Kidney Disease Research Collaborative, Translational Research Institute, Brisbane 4102, Australia.
Department of Nephrology, Princess Alexandra Hospital, Brisbane 4075, Australia.
Int J Environ Res Public Health. 2022 Aug 25;19(17):10572. doi: 10.3390/ijerph191710572.
We retrospectively analyzed data on the excretion of cadmium (E), β-microglobulin (E) and N-acetyl-β-D-glucosaminidase (E), which were recorded for 734 participants in a study conducted in low- and high-exposure areas of Thailand. Increased E and E were used to assess tubular integrity, while a reduction in the estimated glomerular filtration rate (eGFR) was a criterion for glomerular dysfunction. E, E and E were normalized to creatinine clearance (C) as E/C, E/C and E/C to correct for interindividual variation in the number of surviving nephrons and to eliminate the variation in the excretion of creatinine (E). For a comparison, these parameters were also normalized to E as E/E, E/E and E/E. According to the covariance analysis, a Cd-dose-dependent reduction in eGFR was statistically significant only when E was normalized to C as E/C ( = 11.2, < 0.001). There was a 23-fold increase in the risk of eGFR ≤ 60 mL/min/1.73 m in those with the highest E/C range ( = 0.002). In addition, doubling of E/C was associated with lower eGFR (β = -0.300, < 0.001), and higher E/C (β = 0.455, < 0.001) and E/C (β = 0.540, < 0.001). In contrast, a covariance analysis showed a non-statistically significant relationship between E/E and eGFR ( = 1.08, = 0.165), while the risk of low eGFR was increased by 6.9-fold only among those with the highest E/E range. Doubling of E/E was associated with lower eGFR and higher E/E and E/E, with the β coefficients being smaller than in the C-normalized dataset. Thus, normalization of Cd excretion to C unravels the adverse effect of Cd on GFR and provides a more accurate evaluation of the severity of the tubulo-glomerular effect of Cd.
我们回顾性分析了在泰国低暴露区和高暴露区进行的一项研究中 734 名参与者的镉排泄（E）、β-微球蛋白（E）和 N-乙酰-β-D-氨基葡萄糖苷酶（E）的数据。E 和 E 的增加用于评估肾小管完整性，而估算肾小球滤过率（eGFR）的降低是肾小球功能障碍的标准。E、E 和 E 用肌酐清除率（C）标准化为 E/C、E/C 和 E/C，以校正个体间存活肾单位数量的差异，并消除肌酐排泄（E）的差异。为了进行比较，这些参数也用 E 标准化为 E/E、E/E 和 E/E。根据协方差分析，只有当 E 用 C 标准化为 E/C 时，eGFR 与 Cd 剂量呈依赖性降低才有统计学意义（=11.2，<0.001）。E/C 最高范围的个体 eGFR≤60 mL/min/1.73 m 的风险增加了 23 倍（=0.002）。此外，E/C 加倍与较低的 eGFR 相关（β=-0.300，<0.001），E/C （β=0.455，<0.001）和 E/C（β=0.540，<0.001）升高。相比之下，协方差分析显示 E/E 与 eGFR 之间没有统计学意义的关系（=1.08，=0.165），而只有在 E/E 最高范围的个体中，低 eGFR 的风险才增加了 6.9 倍。E/E 加倍与较低的 eGFR 和较高的 E/E 和 E/E 相关，β系数小于 C 标准化数据集。因此，将 Cd 排泄用 C 标准化可以揭示 Cd 对 GFR 的不良影响，并更准确地评估 Cd 对肾小管-肾小球效应的严重程度。
