Uric Acid, the Metabolic Syndrome, and Renal Disease

Abstract

Metabolic syndrome, characterized by truncal obesity, hypertriglyceridemia, elevated BP, and insulin resistance, is recognized increasingly as a major risk factor for kidney disease and also is a common feature of patients who are on dialysis. One feature that is common to patients with metabolic syndrome is an elevated uric acid. Although often considered to be secondary to hyperinsulinemia, recent evidence supports a primary role for uric acid in mediating this syndrome. Specifically, fructose, which rapidly can cause metabolic syndrome in rats, also raises uric acid, and lowering uric acid in fructose-fed rats prevents features of the metabolic syndrome. Uric acid also can accelerate renal disease in experimental animals and epidemiologically is associated with progressive renal disease in humans. It is proposed that fructose-and purine-rich foods that have in common the raising of uric acid may have a role in the epidemic of metabolic syndrome and renal disease that is occurring throughout the world.J Am Soc Nephrol 17: S165-S168, . doi: 10.1681 T he metabolic syndrome is defined as a syndrome of truncal obesity, insulin resistance, elevated BP, hypertriglyceridemia, and hyperuricemia (Table 1) (1-4). The prevalence of metabolic syndrome has been increasing at an alarming rate throughout the world. In the United States, the current prevalence is estimated to be 27% (29% in women and 25.2% in men) (5); in Europe, it is 15.7% in men and 14.2% in women (6); and in China it is 13.7% (9.8% in men and 17.8% in women) (7).The presence of metabolic syndrome is strongly associated with the development of diabetes (8), hypertension (9), cardiovascular disease (10), and all-cause mortality (11). However, recent studies have emphasized that metabolic syndrome also is both associated with and a risk for the development of chronic kidney disease (CKD). For example, in a recent study, the metabolic syndrome was found to be strongly correlated with CKD (defined as GFR Ͻ60 ml/min) and microalbuminuria, and the risk increased progressively with the number of criteria constituting the syndrome (12). In another study of Native Americans without diabetes, a positive relationship was identified between microalbuminuria and features of the metabolic syndrome (13).The mechanism(s) by which metabolic syndrome might accelerate renal disease remains unclear. One possibility relates to the presence of obesity itself. Obesity has been found to be an independent risk factor for CKD (12,14), and treating obesity might stabilize renal function (15) or reverse early hemodynamic abnormalities and glomerular dysfunction (16). Obesity has been associated with a type of focal segmental glomerulosclerosis (FSGS) called "obesity-related glomerulopathy" (17).Hall et al. (18) proposed that lipid deposition in the inner medulla increases intrarenal pressure, leading to decreased tubular flow, which results in increased sodium reabsorption in Henle loop, volume expansion, and the development of systemic hypertension. Obesity also increases the risk...

Uric Acid and Incident Kidney Disease in the Community

“…10 -12 Uric acid may cause these conditions through inhibition of endothelial nitric oxide bioavailability, activation of the renin-angiotensin system, and/or direct effects on endothelial cells and vascular smooth muscle cells. 3 Clinical support for this hypothesis is provided by data from the Health Professionals' Follow-up Study, which suggested that elevated serum uric acid is a risk factor for development of hypertension in younger men. 13 Both direct kidney injury and preexisting systemic hypertension may lead to incident kidney disease associated with uric acid.…”

“…1 Elevated levels of serum uric acid are associated with the development of hypertension and are common in individuals with diabetes and diabetes risk factors. 2,3 Accordingly, uric acid, via effects on renal vasoconstriction and systemic hypertension, may mediate aspects of the relationship between hypertension and kidney disease.…”

Serum uric acid and its association with hypertension, early nephropathy and chronic kidney disease in type 2 diabetic patients

“…4 Uric acid (UA) is the end product of purine metabolism in humans, and approximately 70% of UA are eliminated by the kidney. 5 Several prospective studies have documented that the elevated serum uric acid (SUA) level is associated with the development of T2DM itself, 6 hypertension, 7 cardiovascular disease 8 and the risk factors of metabolic syndrome (MS).…”

Treating gout with pegloticase, a PEGylated urate oxidase, provides insight into the importance of uric acid as an antioxidant in vivo

“…Chronic hyperuricemia leads to the deposition in tissues of monosodium urate (MSU) crystals, which are proinflammatory and cause gout, a form of arthritis affecting 3-5 million people in the United States (9)(10)(11). Both hyperuricemia itself and gout are strongly associated with conditions thought to result from or to cause oxidative stress, including obesity, hypertension, the metabolic syndrome, and cardiovascular disease (CVD) (12)(13)(14)(15)(16)(17)(18).The role of urate in these conditions remains uncertain.…”