Fine Particulate Matter (PM2.5) And Chronic Kidney Disease Part 1
Mar 21, 2023
Abstract
The impact of ambient particulate matter (PM) on public health has become a great global concern, which is especially prominent in developing countries. For health purposes, PM is typically defined by size, with smaller particles having more health impacts. Particles with a diameter <2.5 μm are called PM2.5. Initial research studies have focused on the impact of PM2.5 on respiratory and cardiovascular diseases; nevertheless, an increasing number of data suggested that PM2.5 may affect every organ system in the human body, and the kidney is no exception. The kidney is vulnerable to particulate matter because most environmental toxins are concentrated by the kidney during filtration. According to the high morbidity and mortality related to chronic kidney disease, it is necessary to determine the effect of PM2.5 on kidney disease and its mechanism that needs to be identified.
To understand the current status of PM2.5 in the atmosphere and its potentially harmful kidney effects in different regions of the world this review article was prepared based on peer-reviewed scientific papers, scientific reports, and databases from government organizations published after the year 1998. In this review, we focus on the worldwide epidemiological evidence linking PM2.5 with chronic kidney disease and the effect of PM2.5 on chronic kidney disease (CKD) progression. At the same time, we also discuss the possible mechanisms of PM2.5 exposure leading to kidney damage, to emphasize the contribution of PM2.5 to kidney damage. A global database on PM2.5 and kidney disease should be developed to provide new ideas for the prevention and treatment of kidney disease.
The kidney is one of the indispensable vital organs in the human body. Together with the ureters, bladder, and urethra, it forms the urinary system. The kidneys are a pair of solid organs, one on the left and one on the left. Kidney disease often occurs due to excessive metabolites in the human body, which leads to the overloading of the kidneys. In this case, Cistanche is a very effective kidney-protecting medicine. The various nutrients contained in Cistanche can effectively enhance human immunity and improve the immune function of the kidneys. At the same time, it can also increase the metabolic capacity of the kidneys, promote the excretion of toxic substances in the kidneys, and protect the kidneys from damage.
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Keywords:
Air pollution · Chronic kidney disease · Environmental health · Fine particulate matter · Kidney injury · Urbanization.
Abbreviations:
CI Confidence interval
CKD Chronic kidney disease
HR Hazard ratio
OR Odds ratio
PM2.5 Fine particulate matter
US EPA US Environmental Protection Agency
WHO World Health Organization
1 Introduction
Air pollution is becoming an ever more serious problem due to rapid urban industrialization and modernization (Chen 2007; Power et al. 2018). The World Health Organization (WHO) reports that 90% of the world’s population suffers from a polluted environment, while almost seven million deaths from air pollution every year are caused by exposure to fine particles (an annual average PM2.5 concentration above 10 μg/m3 ) (World Health Organization 2018a, b, c). Air pollutants are composed of gaseous substances, volatile substances, semi-volatile substances, and particulate matter (PM) mixture (Zanobetti et al. 2009). PMs with diameters that are generally 2.5 μm and smaller (e.g., PM2.5) have been found to have a greater impact on human health (Brunekreef and Holgate 2002; Costa et al. 2014).
More than half of the global population is exposed to very low-quality air (PM2.5 concentration > 35 μg/m3 ) (World Development Indicators 2017). After enrichment in PM2.5, the above substances can be deposited in the alveoli through respiration, and can even enter the blood circulation through the gas–blood barrier, thus reaching other tissues and organs, and causing damage to many systems such as respiration, circulation, and so on (Martinelli et al. 2013; Dominici et al. 2006; Zhu et al. 2015; World Health Organization 2018a, b, c).
Over recent years, epidemiological studies have shown an obvious upward trend in the incidence of CKD. The global prevalence rate is about 11–13% and the incidence of adult CKD in China is around 10.8% (Zhang et al. 2012; Hill et al. 2016). Thus, the prevention and treatment of CKD are becoming vital public health problems faced by the whole world. The presence of some comorbidities such as cardiovascular disease(CVD), hypertension, and diabetes is a potential predictor of the rapid aggravation from CKD to end-stage renal disease (ESRD). An increasing number of studies have shown that air pollution may be a new risk factor for CKD (Tonelli et al. 2012; Blum et al. 2020; Lin et al. 2020; Wu et al. 2020).
As an important organ involved in hemofiltration and toxin excretion, kidneys can be easily affected by air pollutants in the blood, which is why the effect of PM2.5 exposure on kidney disease should not be ignored. In this review, we summarized the epidemiological evidence of kidney disease being associated with PM2.5 exposure, as well as the findings about the effects of PM2.5 on the progression of kidney disease. At the same time, we also discussed the possible mechanisms of kidney injury caused by PM2.5 exposure. Based on these findings, we developed a hypothesis that exposure to PM2.5 and CKD is interrelated and there are many biological mechanisms involved in this process.
2 Method
We searched on the World Wide Web for combinations of keywords such as fine particulate matter pollution, PM2.5, source apportionment of fine PM, constituents of PM2.5, PM2.5, and chronic kidney disease (CKD), PM2.5 and end-stage renal disease, PM2.5 and proteinuria in PubMed, Web of Science and Google Scholar. We selected 350 peer-reviewed articles published from 1998 to 2020 containing information on fine PM and related CKD.
Among the articles searched, only articles that met the following criteria were included in the review: (1) Geographical location: Journals from all over the world were considered for the literature review; (2) Sample size: Sample size was not considered in the screening process; (3) Study methodology and statistical analysis: Research methods and the associated statistical analysis were not considered during the screening process; (4) Discussion of health effect: health effects using human or animal subjects. For global and country-specific variations in fine PM, databases from government organizations like the National Clean Air Program (NCAP) in India, the United States Environmental Protection Agency (US EPA) in the USA, European Environment Agency (EEA) in Europe, and World Health Organization (WHO) for the global database were also screened (National Clean Air Programme 2019; European Environment Agency 2019; The U.S. Environmental Protection Agency 2012; World Health Organization 2018a, b, c). This review has selected 133 papers, of which PM2.5 and CKD-related studies were distributed in the following countries (number of papers): China (34), Taiwan, China (5), India (3), Japan (2), South Korea (1), East Asia (1), USA (20), Canada (5), South Africa (1), United Arab Emirates (1), New Zealand (2), France (3), the UK (4), The Netherlands (2), Germany (1), Spain (1), Denmark (1), Greece (1), Europe (3), Global (8).
3 The Compositions of PM2.5
PM2.5 is one of the main components of air pollution and a major risk factor for the global disease burden (Cohen et al. 2017; Monn and Becker 1999). PM2.5 is not a simple pollutant, but a mixture of many substances (Harrison et al. 2004). It often derives from different outdoor emission sources and also has different chemical compositions. Chemical components include trace heavy metals (Cd, Cr, Cu, Mn, Ni, Pb, V, and Zn), organic compounds (volatile components and polycyclic aromatic hydrocarbons), carbonaceous aerosols (elemental carbon and organic carbon), inorganic mineral dust, sea salt and water-soluble inorganic ions (NO3, SO42, Cl, F, NO2, Br, NH4+, Na+, K+, Ca2+, Mg2+) (Tao et al. 2016; Feng et al. 2006; Morakinyo et al. 2016).
To be specific, PM2.5 can also originate from indoor sources. Particles of indoor origin include components derived from biological sources. Biological components include pollen, microorganisms (fungi, bacteria, and viruses,) and organic compounds derived from microorganisms (endotoxin, metabolites, toxins, and other microbial fragments), many of which are known allergens (Douwes et al. 2003). Biological aerosol accounts for 5–34% of indoor pollutants which may trigger the immune response, inflammation response, infectious disease, cancer, and other toxicity (Pollution Issues 2006; Air Quality Direct 2007; Douwes et al. 2000; Fung and Hughson 2003; Samake et al. 2017; Srikanth et al. 2008).
The wide distribution of heavy metals (metallic elements that have a relatively high density compared to water) and carbonaceous aerosols in PM2.5 results in severe biological problems (Zhang et al. 2016; Gadi et al. 2019). The combustion elements such as EC (elemental carbon) and combustion sources such as biomass burning (potassium, as the main trace element) are strongly associated with mortality, compared to other components (Achilleos et al. 2017). Typical fuel oils contain Iron (Fe), Nickel (Ni), Vanadium (V), and Zinc (Zn) and they are reflected in the composition of fly ash produced from fossil-fuel combustion (Vouk and Piver 1983). Exposure to zinc may interfere with vasoconstriction and vasodilation increase the risk of CVD and upregulate the expression of cytokines and stress proteins (Graff et al. 2004).
Exposure to vanadium and chromium potentially has a major role in inducing oxidative DNA damage (Sørensen et al. 2005). Sulfate, ammonium, and nitrate carried in PM2.5, usually found in coal combustion and vehicle emissions, are the main contributors to the haze in China, which can rapidly dissolve in the well-buffered lining fluids of the respiratory system (Harrison and Yin 2000). Polycyclic aromatic hydrocarbons (PAHs) in PM2.5 are formed by incomplete combustion and pyrolysis of organic substances such as coal, oil, natural gas, and wood, which can lead to carcinogenesis and gene mutation (Bandowe et al. 2014; Lundstedt et al. 2007; Yunker et al. 2002). The US Environmental Protection Agency reports that acute exposure to PAHs may be harmful to human health (The U.S. Environmental Protection Agency 2012). However, the PAH levels in the atmosphere in China are generally higher than those in foreign countries (Farmer et al. 2003; Lee et al. 2005; Sharma et al. 2007; Wang et al. 2015).
In addition, studies from many institutions in different countries have shown that the concentration, characteristics, and toxicity of PM2.5 vary with time, season, location, and climate (Bell et al. 2008; Kim et al. 2019; Lee et al. 2019). Fine PM levels and exceedance of national and international standards were several times higher in Asian countries (Mukherjee and Agrawal 2017). The monitoring data of PM2.5 in 45 major cities around the world in 2013 showed that, as a result of the rapid expansion of cities and rapid economic growth, the highly polluted megacities were concentrated in east-central China and the Indo-Gangetic Plain, among which the most polluted areas were Delhi in India, Cairo in Egypt, and Tianjin in China with the highest annual average PM2.5 concentration (89 to 143 μg/m3 ) (Cheng et al. 2016). The satellite data evaluation model from 2004 to 2014 showed that the estimated value of 10-year average PM2.5 in the Beijing-Tianjin metropolitan region (including Beijing, Tianjin, and Hebei) was generally no less than 100 μg/m3.
The 10-year average concentration of PM2.5 in the Sichuan Basin and Yangtze River Delta is generally no less than 85 μg/m3, and it is no less than 55 μg/m3 in Pearl River Delta (Ma et al. 2015). PM2.5 levels vary greatly in different regions of the same country. It is worth noting that a recent study found that China’s average annual PM2.5 concentrations have dropped by 30% and 50% overall (Zhai et al. 2019). PM concentrations collected by the newest air quality monitoring network of the Ministry of Environmental Protection in 190 major cities in China between April 2014 and April 2015 show that the concentration of PM2.5 has a significant seasonal variation, which is highest in winter and lowest in summer (Zhang and Cao 2015). Although PM2.5 levels in China have gradually decreased in recent years, the incidence of CKD is still very high. The reason for this is probably that PM2.5 levels are still higher than the WHO guidelines recommend. In addition, the damage to the kidney caused by long-term exposure to PM2.5 is not transient but usually has a sequelae effect.
Mounting evidence implicates the components of PM2.5 can translocate from the lungs into the circulation and are filtered and excreted by the kidneys. Although currently limited, data on the link between air pollution and kidney injury or disease in human and animal models are also now beginning to emerge.
4 PM2.5 and CKD: Epidemiological Studies
A large cohort study of 100, 629 non-CKD Taiwanese residents aged 20 or over found that long-term exposure to environmental PM2.5 was associated with an increased risk of CKD developing. For every 10 μg/m3 increase in PM2.5 concentration, the risk of CKD increased by 6% (HR:1.06, 95% CI:1.02, 1.10) (Chan et al. 2018). Of note, in this study a single measurement of eGFR <60 mL/ min/1.73 m2 was used to define CKD while it might be due to acute kidney disease or other diseases; thus, some participants might have been misclassified as having CKD based on this criterion.
Currently, a large number of studies have confirmed the epidemiological evidence of the relationship between renal disease and PM2.5 exposure. A large cohort of 2,482,737 veterans in the USA revealed that long-term exposure to PM2.5 was associated with an increased risk of CKD during a median follow-up of 8.52 years. For every 10 μg/m3 increase in PM2.5 concentration, the risk of developing CKD increased by 27% (HR, 1.27; 95% CI, 1.17 to 1.38) (Bowe et al. 2017, 2018). However, the study included only US veterans who were mostly older, white men.
Therefore, the findings might not be generalizable to other populations. Furthermore, the median exposure to PM2.5 of the air quality in the USA is 10–11 μg/m3, which is better than in most countries. A study of 71,151 native biopsies from 938 hospitals in China found that higher PM2.5 exposure was associated with the risk of membranous nephropathy. In areas with PM2.5 > 70 ug/m3, each 10 μg/m3 increase in PM2.5 concentration was associated with 14% higher odds for membranous nephropathy (odds ratio, 1.14; 95% CI, 1.10 to 1.18) (Xu et al. 2016). There were some limitations of this study. First, the study included only patients from whom renal biopsy samples were taken and not the general population.
Furthermore, information on patient residence was limited to the city level, where levels of PM2.5 were generally higher than in other regions and might have led to an underestimation of the effect of PM2.5. It is of great clinical significance to study the dose–response relationship between PM2.5 and the development and progression of CKD across a wide range of exposure levels. Bowe and his colleagues recently quantitated the global burden of CKD attributable to ambient air pollution in 2016 and found that more than 30% of disability-adjusted life years of CKD were related to PM2.5 exposure globally (Bowe et al. 2019). The study used the Global Burden of Disease study data and provided a quantitative analysis of the global burden of CKD attributable to PM2.5. Although its explanations and conclusions are based on a raw analysis, the results provided an intuitive way to translate from the relative risk into the attributable burden of CKD due to PM pollutants. Although its explanations and conclusions were based on raw analysis, the results provided an intuitive way to translate from the relative risk into the attributable burden of CKD due to PM pollutants (Table 1).
There is a strong reason to believe that PM2.5 may be a novel environmental risk factor for CKD. Associations between long-term PM2.5 exposure and death were modified by many factors, such as other air pollutants like ozone and mercury (Lelieveld et al. 2019; Stojan et al. 2019), meteorological factors like temperature, resultant wind, relative humidity, and barometric pressure, epidemiological and social factors like wealth gap between rich and poor (Kioumourtzoglou et al. 2016). However, in the same environment, some people are more likely than others to develop kidney disease. This may be due to the susceptibility of the population.
Previous studies suggested that elderly people and children were especially susceptible to the harmful effects of PM2.5 exposure (Mehta et al. 2016; Bowe et al. 2017, 2018). These studies may be influenced by the aging of the population in Europe and the USA and the mean age of onset of CKD (A risk factor for CKD: age 60 or older) (Inker et al. 2014). Vascular endothelial dysfunction worsens with age, and the vascular endothelium is more sensitive to pollutants and more vulnerable to injury in older people. Also, children and infants are susceptible to harm from inhaling PM2.5 because they inhale more air per pound of body weight than adults – they breathe faster, spend more time outdoors, and have smaller body sizes.
In addition, children’s immature immune systems may cause them to be more susceptible to PM2.5 than healthy adults. Moreover, gender differences may exist in the effect of PM2.5 exposure on CKD. A study of 47,204 Chinese adults aged 18 years or older found that every 10 μg/m3 increase in PM2.5 was positively associated with the prevalence of chronic kidney disease (odds ratio [OR] 1.33, 95% CI 1.25–1.41, p < 0.001). Sex-stratified analyses showed that risk in men (OR 1.42, 95% CI 1.29–1.57) was slightly higher than in women (1.26, 1.17–1.36) (Li et al. 2020). The above-mentioned analyses cannot be generalized. The susceptibility of the population is also affected by differences in age and genetic factors in various regions of the world. Therefore, more global longitudinal studies are needed in the future to directly compare the effects of PM2.5 on CKD.
5 PM2.5 and CKD: Progression and Prevention
In addition to increasing the risk of kidney disease, exposure to PM2.5 has also been associated with an increased risk of CKD progression. A prospective cohort study of 669 veterans in the Boston area from the Veterans Affairs Normative Aging Study Institution revealed that every 2.1 μg/m3 increase in the concentration of PM2.5 results in 1.73 m2 decreases in eGFR (95%CI:2.99 to 0.76) and 0.60 mL/min/1.73m2 decrease in renal function per year (95%CI:0.79 to 0.40). It should be emphasized that the exposure level of PM2.5 in the study population met the environmental air quality requirements of 13.5% in the USA (Standard for 13.0 μg/m3 ).
Thus, it can be speculated that higher levels of PM2.5 exposure can significantly increase the rate of renal dysfunction in exposed patients (Mehta et al. 2016). Other studies have shown that for every 10 mg/m3 increase of PM2.5 concentration, the risk of eGFR decline by 30% increases by 28% (HR, 1.28; 95% CI:1.18 to 1.39), and the risk of ESRD increases by 26% (HR, 1.26;95% CI:1.17 to 1.35) (Bowe et al. 2017, 2018). Road traffic emissions are one of the main sources of PM2.5, which has extensive cyto- and genotoxic effects, which in turn can affect the physiology, development, and mortality of a broad subset of the species that encounter roads (Pérez et al. 2010; Leonard and Hochuli 2017). A study of 1,103 patients with acute ischemic stroke in the Boston area between 1999 and 2004 showed that eGFR levels decreased in patients living closer to major roadways, indicating a decline in renal function. The eGFR levels of patients who live 50 m away from the main road are 3.9 mL/min/1.73m2 lower than in those who live 1,000 m away (95%CI: 1.0–6.7; P ¼ 0.007). The decrease in renal function in patients living 50 m away from the main road is equal to the decrease of natural physiological renal function with the increase of age by 4 years (Lue et al. 2013).
A cross-sectional study of 317 patients with acute pulmonary edema complicated with stage 5 nondialysis chronic nephropathy (CKD 5-ND) in Taiwan found that a high PM2.5 level was associated with an increased risk of acute lung edema in patients with CKD 5-ND. High ambient temperature in hot seasons and low ambient temperature in cold seasons were also associated with increased risk (Chiu et al. 2018). There is an approximately linear correlation between the relative changes of albuminuria over a one-year interval and the risk of CKD, and the presence of albuminuria may be a predictor of CKD aggravation (Sumida et al. 2017). A study of 812 patients with T2DM in Taiwan found that the albumin-to-creatinine ratio (ACR) in patients with exposure to high-level PM2.5 increased by 3.96 m g/g, while in patients with low-level, it increased by 3.17 mg/g, indicating that the exposure to higher levels of PM2.5 and CO can increase albuminuria in patients with T2DM (Chin et al. 2018).
Another clinical cohort study of patients with SLE living on Montreal Island showed that the levels of PM2.5 exposure are associated with the anti-dsDNA and the tubular cell type, reflecting severe renal inflammation (Bernatsky et al. 2010). It has been shown that kitchen fumes contain high concentrations of PM2.5. By comparing the levels of exposure to PM2.5, VOC, and PAH from the working environment and the burden of these toxic substances on the body in 94 chefs and controls, the cross-sectional study revealed that PM2.5 may result in microalbuminuria in kitchen workers (Singh et al. 2016). Smoking is also an important source of indoor PM2.5. A cross-sectional analysis of 15,179 participants in the third National Health and Nutrition Survey in the USA found that in passive smokers, who were grouped by a quartile of serum cotinine levels, the risk of microalbuminuria in the highest group was 1.41 times higher than that in the lowest group (Hogan et al. 2007).
Although there is some evidence that CKD progression is associated with PM2.5 pollution, it is manifested in an increased risk of progression to ESRD, an increase in albuminuria, a decrease in eGFR levels, and the emergence of complications such as pulmonary edema. Current data were based on a few cohort studies and were limited to some countries, lacking globally large-scale and long-term cohort studies.
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