Molecular phenotyping of clinical AKI with novel urinary biomarkers

Am J Physiol Renal Physiol. 2015 Sep 1;309(5):F406-13. doi: 10.1152/ajprenal.00682.2014. Epub 2015 Jun 17.

Abstract

Acute kidney injury (AKI) is a common hospital complication. There are no effective treatments to minimize kidney injury or limit associated morbidity and mortality. Currently, serum creatinine and urine output remain the gold standard used clinically in the diagnosis of AKI. Several novel biomarkers can diagnose AKI earlier than elevations of serum creatinine and changes in urine output. Recent long-term observational studies have elucidated a subgroup of patients who have positive biomarkers of AKI but do not meet criteria for AKI by serum creatinine or urine output, termed subclinical AKI. These patients with subclinical AKI have increased risk of both short- and long-term mortality. In this review, we will highlight the implications of what these patients may represent and the need for better phenotyping of AKI by etiology, severity of injury, and ability to recover. We will discuss two AKI biomarkers, neutrophil gelatinase-associated lipocalin (NGAL) and breast regression protein-39 (BRP-39)/YKL-40, that exemplify the need to characterize the complexity of the biological meaning behind the biomarker, beyond elevated levels reporting on tissue injury. Ultimately, careful phenotyping of AKI will lead to identification of therapeutic targets and appropriate patient populations for clinical trials.

Keywords: NGAL; chitinase 3-like 1; heterogeneity; outcomes; subclinical injury.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acute Kidney Injury / blood
  • Acute Kidney Injury / diagnosis*
  • Acute Kidney Injury / urine
  • Acute-Phase Proteins / urine*
  • Biomarkers / blood
  • Biomarkers / urine
  • Creatinine / blood
  • Glycoproteins / urine*
  • Humans
  • Lipocalin-2
  • Lipocalins / urine*
  • Phenotype
  • Proto-Oncogene Proteins / urine*

Substances

  • Acute-Phase Proteins
  • Biomarkers
  • Glycoproteins
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Proto-Oncogene Proteins
  • Creatinine