LEAD-INDUCED NEPHROPATHY - RELATIONSHIP BETWEEN VARIOUS BIOLOGICAL EXPOSURE INDEXES AND EARLY MARKERS OF NEPHROTOXICITY

Lead nephropathy in adults is silent and insidious, characterized by t he 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 i ncrease 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 chro nic exposure to describe meaningful dose-response and dose-effect rela tionships. Traditionally, blood lead (PbB) was used, but the current b lood lead level (PbBrec) is more an indicator of recent exposure. Time -integrated blood lead indices (PbBint) derived from repeated serial P bB measurements can be used as indices of chronic exposure. In 128 lea d-exposed workers, the PbBint was the most important exposure variable in describing the variability in urinary alpha(1)-microglobulin (U al pha(1)m), urinary beta(2)-microglobulin (U beta(2)m), and urinary reti nol binding protein (URBP). U alpha(1)m was the only marker that was s ignificantly higher in the exposed group, with a good dose-response an d 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 h as a better correlation than PbBrec. Furthermore, U alpha(1)m may be t he most sensitive of the markers because of its higher molecular weigh t. (C) 1995 Wiley-Liss, Inc.