Oral Melatonin for Colistin-induced Nephrotoxicity Reduction in Intensive Care Unit: A Randomized Placebo Controlled Clinical Trial

Background: Colistin is a drug of choice against multidrug-resistance (MDR) bacteria. The most important side effect of colistin is nephrotoxicity, observed in 20 - 54% of patients. According to the studies that examined its antioxidant effect, it can reduce the kidney toxicity of various drugs, including colistin. Objectives: This study aimed to investigate melatonin's effect on reducing colistin-induced kidney toxicity to use this drug with fewer complications. Methods: This double-blind, randomized clinical trials with two groups involved 56 critically ill adults infected by MDR bacteria. The intervention group received 3 mg of oral melatonin simultaneously with intravenous colistin, which continued until the end of the treatment. The control group received placebo orally with IV colistin. We measured urine volume, blood creatinine, and blood urea nitrogen (BUN) daily and determined the patients with renal failure using the KDIGO guideline. STATA software analyzed data with a P-value of less than 0.05 as the significance level. Results: Data obtained from recipients were analyzed for age (P-value = 0.357), gender (P-value = 0.945), weight (P-value = 0.438), APACHE score (P-value = 0.162). We did not observe significant difference in acute kidney injury (AKI) criteria between the two groups. Compared to the control group, melatonin did not decrease blood creatinine (P-value = 0.110) and BUN (P-value = 0.567) and, made no change of urinary volume (P-value = 0.913). There was no decrease in kidney failure in the intervention group compared to the control group. As a result, we did not find a significant difference in outcome of the two groups. Conclusions: We did not reveal any significant difference in the AKI criteria including blood creatinine, BUN, and daily urine volume with the addition of melatonin in participants receiving colistin; However, no complication was observed in the intervention group who received melatonin.