Blood lead level and measured glomerular filtration rate in children with chronic kidney disease

Jeffrey J Fadrowski, Alison G Abraham, Ana Navas-Acien, Eliseo Guallar, Virginia M Weaver, Susan L Furth, Jeffrey J Fadrowski, Alison G Abraham, Ana Navas-Acien, Eliseo Guallar, Virginia M Weaver, Susan L Furth

Abstract

Background: The role of environmental exposure to lead as a risk factor for chronic kidney disease (CKD) and its progression remains controversial, and most studies have been limited by a lack of direct glomerular filtration rate (GFR) measurement.

Objective: We evaluated the association between lead exposure and GFR in children with CKD.

Methods: In this cross-sectional study, we examined the association between blood lead levels (BLLs) and GFR measured by the plasma disappearance of iohexol among 391 participants in the Chronic Kidney Disease in Children (CKiD) prospective cohort study.

Results: Median BLL and GFR were 1.2 µg/dL and 44.4 mL/min per 1.73 m2, respectively. The average percent change in GFR for each 1-µg/dL increase in BLL was -2.1 (95% CI: -6.0, 1.8). In analyses stratified by CKD diagnosis, the association between BLL and GFR was stronger among children with glomerular disease underlying CKD; in this group, each 1-µg/dL increase in BLL was associated with a -12.1 (95% CI: -22.2, -1.9) percent change in GFR. In analyses stratified by anemia status, each 1-µg/dL increase in BLL among those with and without anemia was associated with a -0.3 (95% CI: -7.2, 6.6) and -4.6 (95% CI: -8.9, -0.3) percent change in GFR, respectively.

Conclusions: There was no significant association between BLL and directly measured GFR in this relatively large cohort of children with CKD, although associations were observed in some subgroups. Longitudinal analyses are needed to examine the temporal relationship between lead and GFR decline, and to further examine the impact of underlying cause of CKD and anemia/hemoglobin status among patients with CKD.

Conflict of interest statement

The authors declare they have no actual or potential competing financial interests.

References

    1. Åkesson A, Lundh T, Vahter M, Bjellerup P, Lidfeldt J, Nerbrand C, et al. Tubular and glomerular kidney effects in Swedish women with low environmental cadmium exposure. Environ Health Perspect. 2005;113:1627–1631.
    1. Apostolou A, Garcia-Esquinas E, Fadrowski JJ, McClaine P, Weaver VM, Navas-Acien A.2011Secondhand tobacco smoke: a source of lead exposure in US children and adolescents. Am J Public Health 1024714–722.; .10.2105/AJPH.2011.300161
    1. Ardissino G, Testa S, Daccò V, Viganò S, Taioli E, Claris-Appiani A, et al. Proteinuria as a predictor of disease progression in children with hypodysplastic nephropathy. Data from the Ital Kid Project. Pediatr Nephrol. 2004;19(2):172–177.
    1. ATSDR (Agency for Toxic Substances and Disease Registry). Toxicological Profile for Lead. 2007. Available: [accessed 1 March 2012]
    1. CDC (Centers for Disease Control and Prevention). Fourth National Report on Human Exposure to Environmental Chemicals. 2009. Available: [accessed 29 February 2012]
    1. CDC (Centers for Disease Control and Prevention). Healthy Weight: Body Mass Index. 2012a. Available: [accessed 1 March 2012]
    1. CDC (Centers for Disease Control and Prevention). The Fourth National Report on Human Exposure to Environmental Chemicals, Updated Tables, February 2012. 2012b. Available: [accessed 27 May 2012]
    1. Clayton CA, Pellizzari ED, Whitmore RW, Perritt RL, Quackenboss JJ. National Human Exposure Assessment Survey (NHEXAS): distributions and associations of lead, arsenic and volatile organic compounds in EPA region 5. J Expo Anal Environ Epidemiol. 1999;9(5):381–392.
    1. Copelovitch L, Warady BA, Furth SL. Insights from the Chronic Kidney Disease in Children (CKiD) study. Clin J Am Soc Nephrol. 2011;6(8):2047–2053.
    1. de Burbure C, Buchet JP, Leroyer A, Nisse C, Haguenoer JM, Mutti A, et al. Renal and neurologic effects of cadmium, lead, mercury, and arsenic in children: evidence of early effects and multiple interactions at environmental exposure levels. Environ Health Perspect. 2006;114:584–590.
    1. deSilva PE. Blood lead levels and the haematocrit correction. Ann Occup Hyg. 1984;28(4):417–428.
    1. Ekong EB, Jaar BG, Weaver VM. Lead-related nephrotoxicity: a review of the epidemiologic evidence. Kidney Int. 2006;70(12):2074–2084.
    1. Evans M, Elinder CG. Chronic renal failure from lead: myth or evidence-based fact? Kidney Int. 2011;79(3):272–279.
    1. Fadrowski JJ, Navas-Acien A, Tellez-Plaza M, Guallar E, Weaver VM, Furth SL. Blood lead level and kidney function in US adolescents: the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2010;170(1):75–82.
    1. Fadrowski JJ, Neu AM, Schwartz GJ, Furth SL. Pediatric GFR estimating equations applied to adolescents in the general population. Clin J Am Soc Nephrol. 2011;6(6):1427–1435.
    1. Fadrowski JJ, Pierce CB, Cole SR, Moxey-Mims M, Warady BA, Furth SL. Hemoglobin decline in children with chronic kidney disease: baseline results from the chronic kidney disease in children prospective cohort study. Clin J Am Soc Nephrol. 2008;3(2):457–462.
    1. Furth SL, Cole SR, Moxey-Mims M, Kaskel F, Mak R, Schwartz G, et al. Design and methods of the Chronic Kidney Disease in Children (CKiD) prospective cohort study. Clin J Am Soc Nephrol. 2006;1(5):1006–1015.
    1. GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. Lancet. 1997;349(9069):1857–1863.
    1. Hu H, Rabinowitz M, Smith D. Bone lead as a biological marker in epidemiologic studies of chronic toxicity: conceptual paradigms. Environ Health Perspect. 1998;106:1–8.
    1. Inglis JA, Henderson DA, Emmerson BT. The pathology and pathogenesis of chronic lead nephropathy occurring in Queensland. J Pathol. 1978;124(2):65–76.
    1. Khalil-Manesh F, Gonick HC, Cohen AH, Alinovi R, Bergamaschi E, Mutti A, et al. Experimental model of lead nephropathy. I. Continuous high-dose lead administration. Kidney Int. 1992;41(5):1192–1203.
    1. Kim R, Rotnitsky A, Sparrow D, Weiss S, Wager C, Hu H. A longitudinal study of low-level lead exposure and impairment of renal function. The Normative Aging Study. JAMA. 1996;275(15):1177–1181.
    1. Kim Y, Lee BK.2012Increased erythrocyte lead levels correlate with decreased hemoglobin levels in the Korean general population: analysis of 2008–2010 Korean National Health and Nutrition Examination Survey data. Int Arch Occup Environ Health;10.1007/s00420-012-0811-3[Online 23 August 2012]
    1. Lanphear BP, Burgoon DA, Rust SW, Eberly S, Galke W. Environmental exposures to lead and urban children’s blood lead levels. Environ Res. 1998;76(2):120–130.
    1. Levin R, Brown MJ, Kashtock ME, Jacobs DE, Whelan EA, Rodman J, et al. Lead exposures in U.S. children, 2008: implications for prevention. Environ Health Perspect. 2008;116:1285–1293.
    1. Lin C, Kim R, Tsaih SW, Sparrow D, Hu H. Determinants of bone and blood lead levels among minorities living in the Boston area. Environ Health Perspect. 2004;112:1147–1151.
    1. Lin JL, Lin-Tan DT, Hsu KH, Yu CC. Environmental lead exposure and progression of chronic renal diseases in patients without diabetes. N Engl J Med. 2003;348(4):277–286.
    1. Lin JL, Lin-Tan DT, Li YJ, Chen KH, Huang YL. Low-level environmental exposure to lead and progressive chronic kidney diseases. Am J Med. 2006;119(8):707.e1–707.e9.
    1. Lin JL, Tan DT, Hsu KH, Yu CC. Environmental lead exposure and progressive renal insufficiency. Arch Intern Med. 2001;161(2):264–271.
    1. Lin-Tan DT, Lin JL, Yen TH, Chen KH, Huang YL. Long-term outcome of repeated lead chelation therapy in progressive non-diabetic chronic kidney diseases. Nephrol Dial Transplant. 2007;22(10):2924–2931.
    1. Litwin M. Risk factors for renal failure in children with non-glomerular nephropathies. Pediatr Nephrol. 2004;19(2):178–186.
    1. Moel DI, Sachs HK. Renal function 17 to 23 years after chelation therapy for childhood plumbism. Kidney Int. 1992;42(5):1226–1231.
    1. Muntner P, He J, Vupputuri S, Coresh J, Batuman V. Blood lead and chronic kidney disease in the general United States population: results from NHANES III. Kidney Int. 2003;63(3):1044–1050.
    1. Muntner P, Menke A, DeSalvo KB, Rabito FA, Batuman V. Continued decline in blood lead levels among adults in the United States: the National Health and Nutrition Examination Surveys. Arch Intern Med. 2005;165(18):2155–2161.
    1. National Center for Health Statistics. National Health and Nutrition Examination Survey, 2003–2004. 2012. Available: [accessed 1 March 2012]
    1. National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics. 2004;114(2 suppl 4th report):555–576.
    1. Navas-Acien A, Tellez-Plaza M, Guallar E, Muntner P, Silbergeld E, Jaar B, et al. Blood cadmium and lead and chronic kidney disease in US adults: a joint analysis. Am J Epidemiol. 2009;170(9):1156–1164.
    1. Payton M, Hu H, Sparrow D, Weiss ST. Low-level lead exposure and renal function in the Normative Aging Study. Am J Epidemiol. 1994;140(9):821–829.
    1. Peterson JC, Adler S, Burkart JM, Greene T, Hebert LA, Hunsicker LG, et al. Blood pressure control, proteinuria, and the progression of renal disease. The Modification of Diet in Renal Disease Study. Ann Intern Med. 1995;123(10):754–762.
    1. Poggio ED, Wang X, Greene T, Van Lente F, Hall PM. Performance of the modification of diet in renal disease and Cockcroft-Gault equations in the estimation of GFR in health and in chronic kidney disease. J Am Soc Nephrol. 2005;16(2):459–466.
    1. Rodriguez-Iturbe B, Sindhu RK, Quiroz Y, Vaziri ND. Chronic exposure to low doses of lead results in renal infiltration of immune cells, NF-κB activation, and overexpression of tubulointerstitial angiotensin II. Antioxid Redox Signal. 2005;7(9–10):1269–1274.
    1. Rule AD, Larson TS, Bergstralh EJ, Slezak JM, Jacobsen SJ, Cosio FG. Using serum creatinine to estimate glomerular filtration rate: accuracy in good health and in chronic kidney disease. Ann Intern Med. 2004;141(12):929–937.
    1. Schwartz GJ, Brion LP, Spitzer A. The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. Pediatr Clin North Am. 1987;34(3):571–590.
    1. Schwartz GJ, Furth S, Cole SR, Warady B, Munoz A. Glomerular filtration rate via plasma iohexol disappearance: pilot study for chronic kidney disease in children. Kidney Int. 2006;69(11):2070–2077.
    1. Schwartz GJ, Haycock GB, Spitzer A. Plasma creatinine and urea concentration in children: normal values for age and sex. J Pediatr. 1976;88(5):828–830.
    1. Schwartz GJ, Muñoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, et al. New equations to estimate GFR in children with CKD. J Am Soc Nephrol. 2009;20(3):629–637.
    1. Skerfving S, Bergdahl IA. In: Handbook on The Toxicology of Metals, 3rd ed. (Nordberg GF, Fowler BA, Nordberg M, Friberg LT, eds). London:Academic Press, 599–643; 2007. Lead.
    1. Spector JT, Navas-Acien A, Fadrowski J, Guallar E, Jaar B, Weaver VM. Associations of blood lead with estimated glomerular filtration rate using MDRD, CKD-EPI and serum cystatin C-based equations. Nephrol Dial Transplant. 2011;26(9):2786–2792.
    1. Staessen JA, Lauwerys RR, Buchet JP, Bulpitt CJ, Rondia D, Vanrenterghem Y, et al. Impairment of renal function with increasing blood lead concentrations in the general population. The Cadmibel Study Group. N Engl J Med. 1992;327(3):151–156.
    1. Staessen JA, Nawrot T, Hond ED, Thijs L, Fagard R, Hoppenbrouwers K, et al. Renal function, cytogenetic measurements, and sexual development in adolescents in relation to environmental pollutants: a feasibility study of biomarkers. Lancet. 2001;357(9269):1660–1669.
    1. Staples A, LeBlond R, Watkins S, Wong C, Brandt J. Validation of the revised Schwartz estimating equation in a predominantly non-CKD population. Pediatr Nephrol. 2010;25(11):2321–2326.
    1. Steenland K, Selevan S, Landrigan P. The mortality of lead smelter workers: an update. Am J Public Health. 1992;82(12):1641–1644.
    1. Stevens LA, Coresh J, Feldman HI, Greene T, Lash JP, Nelson RG, et al. Evaluation of the modification of diet in renal disease study equation in a large diverse population. J Am Soc Nephrol. 2007;18(10):2749–2757.
    1. Tsaih SW, Korrick S, Schwartz J, Amarasiriwardena C, Aro A, Sparrow D, et al. Lead, diabetes, hypertension, and renal function: the Normative Aging Study. Environ Health Perspect. 2004;112:1178–1182.
    1. U.S. Department of Health and Human Services. The 2009 HHS Poverty Guidelines. 2009. Available: [accessed 1 March 2012]
    1. Vaziri ND. Mechanisms of lead-induced hypertension and cardiovascular disease. Am J Physiol Heart Circ Physiol. 2008;295(2):H454–H465.
    1. Wedeen RP, Malik DK, Batuman V. Detection and treatment of occupational lead nephropathy. Arch Intern Med. 1979;139(1):53–57.
    1. Wingen AM, Fabian-Bach C, Schaefer F, Mehls O. Randomised multicentre study of a low-protein diet on the progression of chronic renal failure in children. European Study Group of Nutritional Treatment of Chronic Renal Failure in Childhood. Lancet. 1997;349(9059):1117–1123.
    1. Wong CS, Pierce CB, Cole SR, Warady BA, Mak RH, Benador NM, et al. Association of proteinuria with race, cause of chronic kidney disease, and glomerular filtration rate in the chronic kidney disease in children study. Clin J Am Soc Nephrol. 2009;4(4):812–819.
    1. Wong H, Mylrea K, Feber J, Drukker A, Filler G.2006Prevalence of complications in children with chronic kidney disease according to KDOQI. Kidney Int 703): 585–590.
    1. Wuhl E, Mehls O, Schaefer F. Antihypertensive and antiproteinuric efficacy of ramipril in children with chronic renal failure. Kidney Int. 2004;66(2):768–776.
    1. Yu CC, Lin JL, Lin-Tan DT. Environmental exposure to lead and progression of chronic renal diseases: a four-year prospective longitudinal study. J Am Soc Nephrol. 2004;15(4):1016–1022.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel