Abstract Background Annual influenza vaccination is recommended for individuals with chronic kidney disease (CKD); however, guideline adherence is suboptimal potentially related to lack of awareness of vaccine availability and effectiveness. Purpose This prespecified analysis of the NUDGE-FLU-CHRONIC trial investigated the effectiveness of digital behavioral nudges on influenza vaccine uptake based on the presence or absence of CKD. Methods NUDGE-FLU-CHRONIC was a randomized, nationwide trial, conducted during the 2023/2024 influenza season including younger and middle-aged (18-64 years) Danish citizens with chronic illnesses (making them eligible for the free Danish vaccine program). Participants were randomized in a ratio of 2.45:1:1:1:1:1:1 to receive either usual care (no letter) or one of six different letter-based nudges, delivered via the governmental electronic letter system on September 26, 2023. Baseline and outcome data were obtained with the Danish nationwide registers. Primary endpoint was receipt of an influenza vaccine no later than January 1, 2024. Results A total of 299,881 individuals were randomized in NUDGE-FLU-CHRONIC trial, among them, 15,208 (5.1%) had a history of CKD. Participants with CKD had a median age was 53.1 years (IQR, 42.2-59.6) and 46.0% were female. During follow-up, 43.7% of participants with CKD were vaccinated compared with 35.8% of participants without CKD (p<0.001). Any letter was highly effective in increasing influenza vaccination in the overall population but was slightly less effective in those with a history of CKD (p for interaction = 0.005). In participants with CKD, any letter increased vaccination by 25% versus no letter (46.3% vs. 37.1%; difference, 9.3 percentage points; 99.29%CI, 6.9-11.6; RR, 1.25; 99.29%CI, 1.18-1.33). In participants without CKD, any letter increased vaccination by 43% (39.2% vs. 27.4%; difference, 11.8 percentage points; 99.29%CI, 11.3-12.3; RR, 1.43; 99.29%CI, 1.41-1.45). Similar patterns were observed when assessing each intervention letter individually (Figure 1). Effectiveness of any letter vs. usual care was consistent across CKD subgroups, except for concomitant diabetes vs no diabetes (Figure 2). There was no observed effect modification by CKD duration (p for interaction = 0.78) or by estimated glomerular filtration rate (p for interaction = 0.78) modelled continuously for any letter vs. usual care. Conclusion In this prespecified analysis from the nationwide NUDGE-FLU-CHRONIC trial, only approximately 1 in 3 younger and middle-aged adults with CKD received influenza vaccination. Digital nudge letters emphasizing the importance of annual influenza vaccination significantly boosted rates of vaccination across a broad range of individuals with CKD.Figure 1Figure 2