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Abstract

The harm of air pollution to public health has become a research hotspot, especially atmospheric fine-particulate matter (PM_2.5). In recent years, epidemiological investigations have confirmed that PM_2.5 is closely related to chronic kidney disease and membranous nephropathy Basic research has demonstrated that PM_2.5 has an impact on the normal function of the kidneys through accumulation in the kidney, endothelial dysfunction, abnormal renin-angiotensin system, and immune complex deposition. Moreover, the mechanism of PM_2.5 damage to the kidney involves inflammation, oxidative stress, apoptosis, DNA damage, and autophagy. In this review, we summarized the latest developments in the effects of PM_2.5 on kidney disease in human and animal studies, so as to provide new ideas for the prevention and treatment of kidney disease.

Keywords

kidney disease inflammatory oxidative stress apoptotic DNA damage autophagy

Introduction

The latest released data from the Global Burden of Disease showed that air pollution became the fourth largest risk factor worldwide in 2019. The risk of exposure to air pollution increased significantly between 2010 and 2019, and there was an increasing trend. The main compound of air pollution is PM_2.5, which consists of particulate matter with an aerodynamic diameter of less than 2.5 μm.¹ In recent years, a large number of evidences have shown that PM_2.5 plays an important role in the occurrence and development of renal injury and increases the risk of nephropathy.

Data published by the World Health Organization (WHO) indicated that kidney disease was one of the top 10 causes of death worldwide in 2019.² Kidney disease not only directly causes death but CKD is also an important risk factor for cardiovascular disease.³ It is necessary to study the effects of PM_2.5 on kidney disease and conduct effective prevention and treatment to improve public health.

In this paper, we first introduce the sources, composition and toxic effects of PM_2.5, then sort out the relationship between PM_2.5 and kidney disease, and finally deeply explore the mechanism of PM_2.5-induced kidney injury. In order to provide new ideas for the prevention and treatment of nephropathy.

Sources, composition, and hazards of PM_2.5

With the development of modern industry, the main sources and components of PM_2.5 have changed. Reports on PM_2.5 and public health have also gradually attracted attention.⁴

The sources of PM_2.5 are classified into three categories: natural sources, secondary particulate matter, and anthropogenic sources. At this stage, PM_2.5 mainly comes from anthropogenic sources. Anthropogenic sources are further divided into fixed and mobile sources. Epidemiological surveys focus on cooking smoke, welding smoke, cigarette smoke, smoke from heating emissions, and traffic exhaust from mobile sources in fixed sources.^5–10

The composition of PM_2.5 is very complex and uncertain. The main components include elemental carbon, biological substances, inorganic components, organic components, and trace elements.¹¹ The key components of PM_2.5 that are harmful to health vary in different spaces. For example, PM_2.5 in welding fumes is rich in metals. PM_2.5 in cooking smoke is rich in organic matter.¹² It is reported that PM_2.5 exposure could cause accumulation of chromium and cadmium in the kidney. The deposition of particulate matter and its components in the body cause a systemic inflammatory response and vasodilation disorder.¹³ Organophosphate esters (OPEs) are found in PM_2.5. However, little is known about their toxic potentials on kidney, except adverse effects on renal proximal tubule cells.¹⁴ Due to the different main components in PM_2.5, they have differences in toxic effects on the body. In addition to considering the health effects of the main components, attention should also be paid to the combined toxicity of each component.

As a pollutant, PM_2.5 is very harmful to public health. It can easily enter the body and exert toxic effects. Specifically, it includes (1) PM_2.5 is present in aerosols (characterized by long transmission distances and difficulty in sedimentation) and more easily inhaled by the human body.^15,16 (2) PM_2.5 has a high specific surface area and strong adsorption. Harmful substances such as bacteria and viruses are easily adsorbed by PM_2.5.^17–19 (3) the size of PM_2.5 is small and the number is large. A large amount of granular material is retained in the terminal bronchioles and alveoli, even crosses the blood gas barrier, and reaches sites such as the liver and kidneys with blood circulation, causing varying degrees of damage.¹⁷ (4) harmful substances in PM_2.5 produce combined toxic effects in the body.^20–22

PM_2.5 and renal injury

Renal disease affected by PM_2.5

Studies showed that PM_2.5 exposure was strongly associated with kidney injury, especially CKD and MN (Table 1).^23–25 To assess the effect of PM_2.5 on CKD prevalence, Li et al. used data from a national survey of CKD in China, combined with satellite remote sensing technology to estimate ground PM_2.5 concentrations. The results showed that the exposure-response curve between PM_2.5 and CKD prevalence was on the rise over a certain concentration range. Notably, the risk of CKD begun to increase at PM_2.5 concentrations well below the secondary standard set by the China Ambient Air Quality Standard (35 μg/m³). And the effect of PM_2.5 on CKD was harsher in younger adults (<65 years), men, and non-comorbid populations than in older populations (≥65 years), women, and comorbid populations (patients with diabetes and previous cardiovascular system diseases).²⁶ A survey from US residents also showed that PM_2.5 concentrations were positively associated with the risk of CKD. And CKD may be induced by long-term exposure to lower concentrations of PM_2.5.²⁷

Table 1.

Epidemiological studies on the association between PM_2.5 exposure and kidney injury.

Location	Sample size	PM_2.5source	Time	Findings or association	Reference
China	47,204	All	2 years	This study revealed a significant association between ambient PM_2.5 and the prevalence of CKD and albuminuria	²⁸
China	61,447	All	10 years	Long-term exposure to atmospheric PM_2.5 might be an important risk factor of renal failure mortality in the elderly population, especially among participants with existing renal diseases	⁸¹
China	161,970	PM_2.5、 SO₂、NOx、 NO	12 years	This study reported an association between fine-particulate air pollution PM_2.5and occurrences of nephrotic syndrome, suggesting that air pollution might cause nephrotic syndrome	⁸²
China	2,546,047	All	1 year	Exposure to PM₁ and PM_2.5 was associated with reduced renal function among han Chinese at reproductive age	⁸³
China	66	Metal fumes	1 week	Exposure to heavy metals in PM_2.5 increases the risk of renal injury in welding workers.	³⁶
China	1,000,000	All	9 years	a significant positive association between exposure to PM_2.5 level and incidence of end-stage renal disease; but inverse association between exposure to surrounding green spaces and incidence of end-stage renal disease	⁸⁴
USA	669	All	11 years	Long-term PM_2.5 exposure negatively affects renal function and increases renal function decline	⁸⁵
USA	1,164,057	All	1 year	A positive association was observed between county-level PM_2.5 concentration and diagnosed CKD.	²⁷
India	94	Cooking smoke and heat exposure	3 years	Continuous heat exposure in kitchens due to cooking can alter kidney functions	⁴⁷
Canada	237	All	7 years	Short-term variations in air pollution may influence disease activity in established autoimmune rheumatic disease in humans	⁸⁶

MN is a primary glomerular disease associated with autoimmunity. A study analyzed the renal pathological results of 71,151 patients from 938 hospitals in China. It found that the incidence of MN increased year by year during 11 years. The incidence increased more significantly in cities with more severe PM_2.5 pollution. Studies confirmed that long-term exposure to high concentrations of PM_2.5 increased MN incidence risk.²⁸ MN is mainly caused by circulating autoantibodies against podocyte antigens, including the M-type phospholipase A2 receptor (PLA2R) and thrombospondin domain-containing 7A (THSD7A). It is demonstrated that PM_2.5-induced exposure of PLA2R outside the kidneys could increase the incidence of MN.²⁹

Notably, while studies revealed a relationship between PM_2.5 exposure levels and incidence of kidney disease, its effects on kidney disease vary among regions due to the complex sources and composition of PM_2.5.²⁶ It is certain that reducing exposure time and concentration in the PM_2.5 environment can reduce the risk of kidney disease.

The pathways of PM_2.5 affecting kidney

Studies showed that PM_2.5 directly and indirectly affected the kidneys through multiple pathways. Specifically, it may include PM_2.5 accumulation in the kidneys, endothelial dysfunction, renin-angiotensin system (RAS) abnormalities, and immune complex deposition.^13,30

PM_2.5 is mainly inhaled by the respiratory tract. Smaller particulate matter in PM_2.5 crosses the blood gas barrier, then transfers to the kidneys through the blood circulation, and accumulates in the kidneys. When the amounts of harmful substances in PM_2.5 exceeds the level of renal compensation, it will damage the kidneys. Using high resolution of the fluorescent imaging method, PM_0.2 and PM_2.0 particles were found in mice kidneys after an inhalation experiment lasted for 15 min.³¹ Accumulation of cadmium and chromium also occurred in the kidneys of mice exposed to PM_2.5 plus PM_10.13 Although there is ample evidence for accumulation of PM_2.5 components in the kidney, how they enter the kidney remains to be further explored. It may be that macrophages endocytose PM_2.5, which allows PM_2.5 to cross the blood gas barrier and eventually reach the kidneys.³² It is also possible that PM_2.5 adsorbs proteins such as albumin and hemoglobin and follows the blood circulation to the kidneys.³³

Endothelial cells form the inner wall of blood vessels and have the functions of exchanging substances, adjusting vascular permeability, synthesizing and secreting a variety of bioactive substances.³⁴ Since endothelial cells are in direct contact with blood, they are more vulnerable to be damaged by PM_2.5. In addition, peripheral blood or urine tests of truck drivers, welding workers, and traffic commanders revealed an elevated risk of systemic inflammation in humans due to long-term exposure to PM_2.5.^35–38 During systemic inflammation, humoral and cellular inflammatory mediators are activated. PM_2.5 and activated inflammatory mediators damage endothelial cells, which cause endothelial dysfunction, ultimately affecting vascular function. The kidney is a highly vascularized organ that receives 20% of cardiac output. Disturbances in endothelial function may affect renal microcirculation, which in turn leads to renal dysfunction.³⁹

PM_2.5 causes renal injury through RAS imbalance. Male SD rats and BALB/c mice exposed to PM_2.5 had an imbalance in RAS and developed renal injury.^40,41 The expression of angiotensin receptor-1 (AT1R) and angiotensin-converting enzyme (ACE) was increased in mouse renal tissue, which preceded oxidative stress and inflammatory responses in the kidney.⁴² Intervention experiments with compound essential oils (CEOs) in mice showed that CEOs first regulated RAS and then reduced renal injury. However, the mechanism by which PM_2.5 affects RAS still needs to be further explored.⁴³

Currently, the pathway of renal injury caused by antibodies to M-type phospholipase A2 receptor (PLA2R) has not been fully clarified. It is generally accepted that PLA2R is expressed in both lung and kidney. PLA2R in the lungs is phagocytosed and presented to other immune cells by phagocytes activated by PM_2.5. Eventually, antibodies directed against PLA2R that are secreted and released by plasma cells in the blood circulation bind to PLA2R in the kidney to form immune complexes. The deposition of immune complexes in the glomeruli may cause renal injury.⁴⁴

The mechanism of PM_2.5 inducing renal injury

The toxicological mechanism by which PM_2.5 causes damage to the kidney is very complex. Studies showed that most of the potential molecular mechanisms are related to inflammation, oxidative stress, apoptosis, DNA damage, and autophagy. These mechanisms are interactive and interdependent (Figure 1).

Figure 1.

Graphical abstract summarizing the mechanisms of PM_2.5-induced kidney damage.

Inflammatory

Inflammatory response is a protective measure for the immune system to remove harmful irritants and promote body repair. But prolonged inflammatory response hinders the normal function of the body. PM_2.5-exposed mice developed severe renal injury, accompanied by enhanced expression of interleukin-6 (IL-6), type-2 receptor (TNFR2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in tissue samples.⁴⁵ Moreover, long-term exposure of workers to metal aerosols and cooking fumes resulted in systemic inflammation and renal dysfunction.^46–48 Since PM_2.5 directly or indirectly activated inflammatory cells in the kidney, a large number of those cells overexpress and release various inflammatory and chemical factors. They cause a cascade of reactions and inflammatory damage.

Macrophages are important inflammatory cells. Activated macrophages can infiltrate the kidney and promote the development of inflammation.⁴⁹ In the experiment, PM_2.5 upregulated the mRNA of inactive rhomboid-like protein 2 (iRhom2) and TNF-α converting enzyme (TACE) levels in RAW264.7 cells. The expression of NF-κB (IκBα)/nuclear factor kappa-B (NF-κB) and TACE/TNFRs were promoted. Moreover, the macrophages secreted large amounts of cytokines after exposure of PM_2.5, which in turn caused renal injury.⁴⁵

Podocytes, covering the outer layer of the glomerular basement membrane, are the last filtration barrier for the loss of urinary protein and urinary red blood cells in patients with nephritis. It was found that PM_2.5 activated pathways such as iRhom2/TACE/TNF-α in renal macrophages. Abnormalities in these pathways led to the accumulation of IL-1β, IL-6, TNF-a, and caused damage to podocytes.⁵⁰ In addition, PM_2.5 not only stimulated macrophages to release large amounts of inflammatory cytokines to cause podocyte injury but also activated proinflammatory pathways in podocytes. Those exacerbated the inflammatory response.^51–53 Some vitro experiments confirmed that PM_2.5 significantly increased the disintegrate of F-actin stress fibers, promoted cytoskeletal disorganization and dissociation, disrupted the integrity of nuclear structure.⁴⁴ And the results showed PM_2.5 increased the apoptotic rate of podocytes by activating the IκBα/NF-κB inflammatory signaling pathway in MPC5 cells.⁵⁴

Oxidative stress

Oxidative stress plays an important role in the process of renal injury induced by PM_2.5. Oxidative stress occurs when free radical production is excessive and insufficient to be eliminated by the antioxidant defense system, accompanied by accumulation of reactive nitrogen species (RNS) and reactive oxygen species (ROS). Metal and organic components in PM_2.5 promoted free radical production and reduced antioxidant capacity within the cell. This led to peroxidation of lipids on the cell membrane as well as an increase in intracellular Ca²⁺ concentration, ultimately triggering cell damage.^55–58 The kidney is more likely to suffer damage from oxidative stress. When the kidney is stimulated in a short time, it will excrete metabolites and poisons. These stimuli lead to overwhelming ROS production in the kidney as a result.⁵⁹

The NOX family have the capacity to transport electrons across the plasma membrane and to generate superoxide and other downstream ROS. They are the main makers of ROS in the kidney under the influence of PM_2.5. Studies confirmed that short-term PM_2.5 exposure elevated the level of ROS through sustained activation of NOX4. When the antioxidant system is not sufficient to remove excessive ROS, the kidney is damaged that is not visible to the naked eye while there are significant differences in biochemical parameters. ⁴³

Nuclear factor E2-related factor-2 (Nrf₂) signaling is one of the antioxidant defense systems. Nrf₂ is activated by the influence of some factors (e.g., Kelch-like epichlorohydrin-associated protein 1 (KEAP1)), which regulates a series of downstream antioxidants and cytoprotective enzymes.^60,61 Heme oxygenase-1 (HO-1) is one of the downstream antioxidant enzymes. It effectively scavenges ROS by degrading heme groups and promoting biliverdin. The reduced bilirubin in turn reverses oxidative stress. Short-term PM_2.5 exposure activated the Nrf₂/HO-1 pathway in renal tissue, which rescued kidney injury.⁴³ However, long-term exposure to PM_2.5 inhibited the Nrf₂/HO-1 pathway. Since after long-term exposure to PM_2.5, the inflammatory factor TNF-α was maintained at higher levels for a long time, which inhibited the expression of Nrf₂.⁵⁰

The antioxidant enzyme systems downstream of Nrf₂ also include glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD).^62,63 They have the efficacy of converting free radicals to less toxic or harmless substances. The decrease of L-Glutathione (GSH) and SOD levels is a key factor leading to oxidative stress and triggers a series of cascades. In the experiment, PM_2.5 increased ROS but decreased GSH and SOD storage in the kidney, ultimately leading to renal injury.⁴³

C-Jun N-terminal kinase (JNK) is a subfamily of mitogen-activated protein kinase (MAPK) pathways, which is an important antioxidant defense system. JNK can be activated by ROS and inflammatory factors to regulate cellular metabolism and apoptosis by inducing the transcription of downstream genes.^64–66 PM_2.5 could significantly increase the phosphorylation of JNK, decrease the antioxidant enzyme levels, and induce cell death, thereby enhance oxidative stress and damage the kidney.⁴⁵

Apoptotic

PM_2.5 exposure not only causes renal inflammation and oxidative stress but even triggers apoptosis. It is certain that proper apoptosis helps to maintain the normal function of the body, while dysregulation of apoptosis causes serious consequences.⁶⁷

Tubular epithelial cells and podocytes are important cells in the kidney that perform reabsorption and filtration functions. Their excessive apoptosis is closely related to the occurrence and development of renal diseases. Studies showed that PM_2.5 affected the expression of apoptosis-related genes and proteins in HK-2 cells. It could increase the levels of c-fos, caspase-8, and caspase-9, and decrease the levels of P53 and B-cell lymphoma-2 (Bcl-2). Also, in HK-2 cells, traffic-related diesel particulate matter (DPM) not only induced ER stress but also led to mitochondrial damage by increasing mitochondrial ROS. Eventually, the caspase pathway was activated and triggered apoptosis. It also proposed that PM_2.5-induced apoptosis in MPC-5 cells may be related to NF-κB signaling pathways.⁵⁴ In the experiment, PM_2.5 significantly increased the protein expressions of Bax, NF-κB/p65 and p-IκBα, but markedly decreased the protein expressions of Bcl-2, nephrin, and podocin in podocytes.

In addition, heavy metals have a long half-life period. They could accumulate in the body, especially in the kidney after long-term exposure.⁶⁹ This may cause apoptosis of tissues and cells.^69,70 The SD rats were exposed to PM_2.5 plus PM10 for 6 months, then significantly higher levels of cadmium and chromium were found in their kidneys. When the content of cadmium and chromium exceeded the threshold that the kidney beard, it may cause excessive apoptosis of cells in the tubules.^68,71,72

DNA damage

In recent years, studies have confirmed the effects of PM_2.5 on renal DNA. Ordered DNA expression is essential for the normal development of the body, and its abnormal changes may lead to the development of diseases.^73,74 The AJ mice were exposed to traffic-related PM_2.5 for 3 months (from infancy to adulthood).⁷⁵ The levels of oxidative stress-related DNA damage increased in their renal tissue, which may be the result of the massive ROS attack on DNA caused by PM_2.5.

Autophagy

Recently, studies have found the role of autophagy in renal injury caused by benzopyrene (BaP) (a common organic chemical in PM_2.5) and diesel particulate matter.⁷⁶ Autophagy is an important mechanism by which cells cope with intracellular or extracellular stress. During autophagy, some toxic components were degraded by autolysosomes to prevent cell damage.^77,78 However, the efficiency of autophagy could be reduced by PM_2.5. In the experiment, BaP reduced the viability of podocytes in a dose-and time-dependent manner by inhibiting autophagy. And the expression of synaptopodin and desmin (podocyte maturation markers), nephrin and podocin (filtration barrier) were decreased. The autophagy inducer, rapamycin, rescued podocyte injury and restored its filtration function. Diesel particulate matter inhibited the autophagy induced by protein kinase B (PKB)/mammalian target of rapamycin (mTOR) pathway, which attenuated the protective role of autophagy in renal injury.^79,80

Conclusion

This paper provides a solid rationale for PM_2.5 being a key risk factor for kidney disease. Epidemiological studies showed that PM_2.5 increases the risk of kidney disease. In vivo and in vitro studies explained that PM_2.5 may affect renal function through many kinds of pathways. Further studies showed that the toxicological mechanism of PM_2.5 on the kidney was related to inflammation, oxidative stress, apoptosis, DNA damage, and autophagy. However, how these mechanisms affect each other needs to be explored comprehensively and systematically. It is certain that effectively controlling air pollution can reduce the risk of kidney disease. In addition, the susceptible population can be recommended to use rich antioxidant animal and plant drug resources. Medical staff should be aware of the harm of PM_2.5 and recommend patients to reduce relevant environmental exposure, so as to better control the development of kidney disease.

Footnotes

Declaration of conflicting interest

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Natural Science Foundation of China (NSFC, 81872623), and the Liaoning Provincial Natural Science Foundation of China (20180550737).

ORCID iDs

Xiaofang Liu

Guang Yang

Appendix

References

GBD 2019 Risk Factors Collaborators . Global burden of 87 risk factors in 204 countries and territories, 1990-2019: a systematic analysis for the global burden of disease study 2019. Lancet 2020; 396: 1223–1249.

Mathers

. History of global burden of disease assessment at the world health organization. Arch Public Health 2020; 78: 77.

Jankowski

Floege

Fliser

, et al. Cardiovascular disease in chronic kidney disease. Circulation 2021; 143: 1157–1172.

Tan

Duan

, et al. Long-term trends of chemical characteristics and sources of fine particle in foshan city, pearl river delta: 2008-2014. Sci Total Environ 2016; 565: 519–528.

Ahamad

Tanin

Shrestha

. Household smoke-exposure risks associated with cooking fuels and cooking places in Tanzania: a cross-sectional analysis of demographic and health survey data. Int J Environ Res Public Health 2021; 18: 2534.

Fidan

Unlü

Köken

, et al. Oxidant‐antioxidant status and pulmonary function in welding workers. J Occup Health 2005; 47: 286–292.

Brewer

Morgan

Baig

, et al. Public understanding of cigarette smoke constituents: three US surveys. Tob Control 2016; 26: 592–599.

Fan

Wang

. The impact of PM2.5 on mortality in older adults: evidence from retirement of coal-fired power plants in the United States. Environ Health 2020; 19: 28.

Tonne

Elbaz

Beevers

, et al. Traffic-related air pollution in relation to cognitive function in older adults. Epidemiology 2014; 25: 674–681.

10.

Pun

Kazemiparkouhi

Manjourides

, et al. Long-term PM2.5 exposure and respiratory, cancer, and cardiovascular mortality in older US adults. Am J Epidemiol 2017; 186: 961–969.

11.

Bandowe

BAM

Lui

Jones

, et al. The chemical composition and toxicological effects of fine particulate matter (PM2.5) emitted from different cooking styles. Environ Pollut 2021; 288: 117754.

12.

Liu

. Air pollution and kidney diseases: PM2.5 as an emerging culprit. Nephrol Public Health Worldwide 2021; 199: 1–11.

13.

Xiao

Yao

, et al. Age differences in the pulmonary and vascular pathophysiologic processes after long-term real-time exposure to particulate matter in rats. Chemosphere 2020; 261: 127710.

14.

Killilea

Chow

Xiao

, et al. Flame retardant tris(1,3-dichloro-2-propyl)phosphate (TDCPP) toxicity is attenuated by N -acetylcysteine in human kidney cells. Toxicol Rep 2017; 4: 260–264.

15.

Arhami

Shahne

Hosseini

, et al. Seasonal trends in the composition and sources of PM2.5 and carbonaceous aerosol in Tehran, Iran. Environ Pollut 2018; 239: 69–81.

16.

Tobler

Bhattu

Canonaco

, et al. Chemical characterization of PM2.5 and source apportionment of organic aerosol in New Delhi, India. Sci Total Environ 2020; 745: 140924.

17.

Chang

Chong

Wang

, et al. Recent progress in research on PM2.5 in subways. Environ Sci Process Impacts 2021; 23: 642–663.

18.

Wang

Shi

Yan

, et al. Eco-toxicological bioassay of atmospheric fine particulate matter (PM2.5) with photobacterium phosphoreum T3. Ecotoxicol Environ Saf 2016; 133: 226–234.

19.

Xie

Zhang

Tian

, et al. Preexposure to PM2.5 exacerbates acute viral myocarditis associated with Th17 cell. Int J Cardiol 2013; 168: 3837–3845.

20.

Yan

. Airway hyperresponsiveness development and the toxicity of PM2.5. Environ Sci Pollut Res Int 2021; 28: 6374–6391.

21.

Ogino

Nagaoka

Ito

, et al. Involvement of PM2.5-bound protein and metals in PM2.5-induced allergic airway inflammation in mice. Inhal Toxicol 2018; 30: 498–508.

22.

Kim

Park

Lee

, et al. Application of various cytotoxic endpoints for the toxicity prioritization of fine dust (PM2.5) sources using a multi-criteria decision-making approach. Environ Geochem Health 2020; 42: 1775–1788.

23.

Liu

Fan

Huang

. Relationship of chronic kidney disease with major air pollutants - A systematic review and meta-analysis of observational studies. Environ Toxicol Pharmacol 2020; 76: 103355.

24.

Lin

, et al. Air pollutants and subsequent risk of chronic kidney disease and end-stage renal disease: a population-based cohort study. Environ Pollut 2020; 261: 114154.

25.

Chiu

Chang

, et al. High particulate matter 2.5 levels and ambient temperature are associated with acute lung edema in patients with nondialysis stage 5 chronic kidney disease. Nephrol Dial Transpl 2019; 34: 1354–1360.

26.

Huang

Wang

, et al. Long-term exposure to ambient PM2.5 and increased risk of CKD prevalence in China. J Am Soc Nephrol 2021; 32: 448–458.

27.

Bragg-Gresham

Morgenstern

McClellan

, et al. County-level air quality and the prevalence of diagnosed chronic kidney disease in the US medicare population. PLoS One 2018; 13: e0200612.

28.

Wang

Chen

, et al. Long-term exposure to air pollution and increased risk of membranous nephropathy in China. J Am Soc Nephrol 2016; 27: 3739–3746.

29.

Zhang

Huang

Zheng

, et al. A novel insight into the role of PLA2R and THSD7A in membranous nephropathy. J Immunol Res 2021; 2021: 8163298.

30.

Zeng

Zou

, et al. The impact of particulate matter (PM2.5) on human retinal development in hESC-derived retinal organoids. Front Cell Dev Biol 2021; 9: 607341.

31.

, et al. Fluorescent reconstitution on deposition of PM2.5 in lung and extrapulmonary organs. Proc Natl Acad Sci U S A 2019; 116: 2488–2493.

32.

Saint-Georges

Abbas

Billet

, et al. Gene expression induction of volatile organic compound and/or polycyclic aromatic hydrocarbon-metabolizing enzymes in isolated human alveolar macrophages in response to airborne particulate matter (PM2.5). Toxicology 2008; 244: 220–230.

33.

Liu

Zhu

Song

, et al. Characterization of blood protein adsorption on PM2.5 and its implications on cellular uptake and cytotoxicity of PM2.5. J Hazard Mater 2021; 414: 125499.

34.

Hirschi

. Regulation of hemogenic endothelial cell development and function. Annu Rev Physiol 2021; 83: 17–37.

35.

Neophytou

Hart

Cavallari

, et al. Traffic-related exposures and biomarkers of systemic inflammation, endothelial activation and oxidative stress: a panel study in the US trucking industry. Environ Health 2013; 12: 105.

36.

Chuang

Pan

, et al. Urinary neutrophil gelatinase-associated lipocalin is associated with heavy metal exposure in welding workers. Sci Rep 2015; 5: 18048.

37.

Kim

Chen

Boyce

, et al. Exposure to welding fumes is associated with acute systemic inflammatory responses. Occup Environ Med 2005; 62: 157–163.

38.

Tan

Wang

Lin

, et al. Long-term high air pollution exposure induced metabolic adaptations in traffic policemen. Environ Toxicol Pharmacol 2018; 58: 156–162.

39.

Jiang

Persson

, et al. Reactive oxygen species in renal vascular function. Acta Physiol (Oxf) 2020; 229: e13477.

40.

Aztatzi-Aguilar

Uribe-Ramírez

Narváez-Morales

, et al. Early kidney damage induced by subchronic exposure to PM2.5 in rats. Part Fibre Toxicol 2016; 13: 68.

41.

Aztatzi-Aguilar

Pardo-Osorio

Uribe-Ramírez

, et al. Acute kidney damage by PM2.5 exposure in a rat model. Environ Toxicol Pharmacol 2021; 83: 103587.

42.

Sharma

Anders

Gaikwad

. Fiend and friend in the renin angiotensin system: an insight on acute kidney injury. Biomed Pharmacother 2019; 110: 764–774.

43.

Zhang

Fang

, et al. The kidney injury induced by short-term PM2.5 exposure and the prophylactic treatment of essential oils in BALB/c mice. Oxid Med Cell Longev 2018; 2018: 9098627.

44.

Kronbichler

Meijers

, et al. Recent progress in deciphering the etiopathogenesis of primary membranous nephropathy. Biomed Res Int 2017; 2017: 1936372.

45.

Chenxu

Minxuan

Yuting

, et al. iRhom2 loss alleviates renal injury in long-term PM2.5-exposed mice by suppression of inflammation and oxidative stress. Redox Biol 2018; 19: 147–157.

46.

Vinnikov

Tulekov

. Plasma cutting and exposure to PM(2.5) metal aerosol in metalworking, Almaty, Kazakhstan. Occup Environ Med 2020; 78: oemed–2020–106883.

47.

Singh

Kamal

Mudiam

, et al. Heat and PAHs emissions in indoor kitchen air and its impact on kidney dysfunctions among kitchen workers in lucknow, North India. PLoS One 2016; 11: e0148641.

48.

Bian

Gong

Huang

, et al. Deciphering human macrophage development at single-cell resolution. Nature 2020; 582: 571–576.

49.

Chalmers

Chitu

Herlitz

, et al. Macrophage depletion ameliorates nephritis induced by pathogenic antibodies. J Autoimmun 2015; 57: 42–52.

50.

Qin

, et al. Activated iRhom2 drives prolonged PM2.5 exposure-triggered renal injury in Nrf2-defective mice. Nanotoxicology 2018; 12: 1045–1067.

51.

Wright

Beresford

. Podocytes contribute, and respond, to the inflammatory environment in lupus nephritis. Am J Physiol Ren Physiol 2018; 315: F1683–F1694.

52.

Zhao

Feng

Wang

, et al. hnRNP K plays a protective role in TNF-α-induced apoptosis in podocytes. Biosci Rep 2018; 38: BSR20180288.

53.

Zhong

, et al. Protective effects of liraglutide on glomerular podocytes in obese mice by inhibiting the inflammatory factor TNF-α-mediated NF-κB and MAPK pathway. Obes Res Clin Pract 2019; 13: 385–390.

54.

Wan

Liu

Yang

, et al. Triptolide ameliorates fine particulate matter-induced podocytes injury via regulating NF-κB signaling pathway. BMC Mol Cell Biol 2020; 21: 4.

55.

Shi

Qiu

, et al. Investigation of the chemical components of ambient fine particulate matter (PM2.5) associated with in vitro cellular responses to oxidative stress and inflammation. Environ Int 2020; 136: 105475.

56.

Roslan

Giribabu

Karim

, et al. Quercetin ameliorates oxidative stress, inflammation and apoptosis in the heart of streptozotocin-nicotinamide-induced adult male diabetic rats. Biomed Pharmacother 2017; 86: 570–582.

57.

Lee

Kang

, et al. Dust particles-induced intracellular Ca2+ signaling and reactive oxygen species in lung fibroblast cell line MRC5. Korean J Physiol Pharmacol 2017; 21: 327–334.

58.

Liang

Duan

, et al. Review on recent progress in observations, source identifications and countermeasures of PM2.5. Environ Int 2016; 86: 150–170.

59.

George

You

Joy

, et al. Xenobiotic transporters and kidney injury. Adv Drug Deliv Rev 2017; 116: 73–91.

60.

Zhang

Wang

Kang

, et al. Loganin attenuates septic acute renal injury with the participation of AKT and Nrf2/HO-1 signaling pathways. Drug Des Devel Ther 2021; 15: 501–513.

61.

Chuang

Yang

, et al. Acute renal injury induced by endotoxic shock in rats is alleviated via PI3K/Nrf2 pathway. Eur Rev Med Pharmacol Sci 2018; 22: 5394–5401.

62.

Kim

Park

Kim

, et al. Expression of heterologous OsDHAR gene improves glutathione (GSH)-dependent antioxidant system and maintenance of cellular redox status in synechococcus elongatus PCC 7942. Front Plant Sci 2020; 11: 231.

63.

Bai

Zhang

, et al. DIP2A is involved in SOD-mediated antioxidative reactions in murine brain. Free Radic Biol Med 2021; 168: 6–15.

64.

Liao

Tandarich

Hollenbeck

. ROS regulation of axonal mitochondrial transport is mediated by Ca2+ and JNK in drosophila. PLoS One 2017; 12: e0178105.

65.

Zhao

Zhang

, et al. Inhibition of ER stress-activated JNK pathway attenuates TNF-α-induced inflammatory response in bone marrow mesenchymal stem cells. Biochem Biophys Res Commun 2021; 541: 8–14.

66.

Zhong

Zhang

, et al. TREM2/DAP12 complex regulates inflammatory responses in microglia via the JNK signaling pathway. Front Aging Neurosci 2017; 9: 204.

67.

Wang

Liu

, et al. Apoptosis disorder, a key pathogenesis of HCMV-related diseases. Int J Mol Sci 2021; 22: 4106.

68.

Jin

, et al. Correlation between environmental low-dose cadmium exposure and early kidney damage: a comparative study in an industrial zone vs. a living quarter in shanghai, China. Environ Toxicol Pharmacol 2020; 79: 103381.

69.

Bao

Zheng

Wang

. Selenium protects against cadmium-induced kidney apoptosis in chickens by activating the PI3K/AKT/Bcl-2 signaling pathway. Environ Sci Pollut Res Int 2017; 24: 20342–20353.

70.

Jiang

Wen

Zhou

, et al. Low-dose combined exposure of carboxylated black carbon and heavy metal lead induced potentiation of oxidative stress, DNA damage, inflammation, and apoptosis in BEAS-2B cells. Ecotoxicol Environ Saf 2020; 206: 111388.

71.

Chen

Liu

Long

, et al. Alpha lipoic acid attenuates cadmium-induced nephrotoxicity via the mitochondrial apoptotic pathways in rat. J Inorg Biochem 2018; 184: 19–26.

72.

Zheng

, et al. Hexavalent chromium induces renal apoptosis and autophagy via disordering the balance of mitochondrial dynamics in rats. Ecotoxicol Environ Saf 2020; 204: 111061.

73.

Sajid

Khan

Shah

, et al. Proficiencies of Artemisia scoparia against CCl4 induced DNA damages and renal toxicity in rat. BMC Complement Altern Med 2016; 16: 149.

74.

Jia

Kang

Tan

, et al. Nicotinamide mononucleotide attenuates renal interstitial fibrosis after AKI by suppressing tubular DNA damage and senescence. Front Physiol 2021; 12: 649547.

75.

De Oliveira

AAF

de Oliveira

Dias

, et al. Genotoxic and epigenotoxic effects in mice exposed to concentrated ambient fine particulate matter (PM2.5) from São Paulo city, Brazil. Part Fibre Toxicol 2018; 15: 40.

76.

Wang

Zheng

Lee

, et al. Micro- and Nanosized substances cause different autophagy-related responses. Int J Mol Sci 2021; 22: 4787.

77.

Fujimura

Yamamoto

Takabatake

, et al. Autophagy protects kidney from phosphate-induced mitochondrial injury. Biochem Biophys Res Commun 2020; 524: 636–642.

78.

Guo

Shu

, et al. Autophagy protects auditory hair cells against neomycin-induced damage. Autophagy 2017; 13: 1884–1904.

79.

Zhang

Liu

. The benzo[b]fluoranthene in the atmospheric fine particulate matter induces mouse glomerular podocytes injury via inhibition of autophagy. Ecotoxicol Environ Saf 2020; 195: 110403.

80.

Jin

Zhang

, et al. Particulate matter exposure induces the autophagy of macrophages via oxidative stress-mediated PI3K/AKT/mTOR pathway. Chemosphere 2017; 167: 444–453.

81.

Ran

Yang

Sun

, et al. Long-term exposure to ambient fine particulate matter and mortality from renal failure: a retrospective cohort study in Hong Kong, China. Am J Epidemiol 2020; 189: 602–612.

82.

Lin

Hsu

Lin

, et al. Association of exposure to fine-particulate air pollution and acidic gases with incidence of nephrotic syndrome. Int J Environ Res Public Health 2018; 15: 2860.

83.

Wang

Guo

, et al. Association between airborne particulate matter and renal function: an analysis of 2.5 million young adults. Environ Int 2021; 147: 106348.

84.

Chern

Pan

, et al. Effects of surrounding environment on incidence of end stage renal disease. Sci Total Environ 2020; 723: 137915.

85.

Mehta

Zanobetti

Bind

, et al. Long-term exposure to ambient fine particulate matter and renal function in older men: the veterans administration normative aging study. Environ Health Perspect 2016; 124: 1353–1360.

86.

Bernatsky

Fournier

Pineau

, et al. Associations between ambient fine particulate levels and disease activity in patients with systemic lupus erythematosus (SLE). Environ Health Perspect 2011; 119: 45–49.

The influence of PM 2.5 exposure on kidney diseases

Abstract

Keywords

Introduction

Sources, composition, and hazards of PM2.5

PM2.5 and renal injury

Renal disease affected by PM2.5

The pathways of PM2.5 affecting kidney

The mechanism of PM2.5 inducing renal injury

Inflammatory

Oxidative stress

Apoptotic

DNA damage

Autophagy

Conclusion

Footnotes

Declaration of conflicting interest

Funding

ORCID iDs

Appendix

References

Sources, composition, and hazards of PM_2.5

PM_2.5 and renal injury

Renal disease affected by PM_2.5

The pathways of PM_2.5 affecting kidney

The mechanism of PM_2.5 inducing renal injury