title: Lead-induced nephropathy: relationship between various biological exposure indices and early markers of nephrotoxicity.
abstract: Lead nephropathy in adults is silent and insidious, characterized by the absence of proteinuria in its early phase. Of the early markers of nephrotoxicity, urinary N-acetyl-beta-D-glucosaminidase (NAG) appears to be the only one that is elevated in early lead nephropathy. However, the elevation in urinary NAG activity may be a response to a sharp increase in renal burden of lead. Its usefulness as a marker of chronic lead nephropathy is thus in doubt. There is a need, then, to identify a reliable early biological indicator of lead-induced kidney damage. Furthermore, there is also a need to identify suitable markers of chronic exposure to describe meaningful dose-response and dose-effect relationships. Traditionally, blood lead (PbB) was used, but the current blood lead level (PbBrec) is more an indicator of recent exposure. Time-integrated blood lead indices (PbBint) derived from repeated serial PbB measurements can be used as indices of chronic exposure. In 128 lead-exposed workers, the PbBint was the most important exposure variable in describing the variability in urinary alpha 1-microglobulin (U alpha 1 m), urinary beta 2-microglobulin (U beta 2m), and urinary retinol binding protein (URBP). U alpha 1m was the only marker that was significantly higher in the exposed group, with a good dose-response and dose-effect relationship with PbBint. The lack of dose-response and dose-effect relationships in other studies may be due to inappropriate exposure markers as well as less sensitive response markers. PbBint has a better correlation than PbBrec. Furthermore, U alpha 1m may be the most sensitive of the markers because of its higher molecular weight.
authors.affiliation: Department of Community, Occupational and Family Medicine, National University of Singapore.
authors.forename: K S
authors.initials: KS
authors.lastname: Chia
authors.forename: J
authors.initials: J
authors.lastname: Jeyaratnam
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.forename: C
authors.initials: C
authors.lastname: Tan
authors.forename: H Y
authors.initials: HY
authors.lastname: Ong
authors.forename: C N
authors.initials: CN
authors.lastname: Ong
authors.forename: E
authors.initials: E
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000419:Albuminuria; D000510:Alpha-Globulins / Q000652:urine; D000704:Analysis of Variance; D015415:Biomarkers / Q000652:urine*; D001822:Body Burden; D016022:Case-Control Studies; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology / Q000378:metabolism*; D007854:Lead / Q000097:blood; D007855:Lead Poisoning / Q000150:complications / Q000453:epidemiology / Q000378:metabolism*; D016015:Logistic Models; D008297:Male; D016273:Occupational Exposure / Q000009:adverse effects*; D012177:Retinol-Binding Proteins / Q000652:urine; D012680:Sensitivity and Specificity; D013997:Time Factors; D001613:beta 2-Microglobulin / Q000652:urine
chemical_list: D000510:Alpha-Globulins; D015415:Biomarkers; D012177:Retinol-Binding Proteins; D001613:beta 2-Microglobulin; D007854:Lead