Urinary Plasminogen Activator Inhibitor-1: A Biomarker of Acute Tubular Injury

Am J Nephrol. 2021;52(9):714-724. doi: 10.1159/000518455. Epub 2021 Sep 8.


Introduction: Acute kidney injury (AKI) is a threatening, multiaetiological syndrome encompassing a variety of forms and damage patterns. AKI lacks sufficiently specific diagnostic tools to evaluate the distinct combination of pathophysiological events underlying each case, which limits personalized and optimized handling. Therefore, a pathophysiological diagnosis based on new urinary biomarkers is sought for practical (readiness and noninvasiveness) and conceptual reasons, as the urine is a direct product of the kidneys. However, biomarkers found in the urine may also have extrarenal origin, thus conveying pathophysiological information from other organs or tissues. Urinary plasminogen activator inhibitor-1 (PAI-1) has been associated to AKI, although its origin and traffic to the urine are not known.

Methods: Herein, we studied the blood or renal origin of urinary PAI-1 (uPAI-1) in experimental AKI in Wistar rats, by means of the in situ renal perfusion method. For this purpose, urine was collected while the kidneys of rats with AKI showing increased uPAI-1 excretion, and controls, were in situ perfused with a saline solution.

Results: Our results show that during perfusion, PAI-1 remained in the urine of AKI rats, suggesting that renal cells shed this protein directly to the urine. PAI-1 is also significantly increased in the urine of AKI patients. Its low correlation with other urinary markers such as NGAL or NAG suggests that PAI-1 provides complementary and distinct phenotypical information.

Conclusion: In conclusion, uPAI-1 is a biomarker produced by damaged kidneys following AKI, whose precise pathophysiological meaning in AKI needs to be further investigated.

Keywords: Acute kidney injury; Acute tubular necrosis; PAI-1; Tubular injury; Urinary biomarker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / urine*
  • Adult
  • Aged
  • Animals
  • Biomarkers / urine
  • Female
  • Humans
  • Kidney Tubules*
  • Male
  • Middle Aged
  • Plasminogen Activator Inhibitor 1 / urine*
  • Rats
  • Rats, Wistar


  • Biomarkers
  • Plasminogen Activator Inhibitor 1
  • SERPINE1 protein, human