hyperuricemia



Overview of the disease

Definition.

Hyperuricemia is a common biochemical abnormality caused by excess urate production and/or decreased renal excretion of uric acid, or both.

Hyperuricemia is currently defined as a non-same-day, twice fasting blood uric acid >420 µmol/L (micromoles per liter) in adults (men) and >360 µmol/L (women).

Types

Clinically, there are two main categories: primary and secondary.

Primary hyperuricemia

Primary hyperuricemia is caused by inborn purine metabolism abnormality, often associated with obesity, glucose and lipid metabolism disorders, hypertension, atherosclerosis and coronary heart disease.

Secondary hyperuricemia

Caused by excessive production of urate or decreased renal clearance caused by other diseases, drugs, dietary products or toxins.

Incidence

The incidence of hyperuricemia varies greatly depending on geography, ethnicity and dietary habits.

Studies in the past 10 years have shown that the prevalence of hyperuricemia in different regions of China varies widely, ranging from 5.46% to 19.30%, with 9.2% to 26.2% in men and 0.7% to 10.5% in women.

The prevalence increases significantly in men after the age of 30 years, and in women after the age of 50 years, because estrogen inhibits the reabsorption of urate in the proximal renal tubules.

The manifestations of hyperuricemia associated with urate crystal deposition occur on average about 20 years after the elevation of blood uric acid.

People at risk include those with obesity, disorders of glucose and lipid metabolism, hypertension, insulin resistance syndrome, chronic kidney disease, atherosclerosis and coronary heart disease.

Causes

Causes

Primary hyperuricemia

Idiopathic hyperuricemia

The pathogenesis is unknown and may be genetically related.

A few are caused by congenital enzyme defects, familial juvenile hyperuricemic nephropathy, hypoxanthine-guanine phosphoribosyltransferase defects, increased activity of ribulose phosphate pyrophosphate synthetase, type I glycogen accumulation disorder, and hereditary fructose intolerance.

Excessive production of uric acid

Associated with high purine diet (high intake of meat and seafood), excessive alcohol intake, high sugar diet, and enhanced nucleic acid metabolism.

Often combined with clinical manifestations or diseases related to metabolic syndrome, such as obesity, disorders of glucose and lipid metabolism, hypertension, atherosclerosis and coronary heart disease.

Secondary hyperuricemia

Blood system diseases

Such as acute and chronic leukemia, erythrocytosis, multiple myeloma, hemolytic anemia, lymphoma and many solid tumors chemotherapy, due to the large amount of intracellular nucleic acid decomposition and lead to excessive production of uric acid.

Various kidney diseases

Increase in blood uric acid due to decreased excretion of uric acid caused by renal insufficiency and renal tubular diseases.

Taking certain drugs

Commonly diuretics (e.g. hydrochlorothiazide, furosemide, etc.), compounded antihypertensive tablets, beta-blockers, angiotensin-converting enzyme inhibitors, non-closartan angiotensin II receptor blockers, anti-tuberculosis drugs such as pyrazinamide, anti-Parkinson’s disease medications, low-dose aspirin, vitamin B12, tobacco acid, cytotoxic chemotherapeutic drugs, immunosuppressants (tacrolimus, cyclosporine A, azathioprine), and so on.

Others

Excessive production of organic acids that inhibit uric acid excretion, e.g., lactic acidosis, diabetic ketoacidosis, excessive exercise, starvation, alcohol, etc.

Pathogenesis

Uric acid is the end product of purine metabolism, mainly produced by the cellular metabolic decomposition of nucleic acids and other purine compounds and purines in food by the enzyme decomposition.

Hyperuricemia is caused by excessive production of urate and/or decreased renal excretion of uric acid, or a combination of both.

The saturation concentration of uric acid in the body is about 420µmol/L at 37°C. Above this concentration, urate forms crystals that are deposited in a variety of tissues, including the kidneys and synovial membranes of joints, causing tissue damage.

High prevalence of people with hyperuricemia

People with relatives suffering from hyperuricemia.

People with metabolic diseases such as diabetes, hypertension, and hyperlipidemia.

People who are overweight.

People who have too much animal food in their diet.

People taking diuretics.

People with kidney disease.

People with blood system diseases.

People who receive chemotherapy and radiation therapy.

Symptoms

Most patients with primary hyperuricemia do not have clinical symptoms and only have elevated uric acid. If it develops into gout may show related manifestations, such as gouty arthritis, interstitial nephritis and gouty stones.

Main Symptoms

Only fluctuating or persistent increase in blood uric acid.

Most patients have clinical manifestations of metabolic syndrome, such as obesity, elevated blood glucose and dyslipidemia.

Complications

The prevalence of gout increases with age, and about 5% to 12% of hyperuricemia patients may develop gout and develop gouty arthritis, gouty stones, kidney lesions, etc.

Gouty arthritis

Redness, swelling, heat, pain and impaired movement around the joints.

The bunion of the foot is the first to appear, and other joints may also be involved.

When multiple joints are affected, the site is usually asymmetric.

Severe pain in the joints at night.

Fever.

Symptoms last for several days or resolve within 2 weeks.

Deformity of the joints.

Gout stones

Often found in the first metatarsophalangeal joints, auricles, extensor surfaces of the forearms, knuckles, and elbow joints.

Gout stones may be as small as a sesame seed, as large as an egg or larger, and may break down or form fistulas with white tofu-like discharge when squeezed.

Gout stones can develop in older adults with hyperuricemia who are being treated with nonsteroidal anti-inflammatory drugs (NSAIDs) or glucocorticoids, and in patients with asymptomatic hyperuricemia who do not have gouty attacks.

Renal lesions

Gouty nephropathy

The onset of the disease is insidious, with only intermittent proteinuria in the early stages, and there may be increased nocturia.

Renal insufficiency may occur in the late stage, manifested by edema, hypertension, elevated blood urea nitrogen and creatinine.

A minority of patients present with acute renal failure with oliguria or anuria and increased uric acid excretion in the first 24 hours.

Uric acid nephrolithiasis

10% to 25% of gout patients have uric acid stones in the kidneys, in the form of sediment, often asymptomatic.

Renal colic and hematuria may occur with larger stones.

When the stone causes obstruction, it leads to hydronephrosis, pyelonephritis, renal pus or perinephritis, and in severe cases, it can lead to acute renal failure.

Eye lesions

Obese gout patients often have recurrent blepharitis, and gout stones occur in the subcutaneous tissue of the eyelid.

Some of them grow gradually, break down to form ulcers and make white urate discharged to the outside.

Some patients may develop recurrent conjunctivitis, keratitis and scleritis.

Iridocyclitis often accompanies acute arthritic attacks.

The fundus optic disc tends to be mildly congested, and the retina may become exudative, edematous, or exudative retinal detachment.

Consultation

Department of Medicine

Endocrinology

If any of the following conditions exist, prompt medical attention is recommended.

Physical examination reveals a blood uric acid concentration of >420µmol/L in men and >360µmol/L in women.

Sudden redness, swelling and pain in the joints and surrounding tissues.

Preparation for medical treatment

Preparation for medical consultation: registration, preparation of documents, frequently asked questions

Tips for your doctor

It is recommended to record the uric acid value for the doctor’s reference.

Preparation Checklist

When was the first time you noticed elevated uric acid? What is the uric acid value?

Are there any symptoms of redness, swelling, or pain in the skin of the joints, and how long have they lasted?

Do any blood relatives have hyperuricemia?

Are there any allergies to medications, foods or other substances?

Do you enjoy drinking alcohol and eating seafood and animal offal?

Are there any diseases such as diabetes, hypertension, hyperlipidemia, chronic kidney disease, leukemia, etc.?

Laboratory tests: kidney function, urinary uric acid, urine routine, blood routine, liver function

Imaging tests: ultrasound of liver, gallbladder, pancreas, spleen and kidneys, bone and joint X-ray, urography, bone and joint CT, bone and joint magnetic resonance imaging

Other tests: electrocardiogram

Drugs for uric acid excretion: Benzbromarone, Probenecid, Sulfinpyrazone

Drugs to inhibit uric acid production: allopurinol, febuxostat

Alkalizing drugs: sodium bicarbonate tablets

Symptom list

Particular attention needs to be paid to the time of onset of symptoms, special manifestations, etc.

When was the elevated uric acid first noticed? What is the uric acid value?

Are there any symptoms of redness, swelling and pain in the joint skin and how long have they lasted?

Medical History Checklist

Has anyone in a blood relative had hyperuricemia?

Are there any allergies to medications, foods, or other substances?

Is there a preference for alcohol, seafood, or animal offal?

Are there any diseases such as diabetes, hypertension, hyperlipidemia, chronic kidney disease, leukemia, etc.?

Checklist

Test results in the past six months, which can be brought along to the doctor’s office

Laboratory tests: kidney function, urinary uric acid, urine routine, blood routine, liver function

Imaging Tests: Ultrasound of Liver, Gallbladder, Pancreas, Spleen and Both Kidneys, Bone and Joint X-Ray, Plain Film of Urinary Tract, Bone and Joint CT, Bone and Joint Magnetic Resonance Imaging

Other tests: electrocardiogram

Medication List

Medication used in the last 3 months, if there is a medicine box or package, you can bring it to the doctor

Drugs for uric acid excretion: benzbromarone, probenecid, sulfinpyrazone

Drugs to inhibit uric acid production: allopurinol, febuxostat

Alkalizing drugs: sodium bicarbonate tablets

Diagnosis

Diagnosis is based on

Medical history

Providing detailed information will help the doctor to determine the condition and diagnose the disease.

Lifestyle: with high purine diet, excessive alcohol intake, high sugar diet, etc.

Past medical history: history of obesity, disorders of glucose and lipid metabolism, hypertension, atherosclerosis, coronary heart disease, hematologic disorders, or renal disease.

Drug history: history of taking drugs such as diuretics, anti-tuberculosis drugs, cytotoxic chemotherapeutic drugs, immunosuppressants, etc.

Clinical manifestations

Hyperuricemia may have no clinical symptoms, and some may present with gout.

Gouty arthritis may have: redness of the skin, joint tenderness or pressure pain, impaired mobility.

Urolithiasis or renal colic attacks may be characterized by: tenderness to percussion in the renal region or pressure at the costochondral angle.

Laboratory Tests

Blood Uric Acid Measurement

The level of uric acid in the blood is measured.

Blood uric acid concentration is >420µmol/L in men and >360µmol/L in women.

Note: Fasting should be maintained before the test.

Uric Acid Measurement

Measurement of uric acid level in urine.

The measurement of urinary uric acid is of some significance in the diagnosis of the disease, mainly to determine whether the elevation of uric acid is caused by a decrease in excretion.

After 5 days of a normal purine-restricted diet, a daily uric acid excretion of more than 3.57 mmol (millimoles) is considered to be an increase in uric acid production.

Other Tests

Other tests are done mainly to diagnose the presence or absence of gout, such as ultrasound, X-rays, examination of joint fluid or gouty stone contents, CT scan and magnetic resonance imaging (MRI).

Ultrasound

Examines the structure of the kidneys.

It is a non-invasive examination method with simple and convenient features, which mainly determines whether there is gouty kidney stone formation.

Examination of joint fluid or gout stone contents

Joint fluid or gouty stone content examination is of some significance in the diagnosis of gout.

The diagnosis of gouty arthritis can be confirmed by taking a certain amount of joint fluid from the affected joints, and uric acid crystals can be seen through a microscope.

X-ray examination

It can know whether there is any damage to the bone and joint, which is meaningful for the diagnosis of gout, and do the flat film of the urinary tract to know whether there is any kidney stone.

X-ray examination of bone and joint: it can see soft tissue swelling, cartilage edge destruction, irregular joint surface, and the characteristic changes are puncture-like and worm-eaten bone defects. The diagnosis of gout can be confirmed.

Urography: kidney stones are visible.

CT and magnetic resonance imaging

Uneven speckled high-density gouty stone images can be seen in the affected area; dual-energy CT can specifically identify urate crystals, which can be used as one of the imaging screening tools to assist in the diagnosis of gout.

Differential diagnosis

Clinicians need to diagnose whether hyperuricemia is secondary or primary based on history and symptoms, in addition to distinguishing it from other arthritis and kidney stones.

Secondary hyperuricemia

Similarities: Both tests show an increase in uric acid.

Differences: secondary hyperuricemia or gout is more common in children, adolescents, women and the elderly, and the degree of hyperuricemia is more severe; 40% of the patients have increased urinary uric acid excretion in the 24-hour urine; renal involvement is more common, and the incidence of gouty kidneys and uric acid stones is higher, and even acute renal failure occurs; the symptoms of gouty arthritis tend to be milder or atypical; and there is a clear history of related medications, such as diuretics, anti-tuberculosis drugs, cytotoxic chemotherapeutic drugs, etc.

Other arthritis

Rheumatoid arthritis

Similarities: Redness, swelling and pain in the joints.

Differences: Rheumatoid arthritis is common in young and middle-aged women, and the proximal joints of the limbs often show symmetric pike-shaped swelling and deformity, and morning stiffness is obvious. Blood uric acid is not high, rheumatoid factor is positive, and chisel hole-like defects on X-ray are rare.

Septic arthritis and traumatic arthritis

Similarities: both have joint pain, redness and swelling.

Differences: Bacteria can be cultured from the joint capsule fluid in septic arthritis; traumatic arthritis has a history of trauma. Both types of arthritis do not have high blood uric acid levels, and there are no urate crystals in the joint capsule fluid.

Pseudogout

Similarities: Both have joint pain.

Differences: Pseudogout is caused by calcification of articular cartilage and is most common in the elderly, with the knee joint being the most commonly affected. Blood uric acid is normal, and bursal fluid may show calcium pyrophosphate crystals or apatite. x-ray shows linear calcification of cartilage or paracartilage calcification.

Other types of kidney stones

Similarities: Hyperuricemia or atypical gout can present with kidney stones as the first manifestation, and the incidence of urinary tract stones is higher in those with secondary hyperuricemia.

Differences: Pure uric acid stones can be visualized by X-ray without visualization, while other stones, such as calcium stones, can be visualized.

Treatment

Therapeutic goals

Primary hyperuricemia

Control hyperuricemia and prevent urate deposition.

Rapidly terminate acute arthritic episodes.

Prevent uric acid stone formation and renal impairment.

Secondary hyperuricemia

Actively treat the primary disease.

Avoid or minimize the use of drugs and methods that may trigger and/or exacerbate hyperuricemia.

Control acute gouty arthritis attacks as soon as possible.

Treatment

When asymptomatic hyperuricemia is combined with cardiovascular risk factors or cardiovascular diseases (hypertension, abnormal glucose tolerance or diabetes mellitus, hyperlipidemia, coronary heart disease, stroke, heart failure, or renal function abnormalities), blood uric acid value ≥480µmol/L should be actively carried out to lower blood pressure, lower lipids, reduce weight, and improve the insulin resistance and other comprehensive treatment.

Hyperuricemia without cardiovascular risk factors or cardiovascular disease, blood uric acid value ≥540µmol/L should be treated medically.

General treatment

Diet

Control total dietary calories.

Limit the intake of alcohol and high purine foods (e.g. animal liver and kidney, seafood, etc.).

Drink more than 2000 ml of water per day to increase the excretion of uric acid.

Avoid triggers

Use drugs that inhibit uric acid excretion, such as thiazide diuretics, with caution.

Avoid triggering factors and actively treat related diseases.

Monitor the blood uric acid level closely especially during radiotherapy or chemotherapy.

Drug therapy

Aim of treatment: to maintain the normal level of blood uric acid.

Uric acid control range: <420µmol/L without comorbidities; <360µmol/L with comorbidities such as hypertension, diabetes mellitus.

Drugs for uric acid elimination

Commonly used drugs: including benzbromarone, probenecid, sulfinpyrazone and so on.

Effects: It can increase the excretion of uric acid and reduce the uric acid level.

Suitable for: people with good renal function.

Not applicable: Ineffective when endogenous creatinine clearance <30 ml/min; not suitable for those with existing urate stone formation, or daily urinary excretion of urate >3.57 mmol.

Precautions: Drink plenty of water during the use of the drug, people with normal cardiac and renal function need to maintain the urine volume of more than 2000 ml; and take sodium bicarbonate to alkalize the urine, adjust the urine pH to 6.2-6.9.

Adverse reactions: gastrointestinal discomfort, diarrhea, skin rash.

Drugs to inhibit uric acid production

There are allopurinol and febuxostat.

Allopurinol

Effects: Reduce uric acid production.

Suitable for: excessive production of uric acid or those who are not suitable for the use of uric acid elimination drugs.

Not applicable: patients with end stage renal insufficiency (G5) are prohibited; HLA-B*5801 gene positivity, the application of thiazide diuretics and renal insufficiency are the risk factors for adverse effects of allopurinol, the gene screening is performed prior to the administration of allopurinol treatment, and those who are positive are prohibited.

Adverse reactions: allergic skin reactions, hepatic and renal impairment, and lethal exfoliative dermatitis in severe cases.

Febuxostat

NA: Use with caution in patients with severe renal insufficiency (stage G4 to G5).

Adverse reactions: hepatic impairment, nausea, rash, etc.

Newer uric acid-lowering drugs

Commonly used drugs: Labrylase and Prilosec.

Effects: It can decompose uric acid into soluble products for excretion.

Suitable for: hyperuricemia caused by tumor lysis, especially hyperuricemia caused by chemotherapy.

Adverse reactions: allergic reactions, hemolysis, methemoglobinemia.

Alkalizing drugs

Effects: Alkalize the urine, so that uric acid is not easy to accumulate in the urine to form crystals, as an adjunctive drug.

Adverse effects: prolonged administration of large quantities can lead to metabolic alkalosis, and can cause edema due to sodium overload.

Prognosis

Cure

About 5% to 12% of patients with hyperuricemia may develop gout.

Hyperuricemia has a poor prognosis if gouty nephropathy has developed.

Untreated

Higher risk of developing diseases such as gout and gouty nephropathy.

Treated

Early and aggressive treatment can prevent or delay complications such as gout and kidney damage, and most patients can live and work as normal.

Hazards

Hyperuricemia is closely related to the development of many chronic diseases, such as metabolic diseases, cardiovascular and cerebrovascular diseases and renal diseases, etc., and will increase the risk of death if left untreated.

Hyperuricemia, if not actively controlled, may cause gout, recurrent acute arthritis, gouty stones and chronic arthritis, uric acid kidney stones, gouty nephropathy and acute renal failure.

Daily life

Daily life

Patients with hyperuricemia should pay attention to many aspects of their daily life, such as diet and exercise.

Diet management

Dietary principles

Regular time and quantity, small and frequent meals, no overeating, limit high purine animal food.

Control the total calories, with a reasonable proportion of protein, fat and carbohydrates.

Foods to be avoided

Animal offal such as liver and kidneys, seafood with shellfish such as shellfish, oysters and lobsters, as well as thick broths and gravies.

Plant foods such as nori, soybeans, mung beans, and mushroom foods such as hazel mushrooms, monkey head mushrooms and black fungus.

Alcoholic beverages are also banned in cases of acute gout attacks induced by hyperuricemia.

Restricted Foods

Animal foods with high purine content, such as beef, lamb and pork.

Fish foods, such as scallops, sardines, etc.

Foods high in fructose and sucrose, such as honey, citrus, desserts, etc.

All kinds of alcoholic beverages, especially beer and distilled spirits (liquor). Overall alcohol consumption should not exceed 2 alcoholic units/day for men and 1 alcoholic unit/day for women, with 1 alcoholic unit being equivalent to 497 ml of 3.5° beer or 43 ml of 40° distilled spirits.

Suggested food choices

Skimmed or low-fat milk and its products, not more than 300 ml per day.

Eggs, 1 egg per day is recommended.

Adequate amount of fresh vegetables, 500 grams (1 city pound) or more per day.

Consume grains with low glycemic index, such as oats and brown rice.

Eat more fruits rich in potassium and vitamin C, such as bananas, cherries and strawberries.

Other Precautions

Drink plenty of water, not less than 2,000 milliliters per day for those with normal cardiac and renal function.

Use less chili peppers, peppercorns and other stimulating seasonings.

Seafood, meat and high-purine plant foods can reduce the amount of purine by discarding the soup after cooking.

Overweight or obese people should be under the guidance of a doctor to develop a reasonable diet plan, slow weight loss.

Exercise management

Obesity increases the risk of gout in hyperuricemia, and proper exercise should be done to reduce weight.

Moderate-intensity exercise can be performed 3 to 5 times a week, reaching 30 minutes each time.

You can choose aerobic exercises that you are interested in and can adhere to, such as jogging, playing tai chi, swimming and playing badminton.

Medication management

Adherence to medication is very crucial for controlling uric acid, so don’t forget to take your medication even if you are busy every day.

Care needs to be taken to avoid medications that cause elevated blood uric acid, such as diuretics, glucocorticoids, and immunosuppressants.

If there is a need to take medication, you need to consult your doctor and use the medication under the doctor’s guidance.

Daily monitoring of your condition

Test blood uric acid regularly as recommended by your doctor.

Monitor closely for any adverse drug reactions, such as gastrointestinal discomfort and headache.

Pay attention to whether you have joint pain, heat, redness and swelling, as well as urinary pain and abdominal pain.

Prevention

A good lifestyle is helpful in preventing hyperuricemia. Regular medical checkups can detect hyperuricemia as early as possible.

Adjust your diet by eating more vegetables and less high-purine foods (e.g. animal liver, red meat, seafood, etc.).

Drink less alcohol, especially beer.

Exercise regularly and do at least 30 minutes of moderate-intensity activities every day, such as brisk walking, playing tai chi and badminton.

For those who are heavier, they can formulate diet recipes and exercise programs under the guidance of professional doctors and strictly implement them to reduce their weight.

People with normal weight also need to control their diet properly and do exercise to prevent obesity.

Regular medical checkups can focus on indicators such as blood uric acid.

If hyperuricemia has occurred, you need to adhere to the treatment to prevent complications.