Jef Van den Eynde1,2, Art Schuermans3, Jan Y Verbakel4,5, Marc Gewillig2,6, Shelby Kutty1, Karel Allegaert7,8,9, Djalila Mekahli10,11. 1. Helen B. Taussig Heart Center, The Johns Hopkins Hospital and School of Medicine, Baltimore, USA. 2. Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium. 3. Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium. art.schuermans@student.kuleuven.be. 4. Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium. 5. Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK. 6. Pediatric Cardiology, University Hospitals Leuven, Leuven, Belgium. 7. Department of Development and Regeneration, KU Leuven, Leuven, Belgium. 8. Department of Pharmacy and Pharmaceutical Sciences, KU Leuven, Leuven, Belgium. 9. Department of Hospital Pharmacy, Erasmus Medical Center, Rotterdam, Netherlands. 10. Department of Pediatric Nephrology, University Hospitals of Leuven, Leuven, Belgium. 11. PKD Research Group, GPURE, Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
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.
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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