Environmental exposure to cadmium at a level insufficient to induce renal tubular dysfunction does not affect bone density among female Japanese farmers

Some recent research suggests that environmental exposure to cadmium, even at low levels, may increase the risk of osteoporosis, and that the bone demineralization is not just a secondary effect of renal dysfunction induced by high doses of cadmium as previously reported. To investigate the effect of exposure to cadmium at a level insufficient to induce kidney damage on bone mineral density (BMD) and bone metabolism, we conducted health examinations on 1380 female farmers from five districts in Japan who consumed rice contaminated by low-to-moderate levels of cadmium. We collected peripheral blood and urine samples and medical and nutritional information, and measured forearm BMD. Analysis of the data for subjects grouped by urinary cadmium level and age-related menstrual status suggested that cadmium accelerates both the increase of urinary calcium excretion around the time of menopause and the subsequent decrease in bone density after menopause. However, multivariate analyses showed no significant contribution of cadmium to bone density or urinary calcium excretion, indicating that the results mentioned above were confounded by other factors. These results indicate that environmental exposure to cadmium at levels insufficient to induce renal dysfunction does not increase the risk of osteoporosis, strongly supporting the established explanation for bone injury induced by cadmium as a secondary effect.     

Bone resorption and environmental exposure to cadmium in women: a population study

BACKGROUND: Environmental exposure to cadmium decreases bone density indirectly through hypercalciuria resulting from renal tubular dysfunction. OBJECTIVE: We sought evidence for a direct osteotoxic effect of cadmium in women. METHODS: We randomly recruited 294 women (mean age, 49.2 years) from a Flemish population with environmental cadmium exposure. We measured 24-hr urinary cadmium and blood cadmium as indexes of lifetime and recent exposure, respectively. We assessed the multivariate-adjusted association of exposure with specific markers of bone resorption, urinary hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP), as well as with calcium excretion, various calciotropic hormones, and forearm bone density. RESULTS: In all women, the effect sizes associated with a doubling of lifetime exposure were 8.4% (p=0.009) for HP, 6.9% (p=0.10) for LP, 0.77 mmol/day (p=0.003) for urinary calcium, -0.009 g/cm(2) (p=0.055) for proximal forearm bone density, and -16.8% (p=0.065) for serum parathyroid hormone. In 144 postmenopausal women, the corresponding effect sizes were -0.01223 g/cm(2) (p=0.008) for distal forearm bone density, 4.7% (p=0.064) for serum calcitonin, and 10.2% for bone-specific alkaline phosphatase. In all women, the effect sizes associated with a doubling of recent exposure were 7.2% (p=0.001) for urinary HP, 7.2% (p=0.021) for urinary LP, -9.0% (p=0.097) for serum parathyroid hormone, and 5.5% (p=0.008) for serum calcitonin. Only one woman had renal tubular dysfunction (urinary retinol-binding protein >338 microg/day). CONCLUSIONS: In the absence of renal tubular dysfunction, environmental exposure to cadmium increases bone resorption in women, suggesting a direct osteotoxic effect with increased calciuria and reactive changes in calciotropic hormones.     

Occupational cadmium exposure in jig solderers.

The cadmium body burden, blood and urine cadmium concentrations, and renal function were studied in a group of 53 cadmium solderers. The results showed raised blood and urine cadmium concentrations and raised cadmium body burden in all workers (31) with more than five years exposure, with 27 having urine cadmium concentrations in excess of the proposed biological threshold of 10 nmol/mmol creatinine. Renal tubular dysfunction was found in 17 of the subjects with more than five years exposure and in one this was associated with glomerular dysfunction. These data indicate that cadmium body burden and frequency of tubular dysfunction in end users of cadmium may be as high as those found in smelters or production workers. Subjects with tubular dysfunction did not show greatly increased urine cadmium concentrations compared with those without dysfunction, supporting a previous suggestion that tubular dysfunction occurs before the wash out of cadmium from the kidney. At the time of our study, cadmium exposure stopped as cadmium free soldering rods were introduced. Repeat urine samples from 19 subjects, one to two years after exposure ended indicated that there was no further increase in the level of excretion of low molecular weight proteins, perhaps indicating that the tubular proteinuria does not increase or more severe renal dysfunction develop without continuous exposure.     

Occupational cadmium exposure in jig solderers

The cadmium body burden, blood and urine cadmium concentrations, and renal function were studied in a group of 53 cadmium solderers. The results showed raised blood and urine cadmium concentrations and raised cadmium body burden in all workers (31) with more than five years exposure, with 27 having urine cadmium concentrations in excess of the proposed biological threshold of 10 nmol/mmol creatinine. Renal tubular dysfunction was found in 17 of the subjects with more than five years exposure and in one this was associated with glomerular dysfunction. These data indicate that cadmium body burden and frequency of tubular dysfunction in end users of cadmium may be as high as those found in smelters or production workers. Subjects with tubular dysfunction did not show greatly increased urine cadmium concentrations compared with those without dysfunction, supporting a previous suggestion that tubular dysfunction occurs before the wash out of cadmium from the kidney. At the time of our study, cadmium exposure stopped as cadmium free soldering rods were introduced. Repeat urine samples from 19 subjects, one to two years after exposure ended indicated that there was no further increase in the level of excretion of low molecular weight proteins, perhaps indicating that the tubular proteinuria does not increase or more severe renal dysfunction develop without continuous exposure.     

环境镉接触人群尿金属硫蛋白排泄与镉致骨损伤效应

目的研究环境镉接触人群尿金属硫蛋白(UMT)的排泄与镉致骨损伤效应的关系。方法镉污染区居民为环境镉接触人群,非污染区居民为对照人群。人群尿镉(UCd)与血镉(BCd)用原子吸收分光光度法测定,用环境接触量估测总镉摄入量(TCd)。UMT、尿β2微球蛋白(UB2M)、尿视黄醇结合蛋白(URBP)及尿白蛋白(UALB)用ELISA法测定,尿N-乙酰-β-D-氨基葡萄糖苷酶(UNAG)和UNAG同工酶B(UNAGB)用荧光分析法测定,均用尿肌酐校正。单光子骨密度仪测定人群前臂骨密度。结果UMT能反映机体接触镉时镉负荷的变化。而高剂量接触镉可先后导致肾功能障碍及骨质疏松。人群UMT排泄量与骨密度的关系同UMT排泄量本身是否异常有关。根据各指标与尿镉的剂量-反应曲线计算得到的基准剂量95%低限水平BMDL值,从小到大排列为UNAGB、UNAG、UB2M、UMT、URBP、T评分及UALB。结论镉致骨质疏松的发生与镉致肾功能障碍有关并迟于后者。UMT不仅能特异而敏感的反映镉致肾的毒性,而且能在一定程度上反映镉对骨骼的损伤。     

Cadmium and lead in blood in relation to low bone mineral density and tubular proteinuria

Long-term exposure to cadmium may cause kidney and bone damage. Urinary cadmium is commonly used as the dose estimate for the body burden of cadmium. However, elevated levels of cadmium in the urine may reflect not only high levels of cadmium dose but also renal dysfunction. In this study we used blood cadmium as the dose estimate. In addition, we analyzed blood lead. We examined 479 men and 542 women, ages 16-81 years, who were environmentally or occupationally exposed to cadmium and lead. We used urinary protein alpha 1-microglobulin as a marker for tubular proteinuria and measured forearm bone mineral density using dual-energy X-ray absorptiometry. The relationship between blood cadmium and tubular proteinuria was strong, even when we excluded occupationally exposed participants. The subgroup with the highest blood cadmium levels had a 4-fold risk of tubular proteinuria compared to the subgroup with the lowest blood cadmium levels. In the older age group (age > 60), the risk of low bone mineral density (z-score < -1) for the subgroup with the highest blood cadmium levels was almost 3-fold compared to the group with lowest blood cadmium levels. We found no similar associations for lead. The observed effects may be caused by higher cadmium exposure in the past. This study strengthens previous evidence that cadmium exposure may affect both bone mineral density and kidney function.     

Cadmium-induced effects on bone in a population-based study of women

High cadmium exposure is known to cause bone damage, but the association between low-level cadmium exposure and osteoporosis remains to be clarified. Using a population-based women's health survey in southern Sweden [Women's Health in the Lund Area (WHILA) ] with no known historical cadmium contamination, we investigated cadmium-related effects on bone in 820 women (53-64 years of age) . We measured cadmium in blood and urine and lead in blood, an array of markers of bone metabolism, and forearm bone mineral density (BMD) . Associations were evaluated in multiple linear regression analysis including information on the possible confounders or effect modifiers: weight, menopausal status, use of hormone replacement therapy, age at menarche, alcohol consumption, smoking history, and physical activity. Median urinary cadmium was 0.52 microg/L adjusted to density (0.67 microg/g creatinine) . After multivariate adjustment, BMD, parathyroid hormone, and urinary deoxypyridinoline (U-DPD) were adversely associated with concentrations of urinary cadmium (p < 0.05) in all subjects. These associations persisted in the group of never-smokers, which had the lowest cadmium exposure (mainly dietary) . For U-DPD, there was a significant interaction between cadmium and menopause (p = 0.022) . Our results suggest negative effects of low-level cadmium exposure on bone, possibly exerted via increased bone resorption, which seemed to be intensified after menopause. Based on the prevalence of osteoporosis and the low level of exposure, the observed effects, although slight, should be considered as early signals of potentially more adverse health effects. Key words: biochemical bone markers, bone mineral density, cadmium, lead, osteoporosis, women.     

Osteoporosis and renal dysfunction in a general population exposed to cadmium in China

Osteoporosis is a common metabolic disease characterized by low bone mass and microarchitectural deterioration of bone tissue. Many factors are involved in the occurrence of osteoporosis. Cadmium can cause both osteomalacia and osteoporosis and these effects have long been investigated through various epidemiological or experimental studies. The present study examines a possible relationship between cadmium nephropathy and its effects on the skeleton in populations living in a polluted area in southeast China. Monophoton absorptiometry was used to measure bone mineral density in the population and the Z score (the number of SD from the difference between the measured bone density of the individual and the group mean value for sex- and age-matched controls) was introduced to define osteoporosis (Z score < -2). Osteoporosis caused by cadmium exposure was demonstrated in this study on a general population environmentally exposed to cadmium in China. It was found that there were significant differences in the prevalence of osteoporosis among the different urinary cadmium groups (chi2 = 18.84, P = 0.0008). The linear trend test gave chi2 = 16.281, P = 0.00005. There was a dose-response relationship between cadmium exposure (urinary cadmium) and prevalence of osteoporosis. Of 31 subjects with osteoporosis, 23 subjects were suffering from renal dysfunction. The prevalence of renal dysfunction (74.19%) was significantly higher than that in those without osteoporosis (chi2 = 16.53, P < 0.001). Stratum analysis was performed to further assess the relationship between bone damage and renal impairment caused by cadmium. There was a significant difference between those with and without tubular damage (chi2 = 19.92, P = 0.000) but not in those with and without glomerular damage (chi2 = 0.08, P = 0.114). This showed that glomerular dysfunction plays a smaller role than tubular dysfunction in the causation of bone damage. It was found that the prevalence of osteoporosis increases with increasing values of parameters of tubular damage. Osteoporosis caused by cadmium is thus related to kidney dysfunction and especially to tubular damage and its severity but not to glomerular damage. The present study has thus demonstrated the combined adverse effects (osteoporosis and renal dysfunction) caused by environmental exposure to cadmium for the first time in Asia outside the endemic area in Japan.     

Renal Effects of Cadmium Intake of a Japanese General Population in Two Areas Unpolluted by Cadmium

Renal effects of cadmium exposure (i.e., in food products) on people living in two areas unpolluted by cadmium in Japan were investigated. The population comprised 875 inhabitants (i.e., 346 males and 529 females) and 635 inhabitants (i.e., 222 males and 413 females), all of whom in each area were 50+ y of age. The authors used urinary cadmium concentration as an indicator of internal dose, and total urinary protein, β₂-microglobulin, and N-acetyl-β-glucosaminidase were indicators of renal dysfunction. The authors used multiple-regression and logistic-regression analyses to study the relationship between urinary cadmium excretion and the above indicators of renal dysfunction. In the two geographic areas, both analyses revealed that urinary cadmium concentrations were associated significantly with indicators of renal dysfunction. The results suggest that renal dysfunction is related significantly with environmental cadmium exposure in areas of Japan that are not polluted by cadmium.     

沈阳市镉污染区居民尿镉及骨密度调查

目的通过检测脱离环境镉接触人群的尿镉及骨密度，探讨镉致肾损伤的远期效应与骨密度的关系。方法选择在镉污染区连续居住20年以上的居民为调查对象，应用GMY-1型单光子骨密度吸收仪，测量其桡骨远端骨密度（BMD）；用原子吸收分光光度法检测该人群的尿镉（UCd）水平。结果污染区居民的尿镉水平显著高于对照组（P〈0．05），并随着镉污染程度的增加而增高；BMD随着UCd水平的增加而下降，接触组与对照组差异有统计学意义（P〈0．05）。结论长期脱离镉污染环境后，体内镉仍处于一个较高水平，并影响骨代谢导致骨密度下降。     

The effects of environmental cadmium exposure on kidney function: the possible influence of age

The study aimed to assess the possible influence of long-term environmental exposure to cadmium and age at the time of exposure on renal function. The study was a follow-up of the 1991-1994 project concerning 2000 inhabitants of a cadmium-contaminated area in the vicinity of a zinc smelter. Since the smelter was built in the late 1950s but was not operated until 1968, some of the inhabitants were not exposed to cadmium during childhood. For the follow-up, 308 persons who in 1993 presented with Cd-U levels > or = 0.5 microg/L adjusted for specific gravity (1.020) were selected in 2000. The study population included 136 people who were exposed to cadmium in childhood (former children) and 172 adults (unexposed adults) with no such exposure. These two groups were divided into subgroups according to Cd-U levels: < or =1 (group 1), 1-2 (group 2), and > or =2 microg/g creatinine (group 3). Urinary and blood cadmium and the markers of renal tubular dysfunction (beta2 M-U, RBP-U, NAG, NAG-A, NAG-B) and glomerular dysfunction (Alb-U and beta2 M-S) were measured. Persons with a history of occupational exposure to cadmium were excluded from this project. In group 3 of the unexposed adults, concentrations of RPB-U, NAG, NAG-B, and Alb-U were significantly higher than those in group 1. In former children, this could be observed only for RPB-U and Alb-U. Urine concentrations of these markers were higher in all of the subgroups of former children than in the groups of unexposed adults (except for NAG and its two forms). However, these differences were significant only for RBP-U in group 3. The findings indicate that early renal effects in the general population may occur at Cd-U concentrations above 2 microg/g creatinine and at lower levels for NAG-B. Moreover, cadmium exposure in childhood may have a stronger impact the renal function, particularly tubular reabsorption, than the exposure of a mature organism.     

Cadmium exposure and nephropathy in a 28-year-old female metals worker

A 28-year-old female presented for evaluation of left flank pain and polyuria after having been exposed to cadmium in the jewelry manufacturing industry for approximately 3 years. This patient possessed both elevated 24-hr urinary ss2-microglobulin and elevated blood cadmium levels. Approximately 6 months after initial presentation, the patient resigned from her job due to shortness of breath, chest pain, and anxiety. Exposure to cadmium in the jewelry industry is a significant source of occupational cadmium exposure. Other occupational sources include the manufacture of nickel-cadmium batteries, metal plating, zinc and lead refining, smelting of cadmium and lead, and production of plastics. Cadmium is also an environmental pollutant that accumulates in leafy vegetables and plants, including tobacco. Major toxicities anticipated from cadmium exposure involve the renal, pulmonary, and, to a lesser extent, gastrointestinal systems. These include the development of renal proximal tubular dysfunction, glomerular damage with progressive renal disease, and respiratory symptoms including pneumonitis and emphysema. Low-level cadmium exposure has also been associated with increased urinary calcium excretion and direct bone toxicity, effects that recent research suggests may result in the development of osteoporosis. The body burden of cadmium, over half of which may reside in the kidneys, is most often measured through the use of urinary cadmium levels. Blood cadmium measurements generally reflect current or recent exposure and are especially useful in cases with a short exposure period and only minimal accumulation of cadmium in the kidneys. Both ss2-microglobulin and alpha1-microglobulin serve as organ-specific, early-effect biomarkers of tubular proteinuria and thus play a role in identifying early signs of cadmium-induced renal damage in those with potential exposures. In addition to ensuring workplace compliance with Occupational Safety and Health Administration-mandated monitoring and screening measures, it is prudent for those with cadmium exposure to maintain adequate intake of both iron and calcium, appropriate measures even in the absence of exposure.     

Renal effects of cadmium intake of a Japanese general population in two areas unpolluted by cadmium

Renal effects of cadmium exposure (i.e., in food products) on people living in two areas unpolluted by cadmium in Japan were investigated. The population comprised 875 inhabitants (i.e., 346 males and 529 females) and 635 inhabitants (i.e., 222 males and 413 females), all of whom in each area were 50+ y of age. The authors used urinary cadmium concentration as an indicator of internal dose, and total urinary protein, beta2-microglobulin, and N-acetyl-beta-glucosaminidase were indicators of renal dysfunction. The authors used multiple-regression and logistic-regression analyses to study the relationship between urinary cadmium excretion and the above indicators of renal dysfunction. In the two geographic areas, both analyses revealed that urinary cadmium concentrations were associated significantly with indicators of renal dysfunction. The results suggest that renal dysfunction is related significantly with environmental cadmium exposure in areas of Japan that are not polluted by cadmium.     

Heated indoor swimming pools, infants, and the pathogenesis of adolescent idiopathic scoliosis: a neurogenic hypothesis

Background

Exposure to cadmium has been associated with osteoporosis and fracture risk in women and elderly, but studies in children are lacking. In the present study we investigate the association between markers of bone demineralization [urinary calcium (Ca) and deoxypyridinoline (DPD) excretion] and urinary cadmium (Cd) excretion (as an index of lifetime body burden).

Methods

155 schoolchildren from 2 elementary schools in Lahore, Pakistan were included. Urinary Cd was measured as an index of lifetime exposure. We assessed the multivariate-adjusted association of exposure with markers of bone resorption, urinary DPD as well as with Ca excretion.

Results

Urinary Cd averaged 0.50 nmol/mmol creatinine and was not influenced by age, height, weight and socio-economic status (SES). Independent of gender, age, height, weight and SES a doubling of urinary Cd was associated with a 1.72 times (p < 0.0001) increase in urinary DPD and, a 1.21 times (p = 0.02) increase in urinary Ca. Additional adjustment for urinary Ca revealed still significant associations between urinary Cd and urinary DPD. The shape of the association was linear without evidence of a threshold.

Conclusions

Even in young children, low-level environmental exposure to cadmium is associated with evidence of bone resorption, suggesting a direct osteotoxic effect with increased calciuria. These findings might have clinical relevance at older age.     

镉毒性肾损害与镉、锌结合蛋白——Ⅰ.尿金属硫蛋白对镉毒性肾损害的检测价值

采用Sephadex G-75凝胶柱色谱技术对亚急性镉毒性肾损害大鼠肝、肾、血、尿中金属硫蛋白(MT)进行了分离测定。结果表明,镉暴露后,肝、肾、血、尿中MT增多。MT是体内镉的主要存在形式,其在体内镉的运转、蓄积及排泄过程起最重要的作用。尿中MT增高是镉毒性肾损害最早出现的变化之一,它作为低分子蛋白质是肾小管功能障碍的灵敏指标。同时,作为一种镉金属结合蛋白,在反映镉性肾损害有其特异性。     

Tubular and glomerular kidney effects in Swedish women with low environmental cadmium exposure

Cadmium is a well-known nephrotoxic agent in food and tobacco, but the exposure level that is critical for kidney effects in the general population is not defined. Within a population-based women's health survey in southern Sweden (Women's Health in the Lund Area, WHILA), we investigated cadmium exposure in relation to tubular and glomerular function, from 1999 through early 2000 in 820 women (71% participation rate) 53-64 years of age. Multiple linear regression showed cadmium in blood (median, 0.38 microg/L) and urine (0.52 microg/L; density adjusted = 0.67 microg/g creatinine) to be significantly associated with effects on renal tubules (as indicated by increased levels of human complex-forming protein and N-acetyl-beta-D-glucosaminidase in urine), after adjusting for age, body mass index, blood lead, diabetes, hypertension, and regular use of nephrotoxic drugs. The associations remained significant even at the low exposure in women who had never smoked. We also found associations with markers of glomerular effects: glomerular filtration rate and creatinine clearance. Significant effects were seen already at a mean urinary cadmium level of 0.6 microg/L (0.8 microg/g creatinine). Cadmium potentiated diabetes-induced effects on kidney. In conclusion, tubular renal effects occurred at lower cadmium levels than previously demonstrated, and more important, glomerular effects were also observed. Although the effects were small, they may represent early signs of adverse effects, affecting large segments of the population. Subjects with diabetes seem to be at increased risk.     

Dietary exposure to cadmium at close to the current provisional tolerable weekly intake does not affect renal function among female Japanese farmers

Dietary cadmium (Cd) exposure and renal tubular function were investigated in 1381 female farmers from five districts in Japan (Japanese Multi-centered Environmental Toxicant Study project; JMETS). Dietary Cd exposure of the five populations was assessed from the individual Cd concentrations of the rice consumed by the study participants and the quantities of rice consumed daily. The populations showed a sequential difference in dietary Cd exposure, ranging from a level as low as that of the general Japanese population to one close to the current provisional tolerable weekly intake (PTWI). The levels of urinary Cd excretion, an indicator of Cd accumulation in the kidneys, increased along the same sequential pattern as dietary Cd exposure. However, no differences were observed among the populations in levels of urinary alpha 1-microglobulin and beta 2-microglobulin excretion, which are indicators of renal tubular function. These results indicate that the current PTWI is sufficient to prevent Cd-induced renal dysfunction among the general population.     

Follow up of workers previously exposed to silver solder containing cadmium

OBJECTIVES: To study longitudinal biological monitoring data on urinary and blood cadmium collected in a small cohort of nine workers who had been brazing for several years with solders containing cadmium. METHODS: Cadmium was measured by neutron activation analysis in livers and kidneys, and estimates of renal function were carried out in 1983 and 1995. During the intervening period exposure to cadmium was dramatically reduced by local exhaust ventilation control and substitution of the solder containing cadmium. RESULTS: From urinary protein measurements there was evidence within the group of increasing renal tubular damage over the 12 year period, even though exposure to cadmium was dramatically reduced over this period and almost eliminated by 1995. There was no evidence from serum creatinine of decreasing glomerular filtration rate, and the renal tubular handling of calcium, phosphate, or urate had not worsened significantly. Blood and urinary cadmium concentrations reduced significantly over the 12 year period but were still substantial in 1995. Blood cadmium concentrations tended to reflect cadmium body burden in 1995 when exposure had been low for several years, and decreased most significantly during 1983-90. By contrast urinary cadmium concentrations only decreased significantly from about 1990 onwards. Urinary cadmium was not significantly correlated with liver or kidney cadmium concentration in either 1983 or 1995. This may be due to the level of tubular dysfunction in the cohort. Calculated cumulative excretion of cadmium over the 12 year period was substantially greater than the loss of cadmium measured in livers and kidneys and the derived loss in body burden. Reasons for this are discussed. It is possible that in cohorts, where renal damage is apparent, urinary concentrations reflect a substantial component of current exposure rather than stored body losses. CONCLUSIONS: The data reinforce the concept that blood cadmium concentrations may not always reflect recent exposure, but may reflect body burden derived from historical exposure depending on the degree of current exposure; and that the decline in urinary and blood cadmium measurements after removal from, or reduction in, exposure will be slow and depend on the historical body burden.

 

     

A comparison between fecal cadmium and urinary beta2-microglobulin, total protein, and cadmium among Japanese farmers. An epidemiological study of cooperation between Japan and Sweden.

A study was made of 156 farmers living in a cadmium-exposed area and 93 farmers in a reference area. All were between 50 and 69 years of age. Cadmium intake from food was estimated from daily fecal cadmium content, body burden from urinary cadmium concentration, and cadmium-induced renal effects from urinary β₂-microglobulin (β₂-m) and total protein concentration. Average cadmium intake in the reference area was about 40 μg/day and in the exposed area about 150 μg/day. Average urinary cadmium excretion in the reference group was 2 μg/liter and in the exposed group 7.5 μg/liter. Average urinary β₂-m concentration in the reference group was 86 μg/liter and we defined tubular proteinuria as a β₂-m concentration higher than the average plus two standard deviations. With this definition the prevalence rate of tubular proteinuria was 3% in the reference group and 14% in the exposed group. Tubular proteinuria increased with age and with exposure duration. Increased total proteinuria was also more common in the exposed group but the prevalence rate ratio was 2.4 as compared to 4.4 for tubular proteinuria.     

alpha-1-Microglobulin: epidemiological indicator for tubular dysfunction induced by cadmium?

OBJECTIVES: To evaluate the suitability of alpha-1-microglobulin as a marker for cadmium induced renal dysfunction. METHODS: alpha-1- Microglobulin was studied in a cross sectional survey in relation to the body burden of cadmium. Concentrations of alpha-1-microglobulin in 24 h urine of 831 people aged 2-87 years were analysed in association with urinary cadmium excretion, cadmium blood concentration, age, sex, occupational and smoking history, and estimated creatinine clearance. Participants came from a population residentially exposed to cadmium and from two control populations matched for socioeconomic status. RESULTS: The excretion of alpha-1-microglobulin/24 h ranged from 0.1 mg to 176.3 mg and 44.4% of samples showed concentrations near the detection limit. Ordinal logistic regression analysis of people of all ages identified a high risk only for males compared with females (odds ratio (OR) 2.14; 95% confidence interval (95% CI) 1.56 to 2.94), age group, and duration of living on contaminated soil (OR 1.03/year; 95% CI 1.02 to 1.04), but not urinary cadmium excretion (OR 1.30; 95% CI 0.96 to 1.77) as significant predictors. For people < or = 50 years of age a weaker effect of sex (OR 1.76; 95% CI 1.13 to 2.73) and age group and an effect of similar magnitude for the duration of soil exposure (OR 1.03; 95% CI 1.01 to 1.04) were found. Also, the urinary cadmium excretion (OR 2.26; 95% CI 1.38 to 3.70) and occupational exposure (OR 1.71; 95% CI 1.03 to 2.83) were found to be significant in this younger age group. The estimated creatinine clearance had no significant impact on the alpha-1-microglobulin excretion. CONCLUSION: alpha-1- Microglobulin is a suitable marker for early tubular changes only for people < or = 50 years. It may not be sufficiently specific for cadmium, and therefore not a suitable surrogate for cadmium exposure in epidemiological studies.