Supplementary Material for: Chemokine (C-C Motif) Ligand 14 to Predict Persistent Severe Acute Kidney Injury: a Systematic Review and Meta-analysis.

Introduction: In this systematic review and meta-analysis, we aimed to review available data and provide pooled estimates of the predictive performance of urinary chemokine (CC motif) ligand (uCCL14’) for persistent (≥48 hours) severe acute kidney injury (PS-AKI).

Methods: We searched MEDLINE, PubMed, Cochrane Library, and EMBASE for studies published up to April 11, 2023. We considered all studies including adults and reporting on the ability of uCCL14 to predict PS-AKI as defined by AKI persisting for 48 or 72 hours. Data extraction was performed by one investigator using a standardized form. It was checked for adequacy and completeness by another investigator.

Results: After screening, we identified 13 relevant studies. Among those, four (561 patients) provided sufficient data regarding the outcome of interest and were included. Considering each study cut-off value, pooled sensitivity and specificity were 0.85 (95% CI: 0.77- 0.90, I2 = 34.1%) and 0.96 (95% CI: 0.94 – 0.98, I2 = 53.7%) respectively. Pooled positive likelihood ratio (LR), negative LR, and diagnostic odds ratio were 8.98 (95% CI: 4.92 – 16.37, I2 = 23%), 0.25 (95% CI: 0.17 - 0.37, I2 = 0%) and 14.98 (95% CI: 3.55 – 63.27, I2 = 72.9%) respectively. The area under the curve estimated by summary receiver operating characteristics was 0.86 (95% CI: 0.70 - 0.95). Heterogeneity induced by the threshold effect was low (Spearman correlation coefficient: -0.30 p-value = 0.62) but significant for non-threshold effect. Risk of bias and concern for applicability according to the QUADAS-2 criteria was generally low. High risk in the index test due to the absence of prespecified thresholds was a concern for most studies.

Conclusion: Based on current evidence, uCCL14 appears to have a good predictive performance for the occurrence of PS-AKI. Interventional trials to study a biomarker-guided application of AKI care bundles and RRT are indicated.