Abstract

BackgroundPersistent acute kidney injury (AKI) portends worse clinical outcomes and remains a therapeutic challenge for clinicians. A recent study found that urinary C–C motif chemokine ligand 14 (CCL14) can predict the development of persistent AKI. We aimed to externally validate urinary CCL14 for the prediction of persistent AKI in critically ill patients.MethodsThis was a secondary analysis of the prospective multi-center SAPPHIRE study. We evaluated critically ill patients with cardiac and/or respiratory dysfunction who developed Kidney Disease: Improving Global Outcomes (KDIGO) stage 2–3 AKI within one week of enrollment. The main exposure was the urinary concentration of CCL14 measured at the onset of AKI stage 2–3. The primary endpoint was the development of persistent severe AKI, defined as ≥ 72 h of KDIGO stage 3 AKI or death or renal-replacement therapy (RRT) prior to 72 h. The secondary endpoint was a composite of RRT and/or death by 90 days. We used receiver operating characteristic (ROC) curve analysis to assess discriminative ability of urinary CCL14 for the development of persistent severe AKI and multivariate analysis to compare tertiles of urinary CCL14 and outcomes.ResultsWe included 195 patients who developed KDIGO stage 2–3 AKI. Of these, 28 (14%) developed persistent severe AKI, of whom 15 had AKI ≥ 72 h, 12 received RRT and 1 died prior to ≥ 72 h of KDIGO stage 3 AKI. Persistent severe AKI was associated with chronic kidney disease, diabetes mellitus, higher non-renal APACHE III score, greater fluid balance, vasopressor use, and greater change in baseline serum creatinine. The AUC for urinary CCL14 to predict persistent severe AKI was 0.81 (95% CI, 0.72–0.89). The risk of persistent severe AKI increased with higher values of urinary CCL14. RRT and/or death at 90 days increased within tertiles of urinary CCL14 concentration.ConclusionsThis secondary analysis externally validates urinary CCL14 to predict persistent severe AKI in critically ill patients.

Highlights

  • Persistent acute kidney injury (AKI) portends worse clinical outcomes and remains a therapeutic challenge for clinicians

  • Persistent severe AKI was associated with higher non-renal Acute Physiology and Chronic Health Evaluation (APACHE) III scores, greater positive fluid balance, and more vasopressor use at enrollment

  • C motif chemokine ligand 14 (CCL14) and persistent severe AKI Urinary CCL14 showed good prediction for the occurrence of persistent severe AKI with an area under the receiver operating characteristic (ROC) curve (AUC) 0.81 (Fig. 2)

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Summary

Introduction

Persistent acute kidney injury (AKI) portends worse clinical outcomes and remains a therapeutic challenge for clinicians. There are no interventions proven to modify the clinical course for patients with persistent AKI [4] This is likely attributable to the inability to predict those at high risk for development of persistent AKI, a factor that has undoubtedly hampered suitable patient selection for clinical trials and contributed to therapeutic uncertainty for clinicians [5]. The RUBY study described the discovery of urinary C–C motif chemokine ligand-14 (CCL14) to predict the development of persistent severe AKI, defined as Kidney Disease: Improving Global Outcomes (KDIGO) stage 3 AKI for 72 h or greater, among 331 critically ill patients with KDIGO stage 2 or greater AKI (AUC 0.83) [6]. CCL14 is a member of the chemokine family recognized for its role in macrophage trafficking and may contribute to the development of persistent kidney damage, maladaptive repair, and risk for non-recovery of kidney function [6, 7]

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