Cilastatin as a protective agent against drug-induced nephrotoxicity: a literature review

Cilastatin, a dehydropeptidase I inhibitor, has been used alongside imipenem, a broad spectrum antibiotic, in order to reduce its renal metabolism, consequently increasing its urinary recovery and effectiveness for many years. However, this measure could be useful in preventing imipenem-induced renal damage and decreasing the number of nephrotoxicity reports with imipenem. In this review, the authors gathered all available studies focusing on cilastatin use as a nephroprotective agent, beside well-known nephrotoxic medications like vancomycin, cisplatin, cyclosporine, or tacrolimus.PubMed, Scopus, Google Scholar, and Medline databases were searched using key words like 'cilastatin,' 'nephroprotective,' 'nephroprotection,' 'vancomycin,' 'nephrotoxicity,' 'cisplatin,' 'cyclosporine,' 'tacrolimus,' and 'prevention' with varying combinations. All relevant animal and human studies up to the date of publication were included.It seems that cilastatin could potentially be effective against drug-induced nephrotoxicity via mechanisms such as reducing reactive oxygen species (ROS) production, apoptosis, P-glycoprotein suppression, and morphological changes of renal cells. Nearly all the in vitro, in vivo and human studies have supported this hypothesis. Though since cilastatin protective effect has not extensively been researched in humans, its efficacy and widespread use with other nephrotoxic agents is yet to be defined in large well-designed human studies.