Abstract
Background: AKI is a significant complication of coronavirus disease 2019 (COVID-19), with no effective therapy. Niacinamide, a vitamin B3 analogue, has some evidence of efficacy in non-COVID-19-related AKI. The objective of this study is to evaluate the association between niacinamide therapy and outcomes in patients with COVID-19-related AKI.
Methods: We implemented a quasi-experimental design with nonrandom, prospective allocation of niacinamide in 201 hospitalized adult patients, excluding those with baseline eGFR <15 ml/min per 1.73 m 2 on or off dialysis, with COVID-19-related AKI by Kidney Disease Improving Global Outcomes (KDIGO) criteria, in two hospitals with identical COVID-19 care algorithms, one of which additionally implemented treatment with niacinamide for COVID-19-related AKI. Patients on the niacinamide protocol (B3 patients) were compared against patients at the same institution before protocol commencement and contemporaneous patients at the non-niacinamide hospital (collectively, non-B3 patients). The primary outcome was a composite of death or RRT.
Results: A total of 38 out of 90 B3 patients and 62 out of 111 non-B3 patients died or received RRT. Using multivariable Cox proportional hazard modeling, niacinamide was associated with a lower risk of RRT or death (HR, 0.64; 95% CI, 0.40 to 1.00; P =0.05), an association driven by patients with KDIGO stage-2/3 AKI (HR, 0.29; 95% CI, 0.13 to 0.65; P =0.03; P interaction with KDIGO stage=0.03). Total mortality also followed this pattern (HR, 0.17; 95% CI, 0.05 to 0.52; in patients with KDIGO stage-2/3 AKI, P =0.002). Serum creatinine after AKI increased by 0.20 (SEM, 0.08) mg/dl per day among non-B3 patients with KDIGO stage-2/3 AKI, but was stable among comparable B3 patients (+0.01 [SEM, 0.06] mg/dl per day; P interaction=0.03).
Conclusions: Niacinamide was associated with lower risk of RRT/death and improved creatinine trajectory among patients with severe COVID-19-related AKI. Larger randomized studies are necessary to establish a causal relationship.
Keywords: COVID-19; NAD+; SARS-CoV-2; acute kidney injury; acute kidney injury and ICU nephrology; acute renal failure; clinical trial; niacinamide; outcomes; vitamin B3.
【저자키워드】 COVID-19, SARS-CoV-2, clinical trial, Acute kidney injury, outcomes, acute renal failure, acute kidney injury and ICU nephrology, NAD+, niacinamide, vitamin B3., 【초록키워드】 Treatment, coronavirus disease, Efficacy, therapy, protocol, Hospitalized, Mortality, hospital, outcome, ICU, dialysis, AKI, Patient, death, trajectory, Care, patients, association, Evidence, Interaction, creatinine, SEM, criteria, RRT, Algorithms, Primary outcome, 95% CI, lower risk, randomized study, effective therapy, renal, KDIGO, multivariable, evaluate, per day, comparable, driven by, Total, acute kidney, baseline, Improving, patients died, vitamin B3, 【제목키워드】 Improved,