Abstract
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.
Full Text
The Full Text of this article is available as a PDF (483.5 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Alfvén T., Elinder C. G., Carlsson M. D., Grubb A., Hellström L., Persson B., Pettersson C., Spång G., Schütz A., Järup L. Low-level cadmium exposure and osteoporosis. J Bone Miner Res. 2000 Aug;15(8):1579–1586. doi: 10.1359/jbmr.2000.15.8.1579. [DOI] [PubMed] [Google Scholar]
- Barry P. S. A comparison of concentrations of lead in human tissues. Br J Ind Med. 1975 May;32(2):119–139. doi: 10.1136/oem.32.2.119. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berglund M., Akesson A., Nermell B., Vahter M. Intestinal absorption of dietary cadmium in women depends on body iron stores and fiber intake. Environ Health Perspect. 1994 Dec;102(12):1058–1066. doi: 10.1289/ehp.941021058. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Buchet J. P., Roels H., Bernard A., Lauwerys R. Assessment of renal function of workers exposed to inorganic lead, calcium or mercury vapor. J Occup Med. 1980 Nov;22(11):741–750. [PubMed] [Google Scholar]
- Goyer R. A., Epstein S., Bhattacharyya M., Korach K. S., Pounds J. Environmental risk factors for osteoporosis. Environ Health Perspect. 1994 Apr;102(4):390–394. doi: 10.1289/ehp.94102390. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hellström L., Elinder C. G., Dahlberg B., Lundberg M., Järup L., Persson B., Axelson O. Cadmium exposure and end-stage renal disease. Am J Kidney Dis. 2001 Nov;38(5):1001–1008. doi: 10.1053/ajkd.2001.28589. [DOI] [PubMed] [Google Scholar]
- Hu H., Milder F. L., Burger D. E. X-ray fluorescence measurements of lead burden in subjects with low-level community lead exposure. Arch Environ Health. 1990 Nov-Dec;45(6):335–341. doi: 10.1080/00039896.1990.10118752. [DOI] [PubMed] [Google Scholar]
- Ikeda M., Zhang Z. W., Higashikawa K., Watanabe T., Shimbo S., Moon C. S., Nakatsuka H., Matsuda-Inoguchi N. Background exposure of general women populations in Japan to cadmium in the environment and possible health effects. Toxicol Lett. 1999 Sep 5;108(2-3):161–166. doi: 10.1016/s0378-4274(99)00084-3. [DOI] [PubMed] [Google Scholar]
- Järup L., Alfvén T., Persson B., Toss G., Elinder C. G. Cadmium may be a risk factor for osteoporosis. Occup Environ Med. 1998 Jul;55(7):435–439. doi: 10.1136/oem.55.7.435. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Järup L., Berglund M., Elinder C. G., Nordberg G., Vahter M. Health effects of cadmium exposure--a review of the literature and a risk estimate. Scand J Work Environ Health. 1998;24 (Suppl 1):1–51. [PubMed] [Google Scholar]
- Järup L., Elinder C. G. Dose-response relations between urinary cadmium and tubular proteinuria in cadmium-exposed workers. Am J Ind Med. 1994 Dec;26(6):759–769. doi: 10.1002/ajim.4700260605. [DOI] [PubMed] [Google Scholar]
- Järup L., Elinder C. G., Spång G. Cumulative blood-cadmium and tubular proteinuria: a dose-response relationship. Int Arch Occup Environ Health. 1988;60(3):223–229. doi: 10.1007/BF00378700. [DOI] [PubMed] [Google Scholar]
- Järup L., Hellström L., Alfvén T., Carlsson M. D., Grubb A., Persson B., Pettersson C., Spång G., Schütz A., Elinder C. G. Low level exposure to cadmium and early kidney damage: the OSCAR study. Occup Environ Med. 2000 Oct;57(10):668–672. doi: 10.1136/oem.57.10.668. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Järup L., Persson B., Elinder C. G. Blood cadmium as an indicator of dose in a long-term follow-up of workers previously exposed to cadmium. Scand J Work Environ Health. 1997 Feb;23(1):31–36. doi: 10.5271/sjweh.175. [DOI] [PubMed] [Google Scholar]
- Järup L., Rogenfelt A., Elinder C. G., Nogawa K., Kjellström T. Biological half-time of cadmium in the blood of workers after cessation of exposure. Scand J Work Environ Health. 1983 Aug;9(4):327–331. doi: 10.5271/sjweh.2404. [DOI] [PubMed] [Google Scholar]
- Kanis J. A., Delmas P., Burckhardt P., Cooper C., Torgerson D. Guidelines for diagnosis and management of osteoporosis. The European Foundation for Osteoporosis and Bone Disease. Osteoporos Int. 1997;7(4):390–406. doi: 10.1007/BF01623782. [DOI] [PubMed] [Google Scholar]
- Kjellström T., Evrin P. E., Rahnster B. Dose-response analysis of cadmium-induced tubular proteinuria: a study of urinary beta2-microglobulin excretion among workers in a battery factory. Environ Res. 1977 Apr;13(2):303–317. doi: 10.1016/0013-9351(77)90106-2. [DOI] [PubMed] [Google Scholar]
- Koo W. W., Succop P. A., Bornschein R. L., Krug-Wispe S. K., Steinchen J. J., Tsang R. C., Berger O. G. Serum vitamin D metabolites and bone mineralization in young children with chronic low to moderate lead exposure. Pediatrics. 1991 May;87(5):680–687. [PubMed] [Google Scholar]
- Landrigan P. J., Todd A. C. Direct measurement of lead in bone. A promising biomarker. JAMA. 1994 Jan 19;271(3):239–240. [PubMed] [Google Scholar]
- Lauwerys R. R., Buchet J. P., Roels H. The relationship between cadmium exposure or body burden and the concentration of cadmium in blood and urine in man. Int Arch Occup Environ Health. 1976 Mar 9;36(4):275–285. doi: 10.1007/BF00409357. [DOI] [PubMed] [Google Scholar]
- Lilley J., Walters B. G., Heath D. A., Drolc Z. In vivo and in vitro precision for bone density measured by dual-energy X-ray absorption. Osteoporos Int. 1991 Jun;1(3):141–146. doi: 10.1007/BF01625443. [DOI] [PubMed] [Google Scholar]
- Loghman-Adham M. Renal effects of environmental and occupational lead exposure. Environ Health Perspect. 1997 Sep;105(9):928–938. doi: 10.1289/ehp.97105928. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mahaffey K. R., Rosen J. F., Chesney R. W., Peeler J. T., Smith C. M., DeLuca H. F. Association between age, blood lead concentration, and serum 1,25-dihydroxycholecalciferol levels in children. Am J Clin Nutr. 1982 Jun;35(6):1327–1331. doi: 10.1093/ajcn/35.6.1327. [DOI] [PubMed] [Google Scholar]
- Mason H. J., Williams N., Armitage S., Morgan M., Green S., Perrin B., Morgan W. D. Follow up of workers previously exposed to silver solder containing cadmium. Occup Environ Med. 1999 Aug;56(8):553–558. doi: 10.1136/oem.56.8.553. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nordberg M., Winblad B., Basun H. Cadmium concentration in blood in an elderly urban population. Biometals. 2000 Dec;13(4):311–317. doi: 10.1023/a:1009268123320. [DOI] [PubMed] [Google Scholar]
- Schlenker R. A., VonSeggen W. W. The distribution of cortical and trabecular bone mass along the lengths of the radius and ulna and the implications for in vivo bone mass measurements. Calcif Tissue Res. 1976 Apr 13;20(1):41–52. doi: 10.1007/BF02546396. [DOI] [PubMed] [Google Scholar]
- Shimbo S., Zhang Z. W., Moon C. S., Watanabe T., Nakatsuka H., Matsuda-Inoguchi N., Higashikawa K., Ikeda M. Correlation between urine and blood concentrations, and dietary intake of cadmium and lead among women in the general population of Japan. Int Arch Occup Environ Health. 2000 Apr;73(3):163–170. doi: 10.1007/s004200050023. [DOI] [PubMed] [Google Scholar]
- Staessen J. A., Lauwerys R. R., Buchet J. P., Bulpitt C. J., Rondia D., Vanrenterghem Y., Amery A. Impairment of renal function with increasing blood lead concentrations in the general population. The Cadmibel Study Group. N Engl J Med. 1992 Jul 16;327(3):151–156. doi: 10.1056/NEJM199207163270303. [DOI] [PubMed] [Google Scholar]
- Staessen J. A., Roels H. A., Emelianov D., Kuznetsova T., Thijs L., Vangronsveld J., Fagard R. Environmental exposure to cadmium, forearm bone density, and risk of fractures: prospective population study. Public Health and Environmental Exposure to Cadmium (PheeCad) Study Group. Lancet. 1999 Apr 3;353(9159):1140–1144. doi: 10.1016/s0140-6736(98)09356-8. [DOI] [PubMed] [Google Scholar]
- Tencer J., Thysell H., Andersson K., Grubb A. Stability of albumin, protein HC, immunoglobulin G, kappa- and lambda-chain immunoreactivity, orosomucoid and alpha 1-antitrypsin in urine stored at various conditions. Scand J Clin Lab Invest. 1994 May;54(3):199–206. doi: 10.1080/00365519409088425. [DOI] [PubMed] [Google Scholar]
- Tencer J., Thysell H., Grubb A. Analysis of proteinuria: reference limits for urine excretion of albumin, protein HC, immunoglobulin G, kappa- and lambda-immunoreactivity, orosomucoid and alpha 1-antitrypsin. Scand J Clin Lab Invest. 1996 Dec;56(8):691–700. doi: 10.3109/00365519609088816. [DOI] [PubMed] [Google Scholar]