WHAT IS CLINICALLY SIGNIFICANT? Gout and Hyperuricemia in Chronic Kidney Disease

Because humans lack uricase, they cannot convert the uric acid generated during purine metabolism into a soluble form. This can lead to an increased risk for hyperuricemia and monosodium uric acid crys-tallization in joints and tissues, a hallmark of gout. Hyperuricemia can be caused by the overproduction of uric acid, but is more often the result of insufficient kidney uric acid excretion. Because a family history is often seen in primary gout, much research is focused on genes that cause hyperuricemia, notably those that regulate renal uric acid transport, such as human urate transporter 1 (URAT1). 11 Genetic polymorphisms in anion transporters such as URAT-1 and SLC2A9, which encodes for GLUT9, can cause hyperuricemia by decreasing proximal tubular uric acid clearance. Other non-modifiable risk factors for gout include male gender, increasing age, and menopause. Approximately 15% of uric acid clearance occurs via the gastrointestinal tract, and therefore small bowel disease can contribute to increased serum uric acid. 16 A variety of medications can increase serum uric acid, including loop and thiazide diuretics. High intake of meat, shellfish, alcohol, and fructose also can cause hyperuricemia, 17,18 while obesity increases the risk for its development by threefold. 19 For many people, these causes of hyperuricemia will not lead to gout, but for those who are susceptible, these factors may trigger gout attacks. Gout has been steadily increasing worldwide, and is now the most common type of inflammatory arthro-pathy. 11 In the United States alone, its prevalence more than doubled between the 1960s and the 1990s, 20,21 and it is now estimated at 3.9% of U.S. adults (8.3 million adults — 6.1 million men and 2.2 million women). Hyperuricemia is also common, with a prevalence of 6-8% in healthy adults, and a prevalence of 1 in 3 adults who have uncontrolled hypertension and several cardiovascular risk factors. 23 Concomitant-ly, the prevalence of CKD has been increasing, with estimates at 14% of adults in the United States, 24 and 8-16% globally. 25 The parallel rise in gout and CKD (Figure 2) has led to investigations to study their relationship , including a retrospective cohort study based on 54 years of follow-up data from the Framingham Heart Study, which found that the risk of developing gout in CKD doubled compared to subjects not having CKD and gout at baseline (HR=2.09; 95% CI 1.41 to 3.08). This difference remained significant after adjusting for other known gout …