The Association Between Environmental Cadmium Exposure and Parathyroid Hormone Levels.

Cadmium exposure is associated with renal dysfunction and bone damage. Chronic kidney disease and bone loss are also related to parathyroid hormone (PTH). However, whether cadmium exposure affect PTH level is not completely understood. In this study, we observed the association between environmental cadmium exposure and PTH levels in a Chinese population. A ChinaCd study was performed in China in 1990s which included 790 subjects living in heavily, moderately and low cadmium polluted area. 354 of them (121 men and 233 women) also had the data of serum PTH. The cadmium levels in blood (BCd) and urine (UCd) were determined by flame atomic absorption spectrometry. Serum PTH was detected by immunoradiometric assay. Renal function was assessed based on urinary N-acetyl-ß-d-glucosaminidase (UNAG), ß2-microglobulin (UBMG) and urinary albumin (UALB). The median BCd and UCd levels were 4.69 µg/L and 5.50 µg/g creatinine. The BCd, UCd, UNAG, UBMG and UALB levels in subjects with low PTH (< 5.0 ng/L) were significantly higher than those with PTH ≥ 5.0 ng/L (p < 0.05 or p < 0.01). Spearman correlation analysis also showed that UCd level was negatively correlated to PTH levels (r = -0.17, p = 0.008) in women. A weak correlation was also observed between PTH level and BCd in women (r = -0.11, p = 0.09) and UBMG in total population (r = -0.114, p = 0.07). Univariable and mutivariable logistic regression analysis both demonstrated that high BCd (> 10 µg/L) (odds ratio (OR) = 2.26, 95% confidence interval (CI):1.10-4.63; OR = 2.36, 95%CI: 1.11-5.05) and UCd level (> 20 µg/g cr) (OR = 2.84, 95% CI:1.32-6.10; OR = 2.97, 95%CI: 1.25-7.05) were associated with high risk of low PTH. Our data showed that environmental cadmium exposure was associated with low PTH level.

The association between hemoglobin level and osteoporosis in a Chinese population with environmental lead and cadmium exposure.

Low hemoglobin (Hb) level or anemia is associated with osteoporosis and bone fracture. Cadmium (Cd) and lead (Pb) exposure are also risk factors of osteoporosis and anemia. However, the role of anemia in Cd/Pb related bone loss remains unclear. The aim of present study was to investigate the association between Hb level and bone loss in a population with environmental lead and cadmium exposure. One hundred and ninety-four women and 108 men with different levels of Cd/Pb exposure were included in our study. The Cd/Pb exposure was determined using graphite-furnace atomic absorption spectrometry. Forearm bone mineral density (BMD) was determined by peripheral dual-energy X-ray absortiometry. Hb concentration was determined using an automatic blood cellcounter. A logistic model was established to predict the risk of osteoporosis. The BMDs of women that had the highest quartile BCd and BPb were markedly lower than that with the lowest quartile (p < 0.05). The BMD and the prevalence of osteoporosis in men with anemia were lower and higher than that with normal Hb (p < 0.05), respectively. In men, age, BPb and anemia were independent risk factors for osteoporosis. The odds ratio (OR) of men with anemia was 11.28 (95%confidence interval (CI):1.94-65.54) and 19.56 (95%CI: 2.98-128.78) compared to those with normal Hb after adjusting for potential cofounders. No such association was found in women. The area under the curve was 0.88 (95%CI: 0.82-0.96) in predicting osteoporosis using the logistic model in men. Linear discriminant analysis also showed that 90.7% of osteoporosis was correctly classified. Our data show that anemia is associated with incident of osteoporosis in men but not in women that environmentally exposed to Pb and Cd.

The Association Between Cadmium Exposure and Osteoporosis: A Longitudinal Study and Predictive Model in a Chinese Female Population.

Objective: The association between cadmium exposure and osteoporosis has been rarely reported in longitudinal studies. In this study, we investigated the association between osteoporosis and cadmium exposure and developed predictive models in women in a longitudinal cohort. Materials and Methods: In total, 488 women living in southeastern China were included at baseline (1998). Cadmium in blood (BCd) and urine (UCd) and also renal dysfunction biomarkers and bone mineral density (BMD) were determined both at baseline and follow-up. A total of 307 subjects were finally included after excluding subjects that did not have exposure or effect biomarkers. Osteoporosis was defined based on T score ≤ -2.5. Multiple linear regression and multivariate logistic analysis were used to show the association between baseline data and follow-up osteoporosis. Based on the identified associated factors, nomograms were developed to graphically calculate the individual risk of osteoporosis. Results: The baseline BMD in subjects with osteoporosis was significantly lower than that in subjects without osteoporosis (0.59 vs. 0.71 g/cm2, p < 0.05). The prevalence of low bone mass at baseline was higher in subjects with osteoporosis than in those without osteoporosis (23.5 vs. 7.2%, p = 0.001). Logistic regression analysis demonstrated that age [odds ratio (OR) = 1.21, 95% confidence interval (CI): 1.16-1.27], UCd (OR = 1.03, 95% CI: 1.002-1.06) and the presence of low BMD (OR = 3.84, 95% CI: 1.49-9.89) were independent risk factors for osteoporosis. For those subjects with normal baseline BMD, age, UCd, and baseline BMD were also independent risk factors for osteoporosis. The OR value was 1.16 (95% CI: 1.10-1.22) for age, 2.27 (95% CI: 1.03-4.99) for UCd > 10 µg/g creatinine, and 0.39 (95% CI: 0.21-0.72) for BMDbaseline. We developed two nomograms to predict the risk of osteoporosis. The area under the curve was 0.88 (95% CI: 0.84-0.92) for total population and was 0.88 (95% CI: 0.84-0.92) for subjects with normal baseline BMD, respectively. Conclusion: Baseline age, UCd, and BMD were associated with follow-up osteoporosis in women. Nomograms showed good performance in predicting the risk of osteoporosis.

The effects of fermented rye products on gut microbiota and their association with metabolic factors in Chinese adults - an explorative study.

Rye is among the cereals with the highest content of dietary fibre. A high rye food intake has been associated with improved metabolic risk factors in some but not all observational and intervention studies. Whole-grain rye has also been suggested to affect the gut microbiota in individuals with metabolic syndrome. However, it is yet unclear to what extent effects on the gut microbiota mediate the beneficial metabolic responses of whole-grain rye intake. We hypothesized that a high intake of whole grain rye products containing fermented rye bran (FRB) vs. refined wheat based products (RW) could alter the gut microbiota and short-chain fatty acid (SCFA) composition towards a phenotype associated with beneficial metabolic effects in a population not used to such foods. For this purpose, we conducted a post hoc analysis of a 12-week randomized controlled trial in Chinese adults with Helicobacter pylori (HP) infection, with 53 participants consuming RW and 31 participants consuming FRB included in the analysis. Anthropometric measurements and fasting blood and fecal sample analyses as well as 13C-urea breath test were performed at baseline and after a 12-week intervention. At week 12, we observed a higher serum insulin concentration (P-value = 0.038) in the FRB group (n = 31) versus the RW group (n = 53), and this difference was corroborated with alterations in the genus-level relative abundances of the gut microbiota, represented by an increase in Romboutsia and a reduction in Bilophila in the FRB group (n = 22) versus the RW group (n = 46). Compared to the RW group (n = 53), fecal acetic acid concentration was significantly higher in the FRB group (n = 31) at week 12. We also found that fecal acetic and butyric acids positively, while isobutyric, isovaleric and 2-methylbutyric acids inversely, correlated with the gut Romboutsia level among all participants (n = 68) at week 12. We found positive correlations of fecal isobutyric, isovaleric and 2-methylbutyric acids with gut Bilophila (n = 68). In conclusion, our results suggest that the intake of high-fibre rye products could modify gut Romboutsia and Bilophila in a Chinese population with HP infection. These effects are paralleled with favorable modifications of the SCFA concentration and are associated with altered glycemic traits.

The association between estimated glomerular filtration rate and cadmium exposure: An 8-year follow-up study.

BACKGROUND: The associations between cadmium exposure and chronic kidney disease have rarely been reported in longitudinal studies. In this study, we investigated the associations between the estimated glomerular filtration rate and cadmium exposure in a cross-sectional study in a longitudinal cohort. MATERIALS AND METHODS: In total, 790 subjects (≥35 years of age) living in southeastern China were included at 1998. Cadmium in blood (BCd) and urine (UCd) as well as renal dysfunction biomarkers, urinary N-acetyl-ß d-glucosaminidase (UNAG) and albumin (UALB), were determined. 497 subjects were followed at 2006 and a total of 456 subjects were finally included after excluding subjects that did not have exposure or effects biomarkers. The BCd, UCd, UNAG and UALB were determined using baseline methods. At follow-up, the estimated glomerular filtration rate (eGFR) was computed using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Single nucleotide polymorphisms (SNPs) in metallothioneins 1A (MT1A) rs11076161 and MT2A rs28366003 in blood sample were detected using TaqMan allelic discrimination assays. RESULTS: The median of UCd and BCd at baseline was 5.38 µg/g cr and 4.69 µg/L, respectively, and the median UCd and BCd at follow-up was 4.88 µg/g cr and 2.20 µg/L at follow-up. The mean eGFR at follow-up was 88.0 mL/min/1.73 m2 and 15 subjects had new onset of eGFR <60 mL/min/1.73 m2. The eGFR at follow-up was associated with baseline age (ß = -0.66, 95% confidence interval (CI): 0.80 to -0.52), BCd (ß = -0.46, 95% CI: 0.68 to -0.25) and UALB (ß = -0.29, 95% CI: 0.41 to -0.16) after adjusting for confounders. Subgroup analysis in subjects who had low baseline UALB or subjects with or without hypertension showed similar results. A logistic regression model further showed that baseline BCd and UALB were independent risk factors for follow-up CKD. The odds ratios (ORs) were 1.09 (95% CI:1.03-1.16) for UALB, 1.16 (95% CI:1.01-1.33) for BCd, and 6.74 (0.87-29.63) for current hypertension. Baseline BCd, UALB and current hypertension were used to construct the nomogram. Linear discriminant analysis (LCA) showed that 87.6% of CKD was accurately predicted based on the three factors. CONCLUSION: Baseline age, BCd and UALB were associated with follow-up eGFR, and baseline BCd and UALB were predictive factors for incidence of CKD.

The association between life-time dietary cadmium intake from rice and chronic kidney disease.

The association between internal cadmium exposure and chronic kidney disease (CKD) has been investigated before. However, few studies have shown the association between dietary cadmium intake and CKD. In this study, we show the association between life-time dietary cadmium intake and CKD based on a follow-up study. At baseline, we collected blood and urine samples for assays of cadmium and renal effect biomarkers. A questionnaire and food survey was given to each subject to collect diet and lifestyle information for the estimation of cadmium intake. Dietary cadmium, cadmium in blood and urine were regarded as exposure markers. Life-time dietary cadmium intake was estimated based on an individual's daily cadmium intake and exposure time. At follow-up, 467 persons (163 men and 304 women) were finally included. CKD at follow-up was considered if the estimated glomerular filtration rate (eGFR) was less than 60 mL/min/1.73 m2. The eGFR level in subjects in the highest quartile of total dietary cadmium intake (>9.34 g) was significantly lower than in those with a moderate or low intake (p < 0.01). eGFR was negatively associated with total dietary cadmium intake (ß = -0.42, 95% confidence interval (CI): -0.77 to -0.07) after adjustment with confounders. Logistic regression further showed that the risk of CKD in subjects with a high total dietary cadmium intake (>2.2 g) was higher than in those with a low intake (odds ratio (OR) = 18.16, 95%CI: 1.75-188.85). A similar association was found between the baseline urinary albumin (UALB) level and CKD incidence. A predictive model based on UALB and life-time dietary cadmium intake showed an acceptable performance (the area under the curve was 0.77 (95%CI: 0.65-0.88)). Our data show that high dietary cadmium exposure was associated with CKD after controlling for renal tubular dysfunction and internal cadmium exposure.

Nomogram to Predict Cadmium-Induced Osteoporosis and Fracture in a Chinese Female Population.

Cadmium exposure may increase the risk of osteoporosis. However, there is no quick method to get bone mineral density (BMD) unless dual-energy X-ray absorptiometry (DXA) examinations were performed. In the present study, we aimed to identify associated factors to osteoporosis and fracture in a Chinese female population with cadmium exposure and develop nomograms to predict the risk. A total of 488 women was included in this study. Cadmium in blood (BCd) and urine (UCd) were determined as exposure biomarkers. BMD was determined using single-photon absorptiometry. Urinary N-acetyl-ß-d-glucosaminidase (UNAG) and urinary albumin (UALB) were determined as renal function biomarkers. Osteoporosis was defined if T-score < - 2.5. Multiple logistic regression showed that age, BCd, and menopausal status were independent risk factors for osteoporosis. The odds (OR) value was 1.19 (95% confidence interval (CI): 1.14-1.25) for age, 1.05 (95% CI: 1.004-1.10) for BCd, and 4.75 (95% CI: 1.65-13.69) for menopausal status after adjusting with cofounders. Age and UCd were the independent risk factors for bone fracture. Nomograms were developed based on the associated factors. Age was the main determinant for osteoporosis or fracture. Receiver operating curve showed acceptable performance in predicting osteoporosis (area under the curve (AUC) = 0.93, 95CI: 0.90-0.96) and fracture (AUC = 0.67, 95% CI: 0.58-0.75). Linear discriminant analysis (LDA) further showed that 88.9% of osteoporosis and 68.4% of fractures were correctly classified. Our study develops nomograms that may be used to predict cadmium-induced osteoporosis or fracture if BMD data is not available.

A nomogram to predict cadmium-induced renal tubular dysfunction.

Cadmium-induced renal dysfunction varies between individuals. It would be valuable to figure out those susceptible individuals or predict the risk of cadmium induced renal dysfunction. In the present study, we used a nomogram model to identify high-risk of cadmium-induced renal tubular dysfunction. 342 subjects living in low and moderately cadmium polluted areas were included in this study. The daily cadmium intake from food (FCd) was estimated using food survey. The cadmium in blood (BCd) and urine (UCd) were detected by using flame atomic absorption spectrometry. Urinary ß2Microglobulin (UBMG) was chosen as indicator of renal dysfunction. Logistic regression was used to select the independent risk factors for renal dysfunction. Bootstrap self-sampling and calibration curves were performed to quantify our modeling strategy. Age, sex, BCd and TCd were used to construct the nomogam in total population; age, BCd and TCd were adopted in women; age and BCd were used in men. The internal validation showed the C-index was 0.76 (95% 47 confidence interval (CI): 0.71-0.82) in total population, 0.74 (95% CI: 0.69-0.79) in men and 0.78 (95% CI: 0.72-0.84) in women. The area under the curve of the nomogram was 0.77 (95% CI: 0.71-0.83) in total population, 0.82(95% CI: 0.74-0.90) in women and 0.74(95% CI: 0.66-0.82) in men. Nomogram may be a rapid and simple risk assessment tool for predicting high-risk of renal tubular dysfunction in subjects exposed cadmium.

A nomogram for predicting the renal dysfunction in a Chinese population with reduction in cadmium exposure based on an 8 years follow up study.

Cadmium exposure is associated with renal dysfunction. However, the outcome of renal function in subjects who have had a reduction in cadmium exposure for years has not been completely clarified, particularly for individuals with normal baseline renal function. In this study, we used a nomogram model to predict renal dysfunction after a reduction in cadmium exposure in subjects with normal baseline renal function. In 1998, a survey was performed in 790 subjects living in control and cadmium-polluted areas. A total of 497 subjects was followed up in 2006. 404 subjects with normal baseline urinary ß2-microglobulin (UBMG), 373 subjects with normal baseline urinary N-acetyl-ß-d-glucosaminidase (UNAG) and 407 subjects with normal baseline urinary albumin (UALB) were included in this analysis. Cadmium in the blood (BCd) and urine (UCd) was detected using graphite-furnace atomic absorption spectrometry. A logistic regression model was used to identify potential predicting factors of renal function at follow-up. Nomograms were developed based on those predictive factors. Bootstrap self-sampling, calibration curves and receiver operating characteristic (ROC) curves were performed to quantify our modeling strategy. Adjusted and unadjusted logistic regression models both showed that age, BCd and UBMG or UNAG at baseline were independent risk factors for renal tubular dysfunction. Baseline age, sex, BCd and UNAG or UBMG or UALB were used to construct the nomogam. The internal validation showed that the C-index was 0.70-0.74 for predicting renal dysfunction. The area under the curve of the nomogram was 0.70-0.74. Decision curve analysis verified the predictive value of the nomogram. A nomogram may be a useful risk assessment tool for predicting the progress of renal function in a cadmium-exposed population with normal baseline kidney function.

The Association Between Alcohol Consumption and Renal Tubular Dysfunction Induced by Cadmium Exposure.

Alcohol consumption is inversely associated with the risk of chronic kidney diseases. However, this association has not been reported in populations exposed to cadmium. In the present study, we examined the association between alcohol consumption and renal tubular dysfunction in populations living in cadmium-polluted areas. A total of 446 subjects (170 men and 276 women) were finally included in our analysis. The urinary cadmium (UCd) and cadmium in blood (BCd) were determined as the exposure biomarkers. Urinary N-acetyl-ß-D-glucosaminidase (UNAG) and ß2-microgloblin (UBMG) were measured as renal indicators. Alcohol drinking patterns were obtained from a questionnaire and divided into four categories: non-drinking, light drinking (< 3 drinks/week), moderate drinking (3-7 drinks/week), and heavy drinking (> 7 drinks /week). If UNAG was the indicator of renal dysfunction, the prevalence of renal tubular dysfunction was decreased in subjects with alcohol consumption both in men (χ2 = 8.5, p < 0.01) and women (χ2 = 8.3, p < 0.01). The odds ratio (OR) of subjects with light and moderate alcohol drinking was 0.31 (95% confidence interval (CI), 0.1-0.99) and 0.30 (95%CI, 0.1-0.96), respectively, compared with those of non-drinkers after adjusting with the confounders in men. Similar results were observed in women with light drinking (OR = 0.33, 95%CI, 0.15-0.70). Similar trends were observed in those subjects with high BCd (> 3.0 µg/L) or UCd (> 5.0 µg/g creatinine). Our data show that alcohol consumption is inversely associated with cadmium-induced renal tubular dysfunction.

The association between lead and cadmium co-exposure and renal dysfunction.

Both cadmium (Cd) and lead (Pb) exposure can induce kidney damage. However, the effects of combined exposure to Cd and Pb on renal function at environmental levels have not been fully clarified. In this study we investigated the renal function in a Chinese population co-exposed to Cd and Pb. A total of 331 subjects (215 women and 116 men), living in either a control or a polluted area, were included in this study. Cd and Pb in blood and urine (BCd, BPb, UCd, and UPb), and kidney effect markers including urinary N-acetyl-ß-D-glucosaminidase (UNAG) and estimated glomerular filtration rate (eGFR), were determined, and the association between exposure markers and renal effect biomarkers were analyzed. The exposure levels in the polluted area were significantly higher than in the control area (all p < 0.01). The eGFR of subjects in the polluted area was decreased compared with that in the control area (p < 0.01). The subjects with high BCd/BPb (BCd ≥ 2 µg/L, BPb ≥ 100 µg/L) or high UCd/UPb (UCd ≥ 3 µg/g creatinine, UPb ≥ 10 µg/g creatinine) showed higher UNAG and UALB levels compared with other subgroups (p < 0.01). The probability of having elevated UNAG in subjects with high BCd/BPb was greater than those with low BCd/BPb [odds ratio (OR) = 2.6, 95% confidence interval (CI): 1.4-4.7), low BCd/high BPb (OR =3.1, 95% CI: 1.4-6.6), and high BCd/low BPb (OR = 1.7, 95% CI: 0.9-3.2). The OR of subjects with low UCd and high UPb, high UCd and low UPb, and high UCd/UPb were 2.9 (95% CI: 1.4-5.7), 3.3 (95% CI: 1.5-7.2), and 7.7 (95% CI: 4.0-14.7), respectively, compared with those with low UCd/UPb. The risk of decrease in eGFR was also higher in subjects with high UCd/UPb than for those with low UCd/UPb (OR = 7.2, 95% CI: 0.8-62.2). Our data demonstrate that Cd and Pb exposure, alone or in combination, are associated with renal impairment. In addition, co-exposure to Pb and Cd propagates the renal tubular dysfunction compared with Cd or Pb exposure alone.

The association between cumulative cadmium intake and osteoporosis and risk of fracture in a Chinese population.

Bone is one of the target organs for cadmium toxicity. However, few studies have shown the association between cumulative cadmium intake and prevalence of osteoporosis and bone fracture. In the present study, we evaluated the association between cumulative cadmium intake and osteoporosis and risk of fracture in a Chinese population. A total of 790 subjects (488 women and 302 men) living in a control area and two cadmium-polluted areas were included. The cumulative cadmium intake was estimated by a food survey. The bone mineral density was determined by using single-photon absorptiometry. The cumulative cadmium intakes were 0.48, 2.14, and 11.00 g for men, and 0.42, 2.11, and 11.12 g in women in control, and moderately and heavily polluted areas, respectively. In women, the odds ratios (ORs) of subjects with a cadmium intake between 2.21 and 10.63 g and >10.63 g were 1.30 (95% CI: 0.58-2.94) and 2.36 (95% CI: 1.14-5.16), compared with those with a cadmium intake < 0.58 g after adjusting to the confounders for osteoporosis. The ORs of subjects with a cadmium intake >10.63 g were 2.34 (95% CI: 1.23-4.38) for all of the women and 2.62 (95% CI: 1.02-5.58) in women ≥ 60 years old, compared with those with a cadmium intake <10.63 g after adjusting to the confounders for bone fractures. In men, similar trends were observed, but no statistical significance was found. In addition, those subjects with renal tubular dysfunction showed high risk of bone fracture. Our results indicate that a high level of cumulative cadmium intake is associated with an increased rate of osteoporosis and fractures among women.

The benchmark dose estimation of reference levels of serum urate for gout.

Hyperuricemia is the main risk factor for gout. Although the threshold of hyperuricemia has been recommended, the reference levels of serum urate for gout have not been clarified. In the present study, we estimated the reference levels of serum urate for gout. A study has shown the association between serum urate and incidence of gout during 5-15 years of follow-up. We calculated the reference levels of serum urate for gout based on the previous published data by using the benchmark dose (BMD) method. The subjects were divided into six groups according to serum urate levels (6.0, 6.5, 7.5, 8.5, 9.5, and 10 mg/dL). Gamma, LogLogistic, and LogProbit models were used in BMD calculation. If the benchmark response (BMR) was set at 5%, the 95% lower confidence bounds of BMD (BMDL) of serum urate for the total population were 8.09-8.14 mg/dL during 5 years of follow-up, 7.27-7.30 mg/dL during 10 years of follow-up, and 6.73-6.99 mg/dL during 15 years of follow-up. If the BMR was set at 1%, the BMDL further decreased by 1.4 mg/dL. They were 6.68-6.85 mg/dL, 5.97-6.03 mg/dL, and 5.25-5.36 mg/dL, respectively. Similar results were observed in men and women. A threshold of 7.0 mg/dL of serum urate may be not a sufficient goal for protection against gout. A stricter threshold of serum urate (< 6.0 mg/dL) should be made.

The association between dietary cadmium exposure and renal dysfunction - the benchmark dose estimation of reference levels: the ChinaCad study.

The tolerable dietary intake of cadmium was recommended at provisional tolerable monthly intake of 25 µg kg-1 body weight. However, several studies indicated that this tolerable level should be re-evaluated for sufficient health protection. In this study, we show the reference levels of dietary cadmium intake for renal dysfunction by using a benchmark dose (BMD) approach. A total of 790 subjects (302 men and 488 women) living in control and cadmium-polluted areas were included. The dietary cadmium intake was estimated by a food survey. Blood cadmium, urinary cadmium and renal function markers (microalbuminuria, N-acetyl-ß-d-glucosaminidase [NAG] and its isoform B [NAGB], ß2 -microglobulin and retinol binding protein) in urine were measured. We calculated the 95% lower confidence bounds of BMD (BMDLs) of cumulative cadmium intake. In control and two polluted areas, the median cumulative cadmium intake was 0.5, 2.1 and 11.1 g. The odds ratio of the intermediate (1.0-3.0 g), second highest (3.0-11.0 g) and the highest cumulative cadmium intake (>11.0 g) compared with the lowest cumulative cadmium intake (<1.0 g) were 2.8 (95% CI: 1.4-5.8), 8.1 (95% CI: 3.8-17.2) and 11.4 (95% CI: 6.5-26.4) for urinary NAG and 6.6 (95% CI: 3.2-13.8), 14.8 (95% CI: 6.8-32.2) and 22.5 (95% CI: 10.7-47.5) for urinary NAGB. The BMDLs of cumulative cadmium intake were 1.1-1.2 g (benchmark response [BMR] = 5%) for urinary NAG, and were 0.7-0.9 g (BMR = 5%) for urinary NAGB, and were 1.3-1.4 g (BMR = 5%) for urinary ß2 -microglobulin. The BMDLs of cumulative cadmium intake in a Chinese population were lower than the critical standard previously reported. Further evaluations are needed for sufficient health protection.

The references level of cadmium intake for renal dysfunction in a Chinese population.

Recent several studies indicated that a more restrictive dietary intake guideline for cadmium should be made for sufficient health protection. In the present study, we showed the references level of food cadmium intake (FCd) and total cadmium intake (TCd) for renal dysfunction by using benchmark dose (BMD) approach. 342 subjects living in a control and a cadmium polluted area were included in this study. The FCd, TCd and cadmium in urine (UCd) and blood (BCd) were calculated or determined. Urinary ß2Microglobulin (UBMG) was determined as indicator of renal function. The median FCd, TCd, UCd and BCd were 1.4 g, 1.4 g, 3.1 µg/g creatinine(cr) and 1.3 µg/L in control and 3.3 g, 3.6 g, 13.5 µg/g cr and 12.1 µg/L in polluted area. The 95% lower confidence bounds of BMD (BMDLs) of FCd for renal dysfunction were 1.36-1.55 g (BMR = 10%) and 0.88-1.11 g (BMR = 5%). The BMDLs of TCd were 1.29-1.46 g (BMR = 10%) and 0.73-0.95 g (BMR = 5%). FCd and TCd are valuable markers for the predication of renal dysfunction induced by cadmium. The BMDLs of FCd were close to previous report in Japan and the BMDLs of TCd were lower than the critical standard previously reported, in particular at BMR of 5% which can be interpreted as representing the influence of smoking.

The association between serum vitamin D levels and renal tubular dysfunction in a general population exposed to cadmium in China.

Cadmium exposure can cause renal tubular dysfunction. Recent studies show that vitamin D can play multiple roles in the body. However, the association between serum vitamin D levels and renal tubular dysfunction in a general population exposed to cadmium has not been clarified. We performed study to assess the effects of cadmium on serum 25(OH) D levels and the association between serum 25(OH) D levels and renal tubular dysfunction in a population environmentally exposed to cadmium. A total of 133 subjects living in control area and two cadmium polluted areas were included in the present study. Cadmium in urine (UCd) and blood (BCd), urinary ß2Microglobulin (UBMG), urinary retinol binding protein (URBP) and serum 25 (OH) D were determined. Logistic regression was used to estimate the association between 25 (OH) D and prevalence of renal tubular dysfunction. No significant differences were observed in serum 25(OH) D levels among the four quartile of UCd and BCd after adjusting with cofounders. After adjusted with the confounders, the odds ratio (OR) of subjects with 25(OH) D ≥ 40 ng/ml were 0.20 (95%CI: 0.1-0.8) if UBMG was chosen as indicators of renal dysfunction and 0.28 (95%CI: 0.1-1.1) if URBP was chosen as indicators of renal dysfunction, compared with those with 25(OH) D < 30 ng/ml, respectively. Similar results were observed in those subjects living in cadmium polluted areas or with high level of UCd or BCd. Our data indicated that cadmium exposure did not affect serum 25(OH) D level and high 25 (OH) D levels were associated with a decreased risk of renal tubular dysfunction induced by cadmium.

The Association Between Renal Tubular Dysfunction and Zinc Level in a Chinese Population Environmentally Exposed to Cadmium.

Studies in vivo and in vitro have shown a protective effect of zinc against renal dysfunction caused by cadmium exposure. However, limited human data is available. In this study, we evaluated the association between renal tubular dysfunction and body zinc burden in a Chinese population exposed to cadmium. A total of 331 subjects (170 women and 161 men) living in control and cadmium-polluted area were included. Blood cadmium (BCd), urinary cadmium (UCd), serum zinc (SZn), zinc in hair (HZn), Zn/Cd ratio, and urinary ß2Microglobulin (UBMG) were measured. The median UCd, BCd, SZn, and HZn were 2.8 and 13.6 µg/g cr, 1.3 and 12.2 µg/L, 1.31 and 1.12 mg/L, and 0.14 and 0.12 mg/g in subjects living in control and polluted areas. The UBMG level of subjects living in the polluted area was significantly higher than that of the control (0.27 vs 0.11 mg/g cr, p < 0.01). SZn, HZn, and Zn/Cd ratios were negatively correlated with UBMG (p < 0.05 or 0.01). Subjects with high SZn concentrations (≥ 1.62 mg/L) had reduced risks of elevated UBMG [(odds ratio (OR) = 0.26, 95% confidence interval (CI) 0.07-0.99)] after controlling for multiple covariates compared with those with lower zinc levels. A similar result was observed in subjects with high HZn (OR = 0.09, 95% CI 0.02-0.48). The ORs of the second, third, and fourth quartiles of Zn/Cd ratio were 0.40 (95% CI 0.19-0.84), 0.14 (95% CI 0.06-0.37), and 0.01 (95% CI 0.02-0.18) for renal dysfunction compared with those of the first quartile, respectively. For those subjects with high level of UCd, high level of SZn and HZn also had reduced risks of elevated UBMG. The results of the present study show that high zinc body burden is associated with a decrease risk of renal tubular dysfunction induced by cadmium. Zinc nutritional status should be considered in evaluating cadmium-induced renal damage.

Effects of Cadmium Exposure on Age of Menarche and Menopause.

Cadmium exposure can cause several adverse health effects. Animal studies have also shown that cadmium exposure can affect menarche or menopause. However, data is limited in humans. We conducted a retrospective study to assess whether cadmium exposure was associated with different ages of menarche and menopause in a Chinese population. A total of 429 women living in control (n = 137) and two cadmium-polluted areas (n = 292) were included in this study. A total of 223 and 206 subjects were included in the analysis for menarche and menopause, respectively. The median menarche age of population living in the heavily cadmium-polluted area was significantly younger than those in the control area (14.0 vs. 15.0, p < 0.01). Logistic regression showed that the odds ratio (OR) of early occurrence of menarche (<13 years) in the population living in the heavily polluted area and moderately polluted area was 3.7 (95% confidence interval (CI): 1.5-9.7) and 1.3 (95% CI: 0.7-2.6) compared with control, respectively. No significant difference was observed in the age of menopause in the population of these three areas. In conclusion, our data indicated that cadmium exposure may cause early menarche.

Effects of lead and cadmium co-exposure on hemoglobin in a Chinese population.

Cadmium (Cd) and lead (Pb) show adverse effects on hemoglobin. But most studies are focussed on one single agent. In this study, we observed the main and interactive effects of Cd and Pb on the hemoglobin level in a Chinese population. A total of 308 persons (202 women and 106 men), living in controlled and polluted areas, were included in this study. Blood and urine were collected to determine the levels of hemoglobin (Hb), Cd, Pb, and urinary N-acetyl-ß-D-glucosaminidase (UNAG). The Cd and Pb level of subjects living in the polluted area were significantly higher compared to those living in the control area (p<0.05). The level of hemoglobin was declined with the increasing BPb (p<0.05) and BCd in women. The Hb of women and men with the highest level of BCd and BPb were decreased by 8.3g/L and 10.7 g/L compared to those with the lowest level of BCd and BPb, respectively. The Hb level of those women and men with the highest level of UNAG decreased by 4.2g/L and 17.2g/L compared with those with low level of UNAG, respectively. Hb was negatively associated with BPb, BCd, and UNAG. This study evidenced that Cd and Pb can influence Hb level. In addition, our study shows that Cd and Pb may have interactive effects on Hb and Hb level was correlated with tubular dysfunction caused by Cd and Pb exposure.