Cell cycle arrest biomarkers for predicting renal recovery from acute kidney injury: a prospective validation study

Abstract Background: Acute kidney injury (AKI) is a common disease in intensive care unit (ICU). AKI patients with non-recovery of renal function have a markedly increased risk of death compared with recovery patients. The current study aimed to explore and validate the utility of urinary cell cycle arrest biomarkers for predicting non-recovery in patients who developed AKI after ICU admission.Methods: We prospectively and consecutively enrolled 379 critically ill patients who developed AKI after admission to ICU, which divided into a derivation cohort (194 AKI patients) and a validation cohort (185 AKI patients). The biomarkers of urinary tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) were detected at inclusion (day 0) and 24 hours later (day 1). immediately after AKI diagnosis. The optimal cutoff values of biomarkers for predicting non-recovery was estimated in the derivation cohort, and the predictive accuracy of the biomarkers was assessed in the validation cohort. The primary endpoint was non-recovery from AKI (within 7 days).Results: 159 of 379 (41.9 %) patients failed to recover from AKI onset, with 79 in the derivation cohort and 80 in the validation cohort. Urinary [TIMP-2]*[IGFBP7] showed a better prediction for non-recovery than TIMP-2 and IGFBP7 alone, with the AUC of 0.751 (95 % CI 0.701 - 0.852, p < 0.001) and an optimal cutoff value of 1.05 ((ng/mL)2/1000). When [TIMP-2]*[IGFBP7] combined with clinical factors of AKI diagnosed by urine output (UO) criteria, AKI stage 2-3 and nonrenal SOFA score for predicting non-recovery, the AUC was significantly improved to 0.852 (95 % CI 0.750 - 0.891, p < 0.001), which achieved the sensitivity and specificity of 88.8 % (72.9, 98.7) and 92.6 % (80.8, 100.0), respectively.Conclusion: Urinary [TIMP-2]*[IGFBP7] represents a sensitive and specific biomarker to predict failure to recover from AKI. The predictive accuracy can be improved when urinary [TIMP-2]*[IGFBP7] combines with clinical factors of AKI diagnosed by UO criteria, AKI stage 2-3 and nonrenal SOFA score.