High Uric Acid Levels in the Blood

Over the past few decades, there has been a substantial rise in the incidence of hyperuricemia globally. The gradual increase in uric acid levels in the body may be linked to the rising prevalence of obesity, increased intake of sugar-sweetened beverages, alcohol, and purine-rich foods. Compared to developed countries, the prevalence of hyperuricemia tends to be lower in developing countries.

Though about 1 in 5 people shows high uric acid levels, most people with hyperuricemia do not present with any symptoms or any associated health problems.

What Is Hyperuricemia?

Hyperuricemia means the presence of high levels of uric acid in the body.

Whenever we eat something, our body absorbs all the good stuff from the food leaving the waste products to be excreted from the body. Uric acid is one such waste product. It is a chemical that is formed when the body breaks down substances called purines. Normally, purines are produced within the body and can also be found in certain foods and drinks. Most of the uric acid thus formed is sent to the kidneys, from where it’s eliminated through urine. Some uric acid is also eliminated through stools.

If your body produces more than normal amounts of uric acid or eliminates less than normal amounts of uric acid, then you will have hyperuricemia. Sometimes, a combination of both these mechanisms may lead to hyperuricemia.

If you have hyperuricemia, then your physician will take a complete history to determine whether you are symptomatic or asymptomatic and try to identify the causative factors and other coexisting medical problems.

When there are no symptoms, there are usually no special findings on clinical examination. In the presence of symptoms, there can be following findings on examination:

• In acute gouty arthritis, the affected joint is reddish in appearance (erythematous), warm to the touch, swollen, and extremely painful.
• People with long-term gouty arthritis may develop crystalline uric acid deposits (tophi) in the incurved rim or on the ear cartilage, on the inner surface of the forearm, in the thin sac of fluid that lies between the bony tip of the elbow and the skin or in other body tissues.
• In uric acid nephrolithiasis, the person may present with abdominal or flank (part of the body between the hips and the ribs) pain. (Read more - Kidney stones treatment)

Hyperuricemia needs to be differentiated from some other medical conditions that can have similar signs. These include:  

• Alcoholic Ketoacidosis
  A metabolic complication of alcohol use and starvation. 
• Diabetic Ketoacidosis
  A build-up of acids in your blood when your blood sugar level is too high for a long time.
• Gout and Pseudogout
  These are types of inflammatory arthritis.
• Haemolytic Anemia
  A condition in which red blood cells are destroyed in the body before completing their normal lifespan.
• Hodgkin Lymphoma
  A type of cancer which originates from the white blood cells.
• Hyperparathyroidism
  In this condition, there is excess parathyroid hormone in the bloodstream.
• Hypothyroidism
  A condition in which the body doesn’t produce enough thyroid hormones.
• Nephrolithiasis
  Presence of stones within the urinary system.
• Preeclampsia
  A complication of pregnancy where the pregnant woman (who didn’t have high blood pressure before) develops high blood pressure during pregnancy with high levels of protein in their urine.
• Type Ia Glycogen Storage Disease
  A genetic disorder caused by the build-up of glycogen in the body cells.
• Uric Acid Nephropathy
  A condition where the kidney function deteriorates due to high levels of uric acid in the urine.

Causes

Hyperuricemia can be caused due to any of the following three mechanisms:

1. Decreased elimination of uric acid from the kidneys.
2. Increased production of uric acid.
3. A combined mechanism (decreased elimination and increased production of uric acid).

• Decreased elimination of uric acid from the kidneys
  The capacity of the kidneys to excrete uric acid can be diminished due to any of these conditions:
  • High blood pressure.
  • Hormonal problems such as excessive parathyroid hormone in the blood (hyperparathyroidism) or reduced production of thyroid hormones by the body (hypothyroidism).
  • Kidney disorders such as an inability of the kidneys to conserve enough water (Diabetes insipidus) or to remove excess acids from the body resulting in the build-up of lactic acid in the body (Lactic acidosis).
  • Acid builds up in the blood if the blood sugar level is too high for a long time (Diabetic ketoacidosis).
  • Starvation ketosis which occurs in cases of extreme starvation.
  • Chemical poisoning by beryllium or lead.
  • Inflammatory conditions like sarcoidosis.
  • Preeclampsia: A complication of pregnancy where the pregnant woman (who didn't have high blood pressure before) develops high blood pressure during pregnancy with high levels of protein in their urine.
  • Genetic disorders such as Down's syndrome or Bartter's syndrome
  • Intake of drugs such as salicylates (< 2 g per day-found majorly in painkillers), alcohol, diuretics, levodopa-carbidopa (used to treat Parkinson), ethambutol pyrazinamide (used to treat lung TB), nicotinic acid (used for reducing the bad cholesterol in the body), and cyclosporine (used to treat rheumatoid arthritis, severe psoriasis and to prevent rejection of organ after a liver or kidney transplant).
  • Primary idiopathic hyperuricemia in which the uric acid level is high without any identifiable cause.
• Increased production of uric acid
  This can occur due to:
  • Obesity.
  • Excessive exercise or alcohol consumption.
  • Purine-rich diet.
  • Deficiency of an enzyme called HPRT causing overproduction of uric acid.
  • Overactivity of an enzyme called PRS, which causes excessive production and accumulation of uric acid in the body.
  • Any haemolytic process that causes an abnormal breakdown of the red blood cells.
  • Disorders in which there are excess of myelocytes (bone marrow cell) or lymphocytes (a type of white blood cell).
  • Excess production of the red blood cells (a type of cancer called polycythemia vera).
  • Psoriasis (severe) which is an autoimmune skin condition.
  • Paget's disease which is a disease of the bones causing fragile and misshapen bones.
  • Rhabdomyolysis, a condition in which the damaged muscles break down and release their contents into the blood.
  • Primary idiopathic hyperuricemia.
• A combined mechanism (decreased elimination and increased production of uric acid)
  This can occur due to:
  • Alcohol consumption.
  • Shock.
  • Genetic disorders like deficiency of enzymes like G6PD and aldolase B.

Risk Factors

The presence of certain factors may pose you at a higher risk of developing a disease than other people. They are known as risk factors. These include:

• Non-modifiable risk factors
  ​These risk factors cannot be changed.
  • Age
    The risk of developing hyperuricemia increases with age.
  • Gender
    In all age groups, men have a greater risk of developing gout than women. However, with advancing age, the ratio tends to equalize.
  • Genetic factors
    Specific genetic factors influence the serum urate levels and thereby, increase the risk of developing hyperuricemia.
• Modifiable risk factors
  These are the risk factors that can be changed or modified if adequate measures are taken.
  • Obesity
    If you are obese, an excess uric acid in your body from the adipose cells (fat cells) and your kidneys have a difficult time eliminating it.
  • Use of certain medications
    Thiazide diuretics (commonly used to treat high blood pressure), low-dose aspirin, and anti-rejection drugs (prescribed to individuals who have undergone an organ transplant) increase uric acid levels.
  • High purine intake
    Eating a diet rich in meat or seafood and drinking fruit sugar (fructose) sweetened beverages and alcohol (especially beer) increases uric acid levels.
  • Medical conditions
    Untreated high blood pressure and long-standing conditions like diabetes, heart disease, and kidney disease can cause an increase in the body's uric acid levels.

When you are symptom-free, the following dietary guidelines may help in keeping your uric acid levels in check.

• Drink lots of fluids
  Stay well-hydrated. Drinking 5 to 8 glasses of water every day decreases your risk of having a gout attack by 40%.
• Reduce your intake of fructose-sweetened foods
  These include sports drinks/energy drinks, nutrition/cereal bars/granola bars, jams and jellies, candies, ice cream, store-bought baked goods, soda, canned fruits, sweetened yoghurt, and junk food.
• Limit alcohol intake
  Moderate consumption of wine is alright but avoid beer as it particularly increases the risk of hyperuricemia.
• Have low-fat dairy products
  Go for low-fat dairy products like yoghurt, cottage cheese, reduced-fat cheese, and low-fat milk to meet your protein requirements.
• Limit your intake of red meat, fish, and poultry
  Avoid red meat like lamb, pork, and beef. Limit your intake of fatty poultry and high-fat dairy products. Reduce consumption of sardines, tuna, shellfish, and anchovies as they are rich in purines.
• Maintain body weight
  Stay physically active. Moderate physical activity for 150 minutes per week is recommended. Walk, run, swim, or bike for 5 days a week, for at least 30 minutes per session. If you are just starting out to exercise, you can break up these 30 minutes into 3 sessions of 10 minutes each spread out throughout the day. Choose activities which are easy on your joints and ensure safety before exercising. If you are overweight, gradually shed the extra kilos. If you are not obese, then maintain your current weight by regular exercises.

Apart from clinical history, your doctor will also take some tests to confirm the diagnosis:

Laboratory studies

• Serum uric acid
  This value determines how much uric acid is present in your blood.
• Complete blood cell count (CBC)
  The results may be abnormal in people with certain types of anemia, hematologic malignancies (blood cancers), or lead poisoning.
• Electrolytes, BUN, and serum creatinine values
  People with acidosis or kidney disease show abnormal values.
• Liver function tests
  Generally performed in people in whom there is a possibility of malignancy (cancer) or metabolic disorders.
• Serum glucose level
  Values may be abnormal in people with diabetes or glycogen storage diseases.
• Lipid profile
  There will be derangement in values in those with lipid disorders.
• Calcium and phosphate levels
  Values are abnormal in hyperparathyroidism, sarcoidosis, myeloma, and renal disease.
• Thyroid-stimulating hormone level
  This is carried out to rule out problems with the thyroid gland (hypothyroidism).
• Urinary uric acid excretion
  This is recommended in hyperuricemic young males, premenopausal females, patients with a serum uric acid level >11 mg/dL.
• Fractional excretion of urate on a low-purine diet
  This is carried out to determine the degree of underexcretion or in those who have gout the cause for which cannot be determined.
• Spot urine ratio of uric acid to creatinine
  This value helps to differentiate between hyperuricemia due to acute uric acid nephropathy and hyperuricemia due to kidney failure.

Imaging studies

• In case, you have gout your doctor may ask for an X-ray, which may show evidence of joint swelling and kidney cysts.
• In people with hyperuricemia and kidney disease, a renal sonogram may be performed for evaluation of the kidney. This sonogram may also show the presence of uric acid stones.

Joint aspiration

• For diagnosis of acute gouty arthritis, joint aspiration may be performed. It means that the fluid from around the affected joint will be removed using a needle and a syringe. This fluid will be checked for the presence of uric acid crystals.

Asymptomatic hyperuricemia

For people with asymptomatic hyperuricemia, medical treatment is generally not recommended. In these people, lifestyle changes are advised, which include dietary modifications and exercise that may keep uric acid levels in check.

Symptomatic hyperuricemia

Hyperuricemia can be symptomatic in the form of gout, uric acid stones, or uric acid nephropathy.

Gout

• Acute gouty arthritis
  The main aim of treatment for acute gouty arthritis is pain relief. So usually NSAIDs (nonsteroidal anti-inflammatory drugs) are prescribed until signs of inflammation are resolved. They are usually prescribed as a 7-10 day course or for 3-4 days depending on the clinical presentation.
• Chronic gout therapy
  After the symptoms of acute gouty arthritis subside, a person with gouty arthritis enters the inter-critical period. Here usually prophylactic colchicine, uricosuric drugs (drugs which promote excretion of uric acid), and xanthine oxidase inhibitors (drugs which inhibit the production of uric acid) are prescribed.

Uric acid nephrolithiasis

Allopurinol is the drug of choice in such cases.

Uric acid nephropathy

Intravenous saline and drugs to dilute the urine (drugs like furosemide or mannitol) are prescribed to prevent further precipitation of uric acid. Urine alkalization with sodium bicarbonate or acetazolamide may also be done.

Your doctor may refer you to certain specialist doctors depending on the diagnosis and the clinical presentation.

• For people with acute or chronic gouty arthritis, you may be asked to consult a rheumatologist.
• Acute urate nephropathy or chronic renal failure patients may require the opinion of a kidney specialist.
• People who present with symptomatic uric acid nephrolithiasis may be asked to consult a urologist.

Lifestyle management

Hyperuricemia, especially the asymptomatic type, can largely be controlled by lifestyle changes. Symptomatic hyperuricemia is also benefitted from these changes.

Dietary changes

• What not to eat?
  • Avoid red meat like lamb, pork, and beef.
  • Limit your intake of fatty poultry and high-fat dairy products.
  • Reduce consumption of sardines, tuna, shellfish, and anchovies, as they are rich in purines. Avoid sugary foodstuffs like candies, baked food items, and sweetened cereals.
  • Reduce intake of fructose-sweetened beverages and alcohol (especially beer).
• What to eat?
  • Stay well-hydrated by drinking enough water.
  • Have low-fat dairy and lentils as protein sources
  • Have more fruits (especially those rich in vitamin C), vegetables, and whole grains.
• Exercise
  Exercise regularly to maintain a body weight which is ideal for your height. Besides reducing uric acid production, it will also reduce the load on the joints and help in strengthening the joints.

Prognosis

• Asymptomatic hyperuricemia has a good prognosis if the necessary lifestyle changes are made.
• Increased levels of uric acid, if left untreated can become a predisposing factor for gout. In case of very high levels of uric acid, there is increased risk for renal (kidney) disease. Prognosis is good with regular consumption of Allopurinol.

Complications

Hyperuricemia may present with the following complications:

• Gout
  A potentially debilitating form of inflammatory arthritis, which occurs due to the accumulation of tiny, needle-shaped crystals of uric acid in the joints.
• Acute uric acid nephropathy
  A condition in which the kidney function rapidly declines due to high levels of uric acid in the urine.
• Uric acid nephrolithiasis
  In the presence of high urinary uric acid levels, any condition that lowers urinary pH value in the kidney or bladder will lead to uric acid nephrolithiasis (stones in the urinary system).
• Chronic renal insufficiency
  Persistent elevated uric acid levels can lead to chronic renal insufficiency.