BPI Fold-Containing Family A Member 2/Parotid Secretory Protein Is an Early Biomarker of AKI

J Am Soc Nephrol. 2017 Dec;28(12):3473-3478. doi: 10.1681/ASN.2016121265. Epub 2017 Aug 3.

Abstract

AKI is a major cause of morbidity and mortality and an important contributor to the development and progression of CKD. Molecular biomarkers that improve the detection and prognostication of AKI are therefore required. We assessed the utility as such of BPI fold-containing family A member 2 (BPIFA2), also known as parotid secretory protein, which we identified via a multiplex quantitative proteomics screen of acutely injured murine kidneys. In physiologic conditions, BPIFA2 is expressed specifically in the parotid glands and is abundant in salivary secretions. In our study, AKI induced Bpifa2 expression in the kidneys of mice within 3 hours. Furthermore, we detected BPIFA2 protein in plasma and urine in these models as early as 6 hours after injury. However, renal injury did not induce the expression of Bpifa2 in mice lacking Nur77, an immediate early gene expressed in the kidneys during AKI. Notably, patients with AKI had higher blood and urine levels of BPIFA2 than did healthy individuals. Together, our results reveal that BPIFA2 is a potential early biomarker of AKI.

Keywords: ischemia-reperfusion; renal injury; renal ischemia.

MeSH terms

  • Acute Kidney Injury / metabolism*
  • Animals
  • Biomarkers / metabolism*
  • Disease Progression
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Kidney / metabolism
  • Male
  • Mice
  • Microscopy, Fluorescence
  • Nuclear Receptor Subfamily 4, Group A, Member 1 / genetics
  • Parotid Gland / metabolism
  • Promoter Regions, Genetic
  • Protein Folding
  • Proteomics
  • Reperfusion Injury / metabolism
  • Saliva / metabolism
  • Salivary Proteins and Peptides / blood*
  • Salivary Proteins and Peptides / urine*
  • Time Factors

Substances

  • Biomarkers
  • Bpifa2 protein, mouse
  • Nr4a1 protein, mouse
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • Salivary Proteins and Peptides