Effect Of Long-term Exposure To Ambient Fine Particulate Matter(PM_2.5) On Incident Chronic Kidney Disease

Background:Epidemiological evidence from the United States,Europe,Chinese Taiwan and other countries or regions with low-level exposure of fine particulate matter(PM_2.5)suggests that PM_2.5is an important and modifiable risk factor for chronic kidney disease（CKD）;however,due to the difference in exposure background and study population,the conclusions are still inconsistent and uncertain,especially in regions with high-levels exposure of PM_2.5,such as China.Objective:1.To investigate the effect of long-term PM_2.5exposure with different exposure time windows on incident CKD in Chinese mainland;2.To explore the interaction effect of long-term PM_2.5exposure and meteorological factors（including temperature and humidity）on incident CKD;3.To determine the association between major particulate pollutants(Ultrafine particulate matter[PM₁],PM_2.5,and Inhalable particulate matter[PM₁₀])and early renal dysfunction and late outcomes.Methods:1.Including the adults（aged≥18 years）who underwent annual physical examination and completed at least two renal function assessments at the Health Management Center of Third Xiangya Hospital of Central South University from 2005 to 2018.Annual mean PM_2.5concentration was obtained from the Chinese High Air Pollutant（CHAP）dataset,and temperature and humidity levels were obtained from the ERA5-LAND reanalysis dataset of the European Centre for Medium-Range Weather Forecasts.Hazard ratio（HR）and 95%Confidence interval（CI）of long-term PM_2.5exposure with different exposure time windows for CKD were evaluated by the Cox proportional risk model,where the optimal time window was determined for subsequent analysis.The exposure time windows were selected as three different periods:1-10years before baseline,the year of baseline,and the whole follow-up period.Cubic splines were used to fit the dose-response curve between long-term PM_2.5exposure and the risk of CKD.2.The long-term PM_2.5exposure with optimal time window was divided into four groups:low（≤61.21μg/m³）,medium（61.21μg/m³～70.27μg/m³）,high（70.27μg/m³～74.88μg/m³）and extremely high（>74.88μg/m³）.The temperature was divided into two groups:low（≤18.07℃）and high（>18.07℃）.Humidity was divided into two groups:low（≤79.21%）and high（>79.21%）.Temperature and humidity combined with long-term PM_2.5exposure were then cross-divided into 8 groups,respectively.The HR and 95%CI of long-term PM_2.5exposure and incidence of CKD under different temperature or humidity levels were also assessed by the Cox model,with the low-PM_2.5exposure and low-temperature（or low-humidity）group as reference.The product terms of temperature（or humidity）and PM_2.5were put into the Cox model to determine whether there is additive interaction between temperature or humidity and PM_2.5long-term exposure on the risk of CKD.The relative excess risk due to interaction（RERI）,the attributable proportion of interaction（API）,the synergy index（SI）,and the corresponding 95%CI were calculated to determine whether there was an additive interaction between temperature or humidity and long-term PM_2.5exposure on the risk of CKD.3.Three common electronic databases（Pub Med,Web of Science,Embase）were used to search the published literature on ambient particulate pollutants(PM₁,PM_2.5,PM₁₀)and renal function,kidney disease and outcomes using the term of"air pollution","particulate matter","PM₁","PM_2.5","PM₁₀","kidney function","renal function","GFR","chronic kidney disease”,"CKD","mortality",etc.The effects of PM₁,PM_2.5,and PM₁₀on different stages of renal damage（from the decline of renal function to the occurrence of kidney disease and outcome）were quantitatively evaluated by meta-analysis.Results:1.Effect of long-term PM_2.5exposure and incidence of CKD:A total of 72,425 subjects who met the inclusion and exclusion criteria were included,of which 42,249 were male,accounting for 58.3%;mean age was 38 years（IQR:30～48）;and mean concentration of long-term PM_2.5exposure was 68.58μg/m³（IQR:61.21～74.88）.The HR of incident CKD was 1.71（95%CI:1.58～1.85）for per 10μg/m³increase in long-term PM_2.5exposure concentration after adjusting for a series of potential confounders,such as age,gender,and BMI.Stratified analysis showed that the effect of long-term PM_2.5exposure on the risk of incident CKD was more significant in male and older adults（≥65 years）.The dose-response curve showed a sharp increase in the risk of PM_2.5-related CKD,especially at higher-than-average levels of long-term PM_2.5exposure（about 70μg/m³）.2.Joint effect of temperature or humidity and PM_2.5on the incidence of CKD:The risk of incident CKD was higher in population living in the high humidity and high PM_2.5exposure environment;however,there was no consistent trend was observed in the stratified analysis combined with temperature and long-term PM_2.5exposure.The interaction model showed that both humidity and temperature with long-term PM_2.5exposure had a multiplicative interaction on the incidence of CKD（all P-interaction<0.05）.There was an additive interaction between humidity and long-term PM_2.5exposure on the incidence of CKD（RERI=3.59;95%CI:0.97～6.21;AP=0.43;95%CI:0.32～0.53;SI=1.93;95%CI:1.62～2.31）;but no significant additive interaction was observed for temperature.3.Associations between PM with different diameters and different stages of renal damage:A total of 33 studies were finally included in this meta-analysis.The total sample size was 7,705,173,mainly from 7countries or regions,including China,the United States,Poland,Switzerland,Thailand,and South Korea;The average age of the study population ranged from 9.4 to 72.4 years.Meta-analysis results showed that both short-term and long-term exposure to PM_2.5cause a decline in renal function,especially short-term exposure（β=-1.38;95%CI:-2.29～-0.48 andβ=-0.72;95%CI:-1.22～0.23）;Long-term PM₁₀exposure also increased the renal function decline（β=-1.48;95%CI:-2.08～-0.88）.In addition,long-term PM_2.5exposure was associated with an increased risk of kidney disease,including proteinuria and CKD（RR=1.14;95%CI:0.75～1.74 and RR=1.29;95%CI:1.14～1.47）,but there was no statistical correlation between long-term PM_2.5exposure and albuminuria;long-term PM₁₀exposure was also positively associated with an increased risk of CKD（RR=1.15;95%CI:1.09～1.22）.Conclusion:1.Geater long-term PM_2.5exposure is associated with an increased risk of CKD in general population,especially among the older and those with pre-existing cardiovascular disease.2.There is an interaction between humidity or temperature with long-term PM_2.5exposure on CKD,especially humidity promoting the increased risk of PM_2.5-related CKD.3.Ambient PM is closely related to different stages of kidney injury,especially long-term PM_2.5exposure.Figure 11,Table 9,Reference 120.