What medication is most likely causing hyperuricemia (high uric acid levels) in a patient with Hypertension (HTN) and Diabetes Mellitus (DM) taking Metformin, a diuretic (e.g. Furosemide), and an Angiotensin-Converting Enzyme inhibitor (ACEi) who develops gout?

Diuretic-Induced Hyperuricemia and Gout in a Patient with HTN and DM

Furosemide (B) is the medication most likely causing hyperuricemia and gout in this patient with hypertension and diabetes taking metformin, a diuretic, and an ACE inhibitor.

Mechanism of Diuretic-Induced Hyperuricemia

Loop diuretics like furosemide are well-documented to cause hyperuricemia through several mechanisms:

• Decreased renal excretion of uric acid by increasing net uric acid reabsorption in the proximal tubule 1
• Direct inhibition of uric acid secretion in the kidney 2
• Reduction in urinary excretion of uric acid by approximately 40% 2

Evidence Supporting Furosemide as the Causative Agent

The FDA drug label for furosemide specifically mentions that "concomitant use of cyclosporine and furosemide tablets is associated with increased risk of gouty arthritis secondary to furosemide-induced hyperuricemia" 3. This directly implicates furosemide as a cause of hyperuricemia.

The EULAR guidelines for gout management clearly state that "diuretics, widely prescribed in the community, are a common risk factor for gout (OR = 1.72)" 4. The guidelines specifically recommend: "When gout associates with diuretic therapy, stop the diuretic if possible" 4.

Ruling Out Other Medications

1. Metformin (A): There is no evidence in the provided literature that metformin causes hyperuricemia or gout. In fact, metformin is generally considered safe in patients with gout 4.

2. ACE inhibitors (C): ACE inhibitors actually have a mild uricosuric effect and can increase uric acid excretion 5. They may even counteract diuretic-induced hyperuricemia when used at sufficient doses 1, 5. Therefore, the ACE inhibitor is unlikely to be causing the gout.

3. Aspirin (D): While high-dose aspirin can affect uric acid levels, this patient is not mentioned to be taking aspirin, making this an incorrect answer.

Management Considerations

For patients with hypertension who develop gout while on diuretic therapy:

• Consider stopping the diuretic if possible 4
• For hypertension management, consider alternative agents:
  • Losartan (an ARB) has uricosuric properties and may help lower uric acid levels 4, 6
  • ACE inhibitors can be continued as they may have mild uricosuric effects 5

Monitoring Recommendations

For patients who must remain on diuretics:

• Regular monitoring of serum uric acid levels 6
• Consider prophylactic therapy for high-risk patients 6
• Monitor for signs of acute gout attacks 4

In conclusion, among the medications listed, furosemide (B) is most likely responsible for the development of gout in this patient with hypertension and diabetes.