Abstract
Acute kidney injury (AKI) occurs frequently after cardiac surgery in children. Although current diagnostic criteria rely on serum creatinine and urine output, changes occur only after considerable loss of kidney function. This meta-analysis aimed to synthesize the knowledge on novel biomarkers and compare their ability to predict AKI. PubMed/MEDLINE, Embase, Scopus, and reference lists were searched for relevant studies published by March 2021. Diagnostic accuracy parameters were extracted and analyzed using hierarchical summary receiver operating characteristic (HSROC) method. Pooled estimates of the area under the curve (AUC) were calculated using conventional random-effects meta-analysis. Fifty-six articles investigating 49 biomarkers in 8617 participants fulfilled our eligibility criteria. Data from 37 studies were available for meta-analysis. Of the 10 biomarkers suitable for HSROC analysis, urinary neutrophil gelatinase-associated lipocalin (uNGAL) to creatinine (Cr) ratio yielded the highest diagnostic odds ratio (91.0, 95% CI 90.1–91.9), with a sensitivity of 91.3% (95% CI 91.2–91.3%) and a specificity of 89.7% (95% CI 89.6–89.7%). These results were confirmed in pooled AUC analysis, as uNGAL-to-Cr ratio and uNGAL were the only elaborately studied biomarkers (> 5 observations) with pooled AUCs ≥ 0.800. Liver fatty acid-binding protein (L-FABP), serum cystatin C (sCysC), serum NGAL (sNGAL), and interleukin-18 (IL-18) all had AUCs ≥ 0.700.
Conclusion: A variety of biomarkers have been proposed as predictors of cardiac surgery-associated AKI in children, of which uNGAL was the most prominent with excellent diagnostic qualities. However, more consolidatory evidence will be required before these novel biomarkers may eventually help realize precision medicine in AKI management.
What is Known: • Acute kidney injury (AKI) occurs in about 30–60% of children undergoing cardiac surgery and is associated with increased in-hospital mortality and adverse short-term outcomes. However, in current clinical practice, AKI definitions and detection often rely on changes in serum creatinine and urine output, which are late and insensitive markers of kidney injury. • Although various novel biomarkers have been studied for the diagnosis of AKI in children after cardiac surgery, it remains unclear how these compare to one another in terms of diagnostic accuracy. | |
What is New: • Pooled analyses suggest that for the diagnosis of AKI in children who underwent cardiac surgery, NGAL is the most accurate among the most frequently studied biomarkers. • A number of other promising biomarkers have been reported, although they will require further research into their diagnostic accuracy and clinical applicability. |
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Abbreviations
- AKI:
-
Acute kidney injury
- AKIN:
-
Acute Kidney Injury Network
- AUC:
-
Area under the curve
- CI:
-
Confidence interval
- CPB:
-
Cardiopulmonary bypass
- CysC:
-
Cystatin C
- DOR:
-
Diagnostic odds ratio
- FP:
-
False positives
- FN:
-
False negatives
- H-FABP:
-
Heart-type fatty acid-binding protein
- HSROC:
-
Hierarchical summary receiver operating characteristic curve
- HVA-SO4:
-
Homovanillic acid sulfate
- IGFBP7:
-
Insulin-like growth factor-binding protein 7
- IL-6:
-
Interleukin 6
- IL-8:
-
Interleukin 18
- KDIGO:
-
Kidney Disease Improving Global Outcomes
- KIM-1:
-
Kidney injury molecule-1
- KIU:
-
Kallikrein inhibiting units
- L-FABP:
-
Liver fatty acid-binding protein
- LR:
-
Likelihood ratio
- MOOSE:
-
Meta-analysis Of Observational Studies in Epidemiology
- NGAL:
-
Neutrophil gelatinase-associated lipocalin
- NPV:
-
Negative predictive value
- PPV:
-
Positive predictive value
- PRISMA:
-
Preferred Reporting Items for Systematic reviews and Meta-Analyses
- RIFLE:
-
Risk for renal dysfunction, Injury to the kidney, Failure of kidney function, Loss of kidney function and End-stage renal disease
- SCr:
-
Serum creatinine
- TIMP-2:
-
Tissue inhibitor of metalloproteinase 2
- TP:
-
True positives
- TN:
-
True negatives
- UMOD:
-
Uromodulin
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J. Van den Eynde was supported by the Belgian American Educational Foundation.
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Mr. Van den Eynde and Mr. Schuermans conceptualized and designed the study, collected data, carried out the initial analyses, drafted the initial manuscript, and reviewed and revised the manuscript. Profs. Verbakel, Gewillig, Kutty, Allegaert, and Mekahli conceptualized and designed the study, coordinated and supervised data collection, and critically reviewed the manuscript for important intellectual content. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
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Van den Eynde, J., Schuermans, A., Verbakel, J.Y. et al. Biomarkers of acute kidney injury after pediatric cardiac surgery: a meta-analysis of diagnostic test accuracy. Eur J Pediatr 181, 1909–1921 (2022). https://doi.org/10.1007/s00431-022-04380-4
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DOI: https://doi.org/10.1007/s00431-022-04380-4