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Lead blood concentrations and renal function evaluation: Study in an exposed Mexican population
ARTICLE IN PRESS
Environmental Research 100 (2006) 227–231 www.elsevier.com/locate/envres
Lead blood concentrations and renal function evaluation: Study in an exposed Mexican population Maria I. Herna´ndez-Serratoa, Teresa Imelda Fortoulb, Rosalba Rojas-Martı´ neza, Laura R. Mendoza-Alvaradoa, Lourdes Canales-Trevin˜oc, Tommaso Bochichio-Riccardellid, Maria Rosa A´vila-Costab, Gustavo Olaiz-Ferna´ndeza, a Instituto Nacional de Salud Pu´blica. Cuernavaca, Me´xico Departamento de Biologı´a Celular y Tisular, Facultad de Medicina, Universidad Nacional Auto´noma de Me´xico, Mexico c Grupo Precisio´n Diagno´stica S.A. de C.V., Mexico d Unidad de Nefrologı´a, Dia´lisis y Trasplante S.A. de C.V., Cuernavaca, Me´xico
b
Received 14 October 2004; received in revised form 22 February 2005; accepted 7 March 2005 Available online 2 May 2005
Abstract The relation of blood Pb concentrations and renal dysfunction has been reported in association with interstitial fibrosis, tubular atrophy, and decreased glomerular filtration. In this report information about blood Pb concentrations and renal function tests in a population from Oaxaca, Mexico is analyzed. The main changes found were that males had higher blood Pb concentrations than females (Po0:0012); the leading variables associated with this were occupation (glazed pottery workers, P ¼ 0:0001) and the use of glazed pottery for preparing meals (P ¼ 0:0000). Variables that better explain uric acid variability were blood Pb concentrations, sex, weight, and height (r2 ¼ 0:23). Hyperuricemia was associated with blood Pb concentrations above 40 mg/dL (OR ¼ 1.74, 95% CI, 1.12–2.61). SCr was associated with sex, age, and blood Pb, with coefficient r2 ¼ 0:12. Our findings might be related to inadequate control of oven emissions, a situation that will require further analysis and the implementation of preventive measurements for the nonoccupational exposed population. r 2005 Elsevier Inc. All rights reserved. Keywords: Blood Pb; Renal function test; Folk workers; Hyperuricemia; Gender differences
1. Introduction Information about renal function modification and lead (Pb) exposure has been reported (Batuman, 1993; Benett, 1985; Hong et al., 1980), including interstitial fibrosis, tubular atrophy, and decreased glomerular filtration, as well as its irreversible and asymptomatic evolution as a consequence of the exposure (Loghman Adhan, 1997; Nolan and Shaikn, 1992). Those with blood Pb concentrations above 40 mg/dL had a higher risk of renal damage than subjects with lower blood Pb Corresponding author.
E-mail addresses: [email protected] (T.I. Fortoul), [email protected], [email protected] (G. Olaiz-Ferna´ndez). 0013-9351/$ - see front matter r 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.envres.2005.03.004
concentrations (Landrigan, 1990; Staudinger Kevin and Roth Victor, 1998). However, other risk factors for renal damage disclosed in the literature in adults are history of ingestion of leaded paint during childhood, illegal distilled alcohol, such as whiskey, or long history of occupational exposure (Benett, 1985; Ritz et al., 1988; Yu, 1983). Several investigators have reported a correlation between lead exposure and renal dysfunction (Ehrlich et al., 1998; Staessen et al., 1992; Ven-Shing et al., 2002); however, contradictory information about positive correlation of blood Pb concentrations and elevated blood urea nitrogen, creatinine, uric acid, and albumin has been documented (Gerhardsson et al., 1992; Roels et al., 1994; Verschoor et al., 1987).
ARTICLE IN PRESS 228
M.I. Herna´ndez-Serrato et al. / Environmental Research 100 (2006) 227–231
A previous report from our group in Oaxaca, Mexico, studying a population of pottery workers, identified that blood Pb concentrations were above 40 mg/dL, but also the nonexposed population had blood Pb concentrations similar to those found in the pottery workers (Herna´ndez-Serrato et al., 2003). With this information we decided to identify the risk factors related to the blood Pb concentrations in this population and to associate these concentrations with renal function tests.
2. Materials and methods 2.1. Population A cross-sectional study design was utilized with a sample of 553 subjects over the age of 15 yr. Sample size was also determined according to the sample required for the prevalence study on kidney damage. In a prior study, researchers identified the prevalence of kidney damage in the population of Atzompa at 10% (unpublished). A 95% confidence level and 80% precision were applied, along with the expected frequency, from the formula N ¼ Z21x/2 (1P)/E2P, where N is the sample size, Z21x/2 the confidence level, P the frequency of phenomenon, and E2 the desired precision. One out of three homes in a total population of 185 homes was randomly selected based on the population census that reported an average of three residents within the target age group per home. 2.1.1. Questionnaire Data were collected by direct interviews conducted by public health nurses, who first obtained signed informed consent and provided information on study objectives, procedures, and implications to participants. The study was approved by the Human Research Committee from the Institute National of Health Public. The information was obtained by direct interview in the dwellers with a structured questionnaire. The information obtained was demographic characteristics and environmental and occupational data. Past or present history of smoking, alcohol diabetes, hypertension, renal diseases or gout was also included. The sample collection was done in 1996. 2.2. Blood sampling The same day of the interview, two blood samples were obtained by venopuncture. The first sample was obtained with a vacutainer containing EDTA K3 anticoagulant for blood Pb detection. Samples were stored at 4 1C until the analysis was performed. Blood Pb was determined as described elsewhere (Olaiz et al.,
1997) by atomic absorption spectrometry (Perkin–Elmer Model 2100). The second sample was also obtained in a vacutainer tube with no anticoagulant. The tubes were kept at ambient temperature and processed almost immediately for creatinine (SCr), uric acid (AU), urea (U), total proteins (TP) and albumin (A). Colorimetric methods were used in all the samples following the WHO protocols (Fawcett and Scott, 1960; Fossati et al., 1980; Slot, 1965) using a semiautomated clinical chemistry analyzer Microlab 200, Spinreact (Spain). 2.3. Statistical analysis Continuous variables were analyzed in their original distribution scale, and others were categorized. Two groups were structured, taking into account blood Pb concentrations: Group I (0–39.9 mg/dL), Group II (X40 mg/dL). Other independent variables included in the analysis were sex, age, height, weight, occupation, and use of glazed pottery for cooking. Smoking, and alcohol, entered as dummy variables. Those participants with blood AU47.0 mg/dL were considered as hyperuricemic; creatinemia was defined when blood concentrations were above 1.5 mg/dL of SCr, and uremia when blood urea concentrations were over 50 mg/dL. Descriptive analysis included the estimation of mean values and standard deviations (SD) for continuous variables. Categorical variables were compared by the w2 test; odds ratios (OR) were to estimate 95% confidence intervals (CI). Stratified analysis was used to determine possible confounding variables as well as interactions between variables. Multiple regression analysis was used to examine the relation between the renal function test and other variables, with outliers included. Finally, logistic regression was performed to compute the OR based on the comparison between numbers of participants with abnormal values of renal function, and the model was adjusted for age and sex; significance level was set at 0.05. Data were analyzed with the SAS statistics program, version 8.0 for Windows.
3. Results Information was obtained from 413 individuals older than 15 of the 553 originally selected subjects (74.6%). Nonresponse was associated with migration and resistance to blood testing. The majority of respondents were females (62.2%); the mean ages of males and females were 39.7 and 35.7 yr, respectively. In Table 1 average values and standard deviations from the renal function markers are included. The urea mean value in the population was 33.1711.7 mg/dL in 19(4.6%) of the evaluated subjects, and the values were above the
ARTICLE IN PRESS M.I. Herna´ndez-Serrato et al. / Environmental Research 100 (2006) 227–231
229
Table 1 Biological markers of renal function from adults Mean7SD
Age (year) Height Weight U (mg/dL) SCr (mg/dL) AU (mg/dL) Pb (mg/dL)
Po0:001;
General population n ¼ 413
Male n ¼ 156
Female n ¼ 257
Percentage (number) of subjects with abnormal values General population n ¼ 413
37.2716.3 149.4711.4 53.5711.4 33.1711.7 0.970.23 6.471.90 43.5714.5
39.7716.7** 157.277.4* 58.777.8* 33.779.8 1.070.1 7.471.6* 46.6714.1**
35.7715.9 144.6710.7 50.474 32.7712.7 0.970.2 5.871.5 42.2713.3
4.6 2.9 46.2 59.1
(19) (12) (191) (244)
Po0:05.Note: Subjects with abnormal values are defined as having U450 mg/dL, SCr41.5 mg/dL, AU47.0 mg/dL, PbX40 mg/dL.
Table 2 Odds rations for differences blood lead concentration Blood Pb
X40 o40 40–49.9 50–59.9 X60 w2 for trend P value
Glazed pottery used
Exposure occupation
Yes No R.M. (n) (n)
CI 95%
Yes No (n) (n)
R.M.
214 124 95 71 48
1.56–4.27 158 86 Reference 59 110 0.95–3.10 62 53 1.24–5.33 59 22 37 11
3.42 1.00 2.18 5.00 6.27
30 45 20 10 0
2.58 1.00 1.72 2.57 N/A 1.150 0.28358
Smoking
Alcohol consumption
CI 95%
Yes No (n) (n)
R.M.
CI 95%
Yes No (n) (n)
R.M.
CI 95%
2.28–5.13 Reference 1.34–3.53 2.85–5.77 3.13–12.56
47 15 24 14 9
2.46 1.00 2.73 2.14 2.39
1.32–4.56 Reference 1.36–5.48 0.98–4.69 0.96–5.81
67 33 34 17 16
1.58 1.00 1.79 1.09 2.06
0.98–2.54 References 1.03–3.12 0.56–2.11 1.01–4.19
44.109 0.00010
reference values (RV) (20–50 mg/dL). Blood SCr was above RV in 12 (2.9%) subjects, and no differences between sexes was identified (P ¼ 0:1957). When AU was analyzed, 46.2% of the population had blood values above RV and in the male population the concentrations were higher (Po0:0001). Average blood Pb values were 43.5714.5 mg/dL, and in males the concentrations were higher than in females (46.6 vs 42.2 mg/dL, Po0:0012). The main exposure sources for this population are indicated in Table 2. The use of glazed pottery increased 1.7 times for blood Pb concentrations between 40 and 49.9 mg/dL, while in those with 50–59.9 mg/dL the risk was 2.57 (CI, 1.24–5.33); however, this increased risk was statistically significant (P ¼ 0:00001). Glazed pottery workers had the higher risk for blood Pb values compared to those with other occupations not related to pottery, as it is shown in Table 2 and these differences were statistically significant (P ¼ 0:0001). Table 3 shown those variables related to SCr, which were sex, age, and blood Pb concentrations with a coefficient of multiple determination r2 ¼ 0:12 (Po0:001). However, AU was associated with blood Pb concentrations, sex, body weight, and height, which
196 154 90 67 39
4.407 0.03580
174 136 78 64 32
2.41600 0.1200
were the variables that better explained the uric acid blood concentrations, (coefficient r2 ¼ 0:23). Table 4 demonstrates the association between higher seric uric acid and blood Pb concentrations, which was significant, with OR 1.75 (95% CI, 1.16–2.62). There were no significant differences in creatinemia and uremia between subjects in the two categories of blood Pb level. However, subjects with SCr41.5 mg/dl still had an increased percentage of higher blood Pb level.
4. Discussion The present results indicate that blood Pb concentrations were higher in males (46.6 mg/dL) than in females (42.2 mg/dL) in this population. The main risk factors identified were the use of lead glazed pottery and occupation, data consistent with our previous findings and supported by others (Herna´ndez-Avila et al., 1991; Olaiz et al., 1997; Rojas-Lo´pez et al., 1994). When those individuals who worked in glazed pottery production or used it in meal preparation were eliminated, the blood Pb concentration in the remaining population was 32.6 mg/dL. This suggest a possible
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Table 3 Results of multiple regression model of renal function test Variable
Independent variables
Coefficient
SD
P
Serum creatinine
Intercept Sex Age Blood lead concentration
1.1165 0.1213 0.0029 0.0017
0.0623 0.0225 0.0006 0.0007
o0.0001 o0.0001 o0.0001 0.0304
Intercept Age
13.76193 0.1501
0.70463 0.0345
o0.0001 o0.0001
Intercept Blood lead concentration Sex Weight Height
10.6867 0.0167 1.663 0.3030 0.0260
1.5593 0.0060 0.2088 0.0078 0.0087
o0.0001 0.0059 o0.0001 0.0001 0.0032
Serum urea Serum uric acid
Table 4 Relationship between blood Pb and renal function in the population of Oaxaca, Mexico Variables
Hyperuricemia 47 mg/dL p7 mg/dL Uremia 450 mg/dL p50 mg/dL Creatinemia 41.5 mg/dL p1.5 mg/dL
Adjusteda
Blood Pb o40 mg/dL n ¼ 169
X40 mg/dL n ¼ 244
P
OR
95% CI
63 106
128 116
0.0024
1.75
1.16—2.62
5
14
0.1855
2.04
0.71—5.84
164
230 0.5880
1.47
0.41—5.17
4 165
8 236
Note: OR, odds ratio; CI, confidence interval. a Adjusted by sex and age.
chronic environmental exposure to Pb, but we did not monitored the environment to support this assumption; however, in another study, in which environmental Pb concentrations were evaluated around those places in which the glazms is performed, the Pb values were very high (Robin et al., 1999). Our findings might be related to inadequate control of oven emissions from this place, and for this reason, all the population is exposed to Pb in the air, a situation that was evident because of the high blood Pb concentrations in the exposed nonworker population. We consider that the main contribution of this report is the significant association between hyperuricemia and high blood Pb concentrations, which in other studies has been associated with renal function damage as VenShing Wang and others had reported (Chia et al., 1995; Jung et al., 1998). It is also of interest that in this population the uric acid was higher in males than in females; this could be explained as a consequence of the
r2
0.12
0.04
0.23
ingestion of illegal distilled alcohol among males, as we previously reported (Herna´ndez-Serrato et al., 2003). It is important to stress the absence of regulations about the blood Pb limits for those who are exposed to this metal at work. However, with our results, we suggest that the maximum blood Pb concentration should be p40 mg/dL and support this with a blood uric acid determination to eliminate possible renal damage among these workers. Some other authors support the use of blood uric acid as a predictor of the development of renal pathology hypothesis (Johnson et al., 1999, 2003; Kang et al., 2002), which might be analyzed in future studies. Also, an association between blood Pb and creatinemia was observed with r2 ¼ 0:12, which is another biomarker of renal damage and more widely accepted (Levey, 1990; Perrone et al., 1992). These findings point out the need to strengthen the initiative to reduce exposure lead sources, particularly lead-glazed ceramics, and thus lower the lead levels of the population that live near these folk art industrial areas, such as Oaxaca, Mexico. Finally, we stress the importance of the implementation of other preventive measurements, such as the use of personal protection equipment and regular medical supervision in order to prevent renal function damage. We have to emphasize that glazed pottery in Mexico is the source of employment for several families and also an industry that involves folk art and a cultural expression of some ethnic groups in Mexico.
References Batuman, V., 1993. Lead nephropathy gout, and hypertension. Am. J. Med. Sci. 305, 241–247. Benett, W.M., 1985. Lead nephropathy. Kidney Int. 28, 212–220. Chia, K.S., Jeyaratnam, J., Tan, C., Ong, H.Y., Ong, C.N., Lee, E., 1995. Glomerular function of lead workers. Toxicol. Lett. 77, 319–328.
ARTICLE IN PRESS M.I. Herna´ndez-Serrato et al. / Environmental Research 100 (2006) 227–231 Ehrlich, R., Robins, T., Jordaan, E., Miller, S., Mbuli, S., Selby, P., Wynchank, S., Cantrell, A., De Broe, M., D’ Haese, P., Tood, A., Landrigan, P., 1998. Lead absorption and renal dysfunction in a South African battery factory. Occup. Environ. Med. 55, 453–460. Fawcett, J.K., Scott, J.E., 1960. A rapid and precise method for the determination of urea. J. Clin. Pathol. 13, 156–159. Fossati, P., Prencipe, L., Berti, G., 1980. Use of 3,5-dichloro-2hydroxybenzenesulfonic acid/4-aminophenazone chromogenic system in direct enzymic assay of uric acid in serum an urine. Clin. Chem. 26 (2), 227–231. Gerhardsson, L., Chettle, D.R., Englyst, V., Nordberg, G.F., Nyhlin, Scott, M.C., Todd, A.C., Vesterberg, O., 1992. Kidney effects in long-term exposed lead smelter worker. Br. J. Ind. Med. 49, 186–192. Herna´ndez-Avila, M., Romieu, I., Rı´ os, C., et al., 1991. Lead-glazed ceramics as major determinants of blood lead levels in Mexican women. Environ. Health. Perspect. 94, 117–120. Herna´ndez-Serrato, Ma.I., Mendoza-Alvarado, L.R., Rojas-Martı´ nez, R., Gonza´lez-Garza, C., Meghan-Hulme, J., Olaiz Ferna´ndez, G., 2003. Factors associated with lead exposure in Oaxaca, Mexico. J. Expo. Anal. Environ. Epidemiol. 13 (5), 341–347. Hong, C.D., Hanenson, I.B., Lerner, S., Hammond, P.B., Pesce, A.J., Pollak, V.E., 1980. Occupational exposure lead: effects on renal function. Kidney Int. 18, 489–494. Johnson, R.J., Kivlighn, S.D., Kim, Y.G., Suga, S., Fogo, A.B., 1999. Reappraisal of the pathogenesis and consequences of hyperuricemia in hypertension, cardiovascular disease, and renal disease. Am. J. Kidney Dis. 33 (2), 225–234. Johnson, R.J., Kang, D.H., Feig, D., Kivlighn, S., Kanellis, J., Watanabe, S., Tuttle, K.R., Rodriguez-Iturbe, B., Herrera-Acosta, J., Mazzali, M., 2003. Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease? Hypertension 41 (6), 1183–1190. Jung, K.Y., Lee, S.J., Kim, J.Y., Hong, Y.S., Kim, S.R., Kim, J.Y., Song, J.B., 1998. Renal dysfunction indicators in lead exposed workers. J. Occup. Health 40, 103–109. Kang, D.H., Nakagawa, T., Feng, L., Watanabe, S., Han, L., Mazzali, M., Truong, L., Harris, R., Johnson, R.J., 2002. A role for uric acid in the progression of renal disease. J. Am. Soc. Nephrol. 13 (12), 2888–2897. Landrigan, P.J., 1990. Current issues in the epidemiology and toxicology of occupational lead exposure. Environ. Health Perspect. 89, 61–66.
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Levey, A.S., 1990. Measurement of renal function in chronic renal disease. Kidney Int. 38, 167–184. Loghman Adhan, M., 1997. Renal effects of environmental and occupational lead exposure. Environ. Health Perspect. 105 (9), 928–939. Nolan, C.V., Shaikn, Z.A., 1992. Lead nephrotoxicity and associated disorder: biochemical mechanisms. Toxicology 73, 127–146. Olaiz, G., Rojas, R., Fortoul, T.J., Palazuelos, E., 1997. High blood lead levels in ceramic folk art workers, Michoacan, Mexico. Arch. Environ. Health 52 (1), 51–55. Perrone, R.D., Madias, N.E., Levey, A.S., 1992. Serum creatinine as an index of renal function: new insights into old concepts. Clin. Chem. 38, 1933–1953. Ritz, E., Mann, J., Stoeppler, M., 1988. Lead and the kidney. Adv. Nephrol. 17, 241–274. Robin, Hibbert, Zhipeng, Bai, Jaime, Navia, Daniel, M.K., Junfeng (Jin), Zhang, 1999. High lead exposures resulting from pottery production in village in Michoaca´n State, Mexico. J. Expo. Anal. Environ. Epidemiol. 9, 343–351. Roels, H., Lauwerys, R., Konings, J., Buchet, J.P., Bernard, A., Green, S., Bradley, D., Morgan, W., Chettle, D., 1994. Renal function and hyperfiltration capacity in lead smelter worker with high bone lead. Occup. Environ. Med. 51, 505–512. Rojas-Lo´pez, M., Santos-Burgoa, C., Rı´ os, C., et al., 1994. Use of lead-glazed ceramics is the main factor associated to high lead in blood levels in two Mexican rural communities. J. Toxicol. Environ. Health 42, 45–52. Slot, C., 1965. Plasma creatinine determination: a new and specific Jaffe reaction method. Scand. J. Clin. Lab. Invest. 17 (4), 381–387. Staessen, J.A., Robert, R., Lauwerys, Buchet, J.P., et al., 1992. Impairment of renal function with increasing blood lead concentrations in the general population. N. Engl. J. Med. 327, 151–156. Staudinger Kevin, C., Roth Victor, S., 1998. Occupational lead poisoning. Am. Fam. Physician. Ven-Shing, Wang, Ming-Tsung, Lee, Jyh-Yann, Chiou, Chiam-Fang, Guu, Chin-Ching, Wu, Jim-Shoung, Lai, 2002. Relationship between blood lead levels and renal function in lead battery workers. Int. Arch. Occup. Environ. Health 75, 569–575. Verschoor, M., Wibowo, A., Herber, R., van Hemmen, J., Zielhuis, R., 1987. Influence of occupational low-level lead exposure on renal parameters. Am. J. Ind. Med. 12, 341–351. Yu, T.F., 1983. Lead nephropathy and gout. Am. J. Kidney Dis. 2, 555–558.
Environmental Research 100 (2006) 227–231 www.elsevier.com/locate/envres
Lead blood concentrations and renal function evaluation: Study in an exposed Mexican population Maria I. Herna´ndez-Serratoa, Teresa Imelda Fortoulb, Rosalba Rojas-Martı´ neza, Laura R. Mendoza-Alvaradoa, Lourdes Canales-Trevin˜oc, Tommaso Bochichio-Riccardellid, Maria Rosa A´vila-Costab, Gustavo Olaiz-Ferna´ndeza, a Instituto Nacional de Salud Pu´blica. Cuernavaca, Me´xico Departamento de Biologı´a Celular y Tisular, Facultad de Medicina, Universidad Nacional Auto´noma de Me´xico, Mexico c Grupo Precisio´n Diagno´stica S.A. de C.V., Mexico d Unidad de Nefrologı´a, Dia´lisis y Trasplante S.A. de C.V., Cuernavaca, Me´xico
b
Received 14 October 2004; received in revised form 22 February 2005; accepted 7 March 2005 Available online 2 May 2005
Abstract The relation of blood Pb concentrations and renal dysfunction has been reported in association with interstitial fibrosis, tubular atrophy, and decreased glomerular filtration. In this report information about blood Pb concentrations and renal function tests in a population from Oaxaca, Mexico is analyzed. The main changes found were that males had higher blood Pb concentrations than females (Po0:0012); the leading variables associated with this were occupation (glazed pottery workers, P ¼ 0:0001) and the use of glazed pottery for preparing meals (P ¼ 0:0000). Variables that better explain uric acid variability were blood Pb concentrations, sex, weight, and height (r2 ¼ 0:23). Hyperuricemia was associated with blood Pb concentrations above 40 mg/dL (OR ¼ 1.74, 95% CI, 1.12–2.61). SCr was associated with sex, age, and blood Pb, with coefficient r2 ¼ 0:12. Our findings might be related to inadequate control of oven emissions, a situation that will require further analysis and the implementation of preventive measurements for the nonoccupational exposed population. r 2005 Elsevier Inc. All rights reserved. Keywords: Blood Pb; Renal function test; Folk workers; Hyperuricemia; Gender differences
1. Introduction Information about renal function modification and lead (Pb) exposure has been reported (Batuman, 1993; Benett, 1985; Hong et al., 1980), including interstitial fibrosis, tubular atrophy, and decreased glomerular filtration, as well as its irreversible and asymptomatic evolution as a consequence of the exposure (Loghman Adhan, 1997; Nolan and Shaikn, 1992). Those with blood Pb concentrations above 40 mg/dL had a higher risk of renal damage than subjects with lower blood Pb Corresponding author.
E-mail addresses: [email protected] (T.I. Fortoul), [email protected], [email protected] (G. Olaiz-Ferna´ndez). 0013-9351/$ - see front matter r 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.envres.2005.03.004
concentrations (Landrigan, 1990; Staudinger Kevin and Roth Victor, 1998). However, other risk factors for renal damage disclosed in the literature in adults are history of ingestion of leaded paint during childhood, illegal distilled alcohol, such as whiskey, or long history of occupational exposure (Benett, 1985; Ritz et al., 1988; Yu, 1983). Several investigators have reported a correlation between lead exposure and renal dysfunction (Ehrlich et al., 1998; Staessen et al., 1992; Ven-Shing et al., 2002); however, contradictory information about positive correlation of blood Pb concentrations and elevated blood urea nitrogen, creatinine, uric acid, and albumin has been documented (Gerhardsson et al., 1992; Roels et al., 1994; Verschoor et al., 1987).
ARTICLE IN PRESS 228
M.I. Herna´ndez-Serrato et al. / Environmental Research 100 (2006) 227–231
A previous report from our group in Oaxaca, Mexico, studying a population of pottery workers, identified that blood Pb concentrations were above 40 mg/dL, but also the nonexposed population had blood Pb concentrations similar to those found in the pottery workers (Herna´ndez-Serrato et al., 2003). With this information we decided to identify the risk factors related to the blood Pb concentrations in this population and to associate these concentrations with renal function tests.
2. Materials and methods 2.1. Population A cross-sectional study design was utilized with a sample of 553 subjects over the age of 15 yr. Sample size was also determined according to the sample required for the prevalence study on kidney damage. In a prior study, researchers identified the prevalence of kidney damage in the population of Atzompa at 10% (unpublished). A 95% confidence level and 80% precision were applied, along with the expected frequency, from the formula N ¼ Z21x/2 (1P)/E2P, where N is the sample size, Z21x/2 the confidence level, P the frequency of phenomenon, and E2 the desired precision. One out of three homes in a total population of 185 homes was randomly selected based on the population census that reported an average of three residents within the target age group per home. 2.1.1. Questionnaire Data were collected by direct interviews conducted by public health nurses, who first obtained signed informed consent and provided information on study objectives, procedures, and implications to participants. The study was approved by the Human Research Committee from the Institute National of Health Public. The information was obtained by direct interview in the dwellers with a structured questionnaire. The information obtained was demographic characteristics and environmental and occupational data. Past or present history of smoking, alcohol diabetes, hypertension, renal diseases or gout was also included. The sample collection was done in 1996. 2.2. Blood sampling The same day of the interview, two blood samples were obtained by venopuncture. The first sample was obtained with a vacutainer containing EDTA K3 anticoagulant for blood Pb detection. Samples were stored at 4 1C until the analysis was performed. Blood Pb was determined as described elsewhere (Olaiz et al.,
1997) by atomic absorption spectrometry (Perkin–Elmer Model 2100). The second sample was also obtained in a vacutainer tube with no anticoagulant. The tubes were kept at ambient temperature and processed almost immediately for creatinine (SCr), uric acid (AU), urea (U), total proteins (TP) and albumin (A). Colorimetric methods were used in all the samples following the WHO protocols (Fawcett and Scott, 1960; Fossati et al., 1980; Slot, 1965) using a semiautomated clinical chemistry analyzer Microlab 200, Spinreact (Spain). 2.3. Statistical analysis Continuous variables were analyzed in their original distribution scale, and others were categorized. Two groups were structured, taking into account blood Pb concentrations: Group I (0–39.9 mg/dL), Group II (X40 mg/dL). Other independent variables included in the analysis were sex, age, height, weight, occupation, and use of glazed pottery for cooking. Smoking, and alcohol, entered as dummy variables. Those participants with blood AU47.0 mg/dL were considered as hyperuricemic; creatinemia was defined when blood concentrations were above 1.5 mg/dL of SCr, and uremia when blood urea concentrations were over 50 mg/dL. Descriptive analysis included the estimation of mean values and standard deviations (SD) for continuous variables. Categorical variables were compared by the w2 test; odds ratios (OR) were to estimate 95% confidence intervals (CI). Stratified analysis was used to determine possible confounding variables as well as interactions between variables. Multiple regression analysis was used to examine the relation between the renal function test and other variables, with outliers included. Finally, logistic regression was performed to compute the OR based on the comparison between numbers of participants with abnormal values of renal function, and the model was adjusted for age and sex; significance level was set at 0.05. Data were analyzed with the SAS statistics program, version 8.0 for Windows.
3. Results Information was obtained from 413 individuals older than 15 of the 553 originally selected subjects (74.6%). Nonresponse was associated with migration and resistance to blood testing. The majority of respondents were females (62.2%); the mean ages of males and females were 39.7 and 35.7 yr, respectively. In Table 1 average values and standard deviations from the renal function markers are included. The urea mean value in the population was 33.1711.7 mg/dL in 19(4.6%) of the evaluated subjects, and the values were above the
ARTICLE IN PRESS M.I. Herna´ndez-Serrato et al. / Environmental Research 100 (2006) 227–231
229
Table 1 Biological markers of renal function from adults Mean7SD
Age (year) Height Weight U (mg/dL) SCr (mg/dL) AU (mg/dL) Pb (mg/dL)
Po0:001;
General population n ¼ 413
Male n ¼ 156
Female n ¼ 257
Percentage (number) of subjects with abnormal values General population n ¼ 413
37.2716.3 149.4711.4 53.5711.4 33.1711.7 0.970.23 6.471.90 43.5714.5
39.7716.7** 157.277.4* 58.777.8* 33.779.8 1.070.1 7.471.6* 46.6714.1**
35.7715.9 144.6710.7 50.474 32.7712.7 0.970.2 5.871.5 42.2713.3
4.6 2.9 46.2 59.1
(19) (12) (191) (244)
Po0:05.Note: Subjects with abnormal values are defined as having U450 mg/dL, SCr41.5 mg/dL, AU47.0 mg/dL, PbX40 mg/dL.
Table 2 Odds rations for differences blood lead concentration Blood Pb
X40 o40 40–49.9 50–59.9 X60 w2 for trend P value
Glazed pottery used
Exposure occupation
Yes No R.M. (n) (n)
CI 95%
Yes No (n) (n)
R.M.
214 124 95 71 48
1.56–4.27 158 86 Reference 59 110 0.95–3.10 62 53 1.24–5.33 59 22 37 11
3.42 1.00 2.18 5.00 6.27
30 45 20 10 0
2.58 1.00 1.72 2.57 N/A 1.150 0.28358
Smoking
Alcohol consumption
CI 95%
Yes No (n) (n)
R.M.
CI 95%
Yes No (n) (n)
R.M.
CI 95%
2.28–5.13 Reference 1.34–3.53 2.85–5.77 3.13–12.56
47 15 24 14 9
2.46 1.00 2.73 2.14 2.39
1.32–4.56 Reference 1.36–5.48 0.98–4.69 0.96–5.81
67 33 34 17 16
1.58 1.00 1.79 1.09 2.06
0.98–2.54 References 1.03–3.12 0.56–2.11 1.01–4.19
44.109 0.00010
reference values (RV) (20–50 mg/dL). Blood SCr was above RV in 12 (2.9%) subjects, and no differences between sexes was identified (P ¼ 0:1957). When AU was analyzed, 46.2% of the population had blood values above RV and in the male population the concentrations were higher (Po0:0001). Average blood Pb values were 43.5714.5 mg/dL, and in males the concentrations were higher than in females (46.6 vs 42.2 mg/dL, Po0:0012). The main exposure sources for this population are indicated in Table 2. The use of glazed pottery increased 1.7 times for blood Pb concentrations between 40 and 49.9 mg/dL, while in those with 50–59.9 mg/dL the risk was 2.57 (CI, 1.24–5.33); however, this increased risk was statistically significant (P ¼ 0:00001). Glazed pottery workers had the higher risk for blood Pb values compared to those with other occupations not related to pottery, as it is shown in Table 2 and these differences were statistically significant (P ¼ 0:0001). Table 3 shown those variables related to SCr, which were sex, age, and blood Pb concentrations with a coefficient of multiple determination r2 ¼ 0:12 (Po0:001). However, AU was associated with blood Pb concentrations, sex, body weight, and height, which
196 154 90 67 39
4.407 0.03580
174 136 78 64 32
2.41600 0.1200
were the variables that better explained the uric acid blood concentrations, (coefficient r2 ¼ 0:23). Table 4 demonstrates the association between higher seric uric acid and blood Pb concentrations, which was significant, with OR 1.75 (95% CI, 1.16–2.62). There were no significant differences in creatinemia and uremia between subjects in the two categories of blood Pb level. However, subjects with SCr41.5 mg/dl still had an increased percentage of higher blood Pb level.
4. Discussion The present results indicate that blood Pb concentrations were higher in males (46.6 mg/dL) than in females (42.2 mg/dL) in this population. The main risk factors identified were the use of lead glazed pottery and occupation, data consistent with our previous findings and supported by others (Herna´ndez-Avila et al., 1991; Olaiz et al., 1997; Rojas-Lo´pez et al., 1994). When those individuals who worked in glazed pottery production or used it in meal preparation were eliminated, the blood Pb concentration in the remaining population was 32.6 mg/dL. This suggest a possible
ARTICLE IN PRESS M.I. Herna´ndez-Serrato et al. / Environmental Research 100 (2006) 227–231
230
Table 3 Results of multiple regression model of renal function test Variable
Independent variables
Coefficient
SD
P
Serum creatinine
Intercept Sex Age Blood lead concentration
1.1165 0.1213 0.0029 0.0017
0.0623 0.0225 0.0006 0.0007
o0.0001 o0.0001 o0.0001 0.0304
Intercept Age
13.76193 0.1501
0.70463 0.0345
o0.0001 o0.0001
Intercept Blood lead concentration Sex Weight Height
10.6867 0.0167 1.663 0.3030 0.0260
1.5593 0.0060 0.2088 0.0078 0.0087
o0.0001 0.0059 o0.0001 0.0001 0.0032
Serum urea Serum uric acid
Table 4 Relationship between blood Pb and renal function in the population of Oaxaca, Mexico Variables
Hyperuricemia 47 mg/dL p7 mg/dL Uremia 450 mg/dL p50 mg/dL Creatinemia 41.5 mg/dL p1.5 mg/dL
Adjusteda
Blood Pb o40 mg/dL n ¼ 169
X40 mg/dL n ¼ 244
P
OR
95% CI
63 106
128 116
0.0024
1.75
1.16—2.62
5
14
0.1855
2.04
0.71—5.84
164
230 0.5880
1.47
0.41—5.17
4 165
8 236
Note: OR, odds ratio; CI, confidence interval. a Adjusted by sex and age.
chronic environmental exposure to Pb, but we did not monitored the environment to support this assumption; however, in another study, in which environmental Pb concentrations were evaluated around those places in which the glazms is performed, the Pb values were very high (Robin et al., 1999). Our findings might be related to inadequate control of oven emissions from this place, and for this reason, all the population is exposed to Pb in the air, a situation that was evident because of the high blood Pb concentrations in the exposed nonworker population. We consider that the main contribution of this report is the significant association between hyperuricemia and high blood Pb concentrations, which in other studies has been associated with renal function damage as VenShing Wang and others had reported (Chia et al., 1995; Jung et al., 1998). It is also of interest that in this population the uric acid was higher in males than in females; this could be explained as a consequence of the
r2
0.12
0.04
0.23
ingestion of illegal distilled alcohol among males, as we previously reported (Herna´ndez-Serrato et al., 2003). It is important to stress the absence of regulations about the blood Pb limits for those who are exposed to this metal at work. However, with our results, we suggest that the maximum blood Pb concentration should be p40 mg/dL and support this with a blood uric acid determination to eliminate possible renal damage among these workers. Some other authors support the use of blood uric acid as a predictor of the development of renal pathology hypothesis (Johnson et al., 1999, 2003; Kang et al., 2002), which might be analyzed in future studies. Also, an association between blood Pb and creatinemia was observed with r2 ¼ 0:12, which is another biomarker of renal damage and more widely accepted (Levey, 1990; Perrone et al., 1992). These findings point out the need to strengthen the initiative to reduce exposure lead sources, particularly lead-glazed ceramics, and thus lower the lead levels of the population that live near these folk art industrial areas, such as Oaxaca, Mexico. Finally, we stress the importance of the implementation of other preventive measurements, such as the use of personal protection equipment and regular medical supervision in order to prevent renal function damage. We have to emphasize that glazed pottery in Mexico is the source of employment for several families and also an industry that involves folk art and a cultural expression of some ethnic groups in Mexico.
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