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Are oxidative stress and dysregulated mitophagy involved in the progression of feline chronic kidney disease?


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  Dr R Jepson, Prof J Elliott, Dr Elisa Vasilopoulou  No more applications being accepted  Funded PhD Project (Students Worldwide)

About the Project

Feline chronic kidney disease (CKD) is a heterogeneous syndrome responsible for >1 in 8 deaths of cats over 5 years of age. Mineral bone disturbance, proteinuria and low red cell mass are associated with progressive renal injury but how these are linked to molecular mechanisms driving progression remains to be determined. Evidence from other species suggests that exposure of tubular cells to albumin or repeated episodes of ischaemia leads to oxidative stress and induces a pro-inflammatory phenotype of tubular cells. Also, reactive oxygen species (ROS) generated by oxidative stress trigger mitophagy, a process which removes damaged dysfunctional mitochondria and protects cells from further oxidative damage. Dysregulation of mitophagy is thought to exacerbate ROS generation and oxidative stress perpetuating the chronic inflammatory and pro-fibrotic processes.

This PhD project will examine the hypothesis that oxidative stress and dysregulated mitophagy trigger progressive feline CKD. Archived tissue, plasma and urine samples available from cats with stable and progressive CKD are available and the successful candidate will use both retrospective and prospective study design to develop experience in metabolomic and transcriptomic techniques in order to explore and address the following questions:

  1. Is oxidative stress characteristic of the progressive feline CKD metabolome?
  2. How does the renal transcriptome differ in cats with progressive versus non-progressive CKD?
  3. Can urinary transcriptomics be used to identify the pathways activated within the kidney that are associated with progression and be used to monitor response to treatment?
  4. Is there evidence to link dysregulated mitophagy to oxidative stress in progressive CKD?

Funding Notes

This is a four year fully funded studentship, funded by Boehringer Ingelheim. The student will receive a stipend and "Home" rate tuition fees are covered. International applicants are welcome to apply but must be able to fund the difference between "Home" and "Overseas" tuition fees.


1. Chakrabarti S et al., (2012) Clinicopathological variables predicting progression of azotemia in cats with chronic kidney disease. J Vet Intern Med; 26(2):275-81.
2. Chakrabarti S et al., (2013) Histomorphometry of feline chronic kidney disease and correlation with markers of renal dysfunction. Vet Pathol.; 50(1):147-55.
3. Kaushal GP et al., (2019) Molecular Interactions between Reactive Oxygen Species and Autophagy in Kidney Disease. Int. J. Mol. Sci. 2019, 20, 3791; doi:10.3390/ijms20153791
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