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

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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.

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