Lead-induced nephropathy: relationship between various biological exposure indices and early markers of nephrotoxicity.
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.
Chia
K S
KS
Department of Community, Occupational and Family Medicine, National University of Singapore.
Jeyaratnam
J
J
Lee
J
J
Tan
C
C
Ong
H Y
HY
Ong
C N
CN
Lee
E
E
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
D000510:Alpha-Globulins; D015415:Biomarkers; D012177:Retinol-Binding Proteins; D001613:beta 2-Microglobulin; D007854:Lead