Skip to main content
PMC home page
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 1998 Jun;106(6):361–364. doi: 10.1289/ehp.98106361

Hyperproduction of erythropoietin in nonanemic lead-exposed children.

P Factor-Litvak 1, V Slavkovich 1, X Liu 1, D Popovac 1, E Preteni 1, S Capuni-Paracka 1, S Hadzialjevic 1, V Lekic 1, N LoIacono 1, J Kline 1, J Graziano 1
PMCID: PMC1532998  PMID: 9618353

Abstract

Lead (Pb) poisoning has numerous effects on the erythropoietic system, but the precise mechanism whereby high dose exposure causes anemia is not entirely clear. We previously reported that Pb exposure is associated with depressed serum erythropoietin (EPO) in pregnant women residing in a Pb mining town and in a nonexposed town in Kosovo, Yugoslavia. In a prospective study, we tested the hypothesis that blood Pb concentration (BPb) may be associated with depressed EPO in children. BPb, hemoglobin (Hgb), and serum EPO were measured at ages 4.5, 6.5, and 9.5 years in 211, 178, and 234 children, respectively. At 4.5 years of age, mean BPbs were 38.9 and 9.0 microg/dl in the exposed and nonexposed towns, respectively; BPbs gradually declined to 28.2 and 6.5 microg/dl, respectively, by age 9.5 years. No differences were found in Hgb at any age. At age 4. 5 years, a positive association between BPb and EPO (beta = 0.21; p = 0.0001), controlled for Hgb, was found. The magnitude of this association declined to 0.11 at age 6.5 years (p = 0.0103) and 0.03 at age 9.5 years (p = 0.39). These results were confirmed using repeated measures analyses. We concluded that in Pb-exposed children, the maintenance of normal Hgb requires hyperproduction of EPO. With advancing age (and continuing exposure), this compensatory mechanism appears to be failing, suggesting a gradual loss of renal endocrine function due to Pb exposure.

Full text

PDF
361

Images in this article

362Figure 1
on p.362
362Figure 2
on p.362

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baker E. L., Jr, Landrigan P. J., Barbour A. G., Cox D. H., Folland D. S., Ligo R. N., Throckmorton J. Occupational lead poisoning in the United States: clinical and biochemical findings related to blood lead levels. Br J Ind Med. 1979 Nov;36(4):314–322. doi: 10.1136/oem.36.4.314. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berk P. D., Tschudy D. P., Shepley L. A., Waggoner J. G., Berlin N. I. Hematologic and biochemical studies in a case of lead poisoning. Am J Med. 1970 Jan;48(1):137–144. doi: 10.1016/0002-9343(70)90109-9. [DOI] [PubMed] [Google Scholar]
  3. Brownson R. C., Reif J. S., Chang J. C., Davis J. R. An analysis of occupational risks for brain cancer. Am J Public Health. 1990 Feb;80(2):169–172. doi: 10.2105/ajph.80.2.169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Caro J., Erslev A. J. Biologic and immunologic erythropoietin in extracts from hypoxic whole rat kidneys and in their glomerular and tubular fractions. J Lab Clin Med. 1984 Jun;103(6):922–931. [PubMed] [Google Scholar]
  5. Erslev A. J., Caro J. Physiologic and molecular biology of erythropoietin. Med Oncol Tumor Pharmacother. 1986;3(3-4):159–164. doi: 10.1007/BF02934992. [DOI] [PubMed] [Google Scholar]
  6. Factor-Litvak P., Graziano J. H., Kline J. K., Popovac D., Mehmeti A., Ahmedi G., Shrout P., Murphy M. J., Gashi E., Haxhiu R. A prospective study of birthweight and length of gestation in a population surrounding a lead smelter in Kosovo, Yugoslavia. Int J Epidemiol. 1991 Sep;20(3):722–728. doi: 10.1093/ije/20.3.722. [DOI] [PubMed] [Google Scholar]
  7. GRIGGS R. C. LEAD POISONING: HEMATOLOGIC ASPECTS. Prog Hematol. 1964;4:117–137. [PubMed] [Google Scholar]
  8. Grandjean P., Jensen B. M., Sandø S. H., Jøgensen P. J., Antonsen S. Delayed blood regeneration in lead exposure: an effect on reserve capacity. Am J Public Health. 1989 Oct;79(10):1385–1388. doi: 10.2105/ajph.79.10.1385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Graziano J. H., Slavkovic V., Factor-Litvak P., Popovac D., Ahmedi X., Mehmeti A. Depressed serum erythropoietin in pregnant women with elevated blood lead. Arch Environ Health. 1991 Nov-Dec;46(6):347–350. doi: 10.1080/00039896.1991.9934401. [DOI] [PubMed] [Google Scholar]
  10. Hernberg S., Nurminen M., Hasan J. Nonrandom shortening of red cell survival times in men exposed to lead. Environ Res. 1967 Nov;1(3):247–261. doi: 10.1016/0013-9351(67)90017-5. [DOI] [PubMed] [Google Scholar]
  11. Hu H., Watanabe H., Payton M., Korrick S., Rotnitzky A. The relationship between bone lead and hemoglobin. JAMA. 1994 Nov 16;272(19):1512–1517. [PubMed] [Google Scholar]
  12. Krafte-Jacobs B., Williams J., Soldin S. J. Plasma erythropoietin reference ranges in children. J Pediatr. 1995 Apr;126(4):601–603. doi: 10.1016/s0022-3476(95)70360-8. [DOI] [PubMed] [Google Scholar]
  13. LEIKIN S., ENG G. Erythrokinetic studies of the anemia of lead poisoning. Pediatrics. 1963 Jun;31:996–1002. [PubMed] [Google Scholar]
  14. LICHTMAN H. C., FELDMAN F. In vitro pyrrole and porphyrin synthesis in lead poisoning and iron deficiency. J Clin Invest. 1963 Jun;42:830–839. doi: 10.1172/JCI104775. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Murphy M. J., Graziano J. H., Popovac D., Kline J. K., Mehmeti A., Factor-Litvak P., Ahmedi G., Shrout P., Rajovic B., Nenezic D. U. Past pregnancy outcomes among women living in the vicinity of a lead smelter in Kosovo, Yugoslavia. Am J Public Health. 1990 Jan;80(1):33–35. doi: 10.2105/ajph.80.1.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Paglia D. E., Valentine W. N., Dahlgren J. G. Effects of low-level lead exposure on pyrimidine 5'-nucleotidase and other erythrocyte enzymes. Possible role of pyrimidine 5'-nucleotidase in the pathogenesis of lead-induced anemia. J Clin Invest. 1975 Nov;56(5):1164–1169. doi: 10.1172/JCI108192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Piomelli S. A micromethod for free erythrocyte porphyrins: the FEP test. J Lab Clin Med. 1973 Jun;81(6):932–940. [PubMed] [Google Scholar]
  18. Piomelli S., Seaman C., Zullow D., Curran A., Davidow B. Threshold for lead damage to heme synthesis in urban children. Proc Natl Acad Sci U S A. 1982 May;79(10):3335–3339. doi: 10.1073/pnas.79.10.3335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Wasserman G. A., Graziano J. H., Factor-Litvak P., Popovac D., Morina N., Musabegovic A., Vrenezi N., Capuni-Paracka S., Lekic V., Preteni-Redjepi E. Consequences of lead exposure and iron supplementation on childhood development at age 4 years. Neurotoxicol Teratol. 1994 May-Jun;16(3):233–240. doi: 10.1016/0892-0362(94)90044-2. [DOI] [PubMed] [Google Scholar]
  20. Wasserman G. A., Liu X., Lolacono N. J., Factor-Litvak P., Kline J. K., Popovac D., Morina N., Musabegovic A., Vrenezi N., Capuni-Paracka S. Lead exposure and intelligence in 7-year-old children: the Yugoslavia Prospective Study. Environ Health Perspect. 1997 Sep;105(9):956–962. doi: 10.1289/ehp.97105956. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Wasserman G., Graziano J. H., Factor-Litvak P., Popovac D., Morina N., Musabegovic A., Vrenezi N., Capuni-Paracka S., Lekic V., Preteni-Redjepi E. Independent effects of lead exposure and iron deficiency anemia on developmental outcome at age 2 years. J Pediatr. 1992 Nov;121(5 Pt 1):695–703. doi: 10.1016/s0022-3476(05)81895-5. [DOI] [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES