Prevention of colistin induced nephrotoxicity: a review of preclinical and clinical data

ABSTRACT

Introduction: The emergence of antimicrobial resistance in Gram-negative bacteria is a concerning challenge for health systems. The polymyxins, including colistin, are one of the limited available options these pathogens management. Nephrotoxicity, beside neurotoxicity is the major dose-limiting adverse reaction of polymyxins, with an up to 60% prevalence. As oxidative stress, inflammatory pathways and apoptosis are considered as the main mechanisms of colistin-induced kidney damage, various studies have evaluated antioxidant and/or antiapoptotic compounds for its prevention. In this article, we reviewed animal and human studies on these probable preventive measures.

Area covered: PubMed, Scopus, and google scholar databases were searched using several combination of ‘colistin’, ‘polymyxin E’, ‘CMS’, ‘Colistimethate sodium’, ‘nephrotoxicity’, ‘kidney injury’, ‘kidney damage’, ‘renal injury’, ‘renal damage’, ‘nephroprotectants’, ‘renoprotective’, ‘nephroprotective’, and ‘prevention’. All eligible articles including animal and human studies up to the end of 2020 were included.

Expert opinion: Most of available studies are in vivo researches on anti-oxidant and anti-apoptotic agents like NAC, vitamin C and E, silymarin, and curcumin which mostly showed promising findings. However, limited human studies on NAC and vitamin C did not demonstrate considerable efficacy. So, before proposing these compounds, further well-designed randomized clinical trials are necessary.

KEYWORDS:

• Colistin
• polymyxin E
• nephrotoxicity
• prevention
• nephroprotective

Article highlights

• Colistin (polymixin E) is a broad spectrum antibiotic against gram-negative bacteria, is commonly used in hospitalized patients in the treatment of multidrug resistant (MDR) infections, particularly carbapenem resistant strains.

• The incidence of nephrotoxicity with colistin is reported between 20-60% in other studies.

• It is a dose and time dependent adverse effect that presents as acute tubular necrosis.

• Oxidative stress, inflammatory pathways and apoptosis are considered as main mechanisms of colistin-induced kidney damage.

• Most of available studies on prevention of colistin nephrotoxicity are in vivo researches on anti-oxidant and anti-apoptotic agents like NAC, vitamin C and E, silymarin, and curcumin which mostly showed promising findings.

• However, limited human studies on NAC and vitamin C did not demonstrate considerable efficacy. So, before proposing these compounds, further well-designed randomized clinical trials are necessary.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Authors contributions

F Jafari: searched the data bases and wrote the manuscript

S Elyasi: defined the manuscript’s subject and edited the manuscript.

Additional information

Funding

This study was supported by Mashhad University of Medical Science