Usefulness of biomarkers of exposure to inorganic mercury, lead, or cadmium in controlling occupational and environmental risks of nephrotoxicity.

A successful prevention of renal diseases induced by occupational or environmental exposure to toxic metals such as mercury (Hg), lead (Pb), or cadmium (Cd) largely relies on the capability to detect nephrotoxic effects at a stage when they are still reversible or at least not yet compromising renal function. The knowledge of dose-effect/response relations has been useful to control nephrotoxic effects of these metals through a "biological monitoring of exposure approach". Chronic occupational exposure to inorganic mercury (mainly mercury vapor) may result in renal alterations affecting both tubules and glomeruli. Most of the structural or functional renal changes become significant when urinary mercury (HgU) exceeds 50 micrograms Hg/g creatinine. However, a marked reduction of the urinary excretion of prostaglandin E2 was found at a HgU of 35 micrograms Hg/g creatinine. As renal changes evidenced in moderately exposed workers were not related to the duration of Hg exposure, it is believed that those changes are reversible and mainly the consequence of recently absorbed mercury. Thus, monitoring HgU is useful for controlling the nephrotoxic risk of overexposure to inorganic mercury; HgU should not exceed 50 micrograms Hg/g creatinine in order to prevent cytotoxic and functional renal effects. Several studies on Pb workers with blood lead concentrations (PbB) usually below 70 micrograms Pb/dl have disclosed either no renal effects or subclinical changes of marginal or unknown health significance. Changes in urinary excretion+ of eicosanoids was not associated with deleterious consequences on either the glomerular filtration rate (GFR)--estimated from the creatinine clearance (C(Cr))--or renal hemodynamics if the workers' PbB was kept below 70 micrograms Pb/dL. The health significance of a slight renal hyperfiltration state in Pb workers is yet unknown. In terms of Pb body burden, a mean tibia Pb concentration of about 60 micrograms Pb/g bone mineral (that is 5 to 10 times the average "normal" concentration corresponding to a cumulative PbB index of 900 micrograms Pb/dL x year) did not affect the GFR in male workers. This conclusion may not necessarily be extrapolated to the general population, as recent studies have disclosed inverse associations between PbB and GFR at low-level environmental Pb exposure. A 10-fold increase in PbB (e.g., from 4 to 40 micrograms Pb/dL) was associated with a reduction of 10-13 mL/min in the C(Cr) and the odds ratio of having impaired renal function (viz. C(Cr) < 5th percentile: 52 and 43 mL/min in men and women, respectively) was 3.8 (CI 1.4-10.4; p = 0.01). However, the causal implication of Pb in this association remains to be clarified. The Cd concentration in urine (CdU) has been proposed as an indirect biological indicator for Cd accumulation in the kidney. Several biomarkers for detecting nephrotoxic effects of Cd at different renal sites were studied in relation to CdU. In occupationally exposed males, the CdU thresholds for significant alterations of renal markers ranged, according to the marker, from 2.4 to 11.5 micrograms Cd/g creatinine. A threshold of 10 micrograms Cd/g creatinine (corresponding to 200 micrograms Cd/g renal cortex: the critical Cd concentration in the kidney) is confirmed for the occurrence of low-molecular-mass proteinuria (functional effect) and subsequent loss of renal filtration reserve capacity. In workers, microproteinuria was found reversible when reduction or cessation of exposure occurred timely when tubular damage was still mild (beta(2)-microglobulinuria < 1500 micrograms/g creatinine) and CdU had never exceeded 20 micrograms Cd/g creatinine. As the predictive significance of other renal changes (biochemical or cytotoxic) is still unknown, it seems prudent to recommend that occupational exposure to Cd should not allow that CdU exceeds 5 micrograms Cd/g creatinine.(ABSTRACT TRUNCATED)