The α-Helical Amphipathic Peptide Alleviates Colistin-Induced Nephrotoxicity by Maintaining Mitochondrial Function in Both In Vitro and In Vivo Infection Models.

: Colistin is the primary treatment for carbapenem-resistant Gram-negative bacteria (CR-GNB) infections, but its use is limited by nephrotoxicity, which reduces its effectiveness. There is an urgent need for nephroprotective agents to address this toxicity. This study investigated the potential of CMP3029, an α-helical peptide, to protect against colistin-induced nephrotoxicity. : In vitro, CMP3029 was applied to HK-2 cells before colistin exposure, and cell viability and reactive oxygen species (ROS) levels were measured. In infected mice, CMP3029 was administered before colistin treatment, and urinary kidney injury molecule-1 (KIM-1), cystatin C levels, neutrophil gelatinase-associated lipocalin (NGAL), and renal damage were assessed. : CMP3029 preserved cell viability and significantly reduced mitochondrial ROS in HK-2 cells exposed to colistin. CMP3029 lowered urinary biomarkers and mitigated tubular injury in mice, demonstrating significant nephroprotective effects. : These findings suggest that CMP3029 mitigates colistin-induced nephrotoxicity. Given the increasing threat of CR-GNB infections, CMP3029 could be a crucial clinical solution for improving patient outcomes in treating colistin-associated nephrotoxicity.