Renal tubular dysfunction in male inhabitants of a cadmium-polluted area in Toyama, Japan--an eleven-year follow-up study

An eleven-year follow-up study was carried out to elucidate the changes in the level of environmental exposure to cadmium (Cd) from rice after soil replacement of polluted paddy fields and these effects on urinary excretion of Cd in male inhabitants of a Cd-polluted area in Toyama, Japan. In addition, the prevalence of renal tubular dysfunction (RTD) was examined to clarify the progress of Cd-induced RTD. One hundred and twenty-seven male inhabitants born between 1914 and 1929 in 11 districts of the Cd-polluted Jinzu River basin and 31 reference subjects in 2 adjacent districts were examined twice in 1985-86 and 1996-97. The geometric means of Cd concentrations in polished rice (Cd-R) in the Cd-polluted areas were 0.18 ppm in 1985 and 0.21 ppm in 1986; these values were significantly higher than those of the reference areas (0.13 ppm in 1985 and 0.12 ppm in 1986). After 11 years, the Cd-R levels were significantly decreased to approximately half (0.08 ppm in 1996, 0.12 ppm in 1997) due to soil replacement of polluted paddy fields, which has been carried out since 1980. The mean Cd levels in urine (Cd-U) were significantly reduced from 7.9 and 9.5 microg/g creatinine in the initial study to 6.9 and 6.8 microg/g creatinine in the follow-up study. However, the prevalence of RTD, which was determined by urinary beta2-microglobulin exceeding 1 mg/g creatinine and urinary glucose exceeding 150 mg/g creatinine, increased from 18 and 23% in the 1985-86 study to 25 and 32% in the 1996-97 study, and a total of 12 new cases (12%) of RTD were found. Whereas, only one subject (4%) in the reference control areas was identified as RTD. Cd-induced RTD was prevalent, progressive and irreversible for male inhabitants of the Cd-polluted Jinzu River basin, although the environmental exposure to Cd through rice was significantly reduced by soil replacement of polluted paddy fields.     

Urine analysis for detection of cadmium-induced renal changes, with special reference to beta2-microglobulin. A cooperative study between Japan and Sweden.

An analysis of total protein, β₂-microglobulin, glucose, and cadmium was performed on urine samples from people with Itai-itai disease and glomerular kidney disease, as well as on samples from a reference group. Blind analyses of creatinine, protein, and cadmium performed in Japanese and Swedish laboratories correlated well, but there was a tendency toward systematic differences between the laboratories' analyses of creatinine and protein. Within the range of the samples analyzed the difference was never larger than 30%. The use of three different methods of electrophoresis of urine proteins verified that the proteinuria in Itai-itai disease is tubular. On an average, urinary β₂-microglobulin excretion among Itai-itai disease patients was 100–300 times higher than among the reference group, whereas total protein excretion was only 7–17 times higher. In a group of women with different degrees of cadmium exposure urinary excretion of proteins was evaluated with qualitative determination of protein, electrophoresis, and radioimmunoassay of β₂-microglobulin. At slightly elevated β₂-microglobulin excretion the first two methods gave negative results and it was concluded that radioimmunoassay of β₂-microglobulin in urine is a sensitive indicator of cadmium-induced proteinuria.     

Renal effects of low doses of mercury

OBJECTIVES: The present study was aimed at investigating early markers of renal damage and dysfunction in subjects exposed to low doses of mercury from different sources. Different groups of subjects were examined with urinary Hg excretion (HgU) ranging from 0.1 to 35.0 micrograms/g creatinine: 122 occupationally exposed workers, 22 subjects living in a non-polluted area, but consuming large amounts of tuna and sword fish, and 197 controls. METHODS: Several markers of renal changes were measured in urine (albumin, fibronectin, beta 2-microglobulin, retinol-binding protein, tubular antigens, N-acetyl-beta-D-glucosaminidase activity) and serum (beta 2-microglobulin and cystatin C). Serum autoantibodies towards collagen, laminin and tubular antigens were assessed in subjects with abnormal renal markers. The role of glutathione-S-tranferases GSTT1 and GSTM1 polymorphisms in the inter-individual variability of biological response to Hg was also investigated. RESULTS: Renal markers were not correlated with HgU. None of such markers differed significantly between exposed workers and controls, except for urinary beta 2-microglobulin, which was decreased in Hg-exposed workers (GM = 55.8 vs 86.6 micrograms/g creatinine), in the absence of any changes in serum concentration. Subjects usually eating tuna and sword fish showed an increased urinary excretion of beta 2-microglobulin, albumin and fibronectin. Serum titres of auto-antibodies did not differ between the groups. Neither in controls nor in exposed workers were the observed differences modified by the GSTM1 and GSTT1 genotypes. CONCLUSION: The present study did not provide evidence of any changes in kidney integrity and function in subjects exposed to very low levels of inorganic Hg resulting in urinary Hg lower than 35 micrograms/g creatinine. Nor did we obtain evidence of Hg-induced autoimmunity towards kidney components. The potential modifying role of GST polymorphisms could not be clarified in the absence of effects associated with exposure to the risk factor, i.e., to inorganic Hg. Preliminary data suggesting nephrotoxic effects of organic Hg from a diet rich in large fish resulting in increased levels of both blood and urinary Hg--which however did not exceed 20 micrograms/g creatinine--deserves further investigation.     

Health effects of cadmium exposure in the general environment in Japan with special reference to the lower limit of the benchmark dose as the threshold level of urinary cadmium

OBJECTIVES: This study investigates renal dysfunction in areas without known environmental cadmium pollution and calculates the threshold level of urinary cadmium. METHODS: Urinary total protein, beta2-microglobulin (beta2-MG), and N-acetyl-beta-D-glucosaminidase (NAG), used as indicators of renal dysfunction, and urinary cadmium concentration, used as an indicator of cadmium exposure, were measured in two sets of 24-hour urine samples from each of 828 participants (410 men, 418 women), aged 40-59 years and living in three areas without any known environmental cadmium pollution. In multiple regression and logistic regression analyses the association between indicators of cadmium exposure and indicators of renal dysfunction were studied. The lower 95% confidence limit of the dose (benchmark dose) corresponding to a 5% (BMDL5) or 10% (BMDL10) level of each indicator of renal dysfunction above the background level) was calculated as the threshold level of urinary cadmium. RESULTS: With all the expressed units [g creatinine(-1) and day(-1)] in the multiple regression analysis, the partial regression coefficients showed a significant association between urinary cadmium concentration and total protein, beta2-MG, and NAG for both genders, except for total protein for women (g creatinine(-1) and day(-1). The same results were obtained for both genders in the logistic regression analysis. The BMDL10 was 0.6-1.2 microg/g creatinine and 0.8-1.6 microg/day for the men and 1.2-3.6 microg/g creatinine, and 0.5-4.7 microg/day for the women. CONCLUSIONS: Cadmium exposure and the levels of the indicators of renal dysfunction were associated among the men and women aged 40-59 years in areas without any known environmental cadmium pollution. The threshold level of urinary cadmium in Japan seems to be almost the same as in Belgium and Sweden.     

Urinary calcium as a biomarker of renal dysfunction in a general population exposed to cadmium

Urinary beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase have been recommended as sensitive indicators of renal dysfunction induced by cadmium. However, an increase in urinary calcium in early renal damage induced by cadmium has been reported both in humans and in animal experiments. To investigate the feasibility of using urinary calcium as a biomarker of renal dysfunction induced by cadmium, two areas were selected in this study, namely, a polluted area with a 3.71 mg/kg cadmium concentration in rice and a control area with a 0.07 mg/kg cadmium concentration. The total number of participants was 499, made up of 252 in the control group and 247 from the cadmium-polluted area. Urinary cadmium, urinary calcium, and zinc concentrations were measured by atomic absorption spectrometry, and beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase in urine were analyzed. The levels of urinary cadmium and urinary calcium in persons from the exposed area were significantly higher (P < 0.05) than those in the control area for both men and women, but there was no significant difference regarding urinary zinc between the two areas. A significant dose-response relationship between the prevalence of hypercalciuria and the excretion of urinary cadmium was observed, and a significantly increased prevalence of calciuria was found when excretion of urinary cadmium exceeded 2 micrograms/g creatinine. The findings were similar to those for excess urinary secretion of beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase. Because cadmium can affect Ca2+ uptake by tubular cells, with decreased renal Ca2+ reabsorption, calciuria may reflect tubular cell damage caused by cadmium. It was concluded that cadmium exposure can result in increased excretion of urinary calcium in a general population and that there is a significant dose-response relationship. Urinary calcium can therefore be used as a biomarker of renal dysfunction induced by cadmium.     

Dose-response relations between urinary cadmium and tubular proteinuria in cadmium-exposed workers

Cadmium in urine reflects the body burden in cadmium-exposed individuals. Urinary β2-microglobulin is frequently used as a marker of tubular proteinuria with an arbitrarily chosen value (34 μg/mmole creatinine) as the cut-off limit. Both this cut-off level and a lower limit (25 μg/mmole creatinine) were used in a study of the relationship between urinary cadmium and β₂-microglobulin in 561 cadmium-exposed battery workers. There was a clear dose-response relation between the urinary cadmium level and the prevalence of tubular proteinuria ranging from 0.8% in the lowest exposure group, excreting less than 1 nmole cadmium/mmole creatinine, to 46.4% (50.0 for the lower cut-off level) in the highest exposure group with a mean urinary cadmium of 15 nmole/mmole creatinine. The relation between urinary cadmium and tubular proteinuria was also assessed using probit analysis. There was a 10% response at a urinary cadmium of 3 nmole/mmole creatinine. The impact of age on the dose-response relation was explored in two age groups with the cut-off point at 60 years of age, showing a 10% prevalence of tubular proteinuria at urinary cadmium levels of 1.5 nmole/mmole creatinine in this older age group and 5.0 nmole/mmole creatinine in the category under 60 years of age. The study thus indicates that the present health-based limit (10 nmole/mmole creatinine) proposed by the World Health Organization (WHO) is too high and it is suggested that a new limit should be set to 3 nmole/mmole creatinine.     

Estimation of benchmark dose as the threshold levels of urinary cadmium, based on excretion of total protein, beta2-microglobulin, and N-acetyl-beta-D-glucosaminidase in cadmium nonpolluted regions in Japan

Previously, we investigated the association between urinary cadmium (Cd) concentration and indicators of renal dysfunction, including total protein, beta2-microglobulin (beta2-MG), and N-acetyl-beta-D-glucosaminidase (NAG). In 2778 inhabitants 50 years of age (1114 men, 1664 women) in three different Cd nonpolluted areas in Japan, we showed that a dose-response relationship existed between renal effects and Cd exposure in the general environment without any known Cd pollution. However, we could not estimate the threshold levels of urinary Cd at that time. In the present study, we estimated the threshold levels of urinary Cd as the benchmark dose low (BMDL) using the benchmark dose (BMD) approach. Urinary Cd excretion was divided into 10 categories, and an abnormality rate was calculated for each. Cut-off values for urinary substances were defined as corresponding to the 84% and 95% upper limit values of the target population who have not smoked. Then we calculated the BMD and BMDL using a log-logistic model. The values of BMD and BMDL for all urinary substances could be calculated. The BMDL for the 84% cut-off value of beta2-MG, setting an abnormal value at 5%, was 2.4 microg/g creatinine (cr) in men and 3.3 microg/g cr in women. In conclusion, the present study demonstrated that the threshold level of urinary Cd could be estimated in people living in the general environment without any known Cd-pollution in Japan, and the value was inferred to be almost the same as that in Belgium, Sweden, and China.     

Application of the hybrid approach to the benchmark dose of urinary cadmium as the reference level for renal effects in cadmium polluted and non-polluted areas in Japan

Objectives

The aim of this study was to evaluate the reference level of urinary cadmium (Cd) that caused renal effects. An updated hybrid approach was used to estimate the benchmark doses (BMDs) and their 95% lower confidence limits (BMDL) in subjects with a wide range of exposure to Cd.

Methods

The total number of subjects was 1509 (650 men and 859 women) in non-polluted areas and 3103 (1397 men and 1706 women) in the environmentally exposed Kakehashi river basin. We measured urinary cadmium (U-Cd) as a marker of long-term exposure, and β2-microglobulin (β2-MG) as a marker of renal effects. The BMD and BMDL that corresponded to an additional risk (BMR) of 5% were calculated with background risk at zero exposure set at 5%.

Results

The U-Cd BMDL for β2-MG was 3.5 μg/g creatinine in men and 3.7 μg/g creatinine in women.

Conclusions

The BMDL values for a wide range of U-Cd were generally within the range of values measured in non-polluted areas in Japan. This indicated that the hybrid approach is a robust method for different ranges of cadmium exposure. The present results may contribute further to recent discussions on health risk assessment of Cd exposure.     

Serum levels of bone Gla-protein in inhabitants exposed to environmental cadmium

Serum levels of bone Gla-protein (BGP)--the vitamin K-dependent CA2(+)-binding protein--were evaluated in 76 cadmium (Cd)-exposed subjects with renal tubular dysfunction (32 men, 44 women) and 133 nonexposed subjects (53 men, 80 women). Serum BGP levels were higher in the Cd-exposed subjects than in nonexposed subjects. Significant correlations between BGP and each index measured by bone microdensitometry (MD), serum alkaline phosphatase activity, and Cd in blood and urine were found. For all of the Cd-exposed and nonexposed men and women, BGP showed a significant standard partial regression coefficient (multiple regression analysis) with the metacarpal index (MCI), which was one of the MD indicators. Bone Gla-protein also correlated significantly with urinary beta 2-microglobulin in the men and with serum creatinine in the women. Serum BGP values strongly reflect the degree of bone damage and also reflect, although less strongly, the degree of renal damage induced by exposure to Cd.     

No significant effect of iron deficiency on cadmium body burden or kidney dysfunction among women in the general population in Japan

OBJECTIVE: To examine if iron-deficient conditions modify body burden or health effects of cadmium among women in the general population in Japan. METHODS: In 2002, 1,482 women aged 20 to 74 years in six prefectures in Japan provided informed consent to participate in this study. They offered peripheral blood and spot urine samples, and answered questionnaires on their social habits and health conditions. Never-smoking, non-pregnant and non-lactating healthy women (1,190 subjects) were selected from the volunteers. Blood samples were analyzed for serum iron, ferritin and total iron-binding capacity (TIBC) in addition to red blood cell (RBC) counts and hemoglobin (Hb) concentration as markers of anemia and iron deficiency. Urine samples were analyzed for cadmium (Cd), alpha(1)-microglobulin (alpha(1)-MG), beta(2)-microglobulin (beta(2)-MG) as markers of Cd burden and Cd-induced tubular dysfunction; the measures were expressed after being corrected for creatinine (cr) as, e.g., Cd-Ucr. RESULTS: The subjects were classified into anemic (37 women) and iron-deficient (388 women) groups separately from healthy controls (765 women), taking ferritin (<20 ng/ml) and Hb (<10 g/100 ml) as classification indicators. Strictly matched pairs (with regard to age and prefecture) were established for 36 anemic and 280 iron-deficient cases. Comparison between the cases and the matched controls showed that serum iron was lower and TIBC was higher in accordance with lower levels of ferritin and Hb in the anemic and iron-deficient groups, although the RBC count was only slightly reduced (the anemic group) or stayed essentially unchanged (the iron-deficient group). In contrast, no significant increase in Cd-Ucr, alpha(1)-MG, or beta(2)-MG was observed in either the anemic group or the iron-deficient group compared with the matched controls. Cd-Ucr in one case of clinical anemia, however, tended to be higher than the levels among women of the same age range and from the same prefecture. Her alpha(1)-MG-Ucr and beta(2)-MG-Ucr, however, remained un-elevated. CONCLUSIONS: The current level of iron deficiency among women in the general population in Japan may not induce significant increase in Cd body burden or Cd-induced tubular dysfunction.     

Determination of carbonic anhydrase C and beta 2-microglobulin by radioimmunoassay in urine of heavy-metal-exposed subjects and patients with renal tubular acidosis.

Carbonic anhydrase C (CA-C) was measured by the radioimmunoassay in urine specimens from normal individuals, residents in mercury-polluted area, cadmium-exposed workers, lead-exposed workers, and patients with primary or secondary renal tubular acidosis. None of the urine in the normal subjects demonstrated CA-C levels above 40 μg/g creatinine. Some of the cadmium-exposed workers, residents in mercury-polluted area, and patients with renal tubular acidosis excreted large amounts of CA-C that were 10–250 times higher than the normal. Urinary β₂-microglobulin (BMG) was also determined in relation to the CA-C levels. Most of the subjects exposed to heavy metals had high levels of urine CA-C or BMG or both. Some individuals had high levels of urine CA-C although BMG levels were within normal values. These findings seem to suggest that the mechanisms of urinary excretion of these two proteins were different and the quantitative determination of urinary CA-C by radioimmunoassay appears to be also a useful and sensitive test for detecting the renal tubular disorders in environmental exposure of heavy metals or those in renal tubular acidosis.     

Acute lethal toxicity, hyperkalemia associated with renal injury and hepatic damage after intravenous administration of cadmium nitrate in rats

Cadmium nitrate Cd(NO(3))(2) (CdN) is commonly used in Ni-Cd battery factories. The possibility of accidental exposure to CdN is great. CdN is very soluble in water compared to other Cd compounds. Therefore, acute toxicity would be expected to be quick due to rapid absorption after exposure. However, the mechanisms of CdN toxicity have not been fully elucidated. We investigated the acute lethal toxicity and harmful systemic effects of acute exposure to large doses of CdN. The lethal dose and dose-response study of the liver and kidney were determined after intravenous administration of CdN in rats. The LD(50) of CdN was determined to be 5.5 mg/kg. Doses of 2.1, 4.2, 6.3 mg/kg were selected for the dose-response study. Liver injury was induced at doses greater than 4.2 mg/kg. Severe hepatic injury occurred in the 6.3 mg/kg group, which would have been caused by acute exposure to the high concentration of Cd that exceeded the critical concentration in hepatic tissue. A remarkable decrease in urine volume in the 6.3 mg/kg group indicated acute renal failure. A decrease in creatinine clearance suggested acute glomerular dysfunction at doses greater than 4.2 mg/kg. Increases in urinary N-acetyl-beta-D-glucosaminidase/creatinine, beta(2)-microglobulin and glucose in the 6.3 mg/kg group indicated proximal tubular injury. Secretion of K ion was also severely affected by proximal tubular injury and severe decreases in urine volume, and an increase in serum K ion was identified at doses greater than 4.2 mg/kg. Thus severe hyperkalemia might be associated with the cardiac-derived lethal toxicity of CdN.     

The association between renal dysfunction and osteopenia in environmental cadmium-exposed subjects

Two hundred and three cadmium (Cd)-exposed subjects with renal dysfunction and 80 non-exposed subjects were examined to reveal the relationship between Cd-induced renal dysfunction and osteopenia. As biological indicators of renal function, urinary beta 2-microglobulin (beta 2-mg), and serum creatinine, calcium, and phosphorus were selected. Cd in the urine and blood was also measured. The results indicated that significant differences exist between both sexes in Cd-exposed as well as nonexposed subjects. To evaluate the degree of osteopenia, a microdensitometrical (MD) method was used. The relationships between biological parameters and each index of the MD method were analyzed using multivariate analysis. Age, urinary beta 2-mg, and serum creatinine were significantly associated with indices of osteopenia in Cd-exposed men. In contrast, age showed the most significant association with MD indices in women of both groups. However, urinary beta 2-mg was significantly associated with MD indices only in Cd-exposed women. In Cd-exposed subjects, after the number of predictor variables was increased, urinary beta 2-mg was also strongly associated with osteopenia. These results suggest a causal relationship between renal dysfunction and osteopenia in Cd-exposed subjects.     

Effects of elemental mercury exposure at a thermometer plant

This study compares 84 mercury-exposed workers at a thermometer manufacturing facility with 79 unexposed workers for evidence of chronic mercury toxicity. Personal breathing-zone air concentrations of mercury ranged from 25.6 to 270.6 micrograms/m3 for thermometer workers. Urinary mercury levels in the study population ranged from 1.3 to 344.5 micrograms/g creatinine, with eight (10%) participants exceeding 150 micrograms/g creatinine and three workers exceeding 300 micrograms/g creatinine, which indicates increased absorption of mercury among the thermometer workers. All urine mercury levels in the comparison group were compatible with normal background levels in unexposed adults (less than 10 micrograms/g creatinine). Thermometer plant workers reported more symptoms than did controls; in general, these differences were not statistically significant and could not be specifically associated with mercury exposure. Static tremor, abnormal Romberg test, dysdiadochokinesia, and difficulty with heel-to-toe gait were more prevalent among thermometer workers than control workers, which could not be associated with recent mercury exposure; there was some suggestion of an association with chronic exposure. There were no intergroup differences for the standard clinical tests of renal function except for a significantly higher mean specific gravity among the thermometer workers. A positive correlation was found, however, between urinary N-acetyl-b-D-glucosaminidase (NAG) and urinary mercury. There was no consistent evidence for intergroup differences in proximal renal tubule function, as measured by urinary beta 2-microglobulin (B2M) or retinol binding protein (RBP).     

Sodium Intake and Proteinuria/Albuminuria in the Population—Observational,Cross-Sectional Study

Sodium effects on proteinuria are debated. This observational, cross-sectional, population-based study investigated relationships to proteinuria and albuminuria of sodium intake assessed as urinary sodium/creatinine ratio (NaCR). In 482 men and 454 women aged 35–94 years from the Moli-sani study, data were collected for the following: urinary NaCR (independent variable); urinary total proteins/creatinine ratio (PCR, mg/g), urinary albumin/creatinine ratio (ACR, mg/g), and urinary non-albumin-proteins/creatinine ratio (calculated as PCR minus ACR) (dependent variables). High values were defined as PCR ≥ 150 mg/g, ACR ≥ 30 mg/g, and urinary non-albumin-proteins/creatinine ratio ≥ 120 mg/g. Urinary variables were measured in first-void morning urine. Skewed variables were log-transformed in analyses. The covariates list included sex, age, energy intake, body mass index, waist/hip ratio, estimated urinary creatinine excretion, smoking, systolic pressure, diastolic pressure, diabetes, history of cardiovascular disease, reported treatment with antihypertensive drug, inhibitor or blocker of the renin-angiotensin system, diuretic, and log-transformed data of total physical activity, leisure physical activity, alcohol intake, and urinary ratios of urea nitrogen, potassium, and phosphorus to creatinine. In multivariable linear regression, standardized beta coefficients of urinary NaCR were positive with PCR (women and men = 0.280 and 0.242, 95% confidence interval = 0.17/0.39 and 0.13/0.35, p < 0.001), ACR (0.310 and 0.265, 0.20/0.42 and 0.16/0.38, p < 0.001), and urinary non-albumin-proteins/creatinine ratio (0.247 and 0.209, 0.14/0.36 and 0.09/0.33, p < 0.001). In multivariable logistic regression, higher quintile of urinary NaCR associated with odds ratio of 1.81 for high PCR (1.55/2.12, p < 0.001), 0.51 of 1.62 for high ACR (1.35/1.95, p < 0.001), and of 1.84 for high urinary non-albumin proteins/creatinine ratio (1.58/2.16, p < 0.001). Findings were consistent in subgroups. Data indicate independent positive associations of an index of sodium intake with proteinuria and albuminuria in the population.     

Significance of the excretion of urinary indicator proteins for a low level of occupational exposure to cadmium

Urinary cadmium (Cd), N-acetyl-beta-D-glucosaminidase (NAG), metallothionein (MT), beta 2-microglobulin (BMG), and blood cadmium were determined in 79 workers who had been employed at a Cd pigment factory in Japan. The workers who had been dealing with Cd pigment manufacturing processes were estimated to be exposed to cadmium pigment dust at a maximum concentration of 3.0 micrograms/m3/8 h for about 20 years. The urinary Cd level ranged from 0.2 to 9.7 micrograms/g creatinine with a geometric mean of 1.02 micrograms/g creatinine. Pearson's correlation coefficients between logarithm of urinary Cd and that of NAG, MT, and BMG in urine were 0.45, 0.62, and 0.05, respectively. The correlation coefficients between blood Cd and urinary NAG, MT, and BMG were 0.21, 0.40, and -0.074, respectively. When partial correlation coefficients were calculated to exclude the contribution of age factor, urinary Cd turned out to be significantly correlated with urinary MT (r = 0.55) and NAG (r = 0.52). The present results indicate that urinary Cd is more closely associated with urinary MT and NAG than with BMG, and suggest that MT and NAG could be good indicators of Cd absorption in a Cd-exposed population whose mean urinary Cd level is relatively low, or less than 10 micrograms/g creatinine.     

Urinary cadmium excretion is correlated with calcaneal bone mass in Japanese women living in an urban area

Nine hundred eight women aged 40-88 years living in a non-Cd-polluted area in Japan were analyzed for urinary cadmium (Cd), N-acetyl-beta-D-glucosaminidase (NAG) activity, beta(2)-microglobulin (B2MG) concentration, and for the stiffness index (STIFF) of calcaneal bone using an ultrasound method. The urinary Cd in the subjects, with a mean and range of 2.87 and 0.25-11.4 microg/g creatinine, respectively, showed a significant correlation with NAG but not with B2MG. STIFF was significantly inversely correlated with urinary Cd, and the association remained significant after adjusting for age, body weight, and menstrual status, suggesting a significant effect of Cd on the bone loss in these subjects without signs of Cd-induced kidney damage. A two-fold increase in urinary Cd was accompanied by a decrease in STIFF corresponding to a 1.7-year rise in age. These results emphasize the need for reassessment of the significance of Cd exposure in the general Japanese population.     

Assessment of the filtration reserve capacity of the kidney in workers exposed to cadmium.

It has been assessed whether an internal dose of cadmium (Cd), as reflected by a Cd concentration in urine not yet sufficient to induce a significantly increased urinary excretion of various plasma proteins (microproteinuria defined as beta 2-microglobulin in urine greater than 300 micrograms/g creatinine, or retinol-binding protein in urine greater than 300 micrograms/g creatinine, or albumin in urine greater than 15 mg/g creatinine, or a combination of these), may affect the filtration reserve capacity of the kidney. The last was determined by measuring the difference between the baseline creatinine clearance and the maximal creatinine clearance after an acute oral load of protein (400 g of cooked red meat). In total 215 men were examined of whom eventually 87 Cd exposed workers (concentration of Cd in urine greater than 2 micrograms/g creatinine) from zinc/cadmium smelters and 92 control workers (concentration of Cd in urine less than 2 micrograms/g creatinine, absence of microproteinuria, normal fasting serum creatinine) were retained for data analysis performed separately for workers aged less or more than 50 years. Microproteinuria was present in 20 Cd workers, all older than 50. This study confirmed the previous observation that the age related decline of the baseline glomerular filtration rate (GFR) is accelerated in male workers with Cd induced microproteinuria; the same observation was made for the maximal GFR. It was found, however, that a renal Cd burden that had not yet caused microproteinuria did not impair the filtration reserve capacity of the kidney. This study therefore validates the previous estimate of the threshold effect concentration of Cd in urine (10 micrograms/g creatinine) that is intended to prevent the occurrence of microproteinuria in male Cd workers. It should be kept in mind, however, that because of the likely interference of the healthy worker effect, this conclusion may not be directly extrapolated to the general population.     

Concentration of cadmium in rice and urinary indicators of renal dysfunction.

OBJECTIVES: (1) To examine the relation between concentrations of cadmium (Cd) in rice and urinary concentrations of indicators of renal dysfunction and the prevalence of abnormalities in urine in areas polluted by Cd. (2) To establish the maximum allowable concentration of Cd in rice from these findings. METHODS: The target population consisted of 1703 inhabitants (832 men and 871 women) aged over 50 years who consumed home grown rice and had lived in the same hamlet in areas polluted by Cd in the Kakehashi River basin in Ishikawa Prefecture, Japan for at least 30 years. The correlation coefficients between concentrations of Cd in rice and several urinary substances, the prevalence of abnormalities in urine and sex in hamlets polluted by Cd were calculated. Finally, regression analysis was performed for significant indicators to calculate the maximum allowable concentration of Cd in rice based on values in a control group. CONCLUSIONS: Significant correlations between concentration of Cd in rice and concentrations of urinary beta 2-microglobulin, metallothionein, glucose, and aminonitrogen were established. Similarly, there were significant correlations between concentration of Cd in rice and the prevalence of beta 2-microglobulinuria, metallothioneinuria, glucosuria, proteinuria, proteinuria with glucosuria, and aminonitrogenuria. The highest maximum allowable concentration of Cd in rice calculated for these indicators was 0.34 ppm/l and 0.29 ppm/g creatinine. Both values are lower than 0.4 ppm, the tentative limit prescribed by the Japanese government.     

Cardiovascular risk factor distribution above the age of 75 years in a Belgian community

An elderly Belgian population group anno 1986 consisting of 53 men and 110 women above the age of 75 years with a mean age of 80 and 81 years, respectively, is characterized by relative obesity and low diastolic blood pressure, both in men and women. The SBP/DBP ratio is 1.91 in men and 1.88 in women. HDL-cholesterol levels are relatively high in men. Women still have slightly higher HDL-cholesterol levels than men, the difference between women and men being 3.4 mg/dl. In both sexes HDL-cholesterol correlates negatively with body weight. The 24-hour urinary sodium/potassium ratio is 2.9 in men and 2.5 in women. Factors significantly related to diastolic blood pressure in a multiple regression analysis included being on a low-salt diet, the level of 24-hour urinary potassium excretion and of 24-hour urinary creatinine excretion in men, and body weight, heart rate and the level of 24-hour urinary calcium excretion in women. It may be concluded that significant differences exist between the distribution of cardiovascular risk factors in older compared to middle-aged subjects.