Abstract
To investigate the association between night shift work and chronic kidney disease (CKD) risk and evaluate the interacting role of genetic susceptibility. This prospective cohort study included 252,425 participants from the UK Biobank for current night shift analysis and 67,097 for lifetime exposure. Cox proportional hazards models assessed the relationship between various shift patterns and CKD incidence. Formal interaction analyses (additive and multiplicative scales) and sensitivity analyses were conducted. Reporting followed STROBE guidelines. Compared to those who never or rarely worked night shifts, permanent night shift workers had a significantly higher CKD risk (HR 1.19, 95% CI 1.06-1.34). Lifetime analyses revealed significant associations between incident CKD risk and duration, frequency, shift length, and consecutive shifts. Participants with high genetic risk and permanent night shift exposure had the highest CKD risk (HR 2.49, 95% CI 2.07-2.99). Potential interactions between genetic susceptibility and specific night shift patterns were suggested (P < 0.05). Sensitivity analyses further confirmed the robustness of these associations. Night shift work - particularly permanent schedules and adverse shift patterns - increases the risk of CKD, especially among individuals with high genetic predisposition. Optimizing shift schedules may help reduce CKD incidence.</p>