Plasmatic Villin 1 Is a Novel In Vivo Marker of Proximal Tubular Cell Injury During Renal Ischemia-Reperfusion.

Abstract

BACKGROUND:

Early detection of acute kidney injury (AKI), a common condition with a high mortality risk, can be facilitated by specific and reliable biomarkers. Villin 1, a protein typically found in the brush borders of proximal tubular cells, has been detected in urine of patients with AKI, but its possible release in plasma remains unexplored.

METHODS:

We measured the presence of villin 1 by immunohistochemistry on kidney sections and by Western blotting in plasma samples from rats subjected to renal ischemia-reperfusion injury, pigs subjected to renal transplantation and liver transplantation patients that developed AKI. Moreover, rats were treated with necrostatin-1, an inhibitor of programmed necrosis (necroptosis), which occurs in renal tubular cells during AKI. Villin 1 levels were compared with other renal injury markers (creatinine, aspartate transaminase, and heart-type fatty acid binding protein).

RESULTS:

During AKI, plasmatic villin 1 levels corresponded with the severity of kidney injury and dysfunction. Its detection in plasma was associated with a redistribution in the kidney tissue. Unlike the levels of other markers, plasmatic villin 1 decreased already after a short (3 hours) treatment with necrostatin-1 during renal ischemia-reperfusion injury. The presence of plasmatic villin 1 was confirmed in patients who experienced AKI after liver transplantation.

CONCLUSIONS:

Villin 1 is released in plasma during AKI and shows potential as an early marker for proximal tubular injury/necrosis and warrants further investigation.

• Authors: Jean-Paul Decuypere, Laurens J Ceulemans, Tine Wylin, Wim Martinet, Diethard Monbaliu, Jacques Pirenne, Ina Jochmans
• Journal: Transplantation (Transplantation) Vol. 101 Issue 11 Pg. e330-e336 (11 2017) ISSN: 1534-6080 [Electronic] United States
• PMID: 28704336 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• FABP3 protein, rat
• Fatty Acid Binding Protein 3
• Fatty Acid-Binding Proteins
• Imidazoles
• Indoles
• Microfilament Proteins
• VIL1 protein, human
• Vil1 protein, rat
• necrostatin-1
• Creatinine
• Aspartate Aminotransferases

Topics

• Acute Kidney Injury (blood, etiology, pathology, prevention & control)
• Animals
• Aspartate Aminotransferases (blood)
• Biomarkers (blood)
• Creatinine (blood)
• Disease Models, Animal
• Early Diagnosis
• Fatty Acid Binding Protein 3
• Fatty Acid-Binding Proteins (blood)
• Female
• Imidazoles (pharmacology)
• Indoles (pharmacology)
• Kidney Transplantation (adverse effects)
• Kidney Tubules, Proximal (drug effects, metabolism, pathology)
• Liver Transplantation (adverse effects)
• Microfilament Proteins (blood)
• Necrosis
• Predictive Value of Tests
• Rats, Sprague-Dawley
• Reperfusion Injury (blood, etiology, pathology, prevention & control)
• Sus scrofa
• Time Factors