What is Hyperuricemia

Hyperuricemia is an elevated serum uric acid level of greater than 6.8 mg/dL ¹. The normal upper limit of serum urate is 6.8mg/dL, and anything over 7 mg/dL is considered saturated, and symptoms can occur. Hyperuricemia is the result of increased production, decreased excretion of uric acid, or a combination of both processes. The normal serum uric acid level is lower in children than in adults. The upper limit of the reference range for children is 5 mg/dL (0.30 mmol/L). The upper limit of the reference range for men is 7 mg/dL (0.42 mmol/L) and for women is 6 mg/dL (0.36 mmol/L). The tendency to develop hyperuricemia increases with age. Hyperuricemia does not in itself indicate a pathological state because it is very prevalent in the general population. The prevalence rate of asymptomatic hyperuricemia in the general population is estimated at 20-25% and 25% of hospitalized patients, but only 4-6% in premenopausal women ². The most common complication of hyperuricemia is gout which is seen in 5.9% in men and 2% in women of the U.S. population ¹.

Hyperuricemia can also be seen in accelerated purine degradation, in high cell turnover states (hemolysis, rhabdomyolysis, and tumor lysis) and decreased excretion (renal insufficiency and metabolic acidosis). Hyperuricemia can lead to gout and nephrolithiasis. Hyperuricemia has also been implicated as an indicator for diseases like metabolic syndrome, diabetes mellitus, cardiovascular disease, and chronic renal disease ³.

Approximately two thirds of total body urate is produced endogenously, while the remaining one third is accounted for by dietary purines ⁴.

Approximately 70% of the urate produced daily is excreted by the kidneys, while the rest is eliminated by the intestines. However, during renal failure, the intestinal contribution of urate excretion increases to compensate for the decreased elimination by the kidneys.

The blood levels of uric acid are a function of the balance between the breakdown of purines and the rate of uric acid excretion. Theoretically, alterations in this balance may account for hyperuricemia, although clinically defective elimination accounts for most cases of hyperuricemia.

Factors that may cause a hyperuricemia in your blood include:

• Diuretics (water retention relievers)
• Drinking too much alcohol
• Genetics (inherited tendencies)
• Hypothyroidism (underactive thyroid)
• Immune-suppressing drugs
• Niacin, or vitamin B-3
• Obesity
• Psoriasis
• Purine-rich diet — liver, game meat, anchovies, sardines, gravy, dried beans and peas, mushrooms, and other foods
• Renal insufficiency (inability of the kidneys to filter waste)
• Tumor lysis syndrome (a rapid release of cells into the blood caused by certain cancers or by chemotherapy for those cancers)

Also, you may be monitored for high uric acid levels when undergoing chemotherapy or radiation treatment for cancer.

Worldwide, the prevalence of hyperuricemia has increased substantially in recent decades. The progressive increase in serum levels of uric acid levels may be linked to the rising prevalence of overweight and obesity, as well as the increase in consumption of sugar-sweetened beverages, foods rich in purines, and alcohol ⁵.

A Japanese study that used an administrative claims database to ascertain 10-year trends in the prevalence of hyperuricemia concluded that the prevalence of hyperuricemia in the overall study population increased during the 10-year follow-up. When stratified by age, the prevalence increased among groups older than 65 years in both sexes. In those younger than 65 years, men had a prevalence 4 times higher than that in women, but in those older than 65 years, the gender gap narrowed to 1:3 (female-to-male ratio) with gout and/or hyperuricemia.

Hyperuricemia has a higher prevalence (25-40%) in individuals with hypertension and has been associated with increased morbidity in these patients ⁶. In a study of 837 elderly patients with hypertension followed up over 3.5 years, Lin et al found that increases in uric acid levels were independently associated with decline in renal function ⁷. Ding et al ⁸ reported that serum uric acid concentration and prevalence of hyperuricemia were positively associated with osteoarthritis of the knee in a cohort of Chinese women.

The cause for these associations is unknown, but hyperuricemia is probably a marker for comorbid risk factors rather than a causative factor, per se. Results of a cross-sectional study by Yang et al suggested that levels of high-sensitivity C-reactive protein (a nonspecific marker for inflammation) are positively associated with the prevalence of hyperuricemia ⁹.

Although observational studies on hyperuricemia and stroke have yielded conflicting results, a meta-analysis by Li et al ¹⁰ concluded that hyperuricemia may modestly increase the risk of stroke incidence and mortality. The authors reviewed 15 studies that together included 22,571 cases of stroke and 1,042,358 participants. The risk ratio (RR) for the incidence of stroke in patients with hyperuricemia was 1.22 and the risk ratio for mortality was 1.33. The pooled estimate of multivariate risk ratios of both stroke incidence and mortality were higher in women than in men (1.25 vs 1.08 and 1.41 vs 1.26, respectively) ¹⁰.

Risk ratio (RR) is used in the statistical analysis of the data of experimental, cohort and cross-sectional studies, to estimate the strength of the association between treatments or risk factors, and outcome.

Risk ratio (RR) is used to compare the risk of an adverse outcome when receiving a medical treatment versus no treatment (or placebo), or when exposed to an environmental risk factor versus not exposed.

Assuming the causal effect between the exposure and the outcome, values of Risk ratio (RR) can be interpreted as follows:

• Relative risk = 1 means that exposure does not affect the outcome;
• Relative risk < 1 means that the risk of the outcome is decreased by the exposure;
• Relative risk > 1 means that the risk of the outcome is increased by the exposure.

Hyperuricemia causes

Hyperuricemia is caused by having higher-than-normal level of uric acid in your body. Hyperuricemia may occur if:

• Your body makes too much uric acid
• Your body has a hard time getting rid of uric acid
• Combination of overproduction and underexcretion causes

When uric acid builds up in the fluid around the joints (synovial fluid), uric acid crystals form. These crystals cause the joint to become inflamed, causing pain, swelling and warmth, causing a condition called gout.

A high prevalence of hyperuricemia exists in indigenous races of the Pacific, which appears to be associated with a low fractional excretion of uric acid ¹¹. In the United States, African Americans develop hyperuricemia more commonly than whites.

Hyperuricemia, and particularly gouty arthritis, are far more common in men than in women. Only 5% of patients with gout are female, but uric acid levels increase in women after menopause ¹².

Urate Overproduction

Uric acid overproduction may be idiopathic. Known causes include the following:

• Purine rich diet: A diet rich in high-purine meats, organ foods, and legumes can result in an overproduction of uric acid.
• Error of purine metabolism: hypoxanthine phosphoribosyltransferase deficiency, phosphoribosylpyrophosphate synthetase over activity
• Cell breakdown or turnover: lymphoproliferative diseases, myeloproliferative disease, polycythemia vera, Paget disease, psoriasis, tumor lysis, hemolysis, rhabdomyolysis, exercise
• Hypoxanthine guanine phosphoribosyltransferase (HGPRT) deficiency (Lesch-Nyhan syndrome): This is an inherited X-linked disorder. HGRPT catalyzes the conversion of hypoxanthine to inosinic acid, in which PRPP serves as the phosphate donor. The deficiency of HGPRT results in accumulation of 5-phospho-alpha-d-ribosyl pyrophosphate (PRPP), which accelerates purine biosynthesis with a resultant increase in uric acid production. In addition to gout and uric acid nephrolithiasis, these patients develop a neurologic disorder that is characterized by choreoathetosis, spasticity, growth, mental function retardation, and, occasionally, self-mutilation.
• Partial deficiency of HGPRT (Kelley-Seegmiller syndrome): This is also an X-linked disorder. Patients typically develop gouty arthritis in the second or third decade of life, have a high incidence of uric acid nephrolithiasis, and may have mild neurologic deficits.
• Increased activity of 5-phospho-alpha-d-ribosyl pyrophosphate (PRPP) synthetase: This is a rare X-linked disorder in which patients make mutated PRPP synthetase enzymes with increased activity. These patients develop gout when aged 15-30 years and have a high incidence of uric acid renal stones.
• Glycogenoses III, V, and VII
• Exposure to persistent organic pollutants (eg, organochlorine pesticides) ¹³

Decreased Uric acid Excretion

Causes of uric acid underexcretion include the following:

• Idiopathic
• Acute or chronic kidney disease. Renal failure is one of the more common causes of hyperuricemia. In chronic renal failure, the uric acid level does not generally become elevated until the creatinine clearance falls below 20 mL/min, unless other contributing factors exist. This is due to a decrease in urate clearance as retained organic acids compete for secretion in the proximal tubule. In certain renal disorders, such as medullary cystic disease and chronic lead nephropathy, hyperuricemia is commonly observed even with minimal renal insufficiency.
• Acidosis (lactic acidosis, diabetic ketoacidosis, alcoholic ketoacidosis, and starvation ketoacidosis)
• Familial juvenile gouty nephropathy: This is a rare autosomal dominant condition characterized by progressive renal insufficiency. These patients have a low fractional excretion of urate (typically 4%). Kidney biopsy findings indicate glomerulosclerosis and tubulointerstitial disease but no uric acid deposition.
• Hypovolemia,
• Medication/toxin (diuretics, niacin or nicotinic acid, pyrazinamide, ethambutol, low-dose salicylates, cyclosporin, beryllium, salicylates, lead, levodopa, alcohol, nicotinic acid),
• Metabolic syndrome: Metabolic syndrome is characterized by hypertension, obesity, insulin resistance, dyslipidemia, and hyperuricemia and is associated with a decreased fractional excretion of urate by the kidneys ¹⁴.
• Hyperparathyroidism,
• Hypertension,
• Hypothyroidism,
• Bartter syndrome,
• Down syndrome (Trisomy 21) ¹⁵.
• Preeclampsia and eclampsia: The elevated uric acid associated with these conditions is a key clue to the diagnosis because uric acid levels are lower than normal in healthy pregnancies.
• Sarcoidosis,
• Lead intoxication (chronic): History may reveal occupational exposure (eg, lead smelting, battery and paint manufacture) or consumption of moonshine (ie, illegally distilled corn whiskey) because some, but not all, moonshine was produced in lead-containing stills).

Combined causes

• Alcohol: Ethanol increases the production of uric acid by causing increased turnover of adenine nucleotides ¹⁶. Ethanol also decreases uric acid excretion by the kidneys, which is partially due to the production of lactic acid.
• Fructose-sweetened soft drinks: Fructose raises serum uric acid levels by accentuating degradation of purine nucleotides and increasing purine synthesis, and epidemiologic studies have documented a link between sugar-sweetened soft drink intake and serum uric acid levels in several populations ¹⁷. More recently, Lecoultre et al found that fructose-induced hyperuricemia is associated with a decreased renal uric acid excretion ¹⁸.
• Exercise: Exercise may result in enhanced tissue breakdown and decreased renal excretion due to mild volume depletion.
• Deficiency of aldolase B (fructose-1-phosphate aldolase): This is a fairly common inherited disorder, often resulting in gout.
• Glucose-6-phosphatase deficiency (glycogenosis type I, von Gierke disease): This is an autosomal recessive disorder characterized by the development of symptomatic hypoglycemia and hepatomegaly within the first 12 months of life. Additional findings include short stature, delayed adolescence, enlarged kidneys, hepatic adenoma, hyperuricemia, hyperlipidemia, and increased serum lactate levels.

Hyperuricemia pathophysiology

Uric acid (2,6,8 trioxypurine-C5H4N4O3) is the result of purine breakdown. Uric acid in the blood is saturated at 6.4-6.8 mg/dL at ambient conditions, with the upper limit of solubility placed at 7 mg/dL ⁴. At the normal physiological pH of 7.4, uric acid circulates in the ionized form of urate ¹. Purine metabolism mainly occurs in the liver, but it can also be produced in any other tissue that contains xanthine oxidase (intestines). About two-thirds of uric acid is excreted in the kidneys, and a third is excreted into the intestine ¹. In the kidneys, uric acid is filtered and secreted, and 90% is reabsorbed in the proximal tubule. The recent cloning of certain urate transporters will facilitate the understanding of specific mechanisms by which urate is handled in the kidney and small intestines. Other mammals have lower uric acid levels due to the activity of uricase. This enzyme converts urate to the more water soluble form of allantoin ¹⁹.

A urate/anion exchanger (URAT1) has been identified in the brush-border membrane of the kidneys and is inhibited by an angiotensin II receptor blocker, losartan ²⁰. A human organic anion transporter (hOAT1) has been found to be inhibited by both uricosuric drugs and antiuricosuric drugs ²¹, while another urate transporter (UAT) has been found to facilitate urate efflux out of the cells ²². These transporters may account for the reabsorption, secretion, and reabsorption pattern of renal handling of urate.

Urate secretion does appear to correlate with the serum urate concentration because a small increase in the serum concentration results in a marked increase in urate excretion.

Hyperuricemia may occur because of decreased excretion (underexcretors), increased production (overproducers), or a combination of these two mechanisms.

Urate excretion occurs primarily in the kidneys and is responsible for hyperuricemia in 90% of individuals. Underexcretion appears to be a combination of decreased glomerular filtration, decreased tubular secretion, and enhanced tubular reabsorption. The acute or chronic decrease in glomerular filtration can result in hyperuricemia. Proximal tubular reabsorption of uric acid is controlled by URAT1 (uric acid transporter 1). This transported can be stimulated by organic acids (lactate and acetoacetate, and beta-hydroxybutyrate), medications (niacin, pyrazinamide, ethambutol, cyclosporin, and chemotherapy) and reduced extracellular fluid volume resulting in hyperuricemia ³.

While decreased urate filtration may not cause primary hyperuricemia, it can contribute to the hyperuricemia of renal insufficiency. Decreased tubular secretion of urate occurs in patients with acidosis (eg, diabetic ketoacidosis, ethanol or salicylate intoxication, starvation ketosis). The organic acids that accumulate in these conditions compete with urate for tubular secretion. Finally, enhanced reabsorption of uric acid distal to the site of secretion is the mechanism thought to be responsible for the hyperuricemia observed with diuretic therapy and diabetes insipidus.

Urate production is accelerated by purine rich diets, endogenous purine production, and high cell breakdown, and urate overproduction is responsible for a minority of cases of hyperuricemia. Foods rich in purine include all meats but specifically organ meats (kidneys, liver, “sweet bread”), game meats and some seafood (anchovies, herring, scallops). Beer, which is purine rich, also increases uric acid levels by decreasing kidney excretion. Endogenous production of the purine production can be accelerated by phosphoribosylpyrophosphate (PRPP) synthetase activity as well as a defect in the regulatory enzyme hypoxanthine phosphoribosyltransferase (HPRT). A small percentage of overproducers have enzymatic defects that account for their hyperuricemia. These include a complete deficiency of hypoxanthine guanine phosphoribosyltransferase (HGPRT) as in Lesch-Nyhan syndrome, partial deficiency of HGPRT (Kelley-Seegmiller syndrome), and increased production of 5-phospho-alpha-d-ribosyl pyrophosphate (PRPP) activity.  Conditions of accelerated cell breakdown or turnover such as rhabdomyolysis, hemolysis, and tumor lysis can also be a purine source and thus, increase urate production. Glycogenoses types III, IV, and VII can result in hyperuricemia from excessive degradation of skeletal muscle ATP.

Combined mechanisms (underexcretion and overproduction) can also cause hyperuricemia. The most common cause under this group is alcohol consumption, ¹⁶ which results in accelerated hepatic breakdown of ATP and the generation of organic acids that compete with urate for tubular secretion. Enzymatic defects such as glycogenoses type I and aldolase-B deficiency are other causes of hyperuricemia that result from a combination of overproduction and underexcretion.

Urate crystals can engage an intracellular pattern recognition receptor, the macromolecular NALP3 (cryopyrin) inflammasome complex ²³. NALP3 inflammasome may result in interleukin 1 (IL-1) beta production, which, in turn, incites an inflammatory response. Inhibition of this pathway has been targeted as a treatment for hyperuricemia-induced crystal arthritis, with recent reports documenting the efficacy of the IL-1 inhibitors canakinumab and rilonacept for preventing gout flares during the initiation of allopurinol therapy ²⁴.

Zinc and magnesium are important nutrients with anti-inflammatory properties. Chinese studies have linked low dietary levels to hyperuricemia in men. A study by Xie et al ²⁵ in 2697 men and 2471 women indicated that dietary zinc intake was inversely associated with hyperuricemia in middle-aged and older males, but not in females. Wang et al ²⁶ reported that in 5168 subjects, dietary magnesium intake was inversely associated with hyperuricemia, independent of some major confounding factors, but only in males.

Hyperuricemia signs and symptoms

Hyperuricemia does not represent a disease or a specific indication for therapy. The majority of patients with hyperuricemia are asymptomatic and require no long term therapy. The patient may give a history of a purine rich diet or alcohol consumption, specifically beer. Past medical history, as well as current medications, should be reviewed to find a correlation with poor renal excretion of urate or increased production.

The two most common complaints associated with hyperuricemia are gout and uric acid nephrolithiasis.

• With gout, a patient will complain of red hot swollen joint, most commonly in the big toe.
• With nephrolithiasis, patients will complain of flank pain, hematuria, nausea/vomiting, and colicky pain.

Gout is a metabolic disorder that allows for the accumulation of uric acid in the blood and tissues. This leads to the precipitation of urate monohydrate crystals within a joint. When tissues are saturated with urate, crystals will precipitate. Precipitation is enhanced in acidic environments and cold environments, leading to increased precipitation in peripheral joints, such as the great toe. Gout has a male predominance in a 4:1 ratio of men to women. Uric acid levels can be elevated ten to 15 years before clinical manifestations of gout ²⁷.

In uric acid nephrolithiasis, uric acid is handled by the renal system, and three factors can influence uric acid stone formation. These factors are pH of acidic urine, dehydration, and hyperuricosuria. Persistent acidic urine is the most common cause of uric acid stone formation. Hyperuricosuria is defined as uric acid levels that exceed 800 mg/day in men and 750 mg/day in women. It is most commonly associated with increased dietary intake. Uric acid stones are 5% to 10% of all urinary stones ²⁸.

Hyperuricemia diagnosis

Routine screening for hyperuricemia is not recommended ¹⁹.

Laboratory studies may include the following:

• Serum uric acid
• Complete blood cell count (CBC): Values may be abnormal in patients with hemolytic anemia, hematologic malignancies, or lead poisoning.
• Electrolytes, blood urea nitrogen (BUN), and serum creatinine values: These are abnormal in patients with acidosis or renal disease.
• Liver function tests: These are part of the general workup for patients with a possible malignancy or metabolic disorders; in addition, the results are useful as a baseline if allopurinol is used for treatment
• Serum glucose level: This may be abnormal in patients with diabetes or glycogen storage diseases.
• Lipid profile: Results are abnormal in those with dyslipidemia.
• Calcium and phosphate levels: This measurement is needed for the workup of hyperparathyroidism, sarcoidosis, myeloma, and renal disease.
• Thyroid-stimulating hormone (TSH) level: Obtain this value to help rule out hypothyroidism.
• Urinary uric acid excretion
• Fractional excretion of urate on a low-purine diet
• Spot urine ratio of uric acid to creatinine

Urinary uric acid secretion

If uric acid levels are found to be persistently elevated, an estimation of total uric acid excretion may be needed. The estimation of uric acid excretion is recommended in young males who are hyperuricemic, females who are premenopausal, people with a serum uric acid value greater than 11 mg/dL, and patients with gout.

One protocol recommends obtaining two 24-hour urine collections for creatinine clearance and uric acid excretion. The first collection is performed while patients are on their usual diet and alcohol intake. At the end of the first 24-hour collection, serum creatinine and urate levels are checked for an estimation of the creatinine clearance. The patient then goes on a low-purine, alcohol-free diet for 6 days, with a repeat 24-hour urine collection performed on the last day, followed by a serum creatinine and uric acid evaluation.

Depending on the 24-hour urine uric acid levels before the purine-restricted diet and after the purine-restricted diet, patients who are hyperuricemic can be categorized into the following three groups:

• High-purine intake – Prediet value greater than 6 mmol/d, postdiet value less than 4 mmol/d
• Overproducers – Prediet value greater than 6 mmol/d, postdiet value greater than 4.5 mmol/d
• Underexcretors – Prediet value less than 6 mmol/d, postdiet value less than 2 mmol/d

Fractional excretion of urate on a low-purine diet

This test should be used to investigate the degree of underexcretion in patients with hyperuricemia or gout in patients for whom the cause cannot be determined. The fractional excretion of urate is calculated by the following formula:

Fractional excretion of urate = [(urine uric acid)×(serum creatinine)×(100%)]÷[(serum uric acid)×(urine creatinine)]

The reference intervals for patients on a low-purine diet and normal renal function are as follows:

• Males – 7-9.5%
• Females – 10-14%
• Children – 15-22%

Values less than the lower limits of the reference range indicate underexcretion. The formula also circumvents any inaccuracy that may have occurred during urine collection.

Spot urine ratio of uric acid to creatinine

If a 24-hour urine collection is not possible, measure the ratio of uric acid to creatinine from a spot urine collection. A ratio greater than 0.8 indicates overproduction.

The ratio also helps differentiate acute uric acid nephropathy from the hyperuricemia that occurs secondary to renal failure. The ratio is greater than 0.9 in acute uric acid nephropathy and usually less than 0.7 in hyperuricemia secondary to renal insufficiency

Imaging studies

Consider joint x-rays to evaluate joint swelling; however, x-rays are not necessary for the diagnosis of gout.

Renal ultrasounds are indicated in patients with uric acid nephrolithiasis.

Procedures

Joint aspiration may be important in the diagnosis of acute gouty arthritis, in which uric acid crystals are found to be negatively birefringent under polarized microscopy.

Hyperuricemia treatment

The majority of patients are asymptomatic and do not need medical therapy for hyperuricemia as they will never develop gout or nephrolithiasis ¹. The unnecessary cost of medication and potential for adverse effects outweighs the benefit of starting medication. Urate lowering medications in asymptomatic patients are only indicated in those undergoing cytolytic therapy for malignancy to prevent tumor lysis syndrome ²⁹.

Hyperuricemia diet

You can make some changes to your diet to help your hyperuricemia and gout. As always, talk with your doctor before making any changes to your diet or medications.

Your doctor may recommend that you lose weight, if you are overweight, or drink less alcohol. You can also avoid eating foods with lots of purines, since they can increase your uric acid levels. Foods that are high in purines include:

• Anchovies.
• Asparagus.
• Beef kidneys.
• Brains.
• Dried beans and peas.
• Game meats.
• Gravy.
• Herring.
• Liver.
• Mackerel.
• Mushrooms.
• Sardines.
• Scallops.
• Sweetbreads.

Other things you can do:

• get to a healthy weight, but avoid crash diets
• aim for a healthy, balanced diet, with plenty of vegetables and some low-fat dairy foods
• have at least 2 alcohol-free days a week
• drink plenty of fluids to avoid getting dehydrated
• exercise regularly – but avoid intense exercise or putting lots of pressure on joints
• stop smoking
• ask your doctor about vitamin C supplements

Hyperuricemia medications

Urate-lowering medications:

• Allopurinol: xanthine oxidase inhibitors; used as prophylaxis against gouty arthritis, nephrolithiasis, and chemo related hyperuricemia
• Probenecid: inhibits URAT1 result in increased uric acid secretion and used as second-line therapy for gout
• Rasburicase: recombinant uricase that converts uric acid to allantoin which is much more water soluble and readily excreted from the kidneys and used as prophylaxis against chemo-related hyperuricemia ³⁰. Higher doses than usual of rasburicase (600-900 mg/d) are administered to decrease uric acid production prior to chemotherapy in patients with leukemias and lymphomas; allopurinol and hydration are continued for several days. If acute renal failure develops despite these measures, then early hemodialysis is indicated to reduce the total body burden of uric acid, thereby facilitating recovery of renal function. Although rasburicase treatment has become the standard of care for patients at high risk of tumor lysis syndrome, debate continues on whether the profound and rapid lowering of plasma uric acid levels produced by rasburicase has a significant effect on patient outcomes (eg, need for renal replacement therapy and mortality) ³¹.

Medications to treat gout attacks

Drugs used to treat acute attacks and prevent future attacks include:

• Nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs include over-the-counter options such as ibuprofen (Advil, Motrin IB, others) and naproxen sodium (Aleve), as well as more-powerful prescription NSAIDs such as indomethacin (Indocin) or celecoxib (Celebrex). Your doctor may prescribe a higher dose to stop an acute attack, followed by a lower daily dose to prevent future attacks. NSAIDs carry risks of stomach pain, bleeding and ulcers.
• Colchicine. Your doctor may recommend colchicine (Colcrys, Mitigare), a type of pain reliever that effectively reduces gout pain. The drug’s effectiveness may be offset, however, by side effects such as nausea, vomiting and diarrhea, especially if taken in large doses. After an acute gout attack resolves, your doctor may prescribe a low daily dose of colchicine to prevent future attacks.
• Corticosteroids. Corticosteroid medications, such as the drug prednisone, may control gout inflammation and pain. Corticosteroids may be in pill form, or they can be injected into your joint. Corticosteroids are generally used only in people with gout who can’t take either NSAIDs or colchicine. Side effects of corticosteroids may include mood changes, increased blood sugar levels and elevated blood pressure.

Medications to prevent gout complications

If you experience several gout attacks each year, or if your gout attacks are less frequent but particularly painful, your doctor may recommend medication to reduce your risk of gout-related complications. If you already have evidence of damage from gout on joint X-rays, or you have tophi, chronic kidney disease or kidney stones, medications to lower your body’s level of uric acid may be recommended. Options include:

• Medications that block uric acid production. Drugs called xanthine oxidase inhibitors, including allopurinol (Aloprim, Lopurin, Zyloprim) and febuxostat (Uloric), limit the amount of uric acid your body makes. This may lower your blood’s uric acid level and reduce your risk of gout. Side effects of allopurinol include a rash and low blood counts. Febuxostat side effects include rash, nausea, reduced liver function and an increased risk of heart-related death.
• Medication that improves uric acid removal. These drugs, called uricosurics, include probenecid (Probalan) and lesinurad (Zurampic). Uricosuric drugs improve your kidneys’ ability to remove uric acid from your body. This may lower your uric acid levels and reduce your risk of gout, but the level of uric acid in your urine is increased. Side effects include a rash, stomach pain and kidney stones. Lesinurad can be taken only along with an xanthine oxidase inhibitor.

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