The Effect of Cadmium on GFR Is Clarified by Normalization of Excretion Rates to Creatinine Clearance.

Erroneous conclusions may result from normalization of urine cadmium and N-acetyl-ß-D-glucosaminidase concentrations ([Cd]u and [NAG]u) to the urine creatinine concentration ([cr]u). In theory, the sources of these errors are nullified by normalization of excretion rates (ECd and ENAG) to creatinine clearance (Ccr). We hypothesized that this alternate approach would clarify the contribution of Cd-induced tubular injury to nephron loss. We studied 931 Thai subjects with a wide range of environmental Cd exposure. For x = Cd or NAG, Ex/Ecr and Ex/Ccr were calculated as [x]u/[cr]u and [x]u[cr]p/[cr]u, respectively. Glomerular filtration rate (GFR) was estimated according to the Chronic Kidney Disease (CKD) Epidemiology Collaboration (eGFR), and CKD was defined as eGFR < 60 mL/min/1.73m2. In multivariable logistic regression analyses, prevalence odds ratios (PORs) for CKD were higher for log(ECd/Ccr) and log(ENAG/Ccr) than for log(ECd/Ecr) and log(ENAG/Ecr). Doubling of ECd/Ccr and ENAG/Ccr increased POR by 132% and 168%; doubling of ECd/Ecr and ENAG/Ecr increased POR by 64% and 54%. As log(ECd/Ccr) rose, associations of eGFR with log(ECd/Ccr) and log(ENAG/Ccr) became stronger, while associations of eGFR with log(ECd/Ecr) and log(ENAG/Ecr) became insignificant. In univariate regressions of eGFR on each of these logarithmic variables, R2 was consistently higher with normalization to Ccr. Our tabular and graphic analyses uniformly indicate that normalization to Ccr clarified relationships of ECd and ENAG to eGFR.

The inverse association of glomerular function and urinary ß2-MG excretion and its implications for cadmium health risk assessment.

Urinary ß2-microgroblin (ß2-MG) excretion levels above 300 µg/g creatinine are used to indicate defective tubular reabsorption. Arguably, increased urinary ß2-MG excretion could also reflect glomerular filtration rate decline. Thus, we investigated an association between urinary ß2-MG and estimated glomerular filtration rate (eGFR). We studied 527 subjects, aged 30-87 years (mean 51.2), who lived in a rural area of Thailand polluted with cadmium (Cd). Of this cohort, 10.3% had urinary Cd levels <2 µg/g creatinine and 53.5% had urinary Cd levels ≥5 µg/g creatinine. Half (53.1%) of the participants had urinary ß2-MG levels ≥ 300 µg/g creatinine, and 11.6% had low GFR, defined as eGFR <60 mL/min/1.73 m2. Lower eGFR values were associated with older age (ß = -0.568, P < 0.001), higher urinary ß2-MG (ß = -0.170, P < 0.001), higher urinary Cd (ß = -0.103, P = 0.005) and diabetes (ß = 0.074, P = 0.032). An inverse association between eGFR and urinary ß2-MG was evident in subjects with low GFR (ß = -0.332, P = 0.033), but not in those with GFR >90 mL/min/1.73 m2 (ß = -0.008, P = 0.896). These findings suggested Cd-induced nephron loss and reduced tubular reabsorption in low eGFR subjects. Urinary ß2-MG levels <300 µg/g creatinine were associated with 4.66 (95% CI: 1.92, 11.32) fold increase in the POR for low GFR, compared with urinary ß2-MG levels <100 µg/g creatinine. Findings in the present study cast doubt on a cut-off value for urinary ß2-MG, while lending support to the notion that elevated urinary ß2-MG excretion could indicate a fall of GFR.

Risk assessment for Thai population: benchmark dose of urinary and blood cadmium levels for renal effects by hybrid approach of inhabitants living in polluted and non-polluted areas in Thailand.

BACKGROUND: The aim of the present study was to estimate the benchmark doses (BMD) for renal effects for health risk assessment of residents living in Cd-polluted and non-polluted areas in a Thai population. METHODS: The study participants consisted of inhabitants aged 40 years or older who lived in a non-polluted area (40 men and 41 women) and in the environmentally polluted Mae Sot District (230 men and 370 women) located in northwestern Thailand. We measured urinary and blood cadmium (Cd) as markers of long-term exposure and urinary ß2-microglobulin (ß2-MG) and N-acetyl-ß-D-glucosaminidase (NAG) as renal tubular effect markers. An updated hybrid approach was applied to estimate the benchmark doses (BMD) and their 95% lower confidence limits (BMDL) of urinary and blood Cd for Cd-induced renal effects in these subjects. BMD and BMDL corresponding to an additional risk (BMR) of 5% were calculated with the background risk at zero exposure set to 5% after adjusting for age and smoking status. RESULTS: The estimated BMDLs of urinary Cd for renal effect markers were 6.9 for urinary ß2-MG and 4.4 for NAG in men and 8.1 for ß2-MG and 6.1 for NAG µg/g creatinine (Creat) in women. These BMDLs of urinary Cd (µg/g Creat) for NAG were less than the geometric mean urinary Cd in the polluted area (6.5 in men and 7.1 in women). The estimated BMDLs of blood Cd (µg/L) were 6.2 for urinary ß2-MG and 5.0 for NAG in men and 5.9 for ß2-MG and 5.8 for NAG in women. The calculated BMDLs were similar or less compared with the geometric mean blood Cd (µg/L) in the polluted Thai area (6.9 in men and 5.2 in women). CONCLUSION: The BMDLs of urinary and blood Cd for renal effects were estimated to be 4.4-8.1 µg/g Creat and 4.4-6.2 µg/L in the Thai population aged ≥ 40 years old, suggesting that more than 40% of the residents were at risk of adverse renal effects induced by Cd exposure in Thailand.

Bone resorption acceleration and calcium reabsorption impairment in a Thai population with high cadmium exposure.

Some residents of the Mae Sot district in Thailand have suffered long-term exposure to elevated dietary levels of cadmium. To test the hypothesis that chronic dietary cadmium exposure can cause imbalance in calcium dynamics and accelerate bone resorption, a group of these residents (156 men and 256 women aged >/= 50) were selected on the basis of previous records of elevated urinary cadmium and tested for urinary and blood cadmium, bone formation and resorption markers, and the renal tubular dysfunction markers. Both genders had high levels of blood and urinary cadmium and high urinary levels of the markers for renal dysfunction and bone resorption in a dose-response relationship to urinary cadmium. The excretion of bone resorption markers was positively correlated to the ratio of excreted calcium and urinary cadmium. The results of a multivariate regression analysis indicated that bone resorption was accelerated by impaired calcium reabsorption in renal tubules.

Cadmium-exposed population in Mae Sot District, Tak Province: 4 bone mineral density in persons with high cadmium exposure.

OBJECTIVE: To measure bone mineral density in cadmium-exposed persons aged 40 years and older that lived in the 12 contaminated villages in northwestern Thailand. MATERIAL AND METHOD: Five hundred seventy three persons with urinary cadmium levels > or = 5 microg/g creatinine during the 2004-2006 surveys were screened in 2007 for urinary excretion of cadmium, bone formation and resorption markers, and renalfunction markers. Calcaneus bone density was measured in each person by a dual-energy X-ray absorptiometry bone scanner. RESULTS: The mean age of the study persons was 57 years old. The geometric mean level of urinary cadmium for women was significantly higher than that for men. Women had a lower mean of calcaneus bone density than men. The rate of osteoporosis in women (21.5%) was significantly higher than that for men (14.7%). Calcaneus bone density was negatively correlated with urinary excretion of calcium (in both genders) and crosslinked N-telopeptide of type I collagen (in women), after adjusting for other co-variables. Increasing urinary cadmium levels appeared to correlate with reduced bone density in women, but not in men. In both genders, urinary excretion of beta2-microglobulin and N-acetyl-beta-D-glucosaminidase was higher in persons with osteoporosis than those without. CONCLUSION: Bone mineral loss is correlated with urinary cadmium levels and renal dysfunction in this female population.

The Source and Pathophysiologic Significance of Excreted Cadmium.

In theory, the identification of the source of excreted cadmium (Cd) might elucidate the pathogenesis of Cd-induced chronic kidney disease (CKD). With that possibility in mind, we studied Thai subjects with low, moderate, and high Cd exposure. We measured urine concentrations of Cd, ([Cd]u); N-acetyl-ß-d-glucosaminidase, a marker of cellular damage ([NAG]u); and ß2-microglobulin, an indicator of reabsorptive dysfunction ([ß2MG]u). To relate excretion rates of these substances to existing nephron mass, we normalized the rates to creatinine clearance, an approximation of the glomerular filtration rate (GFR) (ECd/Ccr, ENAG/Ccr, and Eß2MG/Ccr). To link the loss of intact nephrons to Cd-induced tubular injury, we examined linear and quadratic regressions of estimated GFR (eGFR) on ECd/Ccr, eGFR on ENAG/Ccr, and ENAG/Ccr on ECd/Ccr. Estimated GFR varied inversely with both ratios, and ENAG/Ccr varied directly with ECd/Ccr. Linear and quadratic regressions of Eß2MG/Ccr on ECd/Ccr and ENAG/Ccr were significant in moderate and high Cd-exposure groups. The association of ENAG/Ccr with ECd/Ccr implies that both ratios depicted cellular damage per surviving nephron. Consequently, we infer that excreted Cd emanated from injured tubular cells, and we attribute the reduction of eGFR to the injury. We suggest that ECd/Ccr, ENAG/Ccr, and eGFR were associated with one another because each parameter was determined by the tubular burden of Cd.

Reduction of trihalomethane formation and detoxification of microcystins in tap water by ozonation.

The efficiency of ozonation in comparison to chlorination for removal of microcystins and production of trihalomethanes (THMs) in water was investigated. One hundred and ninety water samples of ozone and chlorine treated water were collected at a water treatment plant between August 2004 and March 2005. The level of THMs, total organic carbon and residual chlorine were determined. Protein phosphatase 2A inhibition assay was used to detect microcystins and the presence of microcystins was confirmed by HPLC. The results show that 91.5% of the THM species in treated water was chloroform and 8.5% was bromodichloromethane. The mean THM level+/- standard error of mean in chlorinated water (CW) (45.1+/-3.0 microg/L) was higher than the mean of THM level in ozonated water (OW) (18.6+/-2.2 microg/L). In addition, no OW sample exceeded the first stage U.S. EPA maximum THM contaminant level for drinking water (80 microg/L) and only 8% of these samples exceeded the second stage level (40 microg/L). On the other hand, 3% of CW samples exceeded 80 microg/L and 68% exceeded the 40 microg/L level. The microcystin level in all water samples was below the WHO guideline value (1 microg/L) for drinking water.

Urinary Cadmium Threshold to Prevent Kidney Disease Development.

The frequently observed association between kidney toxicity and long-term cadmium (Cd) exposure has long been dismissed and deemed not to be of clinical relevance. However, Cd exposure has now been associated with increased risk of developing chronic kidney disease (CKD). We investigated the link that may exist between kidney Cd toxicity markers and clinical kidney function measure such as estimated glomerular filtration rates (eGFR). We analyzed data from 193 men to 202 women, aged 16−87 years [mean age 48.8 years], who lived in a low- and high-Cd exposure areas in Thailand. The mean (range) urinary Cd level was 5.93 (0.05⁻57) μg/g creatinine. The mean (range) for estimated GFR was 86.9 (19.6−137.8) mL/min/1.73 m². Kidney pathology reflected by urinary β2-microglobulin (β2-MG) levels ≥ 300 μg/g creatinine showed an association with 5.32-fold increase in prevalence odds of CKD (p = 0.001), while urinary Cd levels showed an association with a 2.98-fold greater odds of CKD prevalence (p = 0.037). In non-smoking women, Cd in the highest urinary Cd quartile was associated with 18.3 mL/min/1.73 m² lower eGFR value, compared to the lowest quartile (p < 0.001). Evidence for Cd-induced kidney pathology could thus be linked to GFR reduction, and CKD development in Cd-exposed people. These findings may help prioritize efforts to reassess Cd exposure and its impact on population health, given the rising prevalence of CKD globally.

Bone Fracture Risk and Renal Dysfunction in a Highly Cadmium Exposed Thai Population.

BACKGROUND: Paddy fields in the Mae Sot, Tak Province of Thailand are polluted with unsafe levels of cadmium (Cd). Elderly populations have a high Cd body burden, putting them at elevated risk of renal dysfunction and bone fractures. We aimed to compare bone fracture risk between glomerular dysfunction, proximal tubular dysfunction, and calcium (Ca) handling abnormalities. STUDY DESIGN: A cross-sectional study. METHODS: Serum osteocalcin and cross-linked N-telopeptide of type I collagen were used to detect bone metabolism abnormalities, whereas glomerular filtration rate, serum cystatin C, urinary ß2-microglobulin (ß2-MG) and fractional excretion of calcium (FECa) were used to indicate renal dysfunction. Urinary Cd was used as an exposure marker. RESULTS: FECa >2% was associated with high bone fracture risk in both genders. The adjusted odds of bone fracture risk were 6.029 and 3.288 in men and women, respectively with FECa >2% relative to the FECa < 2% group. Proximal tubular dysfunction and glomerular dysfunction did not significantly relate to the risk of bone fracture. CONCLUSIONS: Abnormal Ca handling is a key risk factor for bone fracture in Cd-exposed people. Men and women were at risk of bone fracture risk at a similar rate. FECa was a specific indicator of Ca wasting and was more cost-effective compared to ß2-MG and serum cystatin C. We recommend using FECa to monitor abnormal Ca metabolism in individuals with FECa>2%. Reduced renal toxicant exposure and Ca supplementation are recommended for Cd-exposed populations to reduce bone fracture risk.

Monitoring of cadmium toxicity in a Thai population with high-level environmental exposure.

This study evaluated the utility of single and combined measurements of cadmium toxicity markers for surveillance purposes, using a sample of 224 individuals, 30-87 years of age, who were residents of cadmium polluted area in Mae Sot District, Tak Province, Thailand. Urinary cadmium levels excreted by them ranged between 1 and 58 microg/g creatinine with geometric mean of 8.2 microg/g creatinine which was 16-fold greater than the average for the general Thai population of 0.5 microg/g creatinine. The urinary markers evaluated were total protein, albumin, N-acetyl-beta-D-glucosaminidase (NAG), lysozyme, beta2-microglobulin (beta2-MG) and alpha1-microglobulin (alpha1-MG). Among these markers, only NAG showed a positive correlation with urinary cadmium in both male and female subjects with and without disease (r=0.43-0.71). Further, the prevalence rates for urinary NAG above 8 units/g creatinine (NAG-uria) increased with exposure levels in a dose dependent manner (p=0.05) among subjects with disease. In contrast, however, increased prevalence of beta2-MG above 0.4 mg/g creatinine (beta2-MG-uria) was associated with cadmium above 5 microg/g creatinine only in those without disease (POR=10.6 and 7.8 for 6-10 and >10 microg/g creatinine). Prevalence rates for abnormal excretion of all other markers, except albumin, were markedly increased among those having beta2-MG-uria with and without disease (chi2-test, p

Differences in the element contents between gunshot entry wounds with full-jacketed bullet and lead bullet.

To elucidate characteristics of gunshot residues in gunshot entry wounds with full-jacketed and lead bullets, element contents in entry gunshot wounds and control skins were analyzed by inductively coupled plasma-atomic emission spectrometry (ICP-AES). It was found that a high content of Fe and Zn was deposited in the gunshot entry wounds with full-jacketed bullet, whereas a high content of Pb was deposited in the gunshot entry wounds with lead (unjacked) bullet. It should be noted that the content of Pb was significantly higher in the gunshot entry wounds with lead bullet than in those with full-jacketed bullet. Regarding the relationships among elements, it was found that there were significant direct correlations between Pb and either Sb or Ba contents in both gunshot entry wounds with full-jacketed and lead bullets. As Pb increased in both gunshot entry wounds, Sb and Ba also increased in the wounds.

Gender-Specific Impact of Cadmium Exposure on Bone Metabolism in Older People Living in a Cadmium-Polluted Area in Thailand.

To elucidate the influence of cadmium exposure on bone metabolism, associations between urinary/blood cadmium and bone resorption/formation markers were investigated in older cadmium exposed men and women. Increased urinary cross-linked N-telopeptide of type I collagen (NTx), a bone resorption marker, was found to be associated with increased levels of parathyroid hormone, fractional excretion of calcium, and urinary/blood cadmium after adjusting for confounding factors in men. In women, urinary NTx was significantly associated with only urinary cadmium and a strong relationship with increased fractional excretion of calcium. Risk for bone metabolic disorders, indicated by high urinary NTx, significantly increased in men with blood cadmium ≥ 10 µg/L or urinary cadmium ≥ 10 µg/g creatinine. Increased osteocalcin level was significantly associated with increased blood cadmium in men. In conclusion, cadmium exposure appeared to have an influence on bone remodeling both bone resorption and formation in this population of older Thai men, and blood cadmium was more closely associated with bone metabolism than urinary cadmium.

Cadmium exposure and age-associated DNA methylation changes in non-smoking women from northern Thailand.

DNA methylation changes with age, and may serve as a biomarker of aging. Cadmium (Cd) modifies cellular processes that promote aging and disrupts methylation globally. Whether Cd modifies aging processes by influencing establishment of age-associated methylation marks is currently unknown. In this pilot study, we characterized methylation profiles in > 450 000 CpG sites in 40 non-smoking women (age 40-80) differentially exposed to environmental Cd from Thailand. Based on specific gravity adjusted urinary Cd, we classified them as high (HE) and low (LE) exposed and age-matched within 5 years. Urinary Cd was defined as below 2 µg/l in the LE group. We predicted epigenetic age (DNAm-age) using two published methods by Horvath and Hannum and examined the difference between epigenetic age and chronologic age (Δage). We assessed differences by Cd exposure using linear mixed models adjusted for estimated white blood cell proportions, BMI, and urinary creatinine. We identified 213 age-associated CpG sites in our population (P < 10-4). Counterintuitively, the mean Δage was smaller in HE vs. LE (Hannum: 3.6 vs. 7.6 years, P = 0.0093; Horvath: 2.4 vs. 4.5 years, P = 0.1308). The Cd exposed group was associated with changes in methylation (P < 0.05) at 12, 8, and 20 age-associated sites identified in our population, Hannum, and Horvath. From the results of this pilot study, elevated Cd exposure is associated with methylation changes at age-associated sites and smaller differences between DNAm-age and chronologic age, in contrast to expected age-accelerating effects. Cd may modify epigenetic aging, and biomarkers of aging warrant further investigation when examining Cd and its relationship with chronic disease and mortality.

DNA methylation is differentially associated with environmental cadmium exposure based on sex and smoking status.

The adverse health effects of cadmium (Cd) are well known in human populations; however, much of what is known about biological mechanisms of Cd comes from in vitro and animal studies. The adverse health outcomes due to high levels of Cd exposure in the population of Mae Sot, Thailand have been extensively characterized. Here, for the first time, this population is being studied in an epigenetic context. The objective of this study was to characterize the association between DNA methylation markers and Cd exposure, taking into account sex and smoking differences, in an adult population at an increased risk of experiencing adverse health outcomes from high body burden of Cd. One hundred and sixty-nine residents from known exposure areas of Mae Sot, Thailand and one hundred residents from non-exposed areas nearby were surveyed in 2012. Urine and blood samples were collected for measurement of urinary Cd (UCd) and DNA methylation of Cd-related markers (DNMT3B, MGMT, LINE-1, MT2A). UCd levels were 7 times higher in the exposed compared to the unexposed populations (exposed median: 7.4 µg/L, unexposed median: 1.0 µg/L, p < 0.001). MGMT hypomethylation was associated with increasing levels of UCd in the total population. Sex-specific associations included MT2A and DNMT3B hypomethylation in women and LINE-1 hypermethylation in men with increasing UCd. Upon subanalysis, these associations separated by smoking status. In summary, environmental Cd exposure is associated with gene-specific DNA methylation in a sex and smoking dependent manner.

Reversed-phase liquid chromatographic-mass spectrometric determination of microcystin-LR in cyanobacteria blooms under alkaline conditions.

Reversed-phase HPLC coupled to the atmospheric pressure ionization-electrospray ionization (API-ESI) MS was used for microcystin-LR detection and quantitation in samples of dried Microcystis aeruginosa cells. An alkaline linear gradient (20 mmol/l ammonium hydroxide-acetonitrile, pH 9.7) was used for elution of the toxic peptides. Limit of detection was 1 microg/ml (20 ng per injection) in the scan mode of MS and 0.1 microg/ml (2 ng per injection) in the case of selective ion monitoring.

Serum aluminium in alumina exposed workers.

This study was performed after skepticism occurred in 1994 when alumina, or aluminium oxide, was thought to be the cause of sickness and death for certain workers at the Northern Industrial Park, Lumphun province, Thailand. Zeeman-graphite furnace atomic absorption spectrometric method has been developed to quantify the aluminium (Al) levels in the serum of 399 workers and 500 blood donors. The results showed that Al levels in the directly (n = 62) exposed workers was significantly different from the indirectly exposed (n = 130) and non-exposed (n = 207) workers and donors. However, symptoms found in the directly exposed workers were not significantly different from those in the indirectly exposed workers. In addition, a high percentage of headache and fatigue found in both directly and indirectly exposed workers suggested that more than one hazard could be involved in the incidence of alumina.

A biomarker found in cadmium exposed residents of Thailand by metabolome analysis.

First, the urinary metabolic profiling by gas chromatography-mass spectrometry (GC-MS), was performed to compare ten cadmium (Cd) toxicosis cases from a Cd-polluted area in Mae Sot (Thailand) with gender-matched healthy controls. Orthogonal partial list square-discrimination analysis was used to identify new biomarker candidates in highly Cd exposed toxicosis cases with remarkable renal tubular dysfunction. The results of the first step of this study showed that urinary citrate was a negative marker and myo-inositol was a positive marker for Cd toxicosis in Thailand. In the second step, we measured urinary citrate in the residents (168 Cd-exposed subjects and 100 controls) and found significantly lower levels of urinary citrate and higher ratios of calcium/citrate and magnesium/citrate, which are risk factors for nephrolithiasis, in highly Cd-exposed residents. Additionally, this inverse association of urinary citrate with urinary Cd was observed after adjustment for age, smoking and renal tubular dysfunction, suggesting a direct effect of Cd on citrate metabolism. These results indicate that urinary citrate is a useful biomarker for the adverse health effects of Cd exposure in a Thai population with a high prevalence of nephrolithiasis.

Modeling cadmium exposures in low- and high-exposure areas in Thailand.

BACKGROUND: Previous U.S. population modeling studies have reported that urinary cadmium (Cd) excretion patterns differ with age, sex, and dietary exposure; associations between Cd exposures and health outcomes also have differed by age and sex. Therefore, it is important to test models used to estimate Cd exposures across an expanded Cd-exposure range. OBJECTIVES: We estimated relative Cd exposures from both diet and smoking in low- and high-exposure scenarios to provide data for improving risk assessment calculations. METHODS: We used a Cd toxicokinetic-based model to estimate Cd exposures based on urinary Cd levels measured for 399 persons in a low-exposure area (Bangkok) and 6,747 persons in a high-exposure area (Mae Sot) in Thailand. RESULTS: In Bangkok, we estimated dietary Cd exposures of 50-56 µg/day for males and 21-27 µg/day for females 20-59 years of age who never smoked. In Mae Sot, we estimated dietary Cd exposures of 188-224 µg/day for males and 99-113 µg/day for females 20-59 years of age who never smoked. In Bangkok, we estimated Cd exposures from smoking to be 5.5-20.4 µg/day for male smokers 20-59 years of age. In Mae Sot, we estimated Cd exposures from smoking to be 9.8-26 µg/day for male heavy smokers and 26 µg/day for female heavy smokers. CONCLUSION: This study provides estimates of Cd exposures from diet and smoking in low- and high-exposure scenarios. Our findings suggest a relatively small safety margin between the established tolerable Cd reference exposure of 62 µg/day and exposure levels previously associated with evidence of kidney and bone effects in Mae Sot residents, where dietary Cd exposures among women were only 1.6-2.1 times the reference value.

Use of the kidney injury molecule-1 as a biomarker for early detection of renal tubular dysfunction in a population chronically exposed to cadmium in the environment.

Cadmium (Cd) has been found as an environmental pollutant in Mae Sot district, Tak province, Thailand. Prolong exposure to high levels of Cd of the resident increases high risk of Cd toxicity especially to kidney which is the primary target of Cd. In order to investigate the early effect of Cd induced renal dysfunction, a kidney injury molecule-1 (KIM-1), a novel biomarker of renal tubular dysfunction, was measured using an enzyme linked immunosorbent assay (ELISA). The method was validated and used to quantify the KIM-1 concentrations in the urine of 700 subjects (260 men, 440 women) who lived in the Cd contaminated area. The KIM-1 concentrations were compared to the concentrations of two conventional renal tubular dysfunction biomarkers, N-acetyl-ß-D-glucosaminidase (NAG) and ß2-microglobulin (ß2-MG). Urinary KIM-1 was correlated with urinary and blood Cd as well as NAG. After adjustment of age and smoking, urinary KIM-1 was correlated with blood Cd more than urinary NAG did. Clear dose response relationships of urinary KIM-1 with urinary Cd were shown in both men and women. These results indicate that the urinary KIM-1 might be more sensitive biomarker than urinary NAG and ß2-MG for an early detection of renal tubular dysfunction. It is useful as a tool to detect renal effect of toxicity due to chronic Cd exposure at high level.

Cadmium induced renal dysfunction among residents of rice farming area downstream from a zinc-mineralized belt in Thailand.

High levels of cadmium (Cd) in paddy soil and rice, and a concurrent increase in urinary Cd of inhabitants in the Mae Sot District, Tak Province, Thailand first emerged in 2003. Risk factors such as occupation, sources of staple food and drinking water as well as biomarkers of adverse renal effects of the increased body burden of Cd were investigated in 795 residents, 30 years or older, whose urinary Cd levels were between 0.02 and 106mug/g creatinine. Farmers who consumed their own rice and residents who sourced drinking water from wells and/or the river demonstrated increased urinary Cd. Age-adjusted mean urinary cadmium for male and female subjects who consumed well water was 5.7mug/g vs. 6.1mug/g creatinine while the corresponding value for male and female subjects who did not consume well water was 3.7mug/g vs. 4.8mug/g creatinine, respectively. Increased urinary levels of beta(2)-microglobulin and N-acetyl-beta-d-glucosaminidase were observed with the increase in urinary Cd, indicating tubular dysfunction and renal damage associated with increase in Cd body burden. Consumption of well water and rice grown in the contaminated area increase the body burden of Cd. Cessation of exposure is essential to prevent and possibly recover from Cd toxicity, especially among the residents whose kidney damage and malfunction may be reversible.