Exposure to phthalates is reported to be associated with increased incidence of microalbuminuria and low-grade albuminuria in children and adolescents. However, this phenomenon of phthalate-related nephrotoxicity is unknown in adults.Urine samples of 1663 adults from the 2012 Shanghai Food Consumption Survey (SHFCS) were measured for 10 metabolites of 6 phthalates and for renal function parameters. Their associations were explored by linear and logistic regression models.Multivariate linear regression analysis showed that all three renal function parameters (albumin-to-creatinine ratio (ACR), β2-microglobulin (B2M), and N-acetyl-β-d-glucosaminidase (NAG)) are positively associated with six metabolites, including mono-benzylphthalate (MBzP), mono-2-ethylhexylphthalate (MEHP), mono-2-ethyl-5-oxohexyphthalate (MEOHP), mono-2-ethyl-5-hydroxyhexylphthalate (MEHHP), mono-2-ethyl-5-carboxypentylphthalate (MECPP), and mono-2-carboxymethyl-hexyl phthalate (MCMHP) (P < 0.05). Logistic analysis showed that the prevalence of hyperALBuria, hyperB2Muria, hyperNAGuria, or potentially impaired renal function (PIRF) were positively associated with urinary levels of MBzP, MEOHP, and MECPP, respectively (P < 0.05). Co-exposure to identified risk metabolites monoethylphthalate (MEP), MBzP, MEHP, MEOHP, MECPP, MEHHP, and MCMHP increased the risk of having impaired renal function.Certain metabolites of phthalates, including bis (2-ethylhexyl) phthalate (DEHP) and benzyle butyl phthalate (BBzP), were associated with impaired renal function in Shanghai adults.

Many studies using experimental and wild animals have reported negative effects of microplastic beads (MPs) ingestion. However, data regarding the lowest observed adverse effect levels (LOAELs) of MPs remain limited. Our aim was to evaluate the adverse effect levels of polyethylene MPs (10–63 μm diameter) with respect to growth, reproduction, and the eyes and kidneys of medaka (Oryzias latipes) under breeding conditions to contribute to future research involving LOAEL determinations. Fish were exposed to 0.009 mg-MPs (approximately 1000 particles)/L to 0.32 mg-MPs (approximately 40,000 particles)/L for 12 weeks. The eyes and kidneys were evaluated by histopathologic analysis. Although histologic analyses indicated an absence of MPs in the tissues, the eyes and kidneys as well as reproduction were adversely affected by increasing MP concentrations. The number of spawned eggs decreased, and changes were noted in the eyes of fish exposed to ≥0.032 mg-MPs/L under breeding conditions. The eyes exhibited thinning of the optic nerve fiber layer and dilatation of retinal capillaries compared with medaka not treated with MPs. Changes in the kidneys were observed in fish exposed to ≥0.065 mg-MPs/L. The mesangial matrix in the glomerulus of the kidneys was expanded compared with non-treated medaka, suggesting a deterioration in renal function. Analyses of an oxidative stress marker in the tissues indicated that lesion progression was associated with increased oxidative stress. Furthermore, a comparison of adverse effect levels suggested that MPs were more toxic to the eyes and reproduction than the kidneys or growth. Our data should prove useful for determining the LOAELs of polyethylene beads on vertebrates and enhance understanding of the mechanism underlying the biological toxicity of polyethylene MPs.

The purpose of the study was to determine Pb and Cd concentrations in humans and to assess the effect of co-exposure to these metals on biomarkers of oxidative stress and nephrotoxicity. Blood and urine levels of Pb and Cd, oxidative stress and urinary renal biomarkers were measured in 77 subjects neighboring a discharge and 52 in the control site. Exposed subjects showed significantly higher levels of lead and cadmium in blood and urine than the controls. Excessive production of reactive oxygen species induced by these metals in exposed subjects conducted to a decrease in antioxidant defense system (GPx, Selenium, GSH) and an increase in lipid peroxidation (MDA). Moreover, changes in markers of nephrotoxicity (high urinary concentrations of total protein, RBP and CC16, as well as GSTα and LDH increased activities) suggested the occurrence of discrete and early signs of impaired renal function for the discharge neighboring population.

The goal of this study was to assess biomarkers of exposure to glyphosate and assess potential associations with renal function in children. Glyphosate is used ubiquitously in agriculture worldwide. While previous studies have indicated that glyphosate may have nephrotoxic effects, few have examined potential effects on kidney function in children. We leveraged three cohorts across different phases of child development and measured urinary levels of glyphosate. We evaluated associations of glyphosate with three biomarkers of kidney injury: albuminuria (ACR), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury marker 1 (KIM-1). Multivariable regression analyses examined associations of glyphosate with kidney injury biomarkers controlling for covariates. We identified glyphosate in 11.1% of the total participants. The herbicide was detected more frequently in the neonate population (30%). Multivariable regression models failed to identify significant associations of log-transformed glyphosate with any of the kidney injury biomarkers, controlling for covariates age, sex, and maternal education. While we confirm detectability of glyphosate in children’s urine at various ages and stages of life, there is no evidence in this study for renal injury in children exposed to low levels of glyphosate. Further studies of larger sample size are indicated to better understand putative deleterious effects of the herbicide after different levels of exposure.

Chronic kidney disease of unknown etiology [CKDu] is a condition characterized by decline in kidney function and is not associated with diabetic nephropathy or hypertensive nephropathy. In this review, we have done a detailed literature analysis on CKDu in India, and then had a comparison with that of Mesoamerica and Sri Lanka. In India, CKDu became the second most common type of CKD after diabetic nephropathy. Silica was seen in the groundwater of both India and Sri Lanka, whereas in Mesoamerica silica exposure through particulate matter was seen among CKDu communities. DDE is a common agrochemical seen in both India and Sri Lanka. The risk factors vary from region to region and it is important to categorize CKDu population based on the risk factors to avoid misinterpretation of the condition as non-CKDu category and to evade further complications. More studies have to be conducted to reveal the detailed pathophysiological mechanisms and its relation with irrational exploitation of environmental resources.

Adolescent females are often environmentally exposed to pesticides by living near agricultural fields, by using pesticides at home, or by having contact with contaminated clothes and pesticide application work tools. This study assessed respiratory, hepatic, renal, and hematological health disorders that might arise due to environmental exposure to pesticides among adolescent females. A cross-sectional study was conducted with 100 adolescent females environmentally exposed to pesticides that had one or more of their family members working as seasonal pesticide applicators and 50 nonexposed (control) adolescent females from Menoufia governorate, Egypt. The studied period of pesticide application season of the cotton crop was from May 1 to September 1, 2017. Participants completed a self-administered questionnaire about pesticide exposure and respiratory, hepatic, renal, and hematological disorders. In addition, serum acetylcholinesterase (AChE), spirometry, complete blood count, and liver and kidney function tests were measured pre and post-pesticide application season. The control adolescent females had a higher AChE activity, a lower prevalence of respiratory symptoms, and higher means of spirometric measurements than the exposed group. During the pre- and postseason, the exposed group presented a prevalence of (6%, 24%) for cough, (4%, 11%) for rhinitis, and (6%, 26%) for dyspnea during the pre and postseason, respectively. In addition, there was a decrease in means of spirometric measurements (FEV₁%, FEV₁/FVC%, FEF ₂₅–₇₅%, and PEF%) in the postseason compared to preseason among the exposed group. Also, there were significant associations between (AChE) activity and both the prevalence of respiratory manifestations and spirometric measurements among the exposed females. On the other hand, there was a statistically significant increase in red blood corpuscle (RBC) and lymphocyte counts, and a statistically significantly lower mean hemoglobin level among the exposed group (postseason) than each of their pre-season values and the control group (P < 0.05). AChE level, total protein, albumin, and albumin/globulin (A/G) ratio levels were statistically significantly lower, while SGPT, SGOT and globulin, blood urea, and serum creatinine mean levels were statistically significantly higher among the exposed group (postseason) than either of their preseason or the control group (P < 0.05). There was a positive correlation between the AChE level and all studied CBC parameters for the exposed group reaching a statistically significant level with basophils (P < 0.05). Also, there was a negative correlation between the AChE level and each of SGPT, SGOT, ALP, globulin, blood urea, and serum creatinine for the exposed group reaching a statistically significant level with each of SGPT and SGOT (P < 0.05). At the same time, a nonsignificant positive correlation was found between AChE level and each of total protein, albumin, and A/G ratio (P > 0.05). So, environmental exposure to organophosphorus pesticides has a detrimental impact on respiratory, hepatic, renal, and hematological systems of adolescent females living in rural districts at the Menoufia governorate. Educational and training intervention programs on pesticide handling and safety precautions are recommended for protecting both pesticide workers and their family members who might be exposed.

Data from National Health and Nutrition Examination Survey for 2003–2016 for US adults aged ≥ 20 years (N = 10,942) were used to study variabilities and associations with urinary albumin creatinine ratio (UACR) in the adjusted concentrations (AGM) of urine bisphenol A (BPA) across various stages of renal function (RF). RF stages considered were RF-1 (eGFR > 90 mL/min/1.73 m²), RF-2 (60 ≤ eGFR ≤ 90 mL/min/1.73 m²), RF-3A (45 ≤ eGFR < 60 mL/min/1.73 m²), and RF-3B/4 (15 ≤ eGFR < 45 mL/min/1.73 m²). Irrespective of gender, race/ethnicity, and smoking status, AGMs for BPA were located on U-curves with point of inflection at RF-2. In general, decreases from RF-1 to RF-2 were followed by increases from RF-2 to RF-3A and from RF-3A to RF-3B/4. For example, AGMs for males were observed to be 1.52, 1.48, 1.61, and 1.69 ng/mL at RF-1, RF-2, RF-3A, and RF-3B/4 respectively. A similar U-curve was observed for those without albuminuria but for those with albuminuria, BPA levels continued increasing until RF-3A before decreasing at RF-3B/4. Severe kidney dysfunction was found to be associated with statistically significantly higher concentrations of BPA in urine. Shape of concentration curves for BPA across RF stages is determined by the balance of actively mediated secretion and reabsorption operating on both sides of renal proximal tubules during each stage of RF. Shape of concentration curves for BPA across various stages of RF was age and concentration dependent. Associations between BPA and UACR were found to be negative (p = 0.02), positive (p = 0.23), negative (p = 0.53), and negative (p < 0.01) respectively at RF-1, RF-2, RF-3A, and RF-3B/4 respectively.

To explore the mechanism of renal toxicity induced by florfenicol (FFC), 120 chicks were randomly divided into 6 groups, 20 in each group. Except for the control group, different doses of FFC (0.15 g/L, 0.3 g/L, 0.6 g/L, 1.2 g/L, and 1.8 g/L) were added to drinking water in the other 5 groups. Five days later, blood was collected from the vein under the wing, and the complete kidneys were obtained as soon as possible, then tested the experimental indicators. The results showed that compared with control group, all doses of FFC significantly reduced the average weight gain of chicks (P < 0.05 or P < 0.01). Except for the 0.15 g/L FFC group, kidney index of chicks in the other doses of FFC groups were significantly increased (P < 0.05 or P < 0.01). The kidney tissues in all FFC groups showed obvious damage, deformities, cell atrophy, and cell gap enlargement. In addition, all doses of FFC significantly increased the contents of uric acid (UA), blood urea nitrogen (BUN), creatinine (CRE) in serum, and malondialdehyde (MDA) in renal tissue (P < 0.05 or P < 0.01), but significantly reduced the levels of glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) in renal tissue (P < 0.05 or P < 0.01). FFC significantly inhibited the mRNA and protein expression levels of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and nicotinamide adenine dinucleotide phosphate: quinone oxidoreductase-1 (NQO-1), and increased the mRNA and protein expression levels of p53, Caspase-3, and Caspase-6 (P < 0.05 or P < 0.01). The apoptotic rate of renal cells in all doses of FFC groups increased significantly (P < 0.05 or P < 0.01). It was concluded that FFC had a certain degree of nephrotoxicity, and with the increase of FFC concentration, the kidney injury of chicks became more and more serious. FFC promoted oxidative stress response in kidney of chicks by inhibiting the expression of related factors in Nrf2-ARE pathway. Moreover, the expression of pro-apoptotic factors was upregulated to improve the apoptosis rate of renal cells, which resulted in excessive apoptosis of renal cells and seriously affected the kidney function of chicks.

Exposure to a single metal has been reported to damage renal function in humans. However, information regarding the association between multiple-metal exposure and markers for early renal impairment in different sexes among the young adult Taiwanese population is scarce. We assessed the association between exposure to arsenic (As), cadmium (Cd), and lead (Pb), and early renal impairment markers using urinary microalbumin (MA), β2-microglobulin (β2MG), and N-acetyl-beta-D-glucosaminidase (NAG) by analyzing 157 young adults aged 20‒29 years, in Taiwan. Inductively coupled plasma mass spectrometry was used to determine urinary As, Cd, and Pb levels. Regression models were applied to different sex groups. The results showed that after adjusting for potential confounding factors and each metal, urinary Cd levels were significantly positively associated with urinary MA (β = 0.523, 95% CI: 0.147–0.899) and β2MG (β = 1.502, 95% CI: 0.635–2.370) in males. However, the urinary Cd level was significantly positively associated with only urinary NAG (β = 0.161, 95% CI: 0.027–0.296) in females. This study thus indicates that the effect of exposure to metals (especially Cd) on early renal impairment among young adults in Taiwan is sex-specific. Our study results could contribute toward developing early intervention programs for decreasing the incidence of renal dysfunction. Further studies are warranted to confirm our findings and clarify the potential mechanisms involved.

This study assessed prophylactic potentials of silymarin against lead-induced hepatorenal toxicity in rats with the respect to its antioxidant and anti-apoptotic activities. Forty male albino rats were distributed into four groups. Control group is provided with distilled water. Lead acetate group was given lead acetate (100 mg/kg bwt) orally for 10 weeks. The third and fourth groups administered silymarin at doses of 50 or 100 mg/kg bwt, respectively, 1 h before administration of lead acetate for 10 weeks. Lead acetate altered liver structure and function that represented by significant elevation of the activities of serum aspartate and alanine aminotransferases and serum levels of urea and creatinine. Hepatic and renal tissues’ malondialdehyde concentrations were increased, while reduced glutathione content and superoxide dismutase and catalase activities were reduced in the lead acetate group. Also, lead acetate increased caspase-3 mRNA expression and inhibited alpha-fetoprotein mRNA expression in hepatic tissues, as well as it altered liver and kidney tissues’ architectures. In contrast, silymarin ameliorated in a dose dependent mannar the toxic effects of lead acetate on the liver and kidneys through modulation of lead acetate which altered liver and kidney function and structures via reducing lipid oxidation and pathological changes of hepatic and renal tissue structure, improving antioxidant defense system of liver and kidneys, and decreasing pro-apoptotic gene expression in hepatic tissue. This study indicated that silymarin ameliorated lead acetate-induced hepatorenal toxicity via its antioxidant and cytoprotective potentials.