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Neutrophil gelatinase-associated lipocalin as predictor of acute kidney injury in neonates with perinatal asphyxia: a systematic review and meta-analysis

Abstract

There is growing evidence that neutrophil gelatinase-associated lipocalin (NGAL) is a promising biomarker of acute kidney injury. The objective of this meta-analysis is to determine the accuracy of serum and urinary NGAL in the detection of acute kidney injury in neonates with perinatal asphyxia. Medline (1966–2018), Scopus (2004–2018), EMBASE (1980–2018), Clinicaltrials.gov (2008–2018), and Google Scholar (2004–2018) databases, along with the reference lists of the electronically retrieved articles, were systematically searched. Eleven studies were included, with a total number of 652 neonates. The summary sensitivity of serum NGAL was 0.818 (95% CI [0.668, 0.909]), the specificity 0.870 (95% CI [0.754, 0.936]), and the area under the curve 0.912. Regarding urinary NGAL, pooled sensitivity was calculated at 0.897 (95% CI [0.829, 0.940]), specificity at 0.729 (95% CI [0.561, 0.850]), and area under the curve at 0.899.

Conclusion: Serum and urinary NGAL represent candidate biomarkers with high performance in the prediction of acute kidney injury in newborns with perinatal asphyxia. Before NGAL can be widely used in clinical practice, future large prospective studies are needed to define the optimal cutoffs and accurately determine which levels are suggestive of post-asphyxial acute kidney injury.

What is Known:
Acute kidney injury is a major cause of morbidity and mortality in perinatal asphyxia.
Current markers are insufficient in predicting post-asphyxial acute kidney injury.
What is New:
Area under the curve for serum and urinary neutrophil gelatinase-associated lipocalin is 0.818 and 0.899, respectively.
Neutrophil gelatinase-associated lipocalin is a useful marker for detecting asphyxiated neonates at risk of developing acute kidney injury.

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Abbreviations

95% CI:

95% confidence intervals

AKI:

Acute kidney injury

AKIN:

Acute Kidney Injury Network

AUC:

Area under the curve

DOR:

Diagnostic odds ratio

ESS:

Effective sample size

GFR:

Glomerular filtration rate

KDIGO:

Kidney Disease: Improving Global Outcomes

LR:

Likelihood ratio

NGAL:

Neutrophil gelatinase-associated lipocalin

PRISMA:

Preferred Reporting Items for Systematic Reviews and Meta-Analyses

ROBINS:

Risk Of Bias In Non-randomized Studies

SROC:

Summary receiver operating characteristic

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Author information

Ioannis Bellos conceived the idea and designed the analysis.

Georgia Fitrou performed the literature search and tabulated the data.

Georgios Daskalakis performed the statistical analysis and wrote the manuscript.

Despina N. Perrea performed the quality assessment and the sensitivity analysis.

Vasilios Pergialiotis contributed to the quality assessment and revised the manuscript.

Correspondence to Ioannis Bellos.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

The present systematic review and meta-analysis is based on aggregated data that were retrieved from studies already retrieved. We did not collect individual patient data and did not have direct contact with patients included.

Additional information

Communicated by Patrick Van Reempts

Electronic supplementary material

Supplemental Table 1

Methodological characteristics of the included studies. (DOCX 20 kb)

Supplemental Table 2

Patients’ characteristics of the included studies. (DOCX 16 kb)

Supplemental Table 3

Outcomes of ROBINS-I evaluation. The overall risk of bias was evaluated as moderate. (DOCX 18 kb)

Supplemental Table 4

Results of the qualitative synthesis. NGAL levels were significantly higher in asphyxiated newborns with acute kidney injury. (DOCX 23 kb)

Supplemental Table 5

Outcomes of the leave-one-out analysis. No single study affected significantly the overall results. (DOCX 14 kb)

Supplemental Figure 1

Forest plots for sensitivity and specificity of serum and urinary NGAL. (PNG 265 kb)

Supplemental Figure 2

Deeks’ funnel plot. No evidence of publication bias is present (p-value >0.05). (PNG 37 kb)

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Bellos, I., Fitrou, G., Daskalakis, G. et al. Neutrophil gelatinase-associated lipocalin as predictor of acute kidney injury in neonates with perinatal asphyxia: a systematic review and meta-analysis. Eur J Pediatr 177, 1425–1434 (2018). https://doi.org/10.1007/s00431-018-3221-z

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Keywords

  • Acute kidney injury
  • Perinatal asphyxia
  • Neutrophil gelatinase-associated lipocalin
  • NGAL
  • Meta-analysis