Ene Patrik, Svensson Maria K, Strand Robin, Kullberg Joel, Ahlström Håkan, Larsson Anders, Lind Lars
Department of Medical Sciences Renal Medicine, Uppsala University Hospital, Uppsala University.
Uppsala Clinical Research Centre, Uppsala.
Clin Kidney J. 2025 Apr 25;18(5):sfaf116. doi: 10.1093/ckj/sfaf116. eCollection 2025 May.
Obesity has been associated with onset and progression of chronic kidney disease (CKD) but causal relationship remains uncertain. This study investigated how obesity causally affects estimated glomerular filtration rate.
Cross-sectional and magnetic resonance imaging (MRI) data analyses were performed within the Prospective Investigation of Obesity, Energy, and Metabolism (POEM) study (502 participants, all aged 50 years). Additionally Mendelian randomization was performed using published summary data. Outcomes were creatinine- and cystatin C-based eGFR. Body mass index (BMI) and waist circumference (WC) were used as exposure variables in the cross-sectional and Mendelian randomization analyses. In the imaging data analyses, eGFR was regressed non-parametrically on tissue volume for each 3D voxel and visualized as a correlation "Imiomics" map.
Negative correlations were shown between cystatin C-based eGFR and BMI [beta = -0.190 (95% CI: -0.280 to -0.100)] and WC [beta = -0.160 (95% CI: -0.250 to -0.060)] in an adjusted model. In contrast, a positive association was found for creatinine-based eGFR [BMI beta = 1.20 (95% CI: 0.030 to 0.210) and WC beta = 0.160 (95% CI: 0.070 to 0.260)]. Similar patterns were found using MRI analysis (Imiomics map). Mendelian randomization implied a negative causal effect of obesity-related measures on cystatin C-based eGFR [BMI beta = -0.031 (95% CI: -0.037 to -0.026) and WC beta = -0.038 (95% CI: -0.045 to -0.031)], but no statistically significant effect was found for creatinine-based eGFR.
This study suggests a causal negative effect of obesity on cystatin C-based, but not creatinine-based eGFR. These findings warrant further research regarding estimations of kidney function when assessing obesity and CKD.
肥胖与慢性肾脏病（CKD）的发生和进展相关，但因果关系仍不明确。本研究调查了肥胖如何因果性地影响估计肾小球滤过率。
在肥胖、能量与代谢前瞻性研究（POEM研究，502名参与者，均为50岁）中进行横断面和磁共振成像（MRI）数据分析。此外，使用已发表的汇总数据进行孟德尔随机化分析。结局指标为基于肌酐和胱抑素C的估算肾小球滤过率（eGFR）。在横断面和孟德尔随机化分析中，将体重指数（BMI）和腰围（WC）用作暴露变量。在成像数据分析中，针对每个三维体素，将eGFR对组织体积进行非参数回归，并可视化为相关的“影像组学”图谱。
在调整模型中，基于胱抑素C的eGFR与BMI [β = -0.190（95%CI：-0.280至-0.100）]和WC [β = -0.160（95%CI：-0.250至-0.060）]呈负相关。相比之下，基于肌酐的eGFR呈正相关[BMI β = 1.20（95%CI：0.030至0.210），WC β = 0.160（95%CI：0.070至0.260）]。使用MRI分析（影像组学图谱）发现了类似模式。孟德尔随机化提示肥胖相关指标对基于胱抑素C的eGFR有负向因果效应[BMI β = -0.031（95%CI：-0.037至-0.026），WC β = -0.038（95%CI：-0.045至-0.031）]，但基于肌酐的eGFR未发现统计学显著效应。
本研究提示肥胖对基于胱抑素C而非基于肌酐的eGFR有因果负向效应。这些发现为评估肥胖和CKD时肾功能的估计提供了进一步研究的依据。
