Association between the changes in renal function and serum uric acid levels during multifactorial intervention and clinical outcome in patients with metabolic syndrome. A post hoc analysis of the ATTEMPT study

Aim: To assess the effects of long-term multifactorial intervention on renal function and serum uric acid (SUA) levels and their association with estimated cardiovascular disease (eCVD) risk and actual CVD events. Methods: This prospective, randomized, target-driven study included 1123 subjects (45.6% men, age 45-65 years) with metabolic syndrome (MetS) but without diabetes or CVD. Patients were randomized to multifactorial treatment. Atorvastatin was titrated from 10-80 mg/day aiming at a low density lipoprotein cholesterol (LDL-C) target of <100 mg/dl (group A) or an LDL-C target of <130 mg/dl (group B). Changes in estimated glomerular filtration rate (eGFR) and SUA levels were recorded in all patients and in the subgroup with stage 3 chronic kidney disease (CKD; eGFR = 30-59 ml/min/1.73 m(2); n = 349). We used ANOVA to compare changes within the same group, unpaired Student t-test to compare results between groups at specific time points, and log-rank test to compare event free survival. Results: The eCVD-risk reduction was greater in group A. In the overall study population, eGFR increased by 3.5% (p<0.001) and SUA levels fell by 5.6% (p<0.001). In patients from group A with stage 3 CKD (group A1; n = 172), eGFR increased by 11.1% (p<0.001) from baseline and by 7.5% (p<0.001) in group B1 (n = 177; p<0.001 vs. the change in group A1). The corresponding fall in SUA levels was 10.7% in group A1 (p<0.001 vs. baseline) and 8.3% in group B1 (p<0.001 vs. baseline and group A1). These changes were mainly attributed to atorvastatin treatment. Among the CKD stage 3 patients there were no CVD events in group A1, while 6 events occurred in group B1 (p = 0.014). Conclusions: Multifactorial intervention in patients with MetS without established CVD improved renal function and reduced SUA levels. These changes were more prominent in stage 3 CKD patients and might have contributed to the reduction in eCVD risk and clinical events.