Dataset Information

Performance of a Standardized Clinical Assay for Urinary C-C Motif Chemokine Ligand 14 (CCL14) for Persistent Severe Acute Kidney Injury.

ABSTRACT:

Background

Clinical use of biomarkers requires the development of standardized assays and establishment of cutoffs. Urinary C-C motif chemokine ligand 14 (CCL14) has been validated to predict persistent severe AKI in critically ill patients with established AKI. We now report on the performance of standardized cutoffs using a clinical assay.

Methods

A second aim of the multicenter RUBY Study was to establish two cutoffs for the prediction of persistent severe AKI (defined as KDIGO stage 3 AKI for at least 72 consecutive hours). Patients who received renal replacement therapy (RRT) or died before achieving 72 hours in stage 3 AKI were also considered to have reached the end point.

Results

A cutoff value for urinary CCL14 of 1.3 ng/ml was determined to achieve high sensitivity (91%; 95% CI, 84% to 96%), and 13 ng/ml achieved high specificity (93%; 95% CI, 89% to 96%). The cutoff of 1.3 ng/ml identifies the majority (91%) of patients who developed persistent severe AKI with a negative predictive value of 92%. The cutoff at 13 ng/ml had a positive predictive value of 72% (with a negative predictive value of 75%). In multivariable adjusted analyses, a CCL14 concentration between 1.3 and 13 ng/ml had an adjusted odds ratio (aOR) of 3.82 (95% CI, 1.73 to 9.12; P=0.001) for the development of persistent severe AKI compared with those with a CCL14 ≤1.3 ng/ml, whereas a CCL14 >13 ng/ml had an aOR of 10.4 (95% CI, 3.89 to 29.9; P<0.001).

Conclusions

Using a clinical assay, these standardized cutoffs (1.3 and 13 ng/ml) allow for the identification of patients at high risk for the development of persistent severe AKI. These results have immediate utility in helping to guide AKI patient care and may facilitate future clinical trials.Clinical Trial registry name and registration number: Identification and Validation of Biomarkers of Acute Kidney Injury Recovery, NCT01868724.

SUBMITTER: Koyner JL

PROVIDER: S-EPMC9337886 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Publications

Performance of a Standardized Clinical Assay for Urinary C-C Motif Chemokine Ligand 14 (CCL14) for Persistent Severe Acute Kidney Injury.

Koyner Jay L JL Chawla Lakhmir S LS Bihorac Azra A Gunnerson Kyle J KJ Schroeder Rebecca R Demirjian Sevag S Hodgson Luke L Frey Jennifer A JA Wilber Scott T ST Kampf J Patrick JP Kwan Thomas T McPherson Paul P Kellum John A JA

Kidney360 20220324 7

<h4>Background</h4>Clinical use of biomarkers requires the development of standardized assays and establishment of cutoffs. Urinary C-C motif chemokine ligand 14 (CCL14) has been validated to predict persistent severe AKI in critically ill patients with established AKI. We now report on the performance of standardized cutoffs using a clinical assay.<h4>Methods</h4>A second aim of the multicenter RUBY Study was to establish two cutoffs for the prediction of persistent severe AKI (defined as KDIGO ...[more]

PMID: 35919538

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Project description: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.

Project description:BackgroundAcute 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.MethodsWe 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).ResultsOf 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).ConclusionsUrinary 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].

Project description: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.

Dataset Information

Performance of a Standardized Clinical Assay for Urinary C-C Motif Chemokine Ligand 14 (CCL14) for Persistent Severe Acute Kidney Injury.

Background

Methods

Results

Conclusions

Publications

Performance of a Standardized Clinical Assay for Urinary C-C Motif Chemokine Ligand 14 (CCL14) for Persistent Severe Acute Kidney Injury.

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