Previous studies have reported an association between metabolic syndrome, proteinuria, incidence and progression of CKD, and ESRD among different ethnic groups (1-6). With an increasing sedentary lifestyle and high rates of obesity, the prevalence of metabolic syndrome stands at 34% (7). The burden of incident and prevalent CKD has also increased in the United States; thus, CKD and metabolic syndrome, in addition to obesity, are major public health problems. Metabolic syndrome is defined by central obesity, hyperglycemia, hypertension, and dyslipidemia (8,9). Diabetes and hypertension are the leading causes of both CKD and ESRD. Because both elevated blood glucose and BP are included in the definition of metabolic syndrome, it is not surprising that recent data suggest a link between metabolic syndrome and CKD. Moreover, metabolic syndrome in the general population increases risk of cardiovascular disease, stroke, and all-cause mortality, as do CKD and microalbuminuria (10). It has not been clear whether these effects of metabolic syndrome are driven by one or more individual factors, are due to clustering of risk factors, or perhaps result from some other concomitant factors. In addition, it is unclear whether the consequences of metabolic syndrome differ according to level of CKD.In this issue of CJASN, Navaneethan and colleagues (11) tackle the subject of metabolic syndrome, CKD progression, and death in a large (n525,868) and diverse population with stage 3-4 CKD. They used a preexisting electronic health record-based CKD registry. The definition of metabolic syndrome was modified from that used by the National Cholesterol Education Program, with body mass index (BMI) instead of waist circumference. This is an acceptable alternative used in the World Health Organization classification of metabolic syndrome and in other similar studies (9). Sixty percent of the cohort was defined as having metabolic syndrome. Multivariate analyses for several risk factors known to influence CKD progression and death showed that metabolic syndrome was associated with an increased risk for ESRD but not for death during a mean follow-up of 2.3 years. Subgroup analyses conducted in patients with urine protein measurements showed that the presence of proteinuria was associated with an increased risk of ESRD and death. Those with metabolic syndrome had much higher odds of proteinuria even after covariate adjustment; however, when the prior ESRD analyses were adjusted for proteinuria, there was no longer an association of metabolic syndrome with ESRD. We previously reported in a secondary analysis of the African-American Study of Kidney Disease and Hypertension (AASK) an association of 31% increased risk of CKD progression to ESRD or death in patients who met criteria for metabolic syndrome, but this was attenuated and no longer significant when adjusted for proteinuria (4). These findings, coupled with those from the current study, suggest that proteinuria may play an important role in the effect of metabolic syndrome on CKD progre...