High uric acid usually comes down to one of two problems: your body is making too much of it, or your kidneys aren’t filtering enough of it out. In most cases, it’s the kidneys. About 90% of the uric acid your kidneys filter from your blood gets reabsorbed back into the body, and only about 10% actually leaves through urine. Anything that tips that balance, whether it’s diet, genetics, medications, or metabolic conditions, can push levels above the threshold for hyperuricemia: 8.0 mg/dL for men or 6.1 mg/dL for women.
Your Kidneys Reabsorb Most Uric Acid
Uric acid is a waste product created when your body breaks down purines, compounds found in your cells and in certain foods. Your kidneys filter it from the blood, but the vast majority gets pulled back into the body through the kidney’s tiny tubules before it ever reaches your urine. This reabsorption is tightly regulated by specialized transport proteins sitting on the surface of kidney cells. Some of these transporters pull uric acid back in, while others push it out into the urine for disposal.
When anything disrupts this system, uric acid accumulates in the blood. Chronic kidney disease is an obvious example: as kidney function declines, less uric acid gets filtered in the first place. But you don’t need full-blown kidney disease for this to happen. Even subtle shifts in how those transport proteins behave, driven by hormones, medications, or genetics, can reduce excretion enough to raise your levels over time.
Genetics Play a Larger Role Than Most People Realize
Two genes have an outsized influence on uric acid levels. One, called ABCG2, codes for a protein that sits on the surface of kidney cells and actively pumps uric acid out into the urine. A common mutation in this gene cuts that pumping capacity by about 53%, meaning significantly less uric acid leaves your body with each pass through the kidneys. This single variant is one of the strongest genetic predictors of gout.
A second gene, SLC2A9, also encodes a uric acid transporter. Variations in this gene can swing levels in either direction, causing unusually high or unusually low uric acid depending on which version you carry. If your uric acid has been elevated for years despite a reasonable diet, inherited differences in these transporters are a likely contributor.
How Diet Drives Uric Acid Up
Purines in food get broken down into uric acid during digestion, so eating a lot of high-purine foods directly increases production. The highest-purine foods, containing 100 to 1,000 mg of purine per 100 grams, include organ meats (liver, kidney, sweetbreads, heart, brains), sardines, anchovies, herring, mackerel, mussels, scallops, and meat-based broths or gravies. Moderate-purine foods include spinach, asparagus, mushrooms, peas, lentils, and shell beans, though these plant sources carry far less risk.
Fructose deserves special attention because it raises uric acid through a completely different pathway than purines. When fructose enters liver cells, it gets rapidly processed in a reaction that burns through ATP, the cell’s energy currency. The leftover molecular fragments from that spent ATP get converted directly into uric acid. This means sugary drinks, fruit juices, and foods sweetened with high-fructose corn syrup can spike uric acid even though they contain zero purines.
Alcohol Has a Double Effect
Beer is the worst offender among alcoholic drinks because it hits you from both sides. It contains compounds that your body converts into uric acid, increasing production. At the same time, the ethanol in beer interferes with the kidney’s uric acid transporters, reducing the amount that gets excreted. This “more in, less out” combination is why beer has a stronger link to gout than other types of alcohol.
Spirits work differently. They’re low in purines, but their high alcohol concentration promotes lactic acid production. Lactic acid competes with uric acid for the same exit route through the kidneys, so when lactic acid is high, uric acid gets backed up. Wine appears to carry the least risk of the three, though heavy consumption of any alcohol can elevate levels.
Insulin Resistance and Metabolic Syndrome
If you carry extra weight around your midsection, have prediabetes, or have been told you have metabolic syndrome, there’s a direct hormonal reason your uric acid may be high. Insulin, the hormone that regulates blood sugar, also affects how your kidneys handle uric acid. Higher insulin levels increase the activity of transporters that pull uric acid back into the blood and decrease the activity of transporters that push it out into urine. The net result is that your kidneys hold onto more uric acid.
Research in both animals and humans confirms this link. In studies on insulin-depleted diabetic rats, uric acid excretion increased significantly because, without insulin’s influence, the kidneys let more of it go. When insulin was reintroduced, excretion dropped again. In humans, the degree of insulin resistance correlates directly with how much uric acid the kidneys reabsorb. This means that for many people, high uric acid isn’t just a dietary problem. It’s a metabolic one, and improving insulin sensitivity through weight loss and exercise can lower levels independent of what you eat.
Medications That Raise Uric Acid
Certain commonly prescribed drugs interfere with the kidney’s ability to clear uric acid. Loop diuretics and thiazide diuretics, often used to treat high blood pressure and fluid retention, are the most well-known culprits. They reduce uric acid excretion through multiple mechanisms: directly increasing reabsorption, decreasing secretion, and concentrating the blood as fluid is lost. The effect is dose-dependent, meaning higher doses cause bigger increases. Over time, diuretic-induced hyperuricemia can trigger new gout or reactivate gout that had been under control.
Low-dose aspirin also reduces uric acid excretion at the kidney level. If you take a daily baby aspirin for heart health and notice rising uric acid, the aspirin may be a contributing factor. Certain immunosuppressant drugs and some cancer treatments that cause rapid cell turnover (releasing large amounts of purines all at once) can also push levels sharply upward.
What Happens When Levels Stay High
Persistently elevated uric acid doesn’t always cause symptoms right away, but it sets the stage for crystal formation. When uric acid concentration in the blood exceeds what can stay dissolved, it begins to precipitate into needle-shaped crystals called monosodium urate. Joints are particularly vulnerable because their surface temperature is cooler than core body temperature, closer to 25°C at peripheral joints compared to 37°C internally, and the slightly alkaline pH of joint fluid (around 7.4) favors this specific crystal form.
The crystallization process follows a predictable sequence. First, uric acid molecules stack together into tiny amorphous clusters. These clusters then clump into larger amorphous masses. Finally, those masses undergo a structural shift into the sharp, filament-like crystals that trigger the intense inflammatory response of a gout attack. Beyond gout, sustained hyperuricemia is associated with kidney stones, progression of chronic kidney disease, high blood pressure, and cardiovascular damage.
Why Multiple Causes Often Overlap
For most people with high uric acid, it’s not a single cause but a combination. You might carry a genetic variant that reduces kidney excretion by half, eat a moderate amount of red meat, drink beer on weekends, and have early insulin resistance from carrying extra weight. Each factor alone might not push you over the threshold, but together they compound. This is also why treatment usually involves more than one change. Reducing high-purine foods helps, but if insulin resistance is driving your kidneys to reabsorb more uric acid, addressing metabolic health and reviewing your medications will often matter just as much.