Pre and post analytical pitfalls of neutrophil gelatinase-associated lipocalin and cell cycle arrest biomarkers predicting acute kidney injury

Giovanni Introcaso, Erminio Sisillo, Valentina Urso, Camilla L’acqua, Alice Bonomi, Roberto Ceriani, Maria Luisa Biondi

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AKI disorder is one of most serious clinical conditions recognized worldwide. In recent years, many improvements were made both for renal biomarkers and to know better the total testing process (TTP) in laboratory medicine including pre and post analytical phases. However, TTP for new renal biomarkers remains an issue. We conducted the present study to determine pre/ post-analytical pitfalls of neutrophil gelatinase-associated lipocalin (NGAL) and tissue inhibitor of metalloproteinase 2-insulin-like growth factor binding protein 7 [TIMP-2]-[IGFBP-7] called Nephrocheck test. Material and Methods. We analyzed urinary samples collected in two previous studies at intensive care unit (ICU) from an adult population undergoing cardiac surgery. We performed measurements using a chemiluminescent method on an automatic analytical platform and a point of care testing Nephrocheck (Astute-Meter). Biochemical results were analyzed without and with the urine creatinine (uCrea) correction. Furthermore, a method to calculate the mean variation rate was applied for different biomarker concentrations using differential equations. Results. A received operating curve for predicting AKI was obtained with AUC value= 0.66 corresponding to the better NGAL cut-off= 29 ng/mL (p= 0.016). A significant association between the NGAL increase and AKI severity was achieved (p= 0.02). NGAL increases showed: NGAL pre= 18.3 (7.7-23.7) ng/mL, NGAL post= 19.2 (3.8-86) ng/mL median (interquartile range) statistically not significant. Analyzing the corresponded urinary creatinines, we found many uCreas with very low concentrations suggesting a possible dilution of patient samples collected. Correction with the urinary creatinine did not have added significant outcomes. It seemed that [TIMP-2]-[IGFBP-7] expressed as Nephrocheck AKI score (ng/mL)2/1000 introduces a variation due to the amplification of TTP errors. Model of differential equations applied to Nephrocheck test results demonstrated a mean variation rate that rises as the biomarker concentration increases. Conclusions: NGAL results on urinary testing had a modest diagnostic accuracy probably due to pre-analytical variability in ICU critical patients. Pre and Post-analytical variability affected Nephrocheck results as observed by the expression of measurements (ng/mL)2/1000. In addition, the too low numerical measurements as fraction of 1 and high variability around the AKI risk score cut-off= 0,3 might determine possible overlap between different patient groups. We suggested an analytical expression for the cell cycle arrest biomarkers as cumulative concentration in linear form (ng/mL).

Original languageEnglish
Article number321
Pages (from-to)22-28
Number of pages7
JournalJournal of Integrated OMICS
Issue number2
Publication statusPublished - 2020


  • Acute kidney injury
  • Differential equation
  • Nephrocheck AKI score
  • NGAL
  • Pre/post analytical variability

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics


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