A number of recent epidemiology studies have evaluated the association between serum uric acid and prevalent or progressive renal disease (see ). Eight of 12 studies suggest in independent role of uric acid in renal disease. The largest, evaluated 177, 570 patients in the US Renal Data System (USRDS) database, followed over 25yrs. Patients in the highest quartile of serum uric acid had a hazard ratio of 2.14 for CKD, which was only exceeded by proteinuria and severe obesity (18
). Obermayr and colleagues reporting on the Vienna Health Screening project, evaluated 21,457 subjects and found that an increase in serum uric acid of 2mg/dL conferred and increased odds ratio (OR) of 1.69 of declining renal function, exceeded only by proteinuria and stage 2 hypertension (19
). In the Atherosclerosis Risk in Communities (ARIC) trial, each increase of 1mg/dL in serum uric acid was associated with a 7-11% increase in incident CKD (20
). The largest effect of serum uric acid on CKD risk was seen in an older trial, the Okinawa Health Study of 6403 subjects in which as serum uric acid >8mg/dL was associated with a 3 fold increase in men and more than 10-fold in women (21
). Other smaller studies listed in show varying degrees of CKD risk (22
Epidemiology of Uric Acid and CKD
Of the 12 recent studies, 4 reported no association between serum uric acid and renal disease. Sturm and colleagues evaluated 227 adults, age 18-65 with non-diabetic kidney disease, in the Mild to Moderate Kidney Disease (MMKD) Study and found that uric acid correlated with renal progression only initial analysis but did not when adjusted for baseline renal function and proteinuria. The study was limited by its small size, high drop out rate (22%) (26
). Chonchol evaluated 5,808 adults in the Cardiovascular Health Study (CHS) and found that quintile of serum uric acid correlated closely with prevalent CKD but not with incident CKD. There was a weak but statistically significant correlation between uric acid and progression of CKD (27
). See and colleagues analyzed 28,745 younger subjects, age 20-49 who underwent routine health screening in Taiwan. As in the CHS, the independent association to incident CKD was weak but uric acid was closely associated with metabolic syndrome and obesity (28
). Finally in a study of 840 adults with CKD 3-4, uric acid was closely correlated with all cause mortality but not independently with progression to CKD 5 (29
). There are several possible explanations for the inconsistency in the epidemiological results.
Variable results for evaluation of risk factors are common in CV and CKD risk and may be due to population differences or random chance. In regard to uric acid specifically, as it has been implicated in the development of hypertension (6
) and cardiovascular disease (7
), the impact of uric acid may be in part through these convention risk factors for CKD. Statistical “removal” of this indirect effect will tend to minimize observed impact and may explain some of the variable results. At this time conclusions must be based on the predominance of observational data but clearly randomized controlled trials would be better. Only moderate to large size, randomized controlled studies of uric acid lowering therapy will provide the necessary data for definitive conclusions.