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Introduction: Depression is common but underrecognized in patients with chronic kidney disease (CKD), especially among racial/ethnic minorities. We examined the association between depressive symptoms and all-cause mortality (including deaths before and after end-stage renal disease [ESRD]) and whether antidepressant use impacts this association, overall, and by race/ethnicity. Methods: We ascertained whether the presence of depressive symptoms, defined by a Beck Depression Inventory II (BDI) score of >14 at cohort enrollment, was associated with all-cause mortality (before or after ESRD) among study participants of the Chronic Renal Insufficient Cohort (CRIC) overall and by race/ethnicity. Models were adjusted for socioeconomic factors, baseline CKD severity, time-updated comorbid conditions, and time-updated antidepressant use. Confirmatory analyses were performed among African American Study of Kidney Disease and Hypertension (AASK) participants. Results: Among 3739 CRIC participants, 16.3% had a baseline BDI of >14; 18.2% reported antidepressant use. Crude mortality rate was 3.16 per 100 person-years during 6.8 years of median follow-up. Baseline BDI >14 was independently associated with higher risk of all-cause mortality (adjusted hazard ratio [aHR]: 1.27; 95% confidence interval: 1.07–1.52) without attenuation by antidepressant use. Differences among white and black individuals were noted (Pinteraction= 0.02) but not among white versus Hispanic individuals (Pinteraction = 0.43) or black versus Hispanic individuals (Pinteraction = 0.22). Depressive symptoms were associated with higher mortality among white individuals (aHR: 1.66; 1.21–2.28), but not Hispanic individuals (aHR: 1.47; 0.95–2.28) or black individuals (aHR: 1.06; 0.82–1.37). Similar results were noted among 611 AASK participants (aHR: 0.99; 0.69–1.42). Conclusions: The presence of depressive symptoms is a risk factor for all-cause mortality among patients with mild-moderate CKD, particularly among white individuals. Further studies are needed to understand the heterogeneity in the response to the presence of depressive symptoms by race. Keywords: AASK, chronic kidney disease, CKD, CRIC, depression, mortality