**5. Conclusions**

The findings presented here have confirmed the phenotype of iron deficiency anaemia in experimental uraemia. It has also been demonstrated that there is both mitochondrial functional adaptation and cellular dysfunction and evidence of changes in renal and systemic oxidative stress. These findings sugges<sup>t</sup> that mitochondrial activity is increased in the remnant kidney tissue to compensate for reduced renal mass. This is supported by the modest decrease in renal function despite the removal of a large majority of renal tissue. The data also sugges<sup>t</sup> that kidney injury may impact on mitochondrial biogenesis, ultra-structure organisation and function. Further work assessing mitochondrial mass will help clarify this further. Correction of iron deficiency anaemia with a bolus of ferumoxytol in uraemic animals was associated with a partial restoration of systemic antioxidant GPx activity and importantly no deterioration in renal function or increase in proteinuria. The data sugges<sup>t</sup> that timely administration of iv iron may help to alleviate the complications of iron deficiency relating to oxidative stress in CKD patients. This study further highlights the need for therapies targeting mitochondria specifically as a part of routine CKD management, in addition to the iron and antioxidant therapies. It is not known if similar observations occur with other iron preparations which may have subtle di fferent physiochemical properties.

**Author Contributions:** F.N., S.B. and A.-M.S. conception and design of research, F.N. perform experiments, F.N performed sample preparations, F.N. prepared figures, drafted manuscript, F.N., S.B. and A.-M.S. edited and revised manuscript and approved final version of manuscript.

**Funding:** This research was funded by a gran<sup>t</sup> from the Takeda and the East Riding cardiac Trust.

**Acknowledgments:** We thank Kath Bulmer, Laura Goodlass, Andrew Gordon and Danielle Webster for their technical support and dedication. Special thanks go to John Greenman and Roger Sturmey for their invaluable contribution to this study.

**Conflicts of Interest:** All authors have received research grants from the East Riding Cardiac Trust, UK and Tadeka, UK, and funding was also received from the Local Hull Teaching Hospitals NHS Trust Renal Research Charitable Fund to fund the project and the salary of Faisal Nuhu. The funders had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
