Data_Sheet_1_Evaluated Glomerular Filtration Rate Is Associated With Non-alcoholic Fatty Liver Disease: A 5-Year Longitudinal Cohort Study in Chinese Non-obese People.docx

ObjectiveEvidence regarding the association between evaluated glomerular filtration rate (eGFR) and non-alcoholic fatty liver disease (NAFLD) is still limited. On that account, the purpose of our research is to survey the link of evaluated eGFR on NAFLD.
MethodsThis study is a retrospective cohort study. Which consecutively and non-selectively collected a total of 16,138 non-obese participants in a Chinese hospital from January 2010 to December 2014. We then used the Cox proportional-hazards regression model to explore the relationship between baseline eGFR and NAFLD risk. A Cox proportional hazards regression with cubic spline functions and smooth curve fitting (the cubic spline smoothing) was used to identify the non-linear relationship between eGFR and NAFLD. Additionally, we also performed a series of sensitivity analyses and subgroup analyses. Data had been uploaded to the DATADRYAD website.
ResultsThe mean age of the included individuals was 43.21 ± 14.95 years old, and 8,467 (52.47%) were male. The mean baseline eGFR was 98.83 ± 22.80 mL/min per 1.73m2. During a median follow-up time of 35.8 months, 2,317 (14.36%) people experienced NAFLD. After adjusting covariates, the results showed that eGFR was negatively associated with incident NAFLD (HR = 0.983, 95%CI: 0.980, 0.985). There was also a non-linear relationship between eGFR and NAFLD, and the inflection point of eGFR was 103.489 mL/min per 1.73 m2. The effect sizes (HR) on the left and right sides of the inflection point were 0.988 (0.984, 0.991) and 0.971 (0.963, 0.979), respectively. And the sensitive analysis demonstrated the robustness of our results. Subgroup analysis showed that eGFR was more strongly associated with incident NAFLD in diastolic blood pressure (DBP) < 90 mmHg, fasting plasma glucose (FPG) ≤ 6.1 mmol/L, high-density lipoprotein cholesterol (HDL-c) < 1 mmol/L, and alanine aminotransferase (ALT) ≥ 40 U/L participants. In contrast, the weaker association was probed in those with DBP ≥ 90 mmHg, ALT < 40 U/L, FPG > 6.1 mmol/L, and HDL-c ≥ 1 mmol/L.
ConclusionThis study demonstrates a negative and non-linear association between eGFR and incident NAFLD in the Chinese non-obese population. eGFR is strongly related to NAFLD when eGFR is above 103 mL/min per 1.73 m2. From a therapeutic perspective, it makes sense to maintain eGFR levels within the inflection point to 130 mL/min/1.73 m2.

目前关于估算肾小球滤过率（evaluated glomerular filtration rate, eGFR）与非酒精性脂肪性肝病（non-alcoholic fatty liver disease, NAFLD）之间关联的客观证据仍较为有限。鉴于此，本研究旨在探讨eGFR与NAFLD的关联。

方法 本研究为回顾性队列研究。于2010年1月至2014年12月期间，在国内某医院连续非选择性纳入共计16138名非肥胖受试者。随后采用Cox比例风险回归模型，探讨基线eGFR与NAFLD发病风险之间的关联。此外，本研究还采用含三次样条函数的Cox比例风险回归及平滑曲线拟合（三次样条平滑法），以明确eGFR与NAFLD之间的非线性关联。同时，本研究还开展了一系列敏感性分析与亚组分析。相关数据已上传至DATADRYAD网站。

结果 纳入受试者的平均年龄为43.21±14.95岁，其中男性8467例，占比52.47%。基线eGFR平均值为98.83±22.80 mL/min/1.73m²。在中位随访35.8个月期间，共计2317名受试者（占比14.36%）新发NAFLD。校正混杂因素后，结果显示eGFR与新发NAFLD呈负相关（风险比（hazard ratio, HR）=0.983，95%置信区间（CI）：0.980, 0.985）。eGFR与NAFLD之间同样存在非线性关联，eGFR的拐点值为103.489 mL/min/1.73m²。在拐点两侧，其效应量（HR）分别为0.988（95%CI：0.984, 0.991）与0.971（95%CI：0.963, 0.979）。敏感性分析证实了本研究结果的稳健性。亚组分析结果显示，在舒张压（diastolic blood pressure, DBP）<90mmHg、空腹血糖（fasting plasma glucose, FPG）≤6.1mmol/L、高密度脂蛋白胆固醇（high-density lipoprotein cholesterol, HDL-c）<1mmol/L以及丙氨酸氨基转移酶（alanine aminotransferase, ALT）≥40U/L的受试者中，eGFR与新发NAFLD的关联更为显著；与之相反，在DBP≥90mmHg、ALT<40U/L、FPG>6.1mmol/L以及HDL-c≥1mmol/L的受试者中，二者的关联强度较弱。

结论 本研究证实，在中国非肥胖人群中，eGFR与新发NAFLD呈负相关且存在非线性关联。当eGFR高于103mL/min/1.73m²时，eGFR与NAFLD的关联更为紧密。从治疗角度而言，将eGFR维持在拐点至130mL/min/1.73m²范围内具有临床意义。