Currently, studies on the association between per-/polyfluoroalkyl substances (PFAS) concentrations and the renal function of residents, especially teenagers, living near fluorochemical industrial plants, are relatively rare, and not all these studies suggested associations. In this cross-sectional study, 775 local teenagers (11–15 years old) were included, and serum concentrations of 18 PFAS were measured. Perfluorooctanoic acid (PFOA) was found to be the dominant PFAS with a concentration of 22.3–3310 ng/mL (mean = 191 ng/mL), accounting for 71.5–99.1% of ΣPFAS. Statistical analyses demonstrated that internal exposure of perfluoroalkyl carboxylic acids (PFCA, C8–C10) was related to the plant. In addition, the prevalence rate of chronic kidney disease (CKD) (35.0%) in the participants was relatively high. A significantly positive association was observed between the increase in PFOA concentration and increasing risk of CKD (OR = 1.741; 95% CI: 1.004, 3.088; p = 0.048) by adjusting for gender, age, body mass index (BMI), and household income. Similar positive correlation was also observed in PFHpA with CKD (OR = 1.628, 95% CI: 1.031, 2.572; p = 0.037). However, no significant correlation was observed for concentrations of other PFAS and CKD (p > 0.05). Furthermore, linear regression analyses demonstrated that none of the PFAS concentrations were significantly correlated with estimated glomerular filtration rate (eGFR) or urine albumin/urine creatinine ratio (ACR) (p > 0.05). However, a significantly negative correlation was observed between PFOA concentration and abnormal ACR (β = −0.141, 95% CI: −0.283, 0.001; p = 0.048) after stratifying by CKD. Sensitivity analyses further confirmed these results. This cross-sectional study is the first, to our knowledge, to investigate the association between PFAS concentrations and renal function in teenagers living near a Chinese industrial plant. Further prospective and metabonomic studies are needed to interpret the results and clarify the biological mechanisms underlying this association.

The understanding for the impact of petrochemical pollutants exposure on renal functions is limited.Our study examined the associations between renal functions and pollutants exposure in adult residents living in the vicinity of a petrochemical industry.We recruited 2069 adult residents near a big petrochemical complex in Taiwan in 2009–2012, and they were categorized into high exposure (HE) and low exposure (LE) groups based on their address to source by 10 km radius. Study subjects were measured the urinary levels of arsenic, cadmium, mercury, thallium, and 1-hydroxypyrene (1-OHP). The estimated glomerular filtration rate (eGFR) was calculated using the Taiwanese Chronic Kidney Disease Epidemiology Collaboration equation, and the chronic kidney disease (CKD) prevalence and risks were defined according to KDIGO 2012 guidelines. Adjusted generalized linear and logistic regression models were applied to evaluate the associations between petrochemical exposure and renal functions.Subjects in the HE areas had significantly lower eGFR, higher CKD prevalence, and higher levels of urinary arsenic, cadmium, mercury, thallium and 1-OHP. The closer to complex and high exposure group of study subjects were significantly associated with the decrease in eGFR, higher ORs for CKD and high-intermediate risk of CKD. In addition, the study subjects who had two-fold urinary arsenic and 1-OHP levels were significantly with decreased 0.68 and 0.49 ml/min/1.73 m2 of eGFR, respectively.Residing closer and higher arsenic and polycyclic aromatic hydrocarbon exposure were associated with the renal impairment and risks of CKD among the residential population near the petrochemical industry.

Atrazine (ATR), one of the most widely used pesticides in agricultural production, are gradually concerned due to potential ecosystem and health risks. Further, the induction of ATR nephrotoxicity and detoxification response is still unknown. To evaluate ATR-induced nephrotoxicity, quails were treated with 0, 50, 250 or 500 mg/kg ATR by gavage administration for 45 days. Histopathology indicated that ATR exposure caused renal tubular epithelial cell swelling and endoplasmic reticulum degeneration, suggesting that ATR exposure causes renal impairment even renal diseases. Notably, ATR interfered cytochrome P450 system (CYP450s) homeostasis by enhancing contents or activities of CYP450s (total CYP450, Cyt b5, AH, APND, NCR and ERND) and the expression of CYP450 isoforms (CYP1A, CYP1B, CYP2C and CYP3A). ATR triggered phase II detoxifying reaction, reflected by the elevated GSH level, GST activity and the up-regulation of GST isoforms (GSTa, GSTa3 and GSTt1) and GSH synthetase (GCLC). Moreover, ABC transporters were activated to expel ATR from the body by increasing expression of MRP1 and P-GP gene. Accompanying these alterations, the nuclear receptors (AHR, CAR and PXR) were activated by ATR in a dose-dependent manner. Analysis results of present study demonstrated that the induction of phase II detoxifying enzyme system and ABC transporters could be modulated by nuclear receptors response and CYP450s disturbance in low-dose ATR-treated quail. In conclusion, all data suggested that nuclear receptors AHR-mediated detoxification pathway was involved in ATR-induced nephrotoxicity. These results provided new evidence about the nephrotoxic effects of ATR on the response of biotransformation and detoxification system.

Ochratoxin A (OTA) is reported to induce nephrotoxicity in animals and humans. Porcine circovirus type 2 (PCV2) could induce porcine dermatitis and nephropathy syndrome. To date, little is known whether virus infection aggravates mycotoxin-induced toxicity. This work aimed to study the effects of PCV2 infection on OTA-induced nephrotoxicity and its mechanism in vivo and vitro. The results in vivo showed that PCV2 infection aggravated OTA-induced poor growth performance, nephrotoxicity, p38 phosphorylation and autophagy as demonstrated by Atg5, LC3 II and p62 protein expressions in kidney of pigs. The results in vitro indicated that PCV2 infection significantly aggravated OTA-induced nephrotoxicity as demonstrated by cell viabilities, annexin V/PI binding and caspase 3 activities, and induced p38 phosphorylation and autophagy in PK15 cells. p38 inhibitor decreased Atg5 and LC3 protein expression induced by PCV2 infection and OTA combined treatment. Adding autophagy inhibitor 3-MA or CQ alleviated the aggravating effects of PCV2 infection on OTA-induced nephrotoxicity. Atg5-specific siRNA eliminated the aggravating effects of PCV2 infection on OTA-induced nephrotoxicity. Taken together, these data indicate that in vivo and in vitro PCV2 infection aggravated OTA-induced nephrotoxicity via p38-mediated autophagy.

We used real-world exposure scenarios to evaluate the effect of six ambient air pollutant (PM₂.₅, PM₁₀, NO₂, SO₂, CO, and O₃) exposure on renal function among older adults without chronic kidney disease (CKD). We recruited 169 older adults without CKD in Beijing, China, for a longitudinal study from 2016 to 2018. The Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (EPI) equations were employed to derive the estimated glomerular filtration rate (eGFR). A linear mixed-effects model with random intercepts for participants was employed to determine the effects of air pollutants on renal function evaluated on the basis of eGFR and urinary albumin/creatinine ratio at different exposure windows (1-, 2-, 3-, 5-, 7-, 14-, 28-, 45-, and 60-days moving averages). An interquartile range (IQR) increase in NO₂ for was associated with significant decreases of in eGFR (MDRD equation) [percentage changes: −4.49 (95% confidence interval: −8.44, −0.37), −5.51 (−10.43, −0.33), −2.26 (−4.38, −0.08), −3.71 (−6.67, −0.65), −5.44 (−9.58, −1.11), −5.50 (−10.24, −0.51), −6.15 (−10.73, −1.33), and −6.34 (−11.17, −1.25) for 1-, 2-, 5-, 7-, 14-, 28-, 45-, and 60-days moving averages, respectively] and in eGFR (EPI equation) [percentage changes: −5.04 (−7.09, −2.94), −6.25 (−8.81, −3.62), −5.16 (−7.34, −2.92), −5.10 (−7.85, −2.28), −5.83 (−8.23, −3.36), −6.04 (−8.55, −3.47) for 1-, 2-, 14-, 28-, 45-, and 60-days moving averages, respectively]. In two-pollutant model, only the association of NO₂ exposure with eGFR remained robust after adjustment for any other pollutant. This association was stronger for individuals with hypertension for the EPI equation or BMI <25 kg/m² for the MDRD equation at lags 1 and 1–2. Our findings suggest that NO₂ exposure is associated with eGFR reduction among older adults without CKD for short (1-, 2-days) and medium (14-, 28-, 45-, 60-days) term exposure periods; thus, NO₂ exposure may contribute to renal impairment.

Di-(2-ethylhexyl) phthalate (DEHP), a plasticizer that is mainly used in the production of polyvinyl alcohol-containing chloride products, has attracted attention due to potential threats to human health and the environment. Nevertheless, knowledge of DEHP-induced nephrotoxicity is still limited. To explore the mechanism of DEHP-induced nephrotoxicity, quail were treated with 0, 250, 500 and 1000 mg/kg DEHP by oral gavage for 45 days. Based on the results of histopathological analysis, DEHP exposure induced a disorganized renal structure, a partially dilated glomerulus and an atrophied Bowman’s space. Renal tubular epithelial cells were unclear, and swelling of columnar epithelial cells was observed, suggesting that DEHP exposure caused renal disease and renal injury. Notably, DEHP interfered with the homeostasis of cytochrome P450 systems (CYP450s) by increasing the activities or contents of CYP450s (total CYP450, Cyt b5, ERND, APND, AH and NCR). The expression levels of certain CYP450 isoforms (CYP1A, CYP1B, CYP2C, CYP2D, CYP2J and CYP3A) were significantly downregulated in the kidney in DEHP-treated quail. Furthermore, DEHP induced the expression of nuclear receptors (AHR, CAR and PXR) in a dose-dependent manner. The results of this study suggested that DEHP-induced nephrotoxicity in quail was associated with the induction of nuclear xenobiotic receptor (NXR) responses and interference with CYP450 homeostasis. In conclusion, all data indicated that DEHP induced nephrotoxicity by triggering NXRs and modulating the cytochrome P450 system. The results of this study provide a new basis for understanding the nephrotoxicity of DEHP.

The level of di-(2-ethylhexyl) phthalate (DEHP) is elevated in chronic kidney disease patients undergoing dialysis. However, statins are unable to reduce the cardiovascular events in chronic dialysis patients. In this study, we investigated the effects of DEHP on statin-conferred pleiotropic effects and the underlying molecular mechanism in peritoneal dialysis (PD) patients and endothelial cells (ECs). In PD patients with serum DEHP level ≥0.0687 μg/mL, statin treatment was not associated with lower risk of cardiovascular disease. In ECs, exposure to DEHP abrogated the simvastatin-induced NO bioavailability and EC-related functions. Additionally, DEHP abolished the anti-inflammatory effect of simvastatin on the tumor necrosis factor α-induced upregulation of adhesion molecules and monocyte adhesion to ECs. Mechanistically, DEHP blunted the activation of transient receptor potential vanilloid type 1 (TRPV1), which is required for NO production by simvastatin in ECs. Notably, DEHP increased the activity and expression of protein phosphatase 2B (PP2B), a negative regulator of TRPV1 activity. The effect of DEHP on PP2B activation was mediated by the activation of the NADPH oxidase/reactive oxygen species (NOX−ROS) pathway. Inhibition of PP2B activity by pharmacological antagonists prevented the inhibitory effects of DEHP on simvastatin-induced Ca²⁺ influx, NO bioavailability, and EC migration, proliferation, tube formation, and anti-inflammatory action. Collectively, DEHP activates the NOX−ROS−PP2B pathway, which in turns inhibits TRPV1/Ca²⁺-dependent signaling and abrogates the statin-conferred pleiotropic protection in ECs.

The associations of air pollution with chronic kidney disease (CKD) have not yet been fully studied. We enrolled 8,497 Taipei City residents older than 65 years and calculated the estimated glomerular filtration rate (eGFR) using the Taiwanese Chronic Kidney Disease Epidemiology Collaboration equation. Proteinuria was assessed via dipstick on voided urine. CKD prevalence and risk of progression were defined according to the KDIGO 2012 guidelines. Land-use regression models were used to estimate the participants’ one-year exposures to PM of different sizes and traffic-related exhaust, PM₂.₅ absorbance, nitrogen dioxide (NO₂), and NOₓ. Generalized linear regressions and logistic regressions were used to examine the associations of one-year air pollution exposures with eGFR, proteinuria, CKD prevalence and risk of progression. The results showed that the interquartile range (IQR) increments of PM₂.₅ absorbance (0.4 × 10⁻⁵/m) and NO₂ (7.0 μg/m³) were associated with a 1.07% [95% confidence interval (CI): 0.54–1.57] and 0.84% (95% CI: 0.37–1.32) lower eGFR, respectively; such relationships were magnified in subjects who had an eGFR >60 ml/min/1.73 m² or who were non-diabetic. Similar associations were also observed for PM₁₀ and PM₂.₅₋₁₀. Two-pollutant models showed that PM₁₀ and PM₂.₅ absorbance were associated with a lower eGFR. The odd ratios (ORs) of CKD prevalence and risk of progression also increased with exposures to PM₂.₅ absorbance and NO₂. In summary, one-year exposures to traffic-related air pollution were associated with lower eGFR, higher CKD prevalence, and increased risk of CKD progression among the elderly population. Air pollution-related impaired renal function was stronger in non-CKD and non-diabetic subjects.

Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants formed from the incomplete combustion of carbon-containing products. Exposure can occur through ingestion or inhalation and has been linked to depression, stroke, liver disease, asthma, diabetes, heart failure, and cancer. Few studies have investigated the association between exposure to PAHs and chronic kidney disease (CKD) in humans. This study aims to investigate the association between seven urinary PAH concentrations (1-hydroxynaphthalene, 2-hydroxynaphthalene, 3-hydroxyfluorene 2-hydroxyfluorene, 1-hydroxyphenanthrene, 1-hydroxypyrene, and 2 & 3-hydroxyphenanthrene) and CKD in the US adult population. A cross-sectional analysis using the 2015–2016 National Health and Nutrition Examination Survey (NHANES) dataset was conducted. CKD was defined with estimated glomerular filtration rate (eGFR) and albumin to creatinine ratio (ACR). Participants with an eGFR < 60 ml/min/1.73m² or ACR > 30 mg/gm were considered to have CKD. A specialized complex survey design analysis package using R version 4.0.3 was used in the data analysis. Multivariate logistic regression was used to study the correlation between seven forms of urinary PAH concentrations and CKD associated with abnormal eGFR or ACR. The models were adjusted for lifestyle and demographic factors. The study included a total of 4117 adults aged ≥ 20 years, with 49.6% males and 50.4% females. Urinary 2-hydroxynaphthalene (OR: 1.600, 95% CI: 1.141, 2.243) was significantly associated with an increased odds of CKD; the other six forms of urinary PAHs were not associated with CKD. Non-Hispanic Black (OR: 1.569, 95% CI: 1.168, 2.108), age of 60 years and older (OR: 2.546, 95% CI: 1.865, 3.476), and BMIs of underweight (OR: 2.386, 95% CI: 1.259, 4.524) and obese (OR: 1.407, 95% CI: 1.113, 1.778) all had significantly increased odds for CKD. Our study concluded that urinary 2-hydroxynaphthalene, a form of PAH, is significantly associated with CKD.

Exposure to dioxins and furans has the potential to affect kidney function and could be associated with chronic kidney disease. Data for US adults aged ≥ 20 years from the National Health and Nutrition Examination Survey for 1999–2004 (N = 4433) were analyzed to study trends in adjusted concentrations (AGM) of 1,2,3,7,8-pentachlorodibenzo-p-dioxin, 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin, 1,2,3,4,6,7,8-heptachlororodibenzo-p-dioxin, 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin, 2,3,4,7,8-pentachlorodibenzofuran, 1,2,3,4,7,8-hexachlorodibenzofuran, 1,2,3,6,7,8-hexachlorodibenzofuran, and 1,2,3,4,6,7,8-heptachlorodibenzofuran across the stages of kidney function (KF). Stages of KF were defined based on estimated glomerular filtration rate or eGFR expressed in mL/min/1.73 m². For KF-1, eGFR was > 90, between 60 and 90 for KF-2, between 45 and 60 for KF-3A, and between 15 and 45 for KF-3B/4. AGMs for 1,2,3,7,8-pentachlorodibenzo-p-dioxin and 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin increased consistently across the full spectrum of kidney function. For example, AGMs for the total population for 1,2,3,7,8-pentachlorodibenzo-p-dioxin were 2.5, 4.5, 9.3, and 14.9 fg/g lipid for KF-1, KF-2, KF-3A, and KF-3B/4, respectively. For other six dioxins/furans, AGMs increased over KF-1 through KF-3A but then decreased for KF-3B/4, for example, 1,2,3,4,6,7,8-heptachlorodibenzofuran for males, and AGMs for KF-1, KF-2, KF-3A, and KF-3B/4 were 7.9, 8.4, 10.7, and 7.5 fg/g lipid, respectively. For 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin and 1,2,3,6,7,8-hexachlorodibenzofuran, smokers were found to have lower AGMs than nonsmokers. For example, for 1,2,3,4,6,7,8-heptaachlorodibenzo-p-dioxin, smoker–nonsmoker AGMs were 22.2 vs. 39.4 fg/g lipid at KF-1, 29.5 vs. 51.4 fg/g lipid at KF-2, 61.6 vs. 72.8 fg/g lipid at KF-3A, and 34.9 vs. 66.4 fg/g lipid at KF-3B/4. The reverse more often than not, was, however, observed for other six dioxins/furans. Smoker–nonsmoker AGMs for 1,2,3,7,8-pentachlorodibenzo-p-dioxin were 2.4 vs. 2.6 fg/g lipid at KF-1, 5.1 vs. 4.0 fg/g lipid at KF-2, 12.7 vs. 6.7 fg/g lipid at KF-3A, and 18.6 vs. 11.9 fg/g lipid at KF-3B/4. In conclusion, lipid-adjusted serum concentrations of dioxins and furans continue increasing as kidney function keeps deteriorating until KF-3A. However, these increases in serum concentrations until KF-3A may be followed by substantial decreases for selected dioxins/furans during KF-3B/4.