Increased Urinary Albumin Excretion But Less Damaged Renal Tubular Structures in Mice with Genetically Decreased Elmo1 Post Ischemia/Reperfusion Injury

Renal ischemia/reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI), a potentially fatal syndrome characterized by a rapid decline in kidney function. The major cause of AKI is IRI. Our prior studies have demonstrated that genetically increased Elmo1 expression in mice aggravated several kidney pathologies including diabetic nephropathy and transition of AKI to chronic kidney disease induced by IRI. However, the effects of decreased expression of Elmo1 on IRI is unclear. We compared the kidney structures and functions between wild type (WT) mice and mice with genetically decreased Elmo1 expression (<i>Elmo1</i> ^<i>L/L</i> ) 5 days after unilateral renal IR surgery. The WT-IRI mice had typical tubular injuries including necrosis and shedding of proximal tubular cells, but these morphological changes were less severe in <i>Elmo1</i> ^<i>L/L</i> -IRI mice. In contrast, the urinary albumin excretion was elevated in <i>Elmo1</i> ^<i>L/L</i> -IRI mice compared with WT counterparts. While the expression of inflammatory markers (e.g., <i>Il6, Tnfa, Cxcl1</i> and <i>Tlr4</i>) was comparable between WT and <i>Elmo1</i> ^<i>L/L</i> mice with IRI which significantly higher than control mice, the expression of antioxidant markers (e.g., <i>Sod1</i> and <i>Sod2</i>) was preserved in <i>Elmo1</i> ^<i>L/L</i> -IRI mice which was significantly decreased in WT-IRI mice. We conclude that <i>Elmo1</i> ^<i>L/L</i> mice had preserved tubular structures but increased urinary albumin excretion after IRI, suggesting that the role of Elmo1 in IRI is complex and it merits future evaluation.