Metabolic Syndrome and the Development of CKD in American Indians: The Strong Heart Study Jaime Lucove, MSPH, 1 Suma Vupputuri, PhD, 1,2 Gerardo Heiss, MD, PhD, 1 Kari North, PhD, 1 and Marie Russell, MD 3 Background: Metabolic impairments that precede type 2 diabetes, such as metabolic syndrome, may contribute to the development of chronic kidney disease (CKD). This study documents the prevalence and incidence of CKD and the prospective association between metabolic syndrome and CKD in American Indians without diabetes in the Strong Heart Study. Study Design: Prospective cohort study. Setting & Participants: American Indians aged 45 to 74 years from 3 geographic regions were recruited by using tribal records and were assessed every 3 years from 1989 to 1999 as part of the Strong Heart Study. Participants with type 2 diabetes, on dialysis therapy, or who received a kidney transplant at baseline examination were excluded. Predictor: Metabolic syndrome, defined using Adult Treatment Panel III criteria. Outcomes & Measurements: CKD was measured by using estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (ACR) dichotomized at conventional cutoff values. The association between metabolic syndrome and incident CKD was evaluated by using multivariable Cox proportional hazards models and binomial regression, with statistical adjustment for confounders (age, sex, study center, education, and smoking). Results: Metabolic syndrome was present in 896 (37.7%) and absent in 1,484 participants (62.3%) at baseline. The prevalence of ACR of 30 mg/g or greater at baseline examination was 12.1%, with 290 new cases and an incidence of 233/10,000 person-years. The prevalence of eGFR less than 60 mL/min/1.73 m 2 was 7.8%, with 189 new cases and an incidence of 138/10,000 person-years. The prevalence of CKD was 17.8%, with 388 new cases and an incidence of 342/10,000 person-years. The adjusted hazard ratio for CKD associated with metabolic syndrome was 1.3 (95% confidence interval [CI], 1.1 to 1.6). Equivalent hazard ratios for ACR greater than 30 mg/g and eGFR less than 60 mL/min/1.73 m 2 were 1.4 (95% CI, 1.0 to 1.9) and 1.3 (95% CI, 1.0 to 1.6), respectively. The relationship between metabolic syndrome and kidney outcomes was stronger in those who developed diabetes during follow-up. Limitations: Intraindividual variability in serum creatinine and ACR measures may have resulted in some misclassification of participants by outcome status. Conclusions: Metabolic syndrome is associated with an increased risk of developing CKD in American Indians without diabetes. The mechanism through which metabolic syndrome may cause CKD in this population likely is the development of diabetes. Am J Kidney Dis 51:21-28. © 2007 by the National Kidney Foundation, Inc. INDEX WORDS: Metabolic syndrome; glomerular filtration rate; albuminuria; chronic kidney disease; American Indians. T he prevalence of end-stage renal disease (ESRD) continues to increase in the United States and represents a growing clinical and public health problem. 1,2 American Indians expe- rience a greater burden of ESRD than whites. The prevalence of ESRD in American Indians is 2.5 times that of whites. 1 Although it is difficult to attribute causes of ESRD, diabetes and hyper- tension are estimated to account for 44% and 27% of incident ESRD, respectively. 1 American Indians also experience a disproportionate bur- den of type 2 diabetes mellitus. 3 From the 1 Department of Epidemiology, University of North Carolina-Chapel Hill; 2 University of North Carolina Kidney Center, Chapel Hill, NC; and 3 Medstar Research Institute, Phoenix, AZ. Received January 23, 2007. Accepted in revised form September 27, 2007. Originally published online as doi: 10.1053/j.ajkd.2007.09.014 on November 28, 2007. This work was performed at the University of North Carolina-Chapel Hill and all Strong Heart Study Cen- ters: Medstar Research Institute, Aberdeen Area In- dian Health Service, Aberdeen Area Tribal Chairmen’s Health Board, Center for American Indian Health Re- search, and University of Oklahoma Health Sciences Center. Address correspondence to Jaime C. Lucove, MSPH, Research Scientist, Allscripts, 27 East Delaware Ave, Pen- nington, NJ. E-mail: jaime_lucove@hotmail.com © 2007 by the National Kidney Foundation, Inc. 0272-6386/07/5101-0004$34.00/0 doi:10.1053/j.ajkd.2007.09.014 American Journal of Kidney Diseases, Vol 51, No 1 (January), 2008: pp 21-28 21