Urinary interleukin 18 for detection of acute kidney injury: a meta-analysis

Abstract

Background: Interleukin 18 (IL-18) has been proposed as a biomarker for the early detection of acute kidney injury (AKI), but a broad range of its predictive accuracy has been reported.

Study design: Meta-analysis of diagnostic test studies.

Setting & population: Various clinical settings of AKI, including after cardiac surgery, after contrast infusion, in the emergency department, or in the intensive care unit.

Selection criteria for studies: Prospective studies that investigated the diagnostic accuracy of IL-18 level to predict AKI.

Index tests: Increasing or increased urinary IL-18 excretion.

Reference tests: The primary outcome was AKI development, mainly based on serum creatinine level (definition varied across studies). The other outcome was in-hospital mortality.

Results: We analyzed data from 23 studies and 7 countries involving 4,512 patients. Of these studies, 18 could be included in the meta-analysis. Across all settings, the diagnostic odds ratio (DOR) for urinary IL-18 level to predict AKI was 4.22 (95% CI, 2.90-6.14), with sensitivity and specificity of 0.58 and 0.75, respectively. The area under the receiver operating characteristic curve (AUROC) of urinary IL-18 level to predict AKI was 0.70 (95% CI, 0.66-0.74). Subgroup analysis showed the DOR/AUROC of urinary IL-18 was 5.32 (95% CI, 2.92-9.70)/0.72 (95% CI, 0.68-0.76) in cardiac surgery patients and 3.65 (95% CI, 1.88-7.10)/0.66 (95% CI, 0.62-0.70) in intensive care unit or coronary care unit patients. After stratification for age, IL-18 level had better diagnostic accuracy in children and adolescents versus adults: 8.12 (95% CI, 3.79-17.41)/0.78 (95% CI, 0.75-0.82) versus 3.31 (95% CI, 2.28-4.80)/0.66 (95% CI, 0.62-0.70). There was no significant difference in predictive performance of urinary IL-18 level among various times.

Limitations: Various clinical settings; different definition of AKI and serum creatinine level as the reference standard test for the diagnosis of AKI.

Conclusions: Urinary IL-18 is a useful biomarker of AKI with moderate predictive value across all clinical settings.

Keywords: Interleukin 18; acute kidney injury; meta-analysis; review.