Integrated lifestyle management to mitigate MASLD risk in patients with chronic kidney disease: a prospective cohort study

This study aimed to investigate whether effective management of multiple lifestyle risk factors could mitigate the elevated risk of metabolic dysfunction-associated steatotic liver disease (MASLD) among individuals with chronic kidney disease (CKD). We analyzed data from the UK Biobank, including 9,877 patients with CKD and 421,043 non-CKD controls, with follow-up through October 31, 2022. Eight lifestyle-related MASLD risk factors (body mass index, diet, physical activity, alcohol consumption, smoking, social connection, sedentary behavior, and sleep duration) were assessed and jointly summarized to reflect the degree of lifestyle risk factor management. Cox proportional hazards models were used to evaluate associations between cumulative lifestyle risk factor management and incident MASLD. Effect modification by sex, type 2 diabetes (T2D), hyperlipidemia, and hypertension was examined using multiplicative interaction terms. All models were adjusted for a comprehensive set of covariates. Missing data were handled using multiple imputation with chained equations, and several sensitivity analyses were conducted to test the robustness. Among individuals with CKD, progressively better joint management of lifestyle risk factors was associated with a stepwise reduction in incident MASLD risk. Each additional lifestyle risk factor managed was associated with a 14% lower risk of MASLD. Optimal lifestyle risk factor control (≥ 7 factors managed) was associated with a 64% reduction in MASLD (HR: 0.36; 95% CI: 0.16–0.79). Notably, among CKD patients achieving optimal lifestyle control MASLD risk was attenuated to a level comparable to that of non-CKD controls (HR: 0.95; 95% CI: 0.49–1.84). The protective association of combined lifestyle risk factor management was less pronounced in individuals with hyperlipidemia or T2D compared to those without these conditions (P for interaction < 0.001). In individuals with CKD, cumulative adherence to optimal lifestyle risk factor management exhibited an inverse association with MASLD development. These findings suggest that comprehensive control of modifiable lifestyle risks may be associated with a mitigation of the elevated MASLD susceptibility observed in CKD populations. This prospective cohort study revealed that a higher degree of multifactorial lifestyle control was significantly associated with a reduced risk of MASLD among CKD patients. Most importantly, our data suggested that achieving optimal control of lifestyle risk factors may attenuate the excess risk of MASLD associated with CKD. These findings highlight the clinical and public health importance of holistic lifestyle management for mitigating MASLD risk in the CKD population.