APH 2002, 60, 203-215:
Controlling the risk of nephrotoxicity in men occupationally exposed to inorganic mercury, lead, or cadmium through monitoring biomarkers of exposure.
Keywords: health surveillance, industry, renal effects, cadmium, mercury, lead
successful prevention of renal diseases occuring in occupational
exposure to toxic heavy metals such as mercury (Hg), lead (Pb), or
cadmium (Cd) largely relies on the capability to detect nephrotoxic
effects at a stage where the renal effects are still reversible or at
least not yet compromising the kidney function. The knowledge of
dose-effect/response relations has been instrumental in setting adequate
surveillance strategies 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 tubuli and glomeruli. Most of the structural and/or functional renal changes become significant when urinary mercury (HgU) exceeds 50 µg Hg/g creatinine. However, a marked reduction of the urinary excretion of prostaglandin E2 was found at a HgU of 35 µg Hg/g creatinine. Renal changes in moderately exposed workers are usually not related to the duration of mercury vapor exposure and the changes are reversible and mainly the consequence of recently absorbed mercury (last six months). Thus, monitoring HgU is useful for controlling the nephtrotoxic risk of overexposure to inorganic mercury; HgU should remain below 50 µg Hg/g creatinine in order to prevent cytotoxic and functional renal effects.
Several studies in lead-exposed workers with blood lead concentrations (PbB) usually below 70 µg 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 found associated with deleterious consequences on the glomerular filtration rate (GFR, estimated as creatinine clearance rate) and renal hemodynamics if the workers' PbB was kept below 70 µg Pb/dL during the whole professional career. The health significance of a slight renal hyperfiltration state in lead workers is yet unknown. In terms of lead body burden, a mean tibia lead concentration of about 60 µg Pb/g bone mineral (that is 5 to 10 times the average "normal" concentration) and which corresponds to a cumulative PbB index of about 900 µg Pb/dL x year is not affecting the GFR in male workers.
The cadmium concentration in urine (CdU) has been proposed as an indirect biological indicator for cadmium accumulation in the kidney cortex. Several biomarkers for detecting nephrotoxic effects of cadmium at different renal sites were studied in relation to CdU. In occupationally exposed male workers, there are distinct CdU thresholds for significant alterations of different renal markers ranging from 2.4 to 11.5 µg Cd/g creatinine. A threshold of 10 µg Cd/g creatinine (corresponding to 200 µg 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 may be reversible when reduction or cessation of exposure occurs at a stage when tubular damage is still mild (þ2 - microglobulinaria <1500 µg/g creatinine) and CdU had never exceeded 20 µg Cd/g creatinine. As the predictive significance of other renal changes (biochemical or cytotoxic) is still unknown, it seems prudent to recommend that the occupational exposure to cadmium should not allow CdU to exceed 5 µg Cd/g creatinine.
These conclusions may not be extrapolated plainly to the general population, as recent studies have disclosed that some population subgroups are more vulnerable to exposure to these heavy metals than healthy male workers in the age range from 20 to 60 years.