Research Partners
Despite our best efforts, the medicines we use to treat our patients can sometimes cause damage to their kidneys. In this project we have focussed on trying to understand better the damage caused to the kidney by an antibiotic called vancomycin. Vancomycin is a very useful antibiotic, particularly as it has activity against a type of resistant bacteria called MRSA (methicillin-resistant staphylococcus aureus), but it can cause acute kidney injury (AKI) in some patients (16% of patients at Alder Hey when we measured this). Thanks to the funding we have been able to continue working with a human kidney cell line called conditionally-immortalised proximal tubule epithelial cells (ciPTECs). The proximal tubule of the kidney is the part injured by vancomycin (and many other medications). Therefore this cell line can help us understand what is happening in our patients. Using these cells our team has been able to show that increasing amounts of vancomycin cause increasing amounts of injury and death in these cells. We have tried to protect these cells by also treating them with other medications (cilastatin, rosuvastatin, montelukast) which we hoped may stop the vancomycin from getting into the cells and causing damage. However, these had no impact on the effect of vancomycin, and it seems able to enter the cells by a variety of different routes. Whatever the route by which vancomycin enters the cells, we have shown that it causes and increase in reactive oxygen species, which then lead to damage and death in the cells. We have shown that adding an antioxidant (ascorbic acid or N-acetylcysteine) led to reduced levels of these reactive oxygen species, although again there was no difference in the amount of cell death. In conclusion, this funding has allowed us to gain experience using the ciPTEC cell line, to show that we can replicate in the cell model, the kidney injury that we see with vancomycin in patients, and to test various approaches to protecting the kidneys. Whilst we have not yet identified a potential way to reduce vancomycin toxicity, this cell model promises to remain a valuable resource in investigating the kidney injury caused by a variety of other medications.