Background: Left ventricular hypertrophy is common and is associated with cardiovascular events and death among patients with known chronic kidney disease. However, the link between reduced glomerular filtration rate (GFR) and left ventricular mass index (LVMI) remains poorly explored among young and middle-aged adults with preserved kidney function. In this study, we examined the association of cystatin C-based estimated GFR (eGFR(cys)) and rapid decline in eGFR with subsequent LVMI. Study Design: Observational study. Setting & Participants: We included 2,410 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort with eGFR(cys) > 60 mL/min/1.73 m(2) at year 15 and who had an echocardiogram obtained at year 25. Predictor: eGFR(cys) at year 15 and rapid decline in eGFR(cys) (defined as >3% per year over 5 years from years 15 to 20). Outcome: LVMI measured at year 25. Measurements: We adjusted for age, sex, race, diabetes, body mass index, low- and high-density lipoprotein cholesterol levels, cumulative systolic blood pressure, and albuminuria. Results: Mean age was 40 +/- 4 (SD) years, 58% were women, and 43% were black. After 10 years of follow-up, mean LVMI was 39.6 +/- 13.4 g/m(2.7). Compared with eGFR(cys) > 90 mL/min/1.73 m(2) (n = 2,228), eGFR(cys) of 60 to 75 mL/min/1.73 m(2) (n = 29) was associated with 5.63 (95% Cl, 0.90-10.36) g/m(2.7) greater LVMI (P = 0.02), but there was no association of eGFR(cys) of 76 to 90 mL/min/1.73 m(2) (n = 153) with LVMI after adjustment for confounders. Rapid decline in eGFR(cys) was associated with higher LVMI compared with participants without a rapid eGFR(cys) decline (beta coefficient, 1.48; 95% Cl, 0.11-2.83; P = 0.03) after adjustment for confounders. Limitations: There were a limited number of participants with eGFR(cys) of 60 to 90 mL/min/1.73 m(2). Conclusions: Among young and middle-aged adults with preserved kidney function, eGFR(cys) of 60 to 75 mL/min/1.73 m(2) and rapid decline in eGFR(cys) were significantly associated with subsequently higher LVMI. Further studies are needed to understand the mechanisms that contribute to elevated LVMI in this range of eGFR(cys). (C) 2016 by the National Kidney Foundation, Inc.