Background: In this study, we investigated the relationship between serum uric acid (SUA) and renal function in a unique patient cohort wherein SUA levels fluctuate during the course of standard care. Methods: Correlation coefficients between SUA and serum creatinine (SCr) and kinetic estimated GFR (KeGFR) were retrospectively investigated in acute myeloid leukemia (AML) patients, and statistically significant and clinically relevant determinants were studied in multiple regression models. Results: One hundred and twenty-six patients were included in the analysis. Baseline SUA was associated with an increased risk for acute kidney injury (AKI; OR 1.27, 95% CI 1.1-1.5, p = 0.003) and laboratory tumor lysis syndrome (OR 1.26, 95% CI 1.1-1.5, p = 0.005). Prophylactic uric acid-lowering therapy and hydration resulted in lower SUA values from baseline in 88.1% of the patients, the lowest values were observed on post-induction day 1 (20.4% reduction). Significant linear correlations were observed between SUA and SCr (r = 0.35, p < 0.001) values with a significant inverse correlation between SUA and KeGFR on day 1 (r = -0.33, p < 0.001) that persisted through day 4. By subgroup analysis, patients with primary AML (r = -0.49, p < 0.001), baseline SUA >5.5 mg/dl (r = -0.41, p = 0.002) and baseline eGFR >60 ml/min/1.73 m2 (r = -0.51, p < 0.001) demonstrated robust relationships between SUA and KeGFR. The relationship was more robust when the groups were combined (primary AML plus baseline SUA >5.5 mg/dl plus baseline eGFR >60 ml/min/1.73 m2, r = -0.52, p < 0.001). Conclusion: The demonstration of linear relationship between SUA and SCr and inverse relationship between SUA and KeGFR reinforces the emerging translational physiological evidence regarding the role of uric acid in AKI.