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

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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