Serum and urinary biomarkers to predict acute kidney injury in premature infants: a systematic review and meta-analysis of diagnostic accuracy

Abstract

Background Premature infants are at high risk for acute kidney injury (AKI) and current diagnostic criteria are flawed. The objective of this study was to determine the diagnostic accuracy of urine and serum biomarkers not currently used in routine clinical practice to predict AKI in premature infants. Method A systematic review was performed that followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy Studies (PRISMA-DTA). Data were extracted on the diagnostic accuracy of AKI biomarkers using serum creatinine or urine output as the reference standard. Quality and validity were assessed using modified Standards for Reporting Diagnostic Accuracy (STARD) criteria. Results We identified 1024 articles, with 15 studies (791 infants) eligible for inclusion. Twenty-seven biomarkers were identified including serum cystatin C and urinary neutrophil gelatinase-associated lipocalin (uNGAL), osteopontin, kidney injury molecule-1, epidermal growth factor, and protein S100-P. However, many were only reported by one study each. A meta-analysis could only be conducted on uNGAL (288 infants from 6 studies) using a hierarchical, random-effects logistic-regression model. uNGAL had a summary sensitivity of 77% (95% CI 58–89%), specificity of 76% (95% CI 57–88%) and AUC-SROC of 0.83 (95% CI 0.80–0.86) for the diagnosis of AKI. By utilising uNGAL, the post-test probability of AKI increased to 52% (95% CI 37–66%) with a positive test and decreased to 9% (95% CI 5–16%) with a negative test if the pre-test probability was 25%. Conclusion uNGAL shows promise as a diagnostically accurate biomarker for AKI in premature infants. Graphical abstract

Serum neutrophil gelatinase-associated lipocalin (NGAL) as a diagnostic tool in pediatric acute appendicitis: a prospective validation study

“…Serum neutrophil gelatinase-associated lipocalin (NGAL), also called lipocalin 2 (LCN2), 24p3 lipocalin or siderocalin is a small protein of 178 amino acids, which is expressed at low concentrations in various tissues of the human body, including the kidney, lung, and gastrointestinal tract. Although classically attributed with the function of sequestering siderophores as a bacteriostatic mechanism, it has recently been shown to be a useful marker in acute kidney injury [ 10 ].…”

Pharmacovigilance of nephrotoxic drugs in neonates: the Pottel method for renal signal detection in ELBW neonates

“…Several biomarkers have been explored in the pediatric and adult literature, but data on the premature neonatal population are limited. In preterm neonates serum cystatin C demonstrates high diagnostic accuracy surpassing Scr but urinary levels yield con icting results [24][25][26][27]. Neutrophil gelatinase-associated lipocalin (NGAL) shows promise in preterm neonates for both serum and urine concentrations but the speci city appears to be limited by strong associations with in ammatory parameters [24,26,28].…”

“…Neutrophil gelatinase-associated lipocalin (NGAL) shows promise in preterm neonates for both serum and urine concentrations but the speci city appears to be limited by strong associations with in ammatory parameters [24,26,28]. A scala of other potential biomarkers, such as urinary kidney injury molecule-1 (uKIM-1) have been investigated in limited studies in premature neonates [24,26,29,30]. Recently various urinary biomarkers were found to be statistically signi cantly elevated in extremely premature neonates treated with or without nephrotoxic drugs, without a signi cant difference in AKI diagnosis showing their potential to detect subclinical kidney (tubular) damage [31].…”

Biomarkers for acute kidney injury in children – where are we now?

“…Since AKI could be a heterogeneous condition with variable etiologies, many studies examined biomarker performance in all children admitted to intensive care units. One systematic review and meta-analysis focused on children in the neonatal intensive care unit included 791 premature infants from 15 studies and evaluated the diagnostic accuracy of several biomarkers of AKI [23 ▪ ]. Among studied biomarkers, urine NGAL had the best performance with a sensitivity of 77%, (95% CI 58–89), specificity of 76% (95% CI 57–88) and summary AUC (0.83, 95% CI 0.80–0.86).…”