Cardiovascular-kidney-liver-metabolic-health:a population-based study on the prognostic impact of the coexistence of metabolic dysfunction-associated steatotic liver disease and chronic kidney disease

Abstract Background Metabolic dysfunction-associated steatotic liver disease (MASLD) and chronic kidney disease (CKD) are emerging non-traditional cardiovascular risk factors. However, the clinical characteristics and prognostic importance of coexistent MASLD and CKD in the general population remain understudied. This study aims to strengthen cardiovascular risk stratification by examining the synergistic effect of MASLD and CKD on cardiovascular outcomes. The examination of MASLD and CKD can inform the prioritisation of biomarkers for risk stratification, and guide primary and secondary preventative strategies in higher risk populations to mitigate CVD and mortality in this comorbid context. Methods This population-based study utilises the National Health and Nutrition Examination Survey (NHANES) 2007-2018 database, examining the prognostic outcomes of community-dwelling adults, stratified by the presence of MASLD and CKD. The primary outcome was all-cause mortality. Secondary outcomes include coronary heart disease, heart failure, stroke and cancer. Cox regression model was constructed to investigate the relationship between MASLD/CKD and all-cause mortality, adjusted for age, prior coronary disease, body-mass index, smoking, lipid and glucose-lowering medications. Sensitivity analysis was performed with hepatic fibrosis and CKD. Hepatic fibrosis was defined based on the serum-based Fibrosis-4 Index (FIB-4), with a threshold of ≥2.67 defining advanced fibrosis. Results A total of 14,818 participants were examined, with a mean follow-up duration of 6.9±3.4 years. Among the cohort, majority of participants had MASLD(-)/CKD(-) (50.8%), followed by MASLD(+)/CKD(-) (34.8%), MASLD(+)/CKD(+) (7.7%) and MASLD(-)/CKD(+) (6.7%) group. Individuals with coexistent MASLD and CKD had the highest rates of obesity (77.6%), hypertension (77.5%), dyslipidemia (67.0%), and diabetes (49.7%), with the highest risk of coronary heart disease (RR 1.786, 95%CI 1.129–2.824, p =0.013) and heart failure (RR 2.334, 95%CI 1.072–5.084, p=0.033). Cox regression demonstrated MASLD(+)/CKD(+) (aHR 3.592, 95%CI 2.087–6.180, p<0.001) and MASLD(-)/CKD(+) (aHR 2.178, 95%CI 1.326–3.577, p=0.002) phenotypes were independent predictors of mortality. Risk stratification was enhanced across fibrosis-CKD phenotypes with more pronounced divergence in survival, as concomitant fibrosis and CKD phenotype portended the least favourable 10-year (aHR 2.629, 95% CI: 1.486–4.651, p<0.001). Conclusion The coexistence of MASLD and CKD embodied increased risk of cardiometabolic multimorbidity, and was an independent predictor of 10-year mortality with stepwise incremental mortality risk observed in high-risk individuals with concomitant advanced hepatic fibrosis and CKD. There is a need for scalable and effective screening systems in facilitating risk prediction and interventional targets within the cardiovascular-kidney-liver-metabolic disease spectrum.