Acute Kidney Injury
Maria G. Tanzi, PharmD
Melatonin use was associated with a significant reduction in vancomycin-related acute kidney injury (AKI), according to results of a single-center, retrospective observational study published recently in Antimicrobial Agents and Chemotherapy.
“The results were surprising, yet in line with the purported mechanism demonstrated in preclinical studies,” said Luigi Brunetti, PharmD, PhD, an associate professor of pharmacy practice and administration at Rutgers University in New Jersey, and one of the study authors.
“Before we can make any recommendation for melatonin, however, prospective clinical studies are required,” said Brunetti. “We are currently in the process of planning such confirmatory studies.”
Background
According to Brunetti, the idea to use melatonin for the prevention of AKI came from an observation his research team made after some in vitro work in the laboratory.
“We were aware that vancomycin-related AKI was related to oxidative stress, and we knew that melatonin had antioxidant properties,” said Brunetti. “When we exposed renal proximal tubules to vancomycin in the lab, we noted that those pre-treated with melatonin did better.”
Study results
Researchers analyzed data from 303 adults admitted to a large community medical center between January 2016 and September 2020 who received vancomycin therapy alone or concurrently with melatonin as part of ordinary care.
All patients had received at least 3 doses of vancomycin and had a creatinine clearance (CrCl) of greater than or equal to 30 mL/min at baseline. Of the 303 patients, 101 received melatonin concurrently (mean number of doses was 6.5 per patient).
The primary endpoint was development of AKI, which was defined as an absolute increase in serum creatinine of 0.3 mg/dL or more, or an increase of 50% or more in serum creatinine.
Baseline characteristics were similar among the two groups, except for the incidence of bacteremia/sepsis, which was greater in the melatonin group—37.6% versus 25.2% in the group taking vancomycin without melatonin.
Results of the multivariable analysis, which controlled for vancomycin AUC, baseline creatinine clearance, and admission to the ICU, found that concurrent use of melatonin was associated with a 63% decreased incidence of AKI.
What’s next
Brunetti said that their pharmacy team has been dosing vancomycin for over a decade via their pharmacokinetic service, and that the team closely evaluates the need for vancomycin, drug concentrations, and trends in the serum creatinine to identify AKI early.
Additionally, the team monitors all broad-spectrum antibiotics as part of the antimicrobial stewardship efforts. He noted that all of these collective strategies not only help to reduce unnecessary antibiotic use, but also decrease the risk of antibiotic-associated AKI.
“While our data are positive, we must appropriately evaluate the safety and efficacy of melatonin for the prevention of vancomycin AKI in prospective trials,” said Brunetti.
Some of the key questions that need to be answered include the optimal dose and frequency of melatonin for its renoprotective effects, and the ideal timing of melatonin dosing as it relates to vancomycin therapy initiation.
In the current analysis, most patients received 5 mg of melatonin; however, some received 3 mg. Additionally, serum levels were not collected in the current analysis, and data suggest that the bioavailability of oral melatonin is highly variable, with wide ranges in serum melatonin levels.
The potential nephroprotective effects of melatonin are intriguing given the common use of vancomycin in the hospital setting, especially with other agents that may be nephrotoxic.
“Melatonin is relatively safe, frequently used, and readily available,” said Brunetti. “However, confirmatory evaluations are needed before it can become a standard for prevention of AKI.”