ABSTRACT
Uric acid (UA) was first identified two centuries ago as one of the main compositions of kidney stones.(1) The pathophysiologic mechanisms responsible for UA stone formation are complex and can be divided into congenital, acquired, and idiopathic causes.(2) There has been a recent interest in the pathogenesis of idiopathic UA nephrolithiasis (IUAN), since the majority of cases of UA stone formation are comprised of IUAN subjects. It has recently been shown that IUAN and the metabolic syndrome (MS) share many of the same characteristic features. Specifically unduly low urinary pH, the principle abnormality responsible for the formation of UA stones, has been directly related to the number of features of the MS.(3)
EPIDEMIOLOGY OF UA NEPHROLITHIASIS AND ITS LINK TO THE MS
The global distribution of UA nephrolithiasis is heterogeneous and the prevalence of UA stones varies throughout different areas of the world. This distribution is highest in the Middle East (4) and certain regions in Europe.(5) With the exception of the Midwestern section of the U.S., due to its widespread Hmong immigrant population (6), UA nephrolithiasis is responsible for 10% of the entire kidney stone burden of the United States.(7)
The MS is an aggregate of features that increases the risk of type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease. A retrospective analysis of the University of Texas Southwestern Medical Center’s stone registry in Dallas, Texas, displayed a high prevalence of MS characteristics present in patients with IUAN.(8-11) This registry also reported a higher prevalence of UA stones among patients with T2DM (12) (Figure 8.1). The result of this study was later confirmed by numerous epidemiologic studies that displayed an association between obesity, weight gain, and T2DM (all of which are characteristics of the MS) and an increased risk for nephrolithiasis.(13, 14) One limitation of these large epidemiologic studies was their lack of identification of stone type. However, T2DM and greater body mass index (BMI) have been shown to be independent risk factors for nephrolithiasis, specifically for UA stones.(15)
ETIOLOGIC MECHANISMS OF UA STONE FORMATION
Low urine volume, unduly acidic urine pH, and hyperuricosuria are three main factors necessary in the development of UA stones. Unduly acidic urine is an invariant feature in UA stone formation. UA nephrolithiasis may develop due to an inborn error in metabolism (2, 16, 17) or secondary causes such as chronic diarrhea (18), strenuous physical exercise (19), and a high purine diet.(20) In IUAN, the most prevalent cause of UA nephrolithiasis, none of the above abnormalities are detected (21) (Figure 8.2).
