A randomised controlled trial of rosuvastatin for the prevention of aminoglycoside-induced kidney toxicity in children with cystic fibrosis

McWilliam, Stephen J.; Rosala-Hallas, Anna; Jones, Ashley P.; Shaw, Victoria; Greenhalf, William; Jaki, Thomas; Smyth, Alan R.; Smyth, Rosalind L.; Pirmohamed, Munir

Abstract

The PROteKT study tested the hypothesis that rosuvastatin can inhibit aminoglycoside-induced nephrotoxicity in children with Cystic Fibrosis (CF). This open label, parallel group, randomised controlled trial recruited children and young people aged 6 to 18 years with CF at 13 paediatric CF treatment centres in the UK. Participants were randomised equally to either receive oral rosuvastatin (10mg once daily) or no intervention (control) throughout clinically indicated treatment with intravenous tobramycin. The primary outcome was the difference between the groups in mean fold-change in urinary Kidney Injury Molecule-1 (KIM-1). Fifty (rosuvastatin n=23, control n =27) participants were recruited between May 2015 and January 2017. Primary outcome data was available for 88% (rosuvastatin n=20, control n=24). The estimated mean treatment difference in the geometric mean-fold change of normalised KIM-1 was 1.08 (95%CI 0.87-1.35, p=0.48). In total there were 12 adverse reactions, all mild, reported by five participants randomised to rosuvastatin, and one serious adverse event in each group. Whilst no protective effect of rosuvastatin was seen, there was a lower than expected level of nephrotoxicity in the cohort. Therefore, we can neither confirm nor refute the hypothesis that rosuvastatin protects against aminoglycoside nephrotoxicity.

Citation

McWilliam, S. J., Rosala-Hallas, A., Jones, A. P., Shaw, V., Greenhalf, W., Jaki, T., …Pirmohamed, M. (2020). A randomised controlled trial of rosuvastatin for the prevention of aminoglycoside-induced kidney toxicity in children with cystic fibrosis. Scientific Reports, 10(1), Article 1796. https://doi.org/10.1038/s41598-020-58790-1

• Journal Article Type: Article
• Acceptance Date: Jan 15, 2020
• Online Publication Date: Feb 4, 2020
• Publication Date: Feb 4, 2020
• Deposit Date: Jan 20, 2020
• Publicly Available Date: Feb 10, 2020
• Journal: Scientific Reports
• Print ISSN: 2045-2322
• Electronic ISSN: 2045-2322
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 10
• Issue: 1
• Article Number: 1796
• DOI: https://doi.org/10.1038/s41598-020-58790-1
• Keywords: Multidisciplinary
• Public URL: https://nottingham-repository.worktribe.com/output/3766936
• Publisher URL: https://www.nature.com/articles/s41598-020-58790-1
• Additional Information: Received: 8 September 2019; Accepted: 15 January 2020; First Online: 4 February 2020; : The authors declare no competing interests.