Objectives: Proteinuria serves as an indicator of both glomerular and renal endothelial injury in chronic kidney disease. However, there is insufficient evidence to predict how proteinuria may affect the incidence of acute kidney injury in the general population. Methods: The study involved 147,911 Korean adults who underwent health checkups between 2005-2006 and 2009-2010. They were categorized into four groups based on changes in proteinuria: negative (negative → negative), resolved (proteinuria ≥1+ → negative), incident (negative → proteinuria ≥1+), persistent: proteinuria ≥1+ → proteinuria ≥1+). We conducted a four-year follow-up to identify the risks of developing acute kidney injury (AKI) according to changes in proteinuria. A multivariate Cox proportional-hazards model was used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for AKI. Results: The AKI risk (expressed as HR [95% CI]) was the highest for persistent proteinuria, followed by incident proteinuria, compared with negative proteinuria (negative: reference, incident: 2.552 [95% CI, 1.926 to 3.380], and persistent: 4.349 [95% CI, 2.462 to 7.683]). When adjusted for age, sex, and underlying disease such as diabetes mellitus, hypertension, and dyslipidemia, the AKI risk exhibited a similar pattern to the crude analysis. Furthermore, completing risk analysis also demonstrated the highest risk in the persistent proteinuria group, followed by incident proteinuria. Conclusions: Proteinuria was significantly associated with developing AKI in the general population. Persistent proteinuria was associated with the highest risk, followed by incident proteinuria. Therefore, if proteinuria occurs or persists during health checkups, information is shared and necessary to prevent AKI development.