Lead nephropathy and lead-related nephrotoxicity
- Virginia M Weaver, MD, MPH
Virginia M Weaver, MD, MPH
- Associate Professor of Environmental Health Sciences and Medicine
- Associate Faculty Member, Welch Center for Prevention, Epidemiology and Clinical Research
- Johns Hopkins Medical Institutions
- Bernard G Jaar, MD, MPH, FASN
Bernard G Jaar, MD, MPH, FASN
- Assistant Professor of Medicine and Epidemiology
- Associate Faculty, Welch Center for Prevention, Epidemiology and Clinical Research
- Johns Hopkins Medical Institutions
- Nephrology Center of Maryland
Chronic lead exposure can affect a variety of organ systems, including the kidney, where it can produce lead nephropathy, a chronic interstitial nephritis. The high level of lead exposure required to cause lead nephropathy is now increasingly rare, particularly in developed countries, due to occupational controls and removal of lead from paint, gasoline, and other environmental sources (figure 1).
However, prolonged lead exposure at the lower levels encountered in developed countries may still contribute to renal toxicity, an association that has been referred to as lead-related nephrotoxicity . This is most likely to occur in patients who have chronic kidney disease (CKD) or are at risk because of diabetes mellitus or hypertension.
The impact of chronic lead exposure on the kidney will be reviewed here. Other clinical manifestations of lead poisoning, as well as the evaluation and management of lead poisoning in adults and children, are discussed separately. (See "Adult occupational lead poisoning" and "Childhood lead poisoning: Clinical manifestations and diagnosis" and "Childhood lead poisoning: Management".)
SOURCES OF LEAD EXPOSURE
There are a number of current sources of lead exposure, which are primarily related to occupational exposures in adults and to ingestion or inhalation of environmental lead in adults and children (table 1). In addition, since lead accumulates in bone, the body lead burden from past exposures also contributes to current exposure.
Exposure sources are discussed in detail elsewhere. (See "Adult occupational lead poisoning", section on 'Sources of exposure' and "Childhood lead poisoning: Exposure and prevention", section on 'Exposure'.)
- Ekong EB, Jaar BG, Weaver VM. Lead-related nephrotoxicity: a review of the epidemiologic evidence. Kidney Int 2006; 70:2074.
- 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.
- Hu H, Payton M, Korrick S, et al. Determinants of bone and blood lead levels among community-exposed middle-aged to elderly men. The normative aging study. Am J Epidemiol 1996; 144:749.
- National Center for Health Statistics, Annest, JL, Mahaffey, K. Blood lead levels for persons ages 6 months-74 years, United States, 1976-80. Vital and Health Statistics. Series 11, No. 233. DHHS Pub. No. (PHS) 84-1683. Public Health Service. Washington. U.S. Government Printing Office, August 1984.
- Centers for Disease Control and Prevention. Fourth National Report on Human Exposure to Environmental Chemicals, Updated Tables. Department of Health and Human Services, Atlanta, GA 2015.
- U.S. Environmental Protection Agency. Air Quality Criteria for Lead (Final) Volume I,. Washington, DC, EPA/600/R-05/144aF-bF, 2006. p. 6. Available: http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=158823.
- Flegal AR, Smith DR. Lead levels in preindustrial humans. N Engl J Med 1992; 326:1293.
- Barbosa F Jr, Tanus-Santos JE, Gerlach RF, Parsons PJ. A critical review of biomarkers used for monitoring human exposure to lead: advantages, limitations, and future needs. Environ Health Perspect 2005; 113:1669.
- Weaver VM, Lee BK, Ahn KD, et al. Associations of lead biomarkers with renal function in Korean lead workers. Occup Environ Med 2003; 60:551.
- Martin D, Glass TA, Bandeen-Roche K, et al. Association of blood lead and tibia lead with blood pressure and hypertension in a community sample of older adults. Am J Epidemiol 2006; 163:467.
- Inglis JA, Henderson DA, Emmerson BT. The pathology and pathogenesis of chronic lead nephropathy occurring in Queensland. J Pathol 1978; 124:65.
- Steenland K, Selevan S, Landrigan P. The mortality of lead smelter workers: an update. Am J Public Health 1992; 82:1641.
- Wedeen RP, Malik DK, Batuman V. Detection and treatment of occupational lead nephropathy. Arch Intern Med 1979; 139:53.
- Khalil-Manesh F, Gonick HC, Cohen AH, et al. Experimental model of lead nephropathy. I. Continuous high-dose lead administration. Kidney Int 1992; 41:1192.
- Bennett WM. Lead nephropathy. Kidney Int 1985; 28:212.
- Goyer RA, Rhyne BC. Pathological effects of lead. Int Rev Exp Pathol 1973; 12:1.
- Wedeen RP, Maesaka JK, Weiner B, et al. Occupational lead nephropathy. Am J Med 1975; 59:630.
- Wedeen RP, Emmerson BT. Lead nephropathy. In: Clinical Nephrotoxins, De Broe ME, Porter GA, Bennette WM, Verpooten GA (Eds), Kluwer Academic Publishers, The Netherlands 2003. p.495.
- Loghman-Adham M. Aminoaciduria and glycosuria following severe childhood lead poisoning. Pediatr Nephrol 1998; 12:218.
- Batuman V, Maesaka JK, Haddad B, et al. The role of lead in gout nephropathy. N Engl J Med 1981; 304:520.
- Craswell PW, Price J, Boyle PD, et al. Chronic renal failure with gout: a marker of chronic lead poisoning. Kidney Int 1984; 26:319.
- Batuman V, Landy E, Maesaka JK, Wedeen RP. Contribution of lead to hypertension with renal impairment. N Engl J Med 1983; 309:17.
- Morgan JM. Chelation therapy in lead nephropathy. South Med J 1975; 68:1001.
- Germain MJ, Braden GL, Fitzgibbons JP. Failure of chelation therapy in lead nephropathy. Arch Intern Med 1984; 144:2419.
- Khalil-Manesh F, Gonick HC, Cohen A, et al. Experimental model of lead nephropathy. II. Effect of removal from lead exposure and chelation treatment with dimercaptosuccinic acid (DMSA). Environ Res 1992; 58:35.
- Sánchez-Fructuoso AI, Blanco J, Cano M, et al. Experimental lead nephropathy: treatment with calcium disodium ethylenediaminetetraacetate. Am J Kidney Dis 2002; 40:59.
- Fischbein A, Hu H. Occupational and environmental exposure to lead. In: Environmental and Occupational Medicine, Rom WN, Markowitz SB (Eds), Lippincott, Williams & Wilkins, Philadelphia 2007. p.954.
- Wedeen RP, Batuman V, Landy E. The safety of the EDTA lead-mobilization test. Environ Res 1983; 30:58.
- Stangle DE, Smith DR, Beaudin SA, et al. Succimer chelation improves learning, attention, and arousal regulation in lead-exposed rats but produces lasting cognitive impairment in the absence of lead exposure. Environ Health Perspect 2007; 115:201.
- Moel DI, Kumar K. Reversible nephrotoxic reactions to a combined 2,3-dimercapto-1-propanol and calcium disodium ethylenediaminetetraacetic acid regimen in asymptomatic children with elevated blood lead levels. Pediatrics 1982; 70:259.
- Sánchez-Fructuoso AI, Torralbo A, Arroyo M, et al. Occult lead intoxication as a cause of hypertension and renal failure. Nephrol Dial Transplant 1996; 11:1775.
- 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; 348:277.
- Lin JL, Lin-Tan DT, Yu CC, et al. Environmental exposure to lead and progressive diabetic nephropathy in patients with type II diabetes. Kidney Int 2006; 69:2049.
- Lin JL, Lin-Tan DT, Li YJ, et al. Low-level environmental exposure to lead and progressive chronic kidney diseases. Am J Med 2006; 119:707.e1.
- Lin-Tan DT, Lin JL, Yen TH, et al. Long-term outcome of repeated lead chelation therapy in progressive non-diabetic chronic kidney diseases. Nephrol Dial Transplant 2007; 22:2924.
- Staessen JA, Lauwerys RR, Buchet JP, et al. Impairment of renal function with increasing blood lead concentrations in the general population. The Cadmibel Study Group. N Engl J Med 1992; 327:151.
- Muntner P, He J, Vupputuri S, et al. Blood lead and chronic kidney disease in the general United States population: results from NHANES III. Kidney Int 2003; 63:1044.
- Payton M, Hu H, Sparrow D, Weiss ST. Low-level lead exposure and renal function in the Normative Aging Study. Am J Epidemiol 1994; 140:821.
- Akesson A, Lundh T, Vahter M, et al. Tubular and glomerular kidney effects in Swedish women with low environmental cadmium exposure. Environ Health Perspect 2005; 113:1627.
- Muntner P, Menke A, DeSalvo KB, et al. Continued decline in blood lead levels among adults in the United States: the National Health and Nutrition Examination Surveys. Arch Intern Med 2005; 165:2155.
- Spector JT, Navas-Acien A, Fadrowski J, et al. Associations of blood lead with estimated glomerular filtration rate using MDRD, CKD-EPI and serum cystatin C-based equations. Nephrol Dial Transplant 2011; 26:2786.
- Navas-Acien A, Tellez-Plaza M, Guallar E, et al. Blood cadmium and lead and chronic kidney disease in US adults: a joint analysis. Am J Epidemiol 2009; 170:1156.
- Chowdhury R, Darrow L, McClellan W, et al. Incident ESRD among participants in a lead surveillance program. Am J Kidney Dis 2014; 64:25.
- Sommar JN, Svensson MK, Björ BM, et al. End-stage renal disease and low level exposure to lead, cadmium and mercury; a population-based, prospective nested case-referent study in Sweden. Environ Health 2013; 12:9.
- Tsaih SW, Korrick S, Schwartz J, et al. Lead, diabetes, hypertension, and renal function: the normative aging study. Environ Health Perspect 2004; 112:1178.
- Kim R, Rotnitsky A, Sparrow D, et al. A longitudinal study of low-level lead exposure and impairment of renal function. The Normative Aging Study. JAMA 1996; 275:1177.
- 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; 15:1016.
- Chowdhury R, Mukhopadhyay A, McClellan W, et al. Survival patterns of lead-exposed workers with end-stage renal disease from Adult Blood Lead Epidemiology and Surveillance program. Am J Med Sci 2015; 349:222.
- Evans M, Fored CM, Nise G, et al. Occupational lead exposure and severe CKD: a population-based case-control and prospective observational cohort study in Sweden. Am J Kidney Dis 2010; 55:497.
- Hu H. A 50-year follow-up of childhood plumbism. Hypertension, renal function, and hemoglobin levels among survivors. Am J Dis Child 1991; 145:681.
- Moel DI, Sachs HK. Renal function 17 to 23 years after chelation therapy for childhood plumbism. Kidney Int 1992; 42:1226.
- Staessen JA, Nawrot T, Hond ED, et al. Renal function, cytogenetic measurements, and sexual development in adolescents in relation to environmental pollutants: a feasibility study of biomarkers. Lancet 2001; 357:1660.
- de Burbure C, Buchet JP, Leroyer 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.
- Fadrowski JJ, Navas-Acien A, Tellez-Plaza M, et al. Blood lead level and kidney function in US adolescents: The Third National Health and Nutrition Examination Survey. Arch Intern Med 2010; 170:75.
- Roels H, Lauwerys R, Konings J, et al. Renal function and hyperfiltration capacity in lead smelter workers with high bone lead. Occup Environ Med 1994; 51:505.
- Hsiao CY, Wu HD, Lai JS, Kuo HW. A longitudinal study of the effects of long-term exposure to lead among lead battery factory workers in Taiwan (1989-1999). Sci Total Environ 2001; 279:151.
- Gonick HC, Cohen AH, Ren Q, et al. Effect of 2,3-dimercaptosuccinic acid on nephrosclerosis in the Dahl rat. I. Role of reactive oxygen species. Kidney Int 1996; 50:1572.
- SOURCES OF LEAD EXPOSURE
- MEASUREMENT OF LEAD DOSE
- LEAD NEPHROPATHY
- Clinical manifestations
- LEAD-RELATED NEPHROTOXICITY
- Studies supporting the association of lead with nephrotoxicity
- - Risk in general population
- - Risk in susceptible patient populations
- - Risk in children
- - Chelation studies
- - Lead-induced hyperfiltration
- Evaluation and therapy
- - Chelation therapy and chronic kidney disease progression
- SUMMARY AND RECOMMENDATIONS