Analysis of urinary C-C motif chemokine ligand 14 (CCL14) and first-generation urinary biomarkers for predicting renal recovery from acute kidney injury: a prospective exploratory study

Abstract

Background: Acute kidney injury (AKI) is a frequent syndrome in the intensive care unit (ICU). AKI patients with kidney function recovery have better short-term and long-term prognoses compared with those with non-recovery. Numerous studies focus on biomarkers to distinguish them. To better understand the predictive performance of urinary biomarkers of renal recovery in patients with AKI, we evaluated C-C motif chemokine ligand 14 (CCL14) and two first-generation biomarkers (cell cycle arrest biomarkers and neutrophil gelatinase-associated lipocalin) in two ICU settings.

Methods: We performed a prospective study to analyze urinary biomarkers for predicting renal recovery from AKI. Patients who developed AKI after ICU admission were enrolled and urinary biomarkers including tissue inhibitor of metalloproteinase-2 (TIMP-2), insulin-like growth factor-binding protein 7 (IGFBP7), CCL14, and neutrophil gelatinase-associated lipocalin (NGAL) were detected on the day of AKI diagnosis. The primary endpoint was non-recovery from AKI within 7 days. The individual discriminative ability of CCL14, [TIMP-2] × [IGFBP7] and NGAL to predict renal non-recovery were evaluated by the area under receiver operating characteristics curve (AUC).

Results: Of 164 AKI patients, 64 (39.0%) failed to recover from AKI onset. CCL14 showed a fair prediction ability for renal non-recovery with an AUC of 0.71 (95% CI 0.63-0.77, p < 0.001). [TIMP-2] × [IGFBP7] showed the best prediction for renal non-recovery with an AUC of 0.78 (95% CI 0.71-0.84, p < 0.001). However, NGAL had no use in predicting non-recovery with an AUC of 0.53 (95% CI 0.45-0.60, p = 0.562). A two-parameter model (non-renal SOFA score and AKI stage) predicted renal non-recovery with an AUC of 0.77 (95% CI 0.77-0.83, p = 0.004). When [TIMP-2] × [IGFBP7] was combined with the clinical factors, the AUC was significantly improved to 0.82 (95% CI 0.74-0.87, p = 0.049).

Conclusions: Urinary CCL14 and [TIMP-2] × [IGFBP7] were fair predictors of renal non-recovery from AKI. Combing urinary [TIMP-2] × [IGFBP7] with a clinical model consisting of non-renal SOFA score and AKI stage enhanced the predictive power for renal non-recovery. Urinary CCL14 showed no significant advantage in predicting renal non-recovery compared to [TIMP-2] × [IGFBP7].

Keywords: Acute kidney injury; CCL14; IGFBP7; NGAL; Prognosis; Renal recovery; TIMP-2.