Statins show therapeutic potential in COVID-19-related acute kidney injury

COVID-19 patients with chronic statin exposure appear to be at lower risk of developing acute kidney injury (AKI) during hospitalization in addition to having reduced levels of inflammation, as reported in a study.

In a cohort of 269 consecutive patients admitted for COVID-19 pneumonia in Bologna, Italy, statin use conferred some protection against the risk of AKI (odds ratio [OR], 0.47, 95 percent confidence interval [CI], 0.23–0.95; p=0.036) in an analysis adjusted for potential confounders, including age, sex, and chronic kidney disease (CKD). Furthermore, statin users had significantly lower C-reactive protein (CRP) levels than nonusers at hospital admission (p=0.048). [Nutr Metab Cardiovasc Dis 2022;doi:10.1016/j.numecd.2022.10.005]

According to the investigators, the anti-inflammatory effects of statin may be responsible for the reduction in the risk of AKI that was observed in the study.

“Indeed, statins have shown to reduce the incidence and progression of AKI in other clinical scenarios like contrast-induced AKI,” they said. [Int J Biol Sci 2020;16:2704-2711; Clin Exp Nephrol 2017;21:175-181]

However, the investigators acknowledged that the evidence on the role of chronic statin therapy in COVID-19-associated AKI was conflicting. One study showed that statins may reduce AKI incidence in patients hospitalized for COVID-19, whereas another reported that exposure to such drugs was an independent risk factor for AKI development in patients with diabetes hospitalized for COVID-19. [Drugs 2021;81:685-695; J Diabetes Res 2021;2021:6666086]

Additional prospective and randomized studies that better define the role of statins in AKI prevention and/or treatment are needed, they added.

In the present study, a total of 65 patients (22.8 percent) were statin users. Compared with nonusers, statin users were older (mean 71 vs 62 years; p<0.001) and had a significantly higher prevalence of hypertension (p=0.0021), diabetes mellitus (p=0.0027), and cardiovascular disease (p<0.001). Moreover, statin users had significantly lower estimated glomerular filtration rate (70 vs 81 mL/min/1.73m²; p=0.001) and a higher mortality rate (16.9 percent vs 6.8 percent).

Statin exposure had no significant effect on all-cause mortality (hazard ratio [HR], 1.98, 95 percent CI, 0.71–5.50; p=0.191) and intensive care unit admission (HR, 0.93, 95 percent CI, 0.52–1.65; p=0.801).

“Several large observational studies on patients with COVID-19 reported that statins may reduce the risk of all-causes in-hospital mortality. This finding has been confirmed by recent systematic reviews and meta-analyses. In our study, although not statistically significant, we observed an increased death rate among patients under statin treatment vs … not chronically treated with statins,” according to the investigators. [Cell Metab 2020;32:176-187.e4; JAMA Netw Open 2020;3:e2029058; J Am Heart Assoc 2020;9:e018475; PLoS One 2021;16:e0253576; Int J Infect Dis 2021;110:374-381]

The finding on mortality, they said, may be explained by the severity of COVID-19 in the study population, where all patients had COVID-19 pneumonia and respiratory failure, with 42.1 percent having severe acute distress syndrome.

“One recent randomized controlled trial on the role of atorvastatin vs placebo in the setting of adults with severe COVID-19 admitted to the ICU (INSPIRATION/INSPIRATION-S trial) has shown no benefits of statin over placebo in several outcomes, including in-hospital death. In fact, as the authors of the INSPIRATION trial hypothesized, it is possible that statins may be beneficial in early COVID-19, before inflammatory irreversible damage occurs,” they said. [BMJ 2022;376:e068407]