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  Assessment of the biological role and predictive qualities of a range of plasma-borne biomarkers for contrast-induced nephropathy


   Institute of Health Research and Innovation

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  Prof Ian Megson, Dr A Treweeke  No more applications being accepted  Funded PhD Project (Students Worldwide)

About the Project

Contrast-induced nephropathy (CIN) is a risk associated with infusion of contrast agents used in X-ray imaging. The aetiology of CIN is not fully understood, but it has long been associated with oxidative stress induced by the contrast medium itself, leading to renal vascular dysfunction and/or necrosis of cells in the nephron. The risk is particularly high in patients with pre-existing renal impairment and diabetes. CIN is the third most common cause of in-hospital acute renal failure and there is a 3-fold increase in hospital mortality in patients with kidney disease who develop CIN.

A number of biomarkers are emerging to establish CIN at an early stage post contrast exposure (e.g. kidney injury molecule 1 and neutrophil gelatinase-associated lipocalin (NGAL). Although these molecules have shown early promise their use in this setting has not been fully evaluated. In addition, there are a number of antioxidant biomarkers that could be useful, not only to highlight risk of CIN, but also to guide the use of antioxidant prophylactics, such as N-acetylcysteine. The aim of this project is to screen several of these biomarkers in clinical samples, to evaluate their potential in CIN and to determine their roles in the aetiology of the disease.

This project will begin with the use existing samples to assess the potential of novel biomarkers for predicting clinical outcome following administration of contrast agents to patients. The samples arose from a complex study designed to assess the therapeutic potential of N-acetylcysteine as an antioxidant therapy/prophylactic to reduce the impact of contrast infusion on renal function. A range of risk markers will be evaluated with a view to determining suitability of prophylactic measures and of identifying patients at risk before hospital discharge. The project will involve work with clinical samples and laboratory experiments (cell culture, vascular functional assays) to explore mechanism.

Additional supervisors: Dr David McEneaney (Southern Health & social Care Trust), Dr Michael Eddleston (University of Edinburgh)


Applicants must possess a minimum of an Honours degree at 2:1 and/or a Master’s Degree (or International equivalent) in a relevant subject.

To apply please complete the standard application form, attaching supporting documentation and send to: [Email Address Removed]

Informal project specific enquiries can be made to: Prof Angus Watson: [Email Address Removed]

Funding Notes

This project is supported by the European Union’s INTERREG VA Programme, managed by the Special EU Programmes Body (SEUPB).

The studentship covers fees, plus a stipend at the RCUK level, for a total of 36 months (including writing-up).

Funding is available for students worldwide.

Students must be domiciled in the Highlands and Islands region during the course of their study to be eligible for funding.


References

Sandilands EA, Cameron S, Paterson F, Donaldson S, Briody L, Crowe J, Donnelly J, Thompson A, Johnston NR, Mackenzie I, Uren N, Goddard J, Webb DJ, Megson IL, Bateman DN, Eddleston M. Mechanisms for an effect of acetylcysteine on renal function after exposure to radio-graphic contrast material: study protocol. BMC Clin Pharmacol, 2012, 12:3.

Treweeke A, Winterburn TJ, Mackenzie I, Barrett F, Barr C, Rushworth G, Dransfield I, MacRury SM, Megson IL. N-acetylcysteine is an anti-atherothrombotic agent in patients with type-2 diabetes with depleted intra-platelet glutathione. Diabetologia 2012; 55:2920-8.

Rushworth GF, Megson IL. Existing and potential therapeutic uses for N-acetylcysteine: the need for conversion to intracellular glutathione for antioxidant benefits. Pharmacol Ther 2014, 141:150-9.

Connolly M, McEneaney D, Menown I, Morgan N, Harbinson M. Novel Biomarkers of Acute Kidney Injury After Contrast Coronary Angiography. Cardiol Rev. 2015 23:240-6.


Treweeke AT, Maskrey BH, Hickson K, Miller JH, Leslie SJ, Megson IL. Iodixanol has a favorable fibrinolytic profile compared to iohexol in cardiac patients undergoing elective angiography. PLoS One. 2016, 11:e0147196.