Renoprotective Effects of Melatonin against Vancomycin-Related Acute Kidney Injury in Hospitalized Patients: a Retrospective Cohort Study

Antimicrob Agents Chemother. 2021 Aug 17;65(9):e0046221. doi: 10.1128/AAC.00462-21. Epub 2021 Aug 17.


Vancomycin is associated with nephrotoxicity, and the mechanism may in part be related to oxidative stress. In vitro and preclinical studies suggest that melatonin supplementation decreases oxidative stress. The objective of this study was to evaluate concomitant use of melatonin and vancomycin and the incidence of acute kidney injury (AKI). We performed a retrospective cohort study at a large community medical center. All consecutive patients admitted to the medical center between January 2016 and September 2020 who received vancomycin therapy alone or concomitantly with melatonin as part of ordinary care were considered for inclusion. The primary endpoint was the development of AKI, defined as an absolute increase in serum creatinine of ≥0.3 mg/dl or a ≥50% increase in serum creatinine. All data were analyzed using descriptive statistics. A multivariable logistic regression was constructed to account for potential confounding variables. We identified a total of 303 adult patients meeting inclusion and exclusion criteria treated with vancomycin, 101 of which received melatonin concomitantly. Overall baseline characteristics were similar between the two groups except for the incidence of bacteremia/sepsis. After controlling for the vancomycin area under the curve, baseline creatinine clearance, and intensive care unit admission in a multivariable logistic regression analysis, melatonin use was associated with a 63% decrease in AKI (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.14 to 0.96; P = 0.041). Melatonin use was associated with a significant reduction in vancomycin-related AKI. Although this was a retrospective study with a small sample size, given the magnitude of the difference seen, further large prospective studies are warranted.

Keywords: acute kidney injury; antioxidant; melatonin; vancomycin.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Kidney Injury* / chemically induced
  • Acute Kidney Injury* / drug therapy
  • Acute Kidney Injury* / prevention & control
  • Adult
  • Anti-Bacterial Agents / adverse effects
  • Drug Therapy, Combination
  • Humans
  • Melatonin* / therapeutic use
  • Piperacillin, Tazobactam Drug Combination
  • Retrospective Studies
  • Vancomycin / adverse effects


  • Anti-Bacterial Agents
  • Piperacillin, Tazobactam Drug Combination
  • Vancomycin
  • Melatonin