Environmental lead exposure has been linked with reduced kidney function. However, evidence about its role in diabetic kidney damage, especially when considering the nutritional status of vitamin D, is sparse. In this observational study, we investigated the association between low-level lead exposure and urinary albumin-to-creatinine ratio (UACR) and assessed potential impact of vitamin D among 4033 diabetic patients in Shanghai, China. Whole blood lead was measured by graphite furnace atomic absorption spectrometry. Serum 25-hydroxyvitamin D [25(OH)D] was tested using a chemiluminescence immunoassay. The associations of blood lead with UACR and albuminuria, defined as UACR ≥30 mg/g, according to 25(OH)D levels were analyzed using linear and Poisson regression models. A doubling of blood lead level was associated with a 10.7% higher UACR (95% CI, 6.19%–15.5%) in diabetic patients with 25(OH)D < 50 nmol/L, whereas the association was attenuated toward null (2.03%; 95% CI, −5.18% to 9.78%) in those with 25(OH)D ≥ 50 nmol/L. Similarly, the risk ratios of prevalent albuminuria per doubling of blood lead level between the two groups were 1.09 (95% CI, 1.03–1.15) and 0.99 (95% CI, 0.86–1.14), respectively. Joint analysis demonstrated that a combination of high blood lead and low 25(OH)D corresponded to significantly higher UACR. Among diabetic patients with 25(OH)D < 50 nmol/L, the increment of UACR relative to blood lead was more remarkable in those with reduced estimated glomerular filtration rate (<60 mL/min/1.73 m²). These results suggested that higher blood lead levels were associated with increased urinary albumin excretion in diabetic patients with vitamin D deficiency. Further prospective studies are needed to validate our findings and to determine whether vitamin D supplementation yields a benefit.

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.

Data (N = 10644) for US adults aged ≥20 years for 2003–2016 from National Health and Nutrition Examination Survey were analyzed to evaluate the impact of co-occurrence of obesity with diabetes, anemia, albuminuria, and hypertension on concentrations of five perfluoroalkyl acids (PFAA), namely, perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorodecanoic acid (PFDA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA). For the total population, males, and females, co-occurrence of obesity with hypertension, albuminuria, anemia, and diabetes was found to be associated with lower adjusted geometric means (AGM) than nonobese for every PFAA. For example for females, for PFOS, AGMs for obese with no diseases, hypertension, albuminuria, anemia, and diabetes were 8.2, 10.8, 5.8, 4.6, and 7.7 ng/mL respectively. In comparison, for PFOS, for nonobese females, AGMs for those with no diseases, hypertension, albuminuria, anemia, and diabetes were found to be 8.9, 13.4, 7.7, 6.0, and 10.2 ng/mL respectively. This implies obesity is associated with higher excretion rates. Females, in general, had lower AGMs than males for both obese and nonobese for every PFAA for every disease group. For example, percent ratios of obese females to males AGMs for PFOA were 66.7%, 87.1%, 88.2%, 70.6%, and 90% for those with no diseases, hypertension, albuminuria, anemia, and diabetes respectively. The ratios of obese to nonobese AGMs for females were lower than males for every PFAA for those with no diseases and hypertension only. For example, for PFOA for those with no diseases, obese to nonobese AGM ratios were 87% for females and 100% for males. Thus, additional excretion of certain PFAAs due to obesity is higher in females than males for those with no diseases and hypertension only.

Concentrations of the pesticide DDT (dichlorodiphenyltrichloroethane) and its metabolite DDE (dichlorodiphenyldichloroethylene), in the blood of Mexican Americans, were evaluated to determine their relationships with diabetes and diabetic nephropathy. The data were derived from the National Health and Nutrition Examination Survey (NHANES) 1999–2004 (unweighted N = 1,411, population estimate = 13,760,609). The sample included teens, 12–19 years old, which accounted for 19.8% of the data. The time of the study overlapped the banning of DDT in Mexico in the year 2000, and those participants born in Mexico were exposed to DDT before they immigrated to the US. We sought to better understand the relationship of DDT with diabetes in a race/ethnicity group prone to develop diabetes and exposed to DDT. In this study, nephropathy was defined as urinary albumin to creatinine ratio >30 mg/g, representing microalbuminuria and macroalbuminuria, and total diabetes was defined as diagnosed and undiagnosed diabetes (glycohemoglobin, A1c ≥ 6.5%). The proportion with the isomer p,p′-DDT >0.086 ng/g (above the maximum limit of detection) was 13.3% for Mexican Americans born in the US, and 36.9% for those born in Mexico. Levels of p,p′-DDT >0.086 ng/g were associated with total diabetes with nephropathy (odds ratio = 4.42, 95% CI 2.23–8.76), and with total diabetes without nephropathy (odds ratio = 2.02, 95% CI 1.19–3.44). The third quartile of p,p′-DDE (2.99–7.67 ng/g) and the fourth quartile of p,p′-DDE (≥7.68 ng/g) were associated with diabetic nephropathy and had odds ratios of 5.32 (95% CI 1.05–26.87) and 14.95 (95% CI 2.96–75.48) compared to less than the median, respectively, whereas p,p′-DDE was not associated with total diabetes without nephropathy. The findings of this study differ from those of a prior investigation of the general adult US population in that there were more associations found with the Mexican Americans sample.

Data from National Health and Nutrition Examination Survey for 2003–2014 for US children aged 6–11 years (N = 2097), adolescents aged 12–19 ears (N = 2642), and adults aged ≥ 20 years (N = 9170) were analyzed to investigate the effects of dietary, demographic, disease, lifestyle, and other factors on concentrations of nine metabolites of polycyclic aromatic hydrocarbons (PAH) in urine. PAHs analyzed were: 1-hydroxynaphthalene, 2-hydroxynaphthalene, 2-hydroxyfluorene, 3-hydroxyfluorene, 9-hydroxyfluorene, 1-hydroxyphenanthrene, 2-hydroxyphenanthrene, 3-hydroxyphenanthrene, and 1-hydroxypyrene. Adults with diabetes were found to have higher adjusted levels of 1-hydroxynaphthalene (4139 vs. 3622 ng/L, p < 0.01) than nondiabetics. Adults with albuminuria had higher adjusted levels of 1-hydroxynaphthalene (4140 vs.3621 ng/L, p < 0.01) and 2-hydroxynaphthalene (6039 vs. 5468 ng/L, p < 0.01) than those without albuminuria. Children with albuminuria had lower adjusted levels of 9-hydroxyfluorene (162 vs. 187 ng/L, p = 0.04), 1-hydroxyphenanthrene (92 vs. 108 ng/L, p < 0.01), and 1-hydroxypyrene (118 vs. 138 ng/L, p < 0.01) than those without albuminuria. The ratios of smoker to nonsmoker adjusted levels for adults varied from a low of 1.4 for 2-hydroxyphenanthrene to a high of 5.6 for 3-hydroxyfluorene. Exposure to environmental tobacco smoke at home was associated with higher levels of most OH-PAHs among children, adolescents, and adults. Consumption of red meat not processed at high temperatures was associated with increased levels of 1-hydroxypyrene (β = 0.00040, p = 0.01), 1-, 2-, and 3-hydroxyphenanthrene, 3-, and 9-hydroxyfluorene. Consumption of red meat processed at high temperatures was associated with increased levels of 2-hydroxynaphthalene (β = 0.00046, p = 0.02) among adults. Consumption of fish processed at high temperatures was associated with decreased levels of 1-hydroxynaphtahlene (β = − 0.00088, p < 0.01), 2-, 3-, and 9-hydroxyfluorene, 1-, 2-, and 3-hydroxyphenanthrene. Among adults, alcohol consumption and caffeine may be associated with increased levels of certain OH-PAHs. Oxidative stress and inflammation associated with exposure to PAHs are associated with albuminuria and have the potential to lead to the development of diabetes.

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.

Melamine and phthalate, mainly di-(2-ethylhexyl) phthalate (DEHP), are ubiquitously present in the general environment. We investigated whether urine melamine levels can modify the relationship between DEHP exposure and markers of early renal damage in children. A nationwide health survey for Children aged ≤12 years possibly exposed to phthalates were enrolled between August 2012 and January 2013. They were administered questionnaires to collect details regarding past DEHP exposure to phthalate-tainted foodstuffs. Urine samples were measured melamine levels, phthalate metabolites and biomarkers of renal damage, including urine microalbumin/creatinine ratio (ACR), N-acetyl-beta-d-glucosaminidase (NAG), and β2-microglobulin. The study included 224 children who had a median urine melamine level (μg/mmol creatinine) of 1.61 ranging 0.18–47.42. Positive correlations were found between urine melamine levels and urine ACR as well as urine NAG levels (both Spearman correlation coefficients r = 0.24, n = 224, p < .001). The higher the past DEHP exposure or urine melamine levels, the higher the prevalence of microalbuminuria. An interaction effect was also found between urine melamine levels and past DEHP exposure on urine ACR. Melamine levels may further modify the effect of past DEHP exposure on urine ACR in children.

Exposures to cadmium and lead can cause oxidative stress, leading to tissue damage resulting in kidney and cardiovascular diseases. The antiaging protein klotho, on the other hand, is known to act as an anti-oxidative agent. How klotho homeostasis interacts with exposure to cadmium and lead has not been reported. Thus, this study was carried to investigate associations of serum klotho with blood and urine cadmium and lead in US adults aged 40–79 years across stages of eGFR-based kidney function and albuminuria defined as urinary albumin/creatinine ratio of > 30 mg/g creatinine. As long as the kidney function was normal (eGFR ≥ 90 mL/min/1.73 m²) or near normal (60 ≤ eGFR < 90 mL/min/1.73 m²), there was no evidence of an association between cadmium exposure and klotho concentrations irrespective of the presence/absence of albuminuria. During kidney dysfunction (15 ≤ eGFR < 60 mL/min/1.73 m²), 10% increases in blood cadmium concentrations resulted in decreases in klotho concentrations between 0.27 and 0.84%. In addition, during severe kidney dysfunction (15 ≤ eGFR < 45 mL/min/1.73 m²), a positive association between urine cadmium and serum klotho concentrations was observed. In the absence of albuminuria and when kidney function was normal or near normal, 10% increases in blood lead concentrations were observed to be associated with modest decreases between 0.28% and 0.37% in serum klotho concentrations. Similar results were observed between the concentrations of urine lead and serum klotho during kidney dysfunction.

Data from the National Health and Nutrition Examination Survey (N = 6141) for the years 2003–2016 for US adults were analyzed to evaluate the impact of glomerular hyperfiltration on the observed concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorodecanoic acid, perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) for several disease groups. Hyperfiltrators were defined as having an estimated glomerular filtration rate (eGFR) ≥ 110 mL/min/1.73 m², and normal filtrators were defined as those having an eGFR between 90 and 110 mL/min/1.73 m². The seven disease groups for which the data were analyzed were as follows: those (i) without any diseases; (ii) with hypertension only; (iii) with albuminuria only; (iv) with anemia only; (v) with diabetes only; (vi) with hypertension and one or more of diabetes, anemia, and albuminuria; and (vii) with two or more of diabetes, anemia, and albuminuria without hypertension. For almost every PFAA, for all seven disease groups except the albuminuria only group, hyperfiltrators had lower adjusted geometric means (AGM) than normal filtrators. For example, for the disease group with hypertension only, for PFOS, the AGMs for hyperfiltrators and normal filtrators were 8.3 and 10.6 ng/mL, respectively, for the total population. For the group with albuminuria only, normal filtrators were found to have higher AGMs than hyperfiltrators for the total population and males. For example, for PFHxS, the AGMs for normal and hyperfiltrators were 0.98 and 1.05 ng/mL, respectively, for the total population. For females, these AGMs for normal and hyperfiltrators were 0.96 and 0.86 ng/mL respectively. Males usually had higher AGMs than females, but the reverse was also true occasionally. Usually, male–female differences were substantially narrower for normal filtrators than hyperfiltrators. Irrespective of the filtration status, the disease group with hypertension only had the highest AGMs for every PFAA. AGMs for the anemia only group were the lowest for every PFAA as compared with other disease groups among hyperfiltrators.

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.