ObjectivesThe performance of renal resistance index (RRI) in predicting persistent sepsis-associated acute kidney injury (S-AKI) remains debatable, and the value of urinary C–C motif chemokine ligand 14 (CCL14) in predicting persistent S-AKI has not been validated yet. Therefore, we aimed to determine the applicability of a urinary biomarker CCL14 for the early detection of persistent S-AKI. Furthermore, the use of RRI obtained from renal Doppler ultrasonography was applied to differentiate transient from persistent S-AKI. Finally, we aimed to evaluate the use of these techniques in predicting different subtypes of S-AKI.MethodsThis prospective observational study was conducted at the internal medicine intensive care unit (ICU) of a university hospital. The RRI was determined within 12 h of ICU admission and the urinary CCL14 was evaluated at T0, T6, T12, and T24. The reversibility of renal dysfunction was assessed within 48 h. The receiver operating characteristic curves were then plotted to assess the diagnostic efficacy of the RRI and urinary CCL14 in predicting persistent S-AKI.ResultsOut of 48 patients, 23 developed persistent S-AKI upon admission. The RRI was higher in the persistent S-AKI group (P= 0.02) and the RRI ≥ 0.679 could predict persistent S-AKI with an area under the receiver operating characteristic curve of 0.79 (95% CI 0.65–0.93), a sensitivity of 91.30% (95% CI 70–98%), and a specificity of 65.20% (95% CI 43–83%). Urinary CCL14 was not significantly different between the two groups at the tested period, showing poor diagnostic performance at T0, T6, T12, and T24, with areas under the receiver operating characteristic curves of 0.56 (95% CI 0.38–0.73), 0.62 (95% CI 0.46–0.79), 0.52 (95% CI 0.35–0.68), and 0.60 (95% CI 0.43–0.77), respectively.ConclusionsThe RRI obtained from renal Doppler ultrasound is extremely effective in predicting persistent S-AKI in critically ill patients, and urinary CCL14 could not distinguish between transient and persistent S-AKIs.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11255-023-03511-6.