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Impact of non‐alcoholic fatty liver disease and fibrosis on mortality and kidney outcomes in patients with type 2 diabetes and chronic kidney disease: A multi‐cohort longitudinal study

医学 内科学 危险系数 肾脏疾病 脂肪肝 队列 2型糖尿病 孟德尔随机化 肝活检 全国健康与营养检查调查 比例危险模型 队列研究 糖尿病 胃肠病学 疾病 置信区间 活检 人口 内分泌学 环境卫生 化学 基因型 基因 生物化学 遗传变异
作者
Lijun Zhao,Qingyue Zeng,Xiaoqin Zhou,Linqiao Tang,Yujia Wang,Qianqian Han,Yutong Zou,Xiang Xiao,Ke Liu,Xuegui Ju,Yucheng Wu,Hongqiang Li,Chuanyi Zhao,Fang Liu
出处
期刊:Diabetes, Obesity and Metabolism [Wiley]
卷期号:26 (10): 4241-4250 被引量:3
标识
DOI:10.1111/dom.15758
摘要

Abstract Aim To evaluate the impact of non‐alcoholic fatty liver disease (NAFLD) presence and fibrosis risk on adverse outcomes in patients with type 2 diabetes and chronic kidney disease. Methods Data were sourced from two longitudinal cohorts: 1172 patients from the National Health and Nutrition Examination Survey (NHANES) and 326 patients from the kidney biopsy cohort at the West China Hospital of Sichuan University. Cox regression estimated hazard ratios (HRs) for NAFLD and liver fibrosis concerning adverse clinical outcomes. Subsequently, a two‐sample Mendelian randomization study using genome‐wide association study statistics explored NAFLD's potential causal link to cardio‐cerebrovascular events. Results In the NHANES cohort, NAFLD stood as an independent risk factor for various outcomes: overall mortality [HR 1.53 (95% confidence interval, CI 1.21‐1.95)], mortality because of cardio‐cerebrovascular diseases [HR 1.63 (95% CI 1.12‐2.37)], heart disease [HR 1.58 (95% CI 1.00‐2.49)], and cerebrovascular disease [HR 3.95 (95% CI 1.48‐10.55)]. Notably, advanced liver fibrosis, identified by a fibrosis‐4 (FIB‐4) score >2.67, exhibited associations with overall mortality, cardio‐cerebrovascular disease mortality and heart disease mortality. Within the kidney biopsy cohort, NAFLD correlated with future end‐stage kidney disease [ESKD; HR 2.17 (95% CI 1.41‐3.34)], while elevated FIB‐4 or NAFLD Fibrosis Scores predicted future ESKD, following full adjustment. Liver fibrosis was positively correlated with renal interstitial fibrosis and tubular atrophy in biopsies. Further Mendelian randomization analysis supported a causal relationship between NAFLD and cardio‐cerebrovascular events. Conclusions In patients with type 2 diabetes and chronic kidney disease, the NAFLD presence and elevated FIB‐4 scores link to heightened mortality risk and ESKD susceptibility. Moreover, NAFLD shows a causal relationship with cardio‐cerebrovascular events.
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