环境镉暴露与相关肾功能改变及尿转化生长因子-β1的关系

Relationships of environmental cadmium exposure with changes of renal function and urinary transforming growth factor-β1

[背景]镉的慢性毒性作用远远超过其他重金属,肾脏是机体镉蓄积的主要器官,镉暴露对肾功能的毒性作用及其剂量反应关系有待进一步研究。[目的]探讨环境镉暴露与肾功能改变及尿转化生长因子(TGF)-β1水平的关系。[方法]采用横断面研究,选择华北某市镉污染灌溉区[后称:镉污染区;其土壤镉水平为0.238 mg·kg^(-1),略低于我国土壤镉环境质量标准(0.3 mg·kg^(-1)),属低水平环境镉暴露区]的居民和非污染区(土壤镉水平为0.077 mg·kg^(-1))的居民为研究对象,研究对象在相应地区的居住年限均大于10年。其中镉污染区229人,非污染区212人。收集研究对象的外周血与尿样,测定其尿镉、尿TGF-β1、尿微量白蛋白(UALB)、尿N-乙酰-β-D-氨基葡萄糖苷酶(UNAG)以及血肌酐(SCr)、尿肌酐(UCr)水平,估算肾小球滤过率(eGFR)。以中位数(M)和第25、75百分位数(P_(25),P_(75))表示上述指标的平均水平及分布;采用Kruskal-Wallis检验比较不同尿镉水平者的肾功能指标及尿TGF-β1水平,尿镉与肾功能指标和尿TGF-β1的相关性分析采用Spearman秩相关分析。调整性别与年龄因素后,通过限制性立方样条分析尿TGF-β1、UALB、UNAG和eGFR与尿镉的关系。[结果]镉污染区人群尿镉水平[M(P_(25),P_(75))]为1.07(0.57,2.61)μg·g^(-1)(以UCr计,后同),高于非污染区人群水平[0.75(0.43,1.21)μg·g^(-1),P<0.001]。镉污染区人群UNAG、UALB水平分别为17.26(12.29,26.11)U·g^(-1)和12.97(8.59,20.88)mg·g^(-1),均高于非污染区人群;eGFR、尿TGF-β1水平分别为56.38(48.63,63.90)mL·min^(-1)和21.22(12.01,36.26)ng·L^(-1),均低于非污染区人群(均P<0.05)。将所有研究对象以内暴露尿镉水平的四分位数分组后,不同尿镉水平人群之间肾功能指标的差异均存在统计学意义(均P<0.05),其中UNAG、UALB、尿TGF-β1随着尿镉水平的升高而升高,eGFR随着尿镉水平的升高而降低。限制性立方样条分析结果显示,UNAG、尿TGF-β1与尿镉的关联强度有统计学意义(χ^(2)=8.24,P=0.0162;χ^(2)=17.90,P<0.001),且呈非线性(χ_(非线性)^(2)=3.93,P非线性=0.0476;χ_(非线性)^(2)=8.60,P非线性=0.0034)。在尿镉水平高于0.750μg·g^(-1)后,UNAG、尿TGF-β1水平随尿镉增加呈增加趋势。[结论]长期低水平镉暴露可能对肾功能和尿TGF-β1水平造成不良影响。

[Background]The chronic toxicity of cadmium far exceeds that of other heavy metals.Cadmium mainly accumulates in the kidney,and its toxic effects on renal function and related doseresponse relationship need to be further studied.[Objective]This experiment evaluates the relationships of environmental cadmium exposure with the changes of renal function and urinary transforming growth factor(TGF)-β1 levels.[Methods]A cross-sectional study was used to recruit 229 residents of a cadmium-polluted irrigation area(a low-level environmental cadmium exposure area where soil cadmium level was 0.238 mg·kg^(-1),slightly lower than the national environmental quality standard limit for soil cadmium of 0.3 mg·kg^(-1))and 212 residents of a non-cadmium-polluted area(where soil cadmium level was 0.077 mg·kg^(-1))in North China.The participants had lived there for more than 10 years.Their peripheral blood and urine samples were collected,the urinary cadmium(UCd),urinary transforming growth factor-β1(UTGF-β1),urinary micro-albumin(UALB),urinary N-acetyl-β-D-glucosaminidase(UNAG),and serum and urinary creatinine levels were measured,and estimated glomerular filtration rate(eGFR)was calculated.The indicators were expressed as median(M)and the 25th and 75th percentages(P_(25),P_(75)).Kruskal-Wallis test was used to compare the renal function indexes and urinary TGF-β1 levels at different UCd levels.Spearman rank correlation analysis was adopted to assess the correlations of UCd with renal function indexes and urinary TGF-β1.The relationships of UCd with urinary TGF-β1,UALB,UNAG,and eGFR were analyzed by restricted cubic spline after adjusting for gender and age.[Results]The UCd level of residents in the cadmium-polluted area was 1.07(0.57,2.61)μg·g^(-1)(adjusted for UCr,thereafter),which was higher than that in the non-cadmium-polluted area[0.75(0.43,1.21)μg·g^(-1),P<0.001].The levels of UNAG and UALB of residents in the cadmiumpolluted area were 17.26(12.29,26.11)U·g^(-1)and 12.97(8.59,20.88)mg·g^(-1),which were higher than those in the non-cadmium-polluted area;the eGFR and urinary TGF-β1 levels were 56.38(48.63,63.90)mL·min^(-1)and 21.22(12.01,36.26)ng·L^(-1),lower than those in the noncadmium-polluted area(all P<0.05).There were significant differences in renal function indexes among the residents grouped by quartiles of UCd levels;specifically,with the increase of UCd levels,UNAG,UALB,and urinary TGF-β1 increased,while eGFR decreased.The results of restricted cubic spline analysis revealed that the correlations of UCd with UNAG and urinary TGF-β1(χ^(2)=8.24,P=0.0162;χ^(2)=17.90,P<0.001)were significant and non-linear(χ_(non-linear)^(2)=3.93,Pnon-linear=0.0476;χ_(non-linear)^(2)=8.60,Pnon-linear=0.0034).When UCd was higher than 0.750μg·g^(-1),UNAG and TGF-β1 showed an increasing trend.[Conclusion]Long-term low-dose cadmium exposure may cause adverse effects on renal function and urinary TGF-β1 levels.