How to manage a patient with impaired renal function and hyperuricaemia on Lisinopril (lisinopril), atorvastatin (atorvastatin), and bendroflumethiazide (bendroflumethiazide) with a history of gout and hypertension?

Management of Declining Renal Function and Hyperuricemia in a Patient on Lisinopril, Atorvastatin, and Bendroflumethiazide

Immediately discontinue bendroflumethiazide, as thiazide diuretics cause hyperuricemia and can worsen renal function, and this is the most likely contributor to both the declining eGFR and rising urate levels in this patient. 1, 2

Immediate Medication Adjustments

Discontinue Bendroflumethiazide

• Thiazide diuretics directly cause hyperuricemia by increasing net uric acid reabsorption in the proximal tubule and should be stopped when gout develops. 1, 2
• Bendroflumethiazide raises serum uric acid levels through volume depletion and reduced uric acid secretion, with this effect occurring even at low doses (2.5 mg daily). 2, 3, 4
• The FDA label explicitly warns that bendroflumethiazide may raise blood uric acid levels and that dosage adjustments of antigout medications may be necessary. 2
• Progressive renal impairment (eGFR dropping from 64 to 46) warrants careful reappraisal of diuretic therapy with consideration of discontinuation. 2

Continue Lisinopril for Blood Pressure Control

• Lisinopril should be continued as ACE inhibitors have mild uricosuric properties and can blunt diuretic-induced hyperuricemia. 4
• ACE inhibitors like lisinopril increase uricosuria by lowering net uric acid reabsorption in the proximal tubule. 4
• No dose adjustment of lisinopril is required with eGFR of 46 mL/min (creatinine clearance >30 mL/min). 5
• Monitor blood pressure closely after stopping bendroflumethiazide and adjust lisinopril dose if needed to maintain BP control. 1

Continue Atorvastatin

• Atorvastatin may have the additional benefit of lowering uric acid levels, unlike simvastatin. 6
• Continue at current dose of 20 mg nocte. 6

Urate-Lowering Therapy Strategy

Timing and Initiation

• Restart allopurinol after confirming repeat kidney function tests, as this patient has multiple high-risk features warranting urate-lowering therapy: hyperuricemia (0.50 mmol/L), history of gout with ongoing joint pain, hypertension, and renal impairment (eGFR 46). 1, 7, 8
• The EULAR guidelines recommend initiating urate-lowering therapy close to the time of first diagnosis in patients with renal impairment, hypertension, and comorbidities. 1

Allopurinol Dosing in Renal Impairment

• Start allopurinol at 50-100 mg daily given the eGFR of 46 mL/min (CKD stage 3), not the previously planned 100 mg dose. 1, 7, 8
• In patients with renal impairment, allopurinol maximum dosage should be adjusted to creatinine clearance, but dose can be titrated upward with close monitoring for adverse events. 1
• Increase by 50-100 mg increments every 2-4 weeks until target serum uric acid <6 mg/dL (0.36 mmol/L) is achieved. 1, 7, 8
• Allopurinol is strongly recommended as first-line urate-lowering therapy for all patients, including those with moderate-to-severe CKD. 1, 7, 8

Flare Prophylaxis

• Initiate colchicine 0.5 mg once daily (not 0.5-1 mg daily) when starting allopurinol, given the renal impairment, and continue for 6 months. 1, 7, 8
• The EULAR guidelines recommend colchicine 0.5-1 mg daily for prophylaxis, with reduced dose in renal impairment. 1, 8
• Colchicine requires dose reduction and monitoring of renal function due to increased risk of toxicity when creatinine clearance is reduced. 1
• If colchicine is contraindicated or not tolerated, use low-dose NSAIDs or low-dose oral glucocorticoids, though NSAIDs should be avoided given the renal impairment. 1, 8

Treatment Target and Monitoring

Serum Uric Acid Target

• Target serum urate <6 mg/dL (0.36 mmol/L) and maintain this lifelong. 1, 8
• Monitor serum urate levels regularly to guide allopurinol dose titration. 1, 8

Renal Function Monitoring

• Repeat kidney function tests and first morning urine albumin-creatinine ratio as planned. 1
• Monitor renal function closely when using allopurinol in patients with renal impairment. 1
• Monitor for signs of allopurinol hypersensitivity syndrome, particularly in patients with severe renal impairment. 7

Alternative Antihypertensive Considerations

If Additional Blood Pressure Control Needed

• Consider losartan as an alternative or additional antihypertensive agent, as it has uricosuric properties and lowers serum uric acid while treating hypertension. 1, 3, 6
• Losartan is exceptional among antihypertensive drugs in possessing mild uricosuric properties and has a specific role in treating hypertensive patients with gout. 1, 3
• Calcium channel blockers (such as amlodipine) are also appropriate alternatives that do not raise uric acid levels. 1, 6

Acute Gout Attack Management

If Acute Flare Occurs

• Use low-dose colchicine (up to 1.5-2 mg total on day 1, then 0.5-1 mg daily) or oral glucocorticoids for acute attacks. 1
• Avoid NSAIDs entirely given the renal impairment (eGFR 46), as they have effects on renal hemodynamics and can worsen kidney function. 1, 7, 6
• Continue paracetamol for ongoing joint pain as it does not affect renal function or uric acid levels. 1
• Do not stop allopurinol during an acute flare; continue urate-lowering therapy with appropriate anti-inflammatory treatment added. 8

Lifestyle Modifications

Non-Pharmacological Management

• Weight loss if appropriate, as obesity is associated with hyperuricemia. 1
• Avoid alcohol, especially beer and spirits, and sugar-sweetened drinks including those with fructose. 1
• Avoid heavy meals and excessive intake of meat and seafood. 1
• Encourage low-fat dairy products, particularly skimmed milk and low-calorie yogurt. 1
• Regular exercise should be advised, as physical activity may decrease excess mortality associated with chronic hyperuricemia. 1

Common Pitfalls to Avoid

• Do not continue thiazide diuretics in patients with gout—this is a potentially modifiable risk factor that directly worsens hyperuricemia. 1, 2
• Do not delay restarting allopurinol in this patient with multiple high-risk features (renal impairment, hypertension, history of gout). 1, 7, 8
• Do not start allopurinol at standard 100 mg dose in patients with eGFR <60 mL/min; use 50-100 mg and titrate slowly. 1, 7
• Do not use full-dose colchicine prophylaxis (1-1.2 mg daily) in patients with renal impairment; reduce to 0.5 mg daily. 1
• Do not use NSAIDs for acute gout attacks in patients with CKD stage 3 or worse. 1, 7, 6
• Do not target serum urate <3 mg/dL long-term, as this is not recommended. 1, 8

Alternative Urate-Lowering Options if Allopurinol Fails

If Target Not Achieved with Allopurinol

• If serum urate target cannot be reached at maximum adjusted allopurinol dose for renal function, switch to febuxostat (though carefully weigh cardiovascular risks) or add a uricosuric agent. 1, 7
• Benzbromarone is effective in patients with renal insufficiency (creatinine clearance >25 mL/min) even with concomitant diuretic administration, and is useful for patients who previously had no improvement with allopurinol. 9, 6
• Febuxostat can be used without dose adjustment in renal impairment, but the FDA-mandated CARES trial showed higher cardiovascular-related death and all-cause mortality compared to allopurinol. 7