Insulin resistance, hypertension, hyperuricemia, and hypercholesterolemia are hypothesized to be important intermediates in the relationship between excess body weight and CKD risk. However, the magnitude of the total effect of excess body weight on ESKD mediated through these four pathways remains to be quantified.

We applied a model for analysis of correlated mediators to population-based data from 100,269 Austrian individuals (mean age 46.4 years). Association of body mass index (BMI) was coalesced with ESKD risk into direct association. Indirect associations were mediated through the triglyceride-glucose (TyG) index (as an indicator of insulin resistance), mean arterial pressure (MAP), uric acid (UA), and total cholesterol (TC).

Mean follow-up was 23.1 years with 463 (0.5%) incident ESKD cases. An unhealthy metabolic profile (prevalence 32.4%) was associated with a markedly increased ESKD risk (multivariably adjusted hazard ratio (aHR), 3.57; 95% CI, 2.89 to 4.40), independent of BMI. A 5-kg/m² higher BMI was associated with a 57% increased ESKD risk (aHR_{total association}, 1.57; 1.38 to 1.77). Of this association, 99% (76% to 140%) arose from all mediators jointly; 33% (22% to 49%) through TyG index; 34% (24% to 50%) through MAP; 30% (21% to 45%) through UA; and 2% (–1% to 4%) through TC. The remaining direct association was nonsignificant (aHR_{direct association}, 1.01; 0.88 to 1.14).

TyG index, MAP, and UA, but not TC, mediate the association of BMI with ESKD in middle-aged adults. Our findings highlight that in addition to weight reduction, the control of metabolic risk factors might be essential in mitigating the adverse effects of BMI on kidney function.

胰岛素抵抗、高血压、高尿酸血症和高胆固醇血症被认为是超重与 CKD 风险之间关系的重要中间因素。然而，体重过重对通过这四种途径介导的 ESKD 的总体影响的大小仍有待量化。

我们对 100,269 名奥地利人（平均年龄 46.4 岁）的人口数据应用了相关中介变量分析模型。体重指数 (BMI) 与 ESKD 风险直接相关。间接关联是通过甘油三酯-葡萄糖 (TyG) 指数（作为胰岛素抵抗的指标）、平均动脉压 (MAP)、尿酸 (UA) 和总胆固醇 (TC) 介导的。

平均随访时间为 23.1 年，共发生 463 例 (0.5%) ESKD 病例。不健康的代谢特征（患病率为 32.4%）与 ESKD 风险显着增加相关（多变量调整风险比 (aHR)，3.57；95% CI，2.89 至 4.40），与 BMI 无关。 BMI 升高 5 kg/m ²与 ESKD 风险增加 57% 相关（aHR_总关联，1.57；1.38 至 1.77）。在这个协会中，99%（76%到140%）是由所有调解员共同产生的；通过 TyG 指数 33%（22% 至 49%）； 34%（24% 至 50%）通过 MAP； 30%（21%至45%）通过UA； 2%（–1% 至 4%）通过 TC。其余直接关联不显着（aHR_直接关联，1.01；0.88 至 1.14）。

TyG 指数、MAP 和 UA（而非 TC）介导中年成人 BMI 与 ESKD 的关联。我们的研究结果强调，除了减轻体重之外，控制代谢危险因素对于减轻体重指数对肾功能的不利影响可能也至关重要。