Association Of Exposure To Arsenic,Lead,and Cadmium With Chronic Kidney Disease And Kidney Stones

Objectives Both chronic kidney disease（CKD）and kidney stones have become the most important public health problems in the world.The etiology of CKD and kidney stones is not completely clear.The identification of risk factors for CKD and kidney stones is of great public health significance for the early prevention and control of these diseases.Environmental heavy metal exposure,especially As,Pb and Cd,may play an important role in the development of these diseases.Findings of previous studies about the relationship between exposure to As,Pb and Cd and CKD or kidney stones are not consistent.In addition,most previous studies focused on the effects of single exposure,and rare studies treated As,Pb and Cd as a mixture and explored the joint effect of As,Pb and Cd on CKD or kidney stones.Therefore,this study investigated the effects of As,Pb and Cd exposure on CKD and kidney stones through three parts.Firstly,we studied the contamination of three toxic heavy metals in water-soil-plant system nearby a non-ferrous metal mining area of Guangxi,and evaluated the non-carcinogenic risk of dietary intake of the three heavy metals by local residents.Secondly,both traditional multivariate logistic regression models and bayesian kernel machine regression（BKMR）were employed to study the independent or joint effect of exposure to As,Pb and Cd on CKD.Finally,we also used BKMR model to analyze the association between single exposure and co-exposure to the three heavy metals and kidney stones.This study analyzed the association of single and joint exposure of As,Pb and Cd with CKD and kidney stones,respectively,from the characteristics of external exposure and health risk assessment of dietary exposure to three heavy metals,and then to the effect of internal exposure,in order to provide scientific reference for the early prevention and intervention of CKD and kidney stones.MethodsPart Ⅰ 36 river water samples,75 paired paddy soil and rice samples,and 128 paired upland soil and plant samples（corn,leafy vegetables,fruit vegetables and legume vegetable）were collected from the mining area.The concentrations of As,Pb and Cd in these samples were detected.Water quality index（WQI）,geo-accumulation index(I_geo),integrated pollution index（IPI）,and biological accumulation coefficient（BAC）were used to analyze the pollution characteristics of As,Pb and Cd in water-soil-plant system.And health risk assessment to dietary heavy metal exposure of As,Pb and Cd were studied in the studied population.Part Ⅱ In total,1281 participants were included.Urinary arsenic（UAs）was determined by atomic fluorescence method,and blood lead（BPb）and urinary cadmium（UCd）levels were determined by graphite-furnace atomic absorption spectrometry.We defined CKD as having an estimated glomerular filtration rate（e GFR）<60 m L/min/1.73 m² or proteinuria.e GFR was calculated by using the Chronic Kidney Disease Epidemiology Collaboration（CKD-EPI）equation.Both traditional multivariate logistic regression models and bayesian kernel machine regression（BKMR）models were employed to study the independent or joint effect of exposure to As,Pb and Cd on CKD.Part Ⅲ Kidney stones were diagnosed with urinary tract ultrasonography.Urinary arsenic（UAs）was determined by atomic fluorescence method.Urinary cadmium（UCd）and blood lead（BPb）levels were determined by graphite-furnace atomic absorption spectrometry.Multivariate logistic regression models and BKMR models were constructed to investigate the association between exposure to UAs,BPb and UCd alone or in combination with kidney stones in adults of different genders.ResultsPart Ⅰ Contamination and Dietary Health Risks Brought by Arsenic,Lead and Cadmium in a Water-Soil-Plant System in a Mining Area（1）The average WQIs in the sampling sites of river ranged from 41 to 5008,indicating the water quality of“Excellent”to“Undrinkable”.The WQI nearby a tailing and an industrial park was significantly worse than those at the other sites.（2）The concentrations of As,Pb and Cd in surface soil samples of the paddy and upland significantly exceeded the risk screening values for soil contamination of agricultural land.（3）The concentration of Pb and Cd in rice samples exceeding the limits accounted for 18.7%and 82.7%,respectively.Compared to fruit and legume vegetables,the concentrations of As,Pb and Cd in leafy vegetables were significantly higher,exceeding the limits by 14.1%,61.2%and 40.0%,respectively.BAC of Cd in rice and lettuce leaves were the highest.（4）The hazard quotients（HQ）of As and Cd,indicating the non-carcinogenic risk,were 4.15 and 1.76 in adult males and 3.40 and 1.45 in adult females.Part Ⅱ Association between Exposure to Arsenic,Lead,and Cadmium and Chronic Kidney Disease（1）All models showed that UAs levels were not significantly associated with risk of CKD,and Cd was found significantly positively associated with CKD.For BPb,the ORs of CKD were 1.22（95%CI:0.91-1.64）in multiple regression model and 1.17（95%CI:0.63,2.17）when comparing the highest quartiles（BPb≥99.5μg/L）with the lowest quartiles（≤48.8μg/L）.（2）The adjusted odds ratio（OR）and 95%confidence interval（95%CI）for CKD was 2.72（95%CI:1.51,4.87）when comparing the highest quartiles（≥4.47μg/g creatinine）with the lowest quartiles（≤1.25μg/g creatinine）of UCd.（3）The BKMR model showed a significant positive joint effect of the mixture of As,Pb and Cd on the risk of CKD when the log₂-transformed metals concentrations were all above the 60th percentile,compared to the median levels.Log₂-transformed UCd was significantly positively associated with CKD when the levels of the other two metals were all fixed at their 25th,50th,and 75th percentiles.In addition,with increased levels of Pb,the positive exposure-response relationship for Cd on CKD became steeper.Part Ⅲ Association between Exposure to Arsenic,Lead,and Cadmium and Kidney Stones（1）The BKMR model showed a significant positive joint effect of the mixture of UAs,BPb and UCd on kidney stones when the log₂-transformed metals concentrations were all above the 55th percentile,compared to the median levels.Log₂-transformed BPb was significantly positively associated with kidney stones when the levels of the other two metals were all fixed at their 25th,50th,and 75th percentiles.In addition,with increased levels of UCd,the positive exposure-response relationship for BPb on kidney stones became steeper.（2）The odds ratio（OR）of kidney stones was 2.83（95%CI:1.38-5.77）in males with high BPb（BPb≥100μg/L）,compared with those with low BPb（BPb<100μg/L）.Compared to those with low BPb and low UCd（BPb<100μg/L and UCd<2μg/g creatinine）,the ORs were 2.58（95%CI:1.17-5.70）and 3.43（95%CI:1.21-9.16）in females and males with high BPb and high UCd（BPb≥100μg/L and UCd≥2μg/g creatinine）,respectively.The OR was 3.16（95%CI:1.26-7.88）in males with high BPb and low UCd（BPb≥100μg/L and UCd<2μg/g creatinine）,compared to those with low BPb and low UCd.Conclusions（1）Heavy metal contamination of water-soil-plant system around the mining area was serious and posed great non-carcinogenic and carcinogenic risks to local residents through consumption of rice and leafy vegetables.（2）As was not associated with CKD.Marginal and positive association between Pb and CKD was found.High Cd exposure was consistently and positively associated with risk of CKD.Co-exposure to As,Pb and Cd is shown to be jointly positive effect on CKD risk and potential synergism between Cd and Pb was also apparent.（3）Pb was positively associated with risk of kidney stones in BKMR model.The co-exposure of As,Pb and Cd had a joint effect on the risk of kidney stones,in which Pb was dominant.There was a potential interaction between the effects of Pb and Cd on kidney stones.Kidney stones risk was increased by high Pb exposure in males,and by Pb and Cd co-exposure in males and females.