Role of Other Agents in Urate Lowering in Patients With Metabolic Syndrome
As noted earlier, patients with gout frequently have metabolic syndrome. Medications used to treat elements of the metabolic syndrome, such as hypertension and hyperlipidaemia, may have effects on SU, and physicians should use agents for these conditions that can lower SU rather than those that can increase SU.
Losartan inhibits the renal urate transporter URAT1, thereby increasing urinary uric acid excretion and lowering SU. Other angiotensin II receptor blockers do not have effects on SU, and switching from other angiotensin II receptor blockers to a combination of losartan and low-dose hydrochlorothiazide results in a significant reduction in SU (6.0 ± 1.3 mg/dl vs 5.7 ± 1.3 mg/dl; P< 0.0039) without adverse effects on blood pressure control. Amlodipine also reduces SU through an increase in renal uric acid clearance. The exact mechanism is not known. It is likely that the increase in renal uric acid clearance occurs through non-specific actions on the renal circulation. The effects of amlodipine on URAT1 are unknown.
Fenofibrate reduces plasma lipids, particularly triglycerides. Fenofibrate, but not other fibrates, has been shown to reduce SU through increased renal uric acid clearance.[13,116,117] In patients with gout receiving allopurinol or benzbromarone, the addition of fenofibrate results in additional SU lowering.[14,15,118] The combination of fenofibrate and losartan has been shown to be additive with regard to urate lowering.
Rheumatology. 2013;52(1):34-44. © 2013 Oxford University Press