Urinary neutral endopeptidase in workers exposed to cadmium: interaction with cigarette smoking

• Published in: Occupational and environmental medicine (London, England) Vol. 54; no. 6; pp. 432 - 436
• Main Authors: Nortier, J, Bernard, A, Roels, H, Deschodt-Lanckman, M, Gueuning, C, Lauwerys, R
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01.06.1997; BMJ Publishing Group; BMJ; BMJ Publishing Group LTD
• Subjects: Acetylglucosaminidase - urine; Adult; Age Factors; Aged; Aged, 80 and over; Analysis of Variance; beta 2-Microglobulin - urine; Biological and medical sciences; Biomarkers - urine; Cadmium; Cadmium - urine; Chemical and industrial products toxicology. Toxic occupational diseases; Cigarette smoking; Creatinine - urine; Enzymes; Excretion; Humans; Kidneys; LLC PK1 cells; Male; Medical sciences; Metals and various inorganic compounds; Microvilli; Middle Aged; Neprilysin - urine; Occupational Exposure; Proteins - metabolism; Proximal tubules; Regression Analysis; Retinol-Binding Proteins - urine; Smelters; Smoking - metabolism; Smoking - urine; Toxicology; Urine; Uteroglobin; Human; Urine; Cadmium; Biological fluid; Urinary system disease; Enzyme; Toxicity; Tobacco smoking; Biological marker; Metalloendopeptidases; Occupational exposure; Biological monitoring; Heavy metal; Peptidases; Renal tubule; Endopeptidase; Hydrolases; Neprilysin; Occupational medicine
• ISSN: 1351-0711; 1470-7926
• DOI: 10.1136/oem.54.6.432

OBJECTIVES: Structural impairment of the renal proximal tubular epithelium induced by cadmium (Cd) was investigated by measuring the concentration of neutral endopeptidase 24.11 (NEP), an ectoenzyme of the apical brush border, in the urine of 106 male workers employed in a Cd smelter (among whom 52 were occupationally exposed to Cd), and by comparing it with other tubular markers (low molecular weight proteins, lysosomal enzymes). METHODS: NEP (EC 3.4.24.11), beta-N-acetyl-glucosaminidase (NAG) (EC 3.2.1.30), and NAG-B isoenzyme activities were measured by fluorimetric assays, whereas the concentrations of retinol binding protein (RBP), beta 2-microglobulin (beta 2M), and Clara cell protein (CC16) were measured by automated latex agglutination techniques. RESULTS: An increased urinary excretion of NEP as well as microproteins was found only in subjects excreting more than 5 micrograms Cd/g creatinine. In this group, NEP concentrations were significantly higher in the subjects who smoked. This significant interaction could not be found for any other marker tested. CONCLUSIONS: The data suggest that NEP enzymuria is high even at low exposures to Cd (with a threshold of urinary cadmium excretion (U-Cd) at 5 micrograms/g creatinine), indicating early structural alterations. Moreover, its particular sensitivity to smoking could be useful in the detection of new population clusters potentially more susceptible to development of nephrotoxic insult.