Background and objectives: Low eGFR is known to be associated with frailty, but the association between the longitudinal decline of eGFR and incident frailty in older persons remains to be determined. The objective of this study was to investigate whether a fast decline on eGFR would be associated with incident frailty.Design, setting, participants, & measurements: Community dwellers, aged ≥70, were included in this secondary analysis of the 5-year Multidomain Alzheimer Preventive Trial (MAPT). eGFR was calculated using CKD-Epidemiology Collaboration equation at baseline and at 6, 12, and 24 months. The lowest quartile of eGFR slope (-4.1 ml/min per 1.73 m2 per yr) defined a fast decline. The frailty phenotype (unintentional weight loss, exhaustion, low physical activity, slow gait, low handgrip strength assessed with a 0-5 score, where higher is worse; a score ≥3 defines frailty) was assessed at baseline, 6, 12, 24, 36, 48, and 60 months. Cox models were used to test the association between fast eGFR decline and incident frailty.Results: A total of 833 participants were frail neither at baseline nor at 2 years and had appropriate follow-up data. Median (IQR) baseline eGFR was 73 (61-84) ml/min per 1.73 m2. Frailty occurred in 95 (11%) participants between 24 and 60 months. Among them, 31/207 (15%) had fast eGFR decline between baseline and 24 months, and 64/626 (10%) did not. In a Cox model adjusted for demographic variables, cardiovascular comorbidity, C-reactive protein, and baseline eGFR, a fast eGFR decline was associated with incident frailty (HR 1.67, 95% CI 1.03 to 2.71). Sensitivity analyses provided consistent findings.Conclusions: In community-dwelling older adults with relatively preserved baseline eGFR, a fast eGFR decline is associated with incident frailty.Trial registration: ClinicalTrials.gov NCT00672685.