Markers of early renal changes induced by industrial pollutants. II. Application to workers exposed to lead.

Abstract

The present study has been carried out in the framework of a collaborative research project on the development of new markers of nephrotoxicity. A battery of more than 20 potential indicators of renal changes has been applied to 50 workers exposed to lead (Pb) and 50 control subjects. After application of selection criteria 41 exposed and 41 control workers were eventually retained for the final statistical analysis. The average blood Pb concentration of exposed workers was 480 micrograms/l and their mean duration of exposure was 14 years. The battery of tests included parameters capable of detecting functional deficits (for example, urinary proteins of low or high molecular weight), biochemical alterations (for example, urinary eicosanoids, glycosaminoglycans, sialic acid) or cell damage (for example, urinary tubular antigens or enzymes) at different sites of the nephron or the kidney. The most outstanding effect found in workers exposed to Pb was an interference with the renal synthesis of eicosanoids, resulting in lower urinary excretion of 6-keto-PGF1 alpha and an enhanced excretion of thromboxane (TXB2). The health significance of these biochemical alterations, detectable at low exposure to Pb is unknown. As they were not associated with any sign of renal dysfunction, they may represent reversible biochemical effects or only contribute to the degradation of the renal function from the onset of clinical Pb nephropathy. The urinary excretion of some tubular antigens was also positively associated with duration of exposure to Pb. Another effect of Pb that might deserve further study is a significant increase in urinary sialic acid concentration.

Renal Effects of Environmental and Occupational Lead Exposure

“…Cardenas et al (113) used a battery of more than 20 potential indicators of renal function in 50 workers exposed to lead and in 50 control subjects. The most striking effect of lead was interference with renal synthesis of eicosanoids, resulting in lower excretion of 6-keto-PGF l. Increased urinary NAG activity was also found in lead-exposed workers.…”

New Approaches for Detecting Thresholds of Human Nephrotoxicity Using Cadmium as an Example

“…Among workers exposed to lead, the excretion of the vasodilator PGI2 was significantly lower than in controls, whereas the excretion of the vasoconstrictor TXB2 was significantly higher. Cadmium exposure among workers was associated with increased excretion of both 6-keto-PGFiu and PGE2 and no change in the excretion of PGF2a or TXB2' These findings may have mechanistic implications for the controversial question of how metal exposure, especially exposure to lead, affects blood pressure (8).…”

“…Through the use of biomarkers of damage to various parts of the nephron, a pattern of damage is emerging that is consistently observed now both in U.S. and European studies of men occupationally exposed to cadmium (4)(5)(6)(7)(8)(9)(10) The lowest observed effect is indicated by a significant prevalence of abnormal 6-keto-prostaglandin Fla (6-keto-PGFi,a) and sialic acid levels in urine at an approximate urine cadmium concentration of 2.4 nmol Cd/mmol creatinine (2.4 pg Cd/g creatinine) (10). Proteins such as albumin and transferrin originate in the plasma and are filtered to a limited degree through the glomerulus, and the protein that is filtered is primarily reabsorbed by the tubules.…”

“…Some of these candidate markers are beginning to be examined in human studies. Excretion of fibronectin has been examined in relation to exposure to three heavy metals (cadmium, lead, and mercury), with no significant changes in excretion seen in the exposed groups (7)(8)(9).…”

“…Excretion of prostanoids [6-keto-PGFiu, PGE2, PGF2a, and thromboxane B2 (TXB2)] was examined in the same three heavy metal exposure studies (7)(8)(9), with different results for exposures to mercury, lead, and cadmium. PGI2 (measured as the stable urinary derivative 6-keto-PGFi.)…”