint is the most common, joint pain began to appear after a few hours of hypersensitivity and significant red, swollen, hot, pain, shoulder, hip and other large joints Less involved, but once the involvement often has exudate, as the lesion progresses, the deposition of urate in the joint gradually increases, joint hypertrophy after frequent attacks, fibrous tissue hyperplasia, joint deformity, stiffness and limited activity.
Gout patients with long-term failure to treat gout nodules (or tophi) at various stages of the disease are caused by hyperuricemia and uric acid being supersaturated, except for the central nervous system due to the blood-brain barrier. The site is more prominent near the joint, and nodules can be found in the subcutaneous tissue of the synovial membrane, tendon sheath, cartilage and auricle, and the bone is eroded in or near the cartilage, which can produce a bone defect in the joint surface. The cortical defect extends outward and upward to form a crater-like defect. The tophi can also break the skin and discharge white urate crystals. Under the microscope, it is a double-folded sodium urate needle. The skin can form a mouthwash and is not easy to heal. Corrosion resistance is less likely to occur.
Hyperuricemia nephropathy urinary changes are mainly mild proteinuria and a small amount of erythrocyte urine. Early renal function changes are the decline of concentrating function, and then gradually affect glomerular filtration function, when there is hypertension, arteriosclerosis, diabetes, When renal cysts and amyloidosis occur simultaneously, renal failure can occur, which is also the fate of gout nephropathy. Foreign reports of gout with hypertension are 40%, and domestic is 63.1%, because 25% to 35% are high. High blood pressure is associated with hyperuricemia, so hyperuricemia is a risk factor for cardiovascular disease. Hyperuricemia is often associated with hypertension, obesity and other risk factors for arteriosclerosis are prone to coronary heart disease, and may also be associated with urate crystals. Deposition on the arterial wall is associated with damage to the intima of the artery.
2. Acute hyperuricemia nephropathy: leukemia, lymphoma and other myeloproliferative diseases and malignant tumors spread widely, especially when receiving radiotherapy and chemotherapy, hyperuricemia when a large amount of uric acid is excreted into the kidney, uric acid crystallizes in the renal tubule The collecting tube and renal pelvis are rapidly deposited, causing an increase in renal tubular pressure and an increase in intraglomerular sac pressure, resulting in a sharp decrease in glomerular filtration rate. The clinical features are an increase in initial uric acid output and polymorphous crystallization in urine. Hematuria and a small amount of proteinuria occur, oliguria and anuria occur when the lesion progresses, may be accompanied by low back pain, nausea, vomiting and lethargy and other urinary symptoms, acute hyperuricemia nephropathy, blood uric acid and uric acid are significantly increased, the literature reports blood Uric acid>1189mol/L (20mg/dl) accounted for 60%; primary gout was only 14%; 20% of patients had 24-hour uric acid output >19.48mol/L, while primary gout only accounted for 6%.
3. Uric acid calculus: 10% to 25% of patients with gout have kidney stones, usually 200 times higher than the normal population. About 20% of uric acid excreted 1000mg per day has stone disease. If 1100mg is discharged, nearly half of the stones have uric acid. Salt stones are also associated with hyperuricemia, blood uric acid 1.37mol / L, 50% have kidney stones, there are some diseases without hyperuricemia and excessive uric acid excretion, but due to less urine, urine High acidity can still occur uric acid stones, such as ileal diarrhea, elderly patients with prostate disease, drinking water is reduced due to dysuria, low urine output, low pH, uric acid stones can also occur.
Symptoms of urate stones mainly include local irritations of the urinary tract, urinary obstruction and secondary infection. These symptoms vary depending on the size, shape, location and presence or absence of stones. The urate stones are mostly round or oval. The surface is smooth or slightly rough, yellowish brown, firm texture, renal colic impediment obstruction, a small number of patients have bilateral renal colic (ie kidney-kidney reflex), hematuria after exercise, row of stones, showing dysuria, Urinary flow interruption and sudden urinary closure (calculus urinary closure), small stones can be discharged from the urine, about 80% of gout patients' stones are not urate, pure uric acid stones are light-transmitting, usually can not be developed, but the diameter More than 2cm of stones may be mixed stones such as calcium oxalate and calcium phosphate. Generally, it can be developed. The upper urinary tract can make the renal pelvis and kidney pelvis deform.
Hyperuricemia and gout in China are common diseases, and have been missed and misdiagnosed, but various joint pains such as rheumatoid arthritis, rheumatoid arthritis, tuberculous arthritis, joint erysipelas, etc. are misdiagnosed as gout It also happens from time to time.
Hyperuricemia
Hyperuricemia is an important biochemical indicator of gout. Long-term hyperuricemia can cause gout, but a few people can have hyperuricemia for many years without the clinical symptoms of gout. After the determination of hyperuricemia, it is judged to be uric acid. Its important to generate too much, mainly by the following:
(1) Urine uric acid excretion >800mg / d (food) or >600mg / d (low diet).
(2) uric acid clearance rate (Cua) > 12 ml / min.
(3) If the ratio of uric acid clearance rate (Cua) to creatinine (Ccr) is >10 genus, the 5% is a decrease in excretion, 5% to 10% is a mixed type, and the random urine and 24h Cua/Ccr are Significantly related, so a simple one-time urine calculation can be used in the clinic.
2. The diagnostic criteria for gout are as follows:
(1) There is uric acid crystals in leukocytes in joint fluid.
(2) Gout nodule needle aspiration or biopsy has sodium urate crystal.
(3) Those with more than 6 of the following 12 items can also be diagnosed (98% accuracy): more than one episode of acute arthritis; single arthritis episode; inflammation peaks within 1 day; joint congestion, swelling; First metatarsophalangeal joint pain or swelling; unilateral first metatarsophalangeal joint swelling and pain; unilateral tibial joint disease; suspicious tophi; elevated serum uric acid; asymmetric single joint pain; X-ray showed subcortical capsule Sexual changes without bone infiltration; joint fluid culture was negative during joint inflammation.
(4) typical single arthritis, followed by an asymptomatic intermittent period; after colchicine treatment, synovitis can be quickly relieved; hyperuricemia exists at the same time, where any of the above four , you can confirm the diagnosis.
3. Diagnosis of uric acid nephropathy
Clinically identified as gout, should pay attention to urine and renal function tests to establish the diagnosis of gout nephropathy, gout such as kidney disease symptoms, more easily missed diagnosis and misdiagnosis, but one of the following conditions in clinical Consider the primary gout kidney.
(1) A family history of gout or joint pain in men over middle age.
(2) Acute asymmetrical arthritis.
(3) sudden arthritis in the middle of the night, and severe pain.
(4) Nocturia, mild abnormalities in polyuria and urine, or renal tubular insufficiency and slowly developing renal dysfunction.
(5) Dehydration and use of diuretics, or joint pain after transfusion.
(6) Obesity, hypertension and diabetes are associated with progressive renal failure.
(7) joint pain accompanied by urinary calculi, especially X-ray negative multiple stones, clinical hyperuricemia, accompanied by changes in urine and renal dysfunction, to consider the diagnosis of uric acid nephropathy.
Examine
Examination of hyperuricemia nephropathy
1. Urine examination: When there is obvious renal tubular dysfunction, polyuria, nocturia, low specific gravity urine or urine osmotic pressure is reduced, a small amount of proteinuria, generally <1.5 ~ 2.0g / 24h, is a small molecular proteinuria Urinary 2-m excretion increased, urinary eosinophils increased, urine culture was positive, hematuria was observed, uric acid increased significantly, 20% of patients with 24h uric acid output >19.48mol/L, polymorphous crystals in urine That is, urate stones, gout kidney disease changes mainly in mild proteinuria and a small amount of red cell urine, analysis of the components of the discharge stones, can determine whether it is urate, but the technical requirements are high, should pay attention to blood and uric acid determination.
2. Blood test: blood uric acid increased significantly. The literature reported that 60% of patients with serum uric acid>1189mol/L (20mg/dl) or blood uric acid reached 1.37mol/L. Early renal function changes are the decline of concentration function, and then gradually affect Glomerular filtration function blood urea nitrogen, creatinine increased, but serum uric acid increased significantly compared with urea nitrogen and creatinine, blood uric acid / serum creatinine > 2.5 (in mg / dl).
3. Renal biopsy: In acute uric acid nephropathy, uric acid crystals are deposited in the renal tubules, collecting ducts, renal pelvis and lower urinary tract, with the most deposition of the kidney papilla, producing intrarenal, external obstruction, chronic uric acid nephropathy, urate Crystallization and uric acid crystals were deposited in the renal interstitial and renal tubules, respectively. The medulla was deposited more than 8 times higher than the cortex. Two urate crystals were observed under light microscopy:
(1) The uric acid crystals are amorphous and appear in the interstitial and tubule lumens.
(2) The needle-shaped uric acid mono-salt-water compound crystallizes and appears in the renal medulla.
Microscopic tophi with urate or uric acid crystals as the nucleus of the lesion, surrounded by lymphocytes, monocytes and plasma cells. As the disease progresses, the tubules are atrophied and degenerated, and the basement membrane is destroyed, accompanied by interstitial scars. Small ball basement membrane thickening and fibrosis, middle and small arteriosclerosis, kidney shrinkage, scarring, tophi can break the skin to discharge white urate crystals, under the microscope is a double-fold sodium urate needle, kidney biopsy Diagnosis of uric acid nephropathy can be established by seeing double-fold uric acid crystals under a polarizing microscope.
4. Renal imaging examination: if urinary tract obstruction causes hydronephrosis and ureteral dilatation, reflux nephropathy or obstructive nephropathy with infection, kidney map, CT scan, radionuclide kidney scan can appear in both kidneys The kidneys are irregular in shape and the renal pelvis is dilated or dull.
X-ray showed subcortical cystic changes without bone infiltration, showing unilateral tibial joint lesions.
5. B-mode ultrasound: showing bilateral kidney lesions are not equal, and contribute to the localization diagnosis of stones.
Diagnosis
Diagnosis and diagnosis of hyperuricemia nephropathy
Uric acid nephropathy should be differentiated from the following diseases.
1. Primary glomerulopathy: The following points are helpful for differential diagnosis:
(1) Serum uric acid rise in uric acid nephropathy is significantly higher than urea nitrogen and creatinine, and blood uric acid/creatinine is >2.5 (in mg/dl).
(2) gout nephropathy arthritis is obvious, frequent attacks, even if there is hyperuricemia in primary glomerulopathy, arthritis rarely occurs, which may be due to its small response to uric acid.
(3) The history of uric acid nephropathy is long, usually only the renal tubular function is impaired; while the glomerular function is less damaged, and the renal function is slow.
(4) Gout stone only appears in primary gout.
(5) Renal biopsy tissue can be seen under polarized light microscopy uric acid crystal can establish the diagnosis of uric acid nephropathy, but due to urate deposition in the deep renal tissue, the puncture kidney tissue is often not deep enough to easily obtain the diseased tissue.
2. Chronic renal insufficiency: Even if there is hyperuricemia in this disease, the possibility of uric acid crystal deposition is very small, so there is no cortical-medullary gradient, and the sodium concentration in the medulla is decreased.
3. Other diseases that cause renal failure and hyperuricemia: the following lesions such as acute renal failure caused by striated muscle lysis, acute pancreatitis, severe dehydration leading to pre-renal azotemia, lead poisoning, polycystic kidney disease, Analgesic nephropathy, obstructive nephropathy caused by bilateral hydronephrosis, familial nephropathy and medullary cyst disease, etc., can cause renal failure and uric acid increased significantly, these lesions are renal damage caused by tubulointerstitial, Should pay attention to the identification of uric acid nephropathy.
The method is to determine the ratio of uric acid/creatinine in urine (in mg/dl), which can distinguish acute hyperuricemia and acute renal failure caused by other causes. The adult ratio of acute renal failure is about 0.5, and the highest is 0.9; However, the ratio of children under 10 years old can be >1, and the ratio of acute hyperuricemia to kidney disease is >1. In the assessment results, age factors should be considered. Uric acid stones account for 5% to 10% of urinary calculi. Hyperuricemia is found. And the important clues of gout, patients with urinary calculi should be alert to the possibility of uric acid stones, B-ultrasound and CT examination can help to locate the diagnosis of stones, the composition analysis of the discharged stones can determine whether it is urate, but the technical requirements are high Should pay attention to blood and urine uric acid determination, in short, chronic uric acid nephropathy must establish the diagnosis of hyperuricemia and gout, for patients with arthritis, tortoise diagnosis is easier, leukemia, lymphoma and other patients with radiotherapy, chemotherapy should be alert to acute Hyperuricemia nephropathy, for urinary calculi, should pay attention to the etiology of the stone, pay attention to the possibility of stones.
