Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.
Renal Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.
Metabolism. 2018 Feb;79:64-76. doi: 10.1016/j.metabol.2017.11.003. Epub 2017 Nov 11.
Recent studies examined the prognostic impact of nonalcoholic fatty liver disease (NAFLD) on the risk of incident chronic kidney disease (CKD). However, the extent to which NAFLD may confer risk of incident CKD is uncertain. We performed a meta-analysis of relevant studies to quantify the magnitude of the association between NAFLD and risk of incident CKD.
We searched PubMed, Scopus and Web of Science from January 1, 2000 to August 31, 2017 using pre-defined keywords to identify large observational cohort studies with a follow-up duration of at least 1year, in which NAFLD was diagnosed by biochemistry, fatty liver index or ultrasonography. No studies with biopsy-proven NAFLD were available for the analysis. Data from selected studies were extracted, and meta-analysis was performed using random-effects modeling.
A total of 9 observational studies with 96,595 adult individuals (34.1% with NAFLD) of predominantly Asian descent, and 4653 cases of incident CKD stage ≥3 (i.e., defined as occurrence of estimated glomerular filtration rate<60ml/min/1.73m, with or without accompanying overt proteinuria) over a median period of 5.2years were included in the final analysis. Patients with NAFLD had a significantly higher risk of incident CKD than those without NAFLD (random-effects hazard ratio [HR] 1.37, 95% CI 1.20-1.53; I=33.5%). Patients with more 'severe' NAFLD (according to ultrasonography and non-invasive fibrosis markers) were also more likely to develop incident CKD (n=2 studies; random-effects HR 1.50, 95% CI 1.25-1.74; I=0%); this risk appeared to be even greater among those with ultrasound-diagnosed NAFLD and a high-intermediate NAFLD fibrosis score (n=1 study; random-effects HR 1.59, 95% CI 1.31-1.93). Sensitivity analyses did not alter these findings. Funnel plot and Egger's test did not reveal significant publication bias.
This largest and most updated meta-analysis to date shows that NAFLD (detected by biochemistry, fatty liver index or ultrasonography) is associated with a nearly 40% increase in the long-term risk of incident CKD. However, the observational nature of the eligible studies does not allow for proving causality. Our findings pave the way for future large, prospective, histologically-based studies.
最近的研究检查了非酒精性脂肪性肝病（NAFLD）对慢性肾脏病（CKD）发病风险的预后影响。然而，NAFLD 可能导致 CKD 发病风险的程度尚不确定。我们进行了一项荟萃分析，以量化 NAFLD 与 CKD 发病风险之间的关联程度。
我们使用预定义的关键字从 2000 年 1 月 1 日至 2017 年 8 月 31 日在 PubMed、Scopus 和 Web of Science 上进行了搜索，以确定随访时间至少为 1 年的大型观察性队列研究，其中 NAFLD 通过生物化学、脂肪肝指数或超声检查诊断。没有可供分析的活检证实的 NAFLD 研究。从选定的研究中提取数据，并使用随机效应模型进行荟萃分析。
共有 9 项观察性研究纳入了 96595 名成年人（34.1%患有 NAFLD），主要为亚洲血统，中位随访时间为 5.2 年，共发生 4653 例 CKD 期≥3（即定义为估计肾小球滤过率<60ml/min/1.73m，伴有或不伴有明显蛋白尿）。与无 NAFLD 者相比，NAFLD 患者发生 CKD 的风险显著增加（随机效应风险比[HR]1.37，95%CI1.20-1.53；I=33.5%）。根据超声和非侵入性纤维化标志物，“更严重”的 NAFLD（n=2 项研究；随机效应 HR1.50，95%CI1.25-1.74；I=0%）患者也更有可能发生 CKD；在超声诊断为 NAFLD 和高-中等 NAFLD 纤维化评分的患者中（n=1 项研究；随机效应 HR1.59，95%CI1.31-1.93），这种风险似乎更大。敏感性分析并未改变这些发现。漏斗图和 Egger 检验未显示出显著的发表偏倚。
这是迄今为止最大和最新的荟萃分析显示，NAFLD（通过生物化学、脂肪肝指数或超声检查检测）与长期发生 CKD 的风险增加近 40%相关。然而，合格研究的观察性质不允许证明因果关系。我们的发现为未来的大型、前瞻性、基于组织学的研究铺平了道路。
