Abstract
<p class="ADMETabstracttext">Gout is a common inflammatory arthritis that is caused by chronically-elevated serum uric acid (sUA) levels (hyperuricemia). In humans, sUA levels are predominantly controlled by a variety of transporters that mediate the elimination of uric acid through the kidneys and intestines, a process that is altered in most gout patients. In this review, we highlight our current understanding of uric acid handling in healthy individuals and gout patients, therapies for gout that target uric acid transporters, and the mechanism of other therapies that alter sUA levels through interactions with uric acid transporters.</p>
Highlights
Gout is a debilitating inflammatory arthritis of increasing prevalence that is caused by chronically elevated levels of serum uric acid, or hyperuricemia, defined as concentrations exceeding 6.8 mg/dL (408 μM)
Genetic studies show that a large number of urate transporters (GLUT9, ABCG2, NPT1/3/4, URAT1, OAT4, MRP4) are important for urate homeostasis in humans [6,7,8] which are expressed in the organs that eliminate uric acid
Dietary purines are imported from the lumen of intestinal enterocytes by the nucleoside transporter CNT2/SLC28A2, which are converted to uric acid by intestinal xanthine oxidase
Summary
Gout is a debilitating inflammatory arthritis of increasing prevalence that is caused by chronically elevated levels of serum uric acid (sUA), or hyperuricemia, defined as concentrations exceeding 6.8 mg/dL (408 μM). Serum urate levels are normally in the range of 3.5-7 mg/dL (210 – 420 μM) [1]. Prolonged hyperuricemia can initiate the precipitation of the uric acid in joints and other tissues, and these deposits can trigger an acute and painful immune response known as a gout flare. Hyperuricemia is strongly and independently associated with a number of other important disorders including hypertension, cardiovascular disease and metabolic syndrome [2]. A number of therapies for gout that lower sUA levels target transporters for uric acid, some which are important drug transporters
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