| EPSRC Reference: |
EP/Y014596/1 |
| Title: |
Quantifying the risk of precipitating drug induced crystalluria (XTALURIA) |
| Principal Investigator: |
Kavanagh, Dr O |
| Other Investigators: |
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| Project Partners: |
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| Department: |
Sch of Pharmacy |
| Organisation: |
Newcastle University |
| Scheme: |
New Investigator Award |
| Starts: |
01 April 2024 |
Ends: |
30 September 2026 |
Value (£): |
332,146
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| No relevance to Underpinning Sectors |
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Summary on Grant Application Form |
In the treatment of any medical condition, the benefits of pharmaceutical care must be balanced against the risks of harm. For all drugs, this removal is carried out by the kidneys (to some degree) and critically - if doctors don't get this balance right - drugs can cause toxicity to this organ with catastrophic consequences. Currently, physicians rely on rules of thumb and their clinical experience to maintain this delicate balance for the majority of patients. This deteriorates to guesswork for new drugs, paediatric and geriatric patients, or other patient groups whose bodily make-up deviates from the rest of the population. This project focuses on one type of drug toxicity which arises through the precipitation of drugs in the urine which can cause mechanical damage to the kidneys.
Acute Kidney Injury (AKI) is poorly diagnosed, ineffectively managed and has been recognised as a condition of global concern. As such, the most effective approach to reducing the healthcare burden of this condition is to prevent it from happening at all. Precipitating Drug induced Acute Kidney Injury (P-DAKI) is one of the most common causes of AKI, resulting from the precipitation of crystals in the kidney which can cause direct damage to this organ. Physicians generally rely on their clinical experience to reduce the risks of and effectively respond to P-DAKI, but this is clearly not enough as recent estimates suggest that P-DAKI occurs in 5% of patients treated with high-dose IV amoxicillin. This lengthens hospital stay and in some cases can lead to death. P-DAKI has also been thought to occur in up to 40% of patients treated with oral antiretrovirals such as indinavir and although atazanavir and darunavir superseded indinavir to reduce this risk, crystalluria still occurs.
This project will take a systematic approach exploring the interface between the chemical fundamentals of the drugs known to cause kidney damage and the chemical composition of urine itself. The ultimate aim is to build clinically relevant tools and guidance to enable physicians to predict the risk of kidney injury. We aim to significantly reduce the risks of P-DAKI by understanding drug behaviour in artificial and human urine with the view to identify specific chemical characteristics that predispose drugs and their metabolites to crystalluria.
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Key Findings |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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Potential use in non-academic contexts |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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Impacts |
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| Description |
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk |
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Sectors submitted by the Researcher |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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| Project URL: |
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| Further Information: |
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| Organisation Website: |
http://www.ncl.ac.uk |