Can Hydrochlorothiazide Cause Gout?

Hydrochlorothiazide, one of the most widely prescribed blood pressure medications in the world, raises uric acid levels in the blood and can trigger gout in susceptible people. The connection is well established: population studies consistently show that people taking thiazide diuretics develop gout at higher rates than those on other classes of blood pressure drugs, and the 2020 American College of Rheumatology gout management guideline specifically recommends switching off hydrochlorothiazide when feasible for patients who already have the disease. But the risk is not as straightforward as “take the pill, get gout,” and the size of the effect, who is most vulnerable, and what to do about it all deserve a closer look.

How Hydrochlorothiazide Raises Uric Acid

Hydrochlorothiazide belongs to a class of drugs called thiazide diuretics, which lower blood pressure partly by making the kidneys excrete more sodium and water. A side effect of that process is reduced excretion of uric acid. The kidneys handle uric acid through a balance of reabsorption and secretion involving specialized transport proteins. Thiazide diuretics disrupt that balance, tipping it toward keeping more uric acid in the blood rather than flushing it out.¹ When uric acid levels climb high enough, the compound can crystallize in joints, causing the intense inflammatory pain known as a gout attack.

One important nuance: the link between diuretic use and gout appears to be almost entirely explained by that rise in uric acid. In the Atherosclerosis Risk in Communities cohort study, thiazide use was associated with a roughly 44% higher risk of developing gout compared with not using a thiazide. But once the researchers accounted for the actual serum uric acid levels, the association essentially disappeared.² In other words, the drug does not cause gout through some separate inflammatory pathway. It causes gout by pushing uric acid up, and that elevated uric acid does the rest. If your uric acid stays in a safe range despite the medication, the gout risk does not seem to increase.

How Large Is the Risk?

The absolute risk of developing gout while taking hydrochlorothiazide is fairly low for any given individual, but compared to people taking other blood pressure drugs, the relative risk is meaningfully higher. A large population-based case-control study found that current use of thiazide diuretics was associated with about a 70% higher odds of developing gout compared with past use.³ That same study found loop diuretics carried an even steeper risk, more than doubling the odds.

A systematic review that pulled together evidence from randomized trials and observational studies found consistent results across study designs: diuretic users developed gout at higher rates than non-users. One randomized trial within that review found that a hydrochlorothiazide-containing regimen had a rate ratio of about 6 compared with placebo, though the confidence interval was wide because gout events were uncommon.⁴ The takeaway from the evidence as a whole is that the risk is real and reproducible, but gout remains a relatively uncommon event even among diuretic users. In a study comparing hydrochlorothiazide with its close cousin chlorthalidone, new-onset gout occurred in about 1.3% of the hydrochlorothiazide group over the study period, not a number that should cause panic.⁵

Dose Matters More Than You Might Expect

Not all hydrochlorothiazide prescriptions carry the same gout risk. A study looking specifically at the dose-response relationship found that doses of 25 mg per day or higher (in hydrochlorothiazide equivalents) were associated with a significantly increased risk of needing gout treatment, while lower doses showed no significant increase.⁶ This is relevant because modern blood pressure guidelines generally favor lower doses of thiazides than were common decades ago. Many patients today take 12.5 mg of hydrochlorothiazide, often as part of a combination pill with another drug. At that dose, the uric acid increase and gout risk appear to be smaller, though not necessarily zero.

The dose threshold also helps explain why some older studies, which used higher thiazide doses, found more dramatic effects than newer research. If your doctor has prescribed a low-dose thiazide and your uric acid levels are being monitored, the situation is less alarming than the headline numbers from population studies might suggest.

Hydrochlorothiazide Versus Chlorthalidone

Chlorthalidone is a thiazide-like diuretic that is sometimes preferred over hydrochlorothiazide for blood pressure control because of stronger evidence from cardiovascular outcome trials. Patients occasionally ask whether switching between the two would affect gout risk. The evidence suggests it would not help. In a direct comparison, new-onset gout rates were statistically indistinguishable between the two drugs: about 1.7% for chlorthalidone and 1.3% for hydrochlorothiazide, a difference that was not significant.⁵ Both drugs raise uric acid through similar mechanisms, so swapping one for the other is unlikely to solve a gout problem.

How Thiazides Compare to Other Blood Pressure Drugs

The more useful comparison is between thiazide diuretics as a class and the other major categories of blood pressure medication. This is where the differences become clinically meaningful. A secondary analysis of the landmark ALLHAT trial, which followed older hypertensive adults for an average of about five years, found that patients randomized to the calcium channel blocker amlodipine had substantially lower gout rates than those on chlorthalidone, with a roughly 37% lower risk during the trial period. The ACE inhibitor lisinopril fell in between, with gout rates lower than chlorthalidone but higher than amlodipine.⁷

A more recent study looking at prescribing cascades, where starting one drug leads to the need for another, found that patients started on thiazide diuretics were about two to two-and-a-half times more likely to need anti-gout medication than patients started on ACE inhibitors or ARBs. Compared with calcium channel blockers and beta-blockers, the increased risk became statistically significant after about six months of use.⁸ The pattern that emerges is clear: if gout risk is a concern, other first-line blood pressure drugs are safer bets than thiazide diuretics.

Losartan and the Uric Acid Exception

Among blood pressure medications, losartan stands out as having a mild uric acid-lowering effect, something unique to this specific ARB and not shared by all drugs in the same class. A large population-based study found that current use of losartan was associated with about a 19% lower risk of developing gout, and the protection appeared to increase with longer use and higher doses.⁹ This makes losartan a particularly attractive option for hypertensive patients who also have elevated uric acid or a history of gout.

When losartan is combined with a low dose of hydrochlorothiazide in a single pill, an interesting tug-of-war plays out. A study in hypertensive patients found that switching from other ARB-thiazide combinations to a fixed-dose losartan/hydrochlorothiazide combination actually lowered uric acid levels, because losartan’s uric acid-excreting effect outweighed the modest increase from the low-dose hydrochlorothiazide.¹⁰ By contrast, when losartan was combined with the calcium channel blocker amlodipine (no thiazide at all), uric acid dropped much more dramatically.¹¹ So losartan can partially offset the thiazide effect, but if keeping uric acid as low as possible is a priority, avoiding the thiazide component altogether works better.

What the Gout Guidelines Say

The 2020 American College of Rheumatology guideline for gout management is blunt on this point: for patients who already have gout, switching hydrochlorothiazide to an alternate antihypertensive is conditionally recommended when feasible, regardless of whether the gout is currently active or in remission.¹² “When feasible” is doing some work in that sentence. For some patients, especially those whose blood pressure is well controlled on hydrochlorothiazide and who have struggled with other medications, the switch may not be straightforward. But the guideline reflects the consensus that keeping a known gout patient on a drug that raises uric acid is a suboptimal choice when alternatives exist.

For people who do not yet have gout but are taking hydrochlorothiazide, the guideline does not mandate a change. The decision becomes a risk-benefit conversation: how well is the blood pressure being controlled? Are there other gout risk factors present, like obesity, heavy alcohol use, or a family history? Is the uric acid already creeping up on bloodwork? These questions shape whether switching is worth the trouble.

Genetics and Individual Vulnerability

The uric acid response to hydrochlorothiazide varies widely between individuals, and part of that variation is genetic. A genome-wide association study in Finnish men identified genetic markers near genes called VEGFC and BRINP3 that were associated with how much a person’s uric acid rose during thiazide treatment.¹³ A separate pharmacogenomic study found that individuals carrying certain risk alleles saw uric acid increases of up to 1.8 mg/dL on hydrochlorothiazide, a clinically significant jump that could push someone from a normal level into hyperuricemia. A composite genetic risk score explained about 11% of the variability in the uric acid response.¹⁴

This means two people on the same dose of hydrochlorothiazide can have very different uric acid responses. One person’s body may handle the drug with barely a blip, while another person’s genetic makeup amplifies the effect. Genetic testing for this purpose is not standard clinical practice yet, but the research suggests that monitoring uric acid levels after starting a thiazide, especially in people with other gout risk factors, is a sensible precaution.

Gender and Age Patterns

Gout has long been more common in men, but the role of diuretics in triggering gout shows an interesting gender dimension. Women with gout are significantly more likely than men with gout to have been taking diuretics as a contributing factor, while men are more often triggered by dietary factors like alcohol and purine-rich foods.¹⁵ This likely reflects prescribing patterns: thiazide diuretics are commonly used in older women for blood pressure management, and estrogen’s protective effect on uric acid levels fades after menopause, creating a vulnerable window.

As for age, the prescribing cascade study found that the increased risk of needing anti-gout medication after starting a thiazide was present across age groups, whether patients were under 50, between 50 and 65, or over 65.⁸ The risk is not confined to the elderly, though older patients tend to have more of the additional risk factors that compound the problem.

If You Already Take Gout Medication

A common concern for people who are on both hydrochlorothiazide and a urate-lowering drug like allopurinol or febuxostat is whether the diuretic undermines the gout medication. The evidence here is more reassuring than you might expect. A study of combined allopurinol and hydrochlorothiazide use found that the diuretic caused a temporary bump in uric acid levels during the first week or so, but this largely resolved by three weeks of continued combined treatment. The researchers concluded that the interaction posed little long-term risk in people with normal kidney function.¹⁶

For febuxostat, the picture is even simpler. A pharmacokinetic study found that taking hydrochlorothiazide alongside febuxostat had no clinically meaningful effect on how febuxostat worked, and no dose adjustment was needed.¹⁷ So while rheumatology guidelines still favor switching off hydrochlorothiazide for gout patients when possible, continuing the diuretic is not a catastrophe if it is needed for blood pressure control and the gout is being actively managed with medication. Your doctor may just need to adjust the urate-lowering dose to account for the headwind the thiazide creates.

When Switching Away From Hydrochlorothiazide Is Not Simple

In practice, switching blood pressure medications is not always as clean as guidelines make it sound. Some patients have resistant hypertension that responds well to diuretics but poorly to other classes. Others are on carefully titrated multi-drug regimens where removing the thiazide would destabilize their blood pressure control. And some patients have been stable on hydrochlorothiazide for years with no uric acid problems and no gout symptoms, making a preemptive switch hard to justify.

For these patients, a more pragmatic approach may include keeping the thiazide at the lowest effective dose (ideally under 25 mg per day), monitoring uric acid levels periodically, choosing combination partners wisely (losartan over other ARBs, for example), and treating hyperuricemia proactively if it develops. The goal is to manage the uric acid consequences of the drug rather than abandon a medication that may be doing important cardiovascular work. Uncontrolled hypertension carries its own serious risks, and a small increase in uric acid has to be weighed against those.

Why Diuretic-Induced Gout Gets Overlooked

One underappreciated aspect of this topic is how often the connection between a new gout diagnosis and a diuretic prescription goes unrecognized. The prescribing cascade study found that a substantial number of patients started on anti-gout medications after beginning thiazide therapy, suggesting that doctors were treating the gout as a new, independent problem rather than as a drug side effect.⁸ Prescribing cascades like this, where the side effect of one drug is treated by adding another drug rather than reconsidering the first one, are a well-known problem in medicine, especially among older adults taking multiple medications.

If you develop gout symptoms after starting hydrochlorothiazide or any diuretic, it is worth asking your prescriber whether the diuretic could be the trigger. The timing is often a clue: the chlorthalidone-versus-hydrochlorothiazide comparison study found that the median time to a first gout episode was about 150 to 180 days after starting the drug.⁵ A gout attack appearing within the first six months of a new diuretic prescription is a pattern that should prompt a medication review, not just a prescription for colchicine.