BACKGROUND: Ultra-processing makes food products more convenient, appealing, and profitable. Recent studies show that high ultra-processed food (UPF) intake is associated with the cardio-metabolic disease.OBJECTIVES: The aim of this study is to investigate the association between UPF consumption and risk of kidney function decline in the general population.METHODS: In a prospective general population-based Lifelines cohort from Northern Netherlands, 78 346 participants free of chronic kidney disease (CKD) at baseline responded to a 110-item food frequency questionnaire. We used multivariable regression analysis to study the association of the proportion (in gram/day) of UPF in the total diet with a composite kidney outcome (incident CKD or a ≥ 30% eGFR decline relative to baseline) and annual change in estimated glomerular filtration rate (eGFR).RESULTS: On average, 37.7% of total food intake came from UPF. After 3.6 ± 0.9 years of follow-up, 2 470 participants (3.2%) reached the composite kidney outcome. Participants in the highest quartile of UPF consumption were associated with a higher risk of the composite kidney outcome (OR 1.27, [95% CI: 1.09, 1.47], P = 0.003) compared with those in the lowest quartile, regardless of macro/micronutrient intake or diet quality. Participants in the highest quartile had a more rapid eGFR decline (β -0.17, [95% CI: -0.23, -0.11], P < 0.001) compared with those in the lowest quartile. Associations were generally consistent across different subgroups.CONCLUSIONS: Higher UPF consumption was associated with a higher risk of a composite kidney outcome (incident CKD or ≥ 30% eGFR decline) and a more rapid eGFR decline in the general population, independent of confounders and other dietary indices.