Table 1.
Important findings implicating renal endothelium in acute kidney injury
| Major findings | Implications | Authors |
|---|---|---|
| During AKI, peritubular capillary blood flow is reduced, and morphology is distorted, as well as loss of endothelial cell function | The vasculature of the kidney plays a role in injury and progression to chronic disease. The endothelium may be a potential target for therapeutics | Andreoli et al. (2009) [7]; Sutton et al. (2002) [22]; Basile et al. (2007) [23] |
| TSP1 is found to bind to CD47 and acts to suppress the NO pathway following IRI | Supplementation of NO mitigates IRI | Isenburg et al. (2007) [21]; Martinez-Mier et al. (2000) [24]; Rodriguez-Pena et al. (2004) [25]; Liu et al. (2007) [26]; Lang et al. (2007) [27] |
| Limiting CD47 activation prevents TSP1 binding in mice. | Mitigates the complications of IRI providing a potential therapeutic | Rogers et al. (2012) [18] |
| A subset of the renal endothelium derived from the renal stroma (marked by Foxd1) gives rise to peritubular capillaries | Foxd1 gives rise to vasculogenic endothelium and contributes to a fibrotic response following AKI | Sims-Lucas et al. (2013) [28]; Hum et al. (2014) [29]; Sequeira-Lopez et al. (2015) [30]; Levinson et al. (2005) [31]; Hatini et al. (1996) [32] |
| Renal endothelial functions contributes to a reduction in renal blood flow following AKI. NOS3 has positive effects on renal endothelial function | Enhanced endothelial function may have protective effects on AKI | Brodsky et al. (2002) [33]; Basile et al. (2014) [34]; Arriero et al. (2004) [35] |
| Following AKI, hypoxic areas remain after normal function is restored. Furthermore, HIF-2α is critical for protection in AKI |
HIFs are implicated as taking part in the pathogenesis of AKI | Ergin et al. (2015) [36]; Kapitisinou et al. (2015) [37] |
| A fluorescence microangiography technique is established for visualization if the microvasculature | An invaluable technique to understand microvasculature alterations | Advani et al. (2011) [38]; Kramann et al. (2014) [11] |
| Inflammatory processes mediated by the immune system are crucial in mediating renal injury | Targeting inflammation may be a potential therapeutic for AKI | Basile et al. (2012) [39]; Bonventre et al. (2004) [40]; Gonclaves et al. (2010) [41]; Jang et al. (2015) [42] |
| Using retinoic acid, M1 macrophages can be suppressed, indirectly inducing M2 macrophages to enhance repair following AKI | Administration of retinoic acid following AKI enhances repair | Chiba et al. (2015) [43] |
| Endothelial cell dysfunction may contribute to the failure of blood to reperfuse an ischemic area | Further implicates endothelial cells as a possible target for therapeutic intervention | Brodsky et al. (2002) [33]; Sutton et al. (2003) [44]; Jang et al. (2015) [42] |
| CDK4/6 is activated early during AKI, and displays protective effects of CDK4/6 inhibitors in animal models of AKI | Rational for the clinical development of CDK4/6 inhibitors for the prevention and treatment of AKI | Flipski et al. (2009) [45]; Ciarimboli et al. (2010) [46]; Sprowl et al. (2014) [47] |
AKI, Acute kidney injury; IRI, ischemia–reperfusion injury; NO, nitric oxide; NOS3, nitric oxide synthase 3; HIF-2α, hypoxia inducible factor-2 alpha; CDK4/6, cyclin-dependent kinase 4/6