Can stopping allopurinol (xanthine oxidase inhibitor) cause flank pain in a patient with a history of gout or hyperuricemia?

Can Stopping Allopurinol Cause Flank Pain?

Stopping allopurinol does not directly cause flank pain, but the resulting rise in serum uric acid can lead to acute uric acid nephropathy, uric acid urolithiasis (kidney stones), or acute gout flares—all of which can present with flank pain. 1

Mechanism of Flank Pain After Allopurinol Discontinuation

When allopurinol is stopped, serum uric acid levels rise as xanthine oxidase is no longer inhibited. This creates several pathways to flank pain:

• Uric acid urolithiasis (kidney stones): Elevated uric acid can precipitate in the urinary tract, forming stones that cause acute flank pain, a recognized complication that allopurinol is specifically used to prevent 1

• Acute uric acid nephropathy: Rapid increases in uric acid can lead to crystal precipitation in renal tubules, causing acute kidney injury with associated flank pain 2

• Gout flares with renal involvement: Sudden fluctuations in serum urate levels trigger acute gout attacks, and while typically affecting peripheral joints, can involve the kidneys or cause referred pain 3

Evidence on Uric Acid Fluctuations and Clinical Consequences

The relationship between uric acid levels and clinical outcomes is well-established:

• Allopurinol effectively lowers serum uric acid and urinary uric acid excretion to normal levels, preventing complications like uric acid nephropathy and urolithiasis 1

• Discontinuing urate-lowering therapy allows serum urate to rise above the saturation point of 6.8 mg/dL (416 µmol/L), at which urate crystallizes and can precipitate in tissues including the kidneys 2

• Patients with a history of urolithiasis are specifically indicated for continuous urate-lowering therapy, and discontinuation would remove this protective effect 4, 5

Clinical Algorithm for Evaluating Flank Pain After Stopping Allopurinol

Step 1: Assess the Timeline

• Flank pain developing days to weeks after stopping allopurinol suggests rising uric acid as the culprit
• Check current serum uric acid level and compare to baseline on allopurinol 5

Step 2: Rule Out Urolithiasis

• Obtain urinalysis looking for hematuria, crystals, or pH <5.5 (favors uric acid stones)
• Consider non-contrast CT if clinical suspicion is high, as uric acid stones are radiolucent on plain films 1

Step 3: Evaluate for Acute Kidney Injury

• Check serum creatinine and compare to baseline
• Acute uric acid nephropathy presents with elevated creatinine, elevated uric acid, and low urine pH 2

Step 4: Consider Gout Flare

• Examine for joint inflammation, though atypical presentations can occur
• Joint aspiration for crystal analysis if accessible joints are involved 2

Management Recommendations

The most important intervention is to restart allopurinol immediately if the patient has indications for urate-lowering therapy, which include:

• History of urolithiasis (strong indication) 4, 5
• Chronic kidney disease stage ≥3 5, 6
• Frequent gout flares (≥2 per year) 5, 6
• Presence of tophi or radiographic damage from gout 5, 6

Restarting Allopurinol Protocol

• Start at low dose: 100 mg daily (or 50 mg daily if CKD stage ≥4) 5, 6
• Provide flare prophylaxis: Colchicine 0.5-1 mg daily for at least 6 months to prevent acute flares triggered by uric acid fluctuations 5, 6
• Titrate gradually: Increase by 100 mg every 2-5 weeks until serum uric acid <6 mg/dL 5, 6
• Monitor closely: Check serum uric acid every 2-5 weeks during titration 5

Critical Pitfalls to Avoid

• Do not assume flank pain is unrelated to allopurinol discontinuation in patients with gout or hyperuricemia—the temporal relationship is clinically significant 1

• Do not delay restarting allopurinol while investigating the cause of flank pain if the patient has clear indications for urate-lowering therapy 5

• Do not restart allopurinol at full dose (300 mg) without prophylaxis—this can trigger severe gout flares due to rapid uric acid lowering 5, 6

• Do not discontinue urate-lowering therapy in patients with history of urolithiasis, CKD, or frequent flares—these patients require lifelong therapy 5

Long-term Considerations

Guidelines explicitly state that serum urate <6 mg/dL should be maintained lifelong once urate-lowering therapy is initiated in patients with a history of gout, urolithiasis, or chronic kidney disease 5. Discontinuation is only considered in highly selected patients after at least 5 years of continuous therapy with complete resolution of tophi and no flares for 2-3 years 5.