Management of Chlorothiazide (Thiazide Diuretic) in a Patient with Gout
When gout occurs in a patient receiving thiazide diuretics like chlorothiazide, the diuretic should be substituted if clinically feasible; for hypertension, switch to losartan (which has uricosuric effects) or a calcium channel blocker, and if the diuretic must be continued for compelling indications such as heart failure, initiate urate-lowering therapy with allopurinol while providing prophylaxis against acute flares. 1
Primary Decision Algorithm: Should the Thiazide Be Stopped?
Step 1: Assess Whether Diuretic Discontinuation Is Feasible
Thiazide and loop diuretics are a common and important risk factor for gout (OR = 1.72), and elimination of non-essential medications that elevate serum urate is a core principle of gout management. 1
The 2016 EULAR guidelines explicitly recommend: "When gout occurs in a patient receiving loop or thiazide diuretics, substitute the diuretic if possible." 1
The 2012 ACR guidelines recommend elimination of prescription medications that elevate serum urate levels where such medications are non-essential for optimal management of comorbidities (e.g., hypertension). 1
Step 2: Identify Compelling Indications to Continue the Diuretic
Do NOT discontinue the thiazide if the patient has established cardiovascular disease or heart failure where diuretic therapy provides proven mortality benefit. 2
In patients with advanced chronic kidney disease (eGFR <30 mL/min/1.73 m²), thiazide-like diuretics such as chlorthalidone remain effective and may be necessary for blood pressure and volume control. 3
Alternative Antihypertensive Agents for Gout Patients
First-Line Substitution: Losartan
For hypertension management in gout patients, losartan is specifically recommended because it has unique uricosuric effects that actively lower serum uric acid levels. 1, 2
The angiotensin II receptor antagonist losartan is not only effective for hypertension but also has a uricosuric action, making it an attractive choice when switching from a thiazide. 1
Second-Line Substitution: Calcium Channel Blockers
Calcium channel blockers are an appropriate alternative as they do not adversely affect uric acid levels. 2
For patients with gout and hypertension, an antihypertensive regimen that does not contain a thiazide should be considered. 1
If the Thiazide Must Be Continued: Gout Management Strategy
Initiate Urate-Lowering Therapy (ULT)
ULT should be considered and discussed with every patient with a definite diagnosis of gout from the first presentation, and is indicated in all patients with recurrent flares. 1
Allopurinol is recommended for first-line ULT in patients with normal kidney function, starting at a low dose (100 mg/day) and increasing by 100 mg increments every 2-4 weeks to reach the target serum uric acid <6 mg/dL (360 µmol/L). 1
In patients with renal impairment, the allopurinol maximum dosage should be adjusted to creatinine clearance. 1
Provide Prophylaxis Against Acute Flares
Prophylaxis against flares is recommended during the first 6 months of ULT. 1
Recommended prophylactic treatment is colchicine 0.5-1 mg/day, a dose that should be reduced in patients with renal impairment. 1
If colchicine is not tolerated or is contraindicated, prophylaxis with NSAIDs at low dosage should be considered if not contraindicated. 1
Treat Acute Flares When They Occur
Recommended first-line options for acute flares are colchicine (within 12 hours of flare onset) at a loading dose of 1 mg followed 1 hour later by 0.5 mg on day 1, and/or an NSAID (plus proton pump inhibitors if appropriate), or oral corticosteroid (30-35 mg/day of equivalent prednisolone for 3-5 days). 1
Colchicine and NSAIDs should be avoided in patients with severe renal impairment. 1
Critical Monitoring Requirements
Monitor serum uric acid levels within 2-4 weeks of initiating or escalating thiazide therapy, as diuretics can raise uric acid levels by approximately 90 µmol/L at standard doses (≥50 mg/day) or about half that increase at low doses (≤25 mg/day). 4, 3
Check electrolytes (potassium, sodium), renal function (creatinine, eGFR), uric acid, and calcium within 2-4 weeks of starting or dose changes. 3
Important Clinical Nuances
The Uric Acid Elevation Is Clinically Significant
Chlorthalidone and other thiazide diuretics directly precipitate gout flares by elevating serum uric acid levels and reducing renal uric acid excretion, making them a well-established trigger for acute gouty arthritis in susceptible patients. 2, 5
Diuretics raise serum uric acid level by increasing uric acid reabsorption and/or decreasing uric acid secretion. 5
Long-Term Cardiovascular Considerations
Analysis from the Hypertension Detection and Follow-up Program found that thiazide-induced uric acid elevation does not appear to injure the kidney, and there is no evidence that pharmacologically lowering uric acid in non-gouty hypertensive patients provides benefit. 6
However, in patients who develop symptomatic gout, the situation changes and active management is required. 7
Gout Is Curable With Proper Management
Gout is curable through a combination of effective patient education and evidence-based, targeted urate-lowering therapy that eliminates the pathogenic urate crystals. 7
Untreated gout can result in disabling irreversible peripheral joint damage and chronic pain, making appropriate intervention essential. 7
Common Pitfalls to Avoid
Do not continue a thiazide diuretic "just because" when losartan or a calcium channel blocker would be equally effective for blood pressure control and would not exacerbate gout. 1, 2
Do not start ULT during an acute flare; wait until the flare has resolved, then initiate allopurinol at a low dose with prophylaxis. 1
Do not use low-dose aspirin discontinuation as a strategy, as the modest effects of aspirin on serum urate are negligible in gout management and cardiovascular protection takes priority. 1
Do not forget to provide prophylaxis when starting ULT, as this is when flares are most likely to occur. 1