Performance of Serum Creatinine and Kidney Injury Biomarkers for Diagnosing Histologic Acute Tubular Injury

Am J Kidney Dis. 2017 Dec;70(6):807-816. doi: 10.1053/j.ajkd.2017.06.031. Epub 2017 Aug 24.


Background: The diagnosis of acute kidney injury (AKI), which is currently defined as an increase in serum creatinine (Scr) concentration, provides little information on the condition's actual cause. To improve phenotyping of AKI, many urinary biomarkers of tubular injury are being investigated. Because AKI cases are not frequently biopsied, the diagnostic accuracy of concentrations of Scr and urinary biomarkers for histologic acute tubular injury is unknown.

Study design: Cross-sectional analysis from multicenter prospective cohort.

Settings & participants: Hospitalized deceased kidney donors on whom kidney biopsies were performed at the time of organ procurement for histologic evaluation.

Predictors: (1) AKI diagnosed by change in Scr concentration during donor hospitalization and (2) concentrations of urinary biomarkers (neutrophil gelatinase-associated lipocalin [NGAL], liver-type fatty acid-binding protein [L-FABP], interleukin 18 [IL-18], and kidney injury molecule 1 [KIM-1]) measured at organ procurement.

Outcome: Histologic acute tubular injury.

Results: Of 581 donors, 98 (17%) had mild acute tubular injury and 57 (10%) had severe acute tubular injury. Overall, Scr-based AKI had poor diagnostic performance for identifying histologic acute tubular injury and 49% of donors with severe acute tubular injury did not have AKI. The area under the receiver operating characteristic curve (AUROC) of change in Scr concentration for diagnosing severe acute tubular injury was 0.58 (95% CI, 0.49-0.67) and for any acute tubular injury was 0.52 (95% CI, 0.45-0.58). Compared with Scr concentration, NGAL concentration demonstrated higher AUROC for diagnosing both severe acute tubular injury (0.67; 95% CI, 0.60-0.74; P=0.03) and any acute tubular injury (0.60; 95% CI, 0.55-0.66; P=0.005). In donors who did not have Scr-based AKI, NGAL concentrations were higher with increasing severities of acute tubular injury (subclinical AKI). However, compared with Scr concentration, AUROCs for acute tubular injury diagnosis were not significantly higher for urinary L-FABP, IL-18, or KIM-1.

Limitations: The spectrum of AKI cause in deceased donors may be different from that of a general hospitalized population.

Conclusions: Concentrations of Scr and kidney injury biomarkers (L-FABP, IL-18, and KIM-1) lack accuracy for diagnosing acute tubular injury in hospitalized deceased donors. Although urinary NGAL concentration had slightly higher discrimination for acute tubular injury than did Scr concentration, its overall AUROC was still modest.

Keywords: Acute kidney injury (AKI); IL-18; KIM-1; L-FABP; NGAL; acute tubular injury (ATI); diagnostic performance; kidney biopsy; kidney histology; kidney injury biomarker; serum creatinine (Scr); subclinical AKI.

MeSH terms

  • Acute Kidney Injury / diagnosis
  • Acute Kidney Injury / metabolism*
  • Acute Kidney Injury / pathology
  • Adult
  • Area Under Curve
  • Biomarkers / metabolism
  • Cohort Studies
  • Creatinine / blood*
  • Cross-Sectional Studies
  • Fatty Acid-Binding Proteins / urine*
  • Female
  • Hepatitis A Virus Cellular Receptor 1 / metabolism*
  • Humans
  • Interleukin-18 / urine*
  • Kidney Transplantation
  • Kidney Tubules / pathology
  • Lipocalin-2 / urine*
  • Male
  • Middle Aged
  • Prospective Studies
  • ROC Curve
  • Severity of Illness Index
  • Tissue Donors*


  • Biomarkers
  • FABP1 protein, human
  • Fatty Acid-Binding Proteins
  • HAVCR1 protein, human
  • Hepatitis A Virus Cellular Receptor 1
  • Interleukin-18
  • LCN2 protein, human
  • Lipocalin-2
  • Creatinine