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Kidney Week

Abstract: TH-PO012

S100A8/S100A9 Diminishes Acute Tubular Injury After Ischemia-Reperfusion

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Westhoff, Timm H., University Hospital Marien Hospital Herne, Herne, Germany
  • Seibert, Felix S., University Hospital Marien Hospital Herne, Herne, Germany
  • Schmidt-Ott, Kai M., Charite - Universitaetsmedizin Berlin, Berlin, Germany
Background

Urinary calprotectin (S100A8/S100A9) has recently been identified as a promising biomarker in acute kidney injury (AKI). It is a mediator of the innate immune system and acts as a danger associated molecular pattern protein (DAMP). It remains elusive, however, whether calprotectin plays a pathophysiological role in AKI. Recently, there was first evidence that it might participate in the control of macrophage-mediated renal repair following ischemia/reperfusion. The present work examines whether calprotectin modulates acute I/R injury by means of a S100A9 -/- mouse model.

Methods

Since S100A8 -/- mice are not viable, S100A9 -/- knockout mice were established on a C57BL/6 background. I/R injury was induced by 25 min of unilateral ligation of the renal artery in S100A9 -/- and wildtype (WT) mice. The extent of tubular injury was assessed by a histological score and neutrophil gelatinase associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1) mRNA expression.

Results

Histological tubular injury was comparable between S100A9 -/- and WT controls at 24h, while transition to fibrosis was aggravated in S100a9-/- mice. After 24h KIM-1 mRNA concentrations were higher in S100A9 -/- than in WT mice. The increase in NGAL mRNA expression was highly significantly larger in S100 A9 -/- than in WT mice at 24h. The difference of both KIM-1 and NGAL expression between the two mice strains disappeared by day 7. Sham operated animals did neither show any tubular injury nor an increase in KIM-1 or NGAL expression.

Conclusion

S100A9 deficiency is associated with increased I/R injury. Acting as an alarm signal, calprotectin may initialize tubular protective mechanisms after the induction of I/R.