Urinary neutral endopeptidase in workers exposed to cadmium: interaction with cigarette smoking.
OBJECTIVE
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.
Nortier
J
J
Laboratoire Pluridisciplinaire de Recherche Expérimentale Biomédicale, Université Libre de Bruxelles.
Bernard
A
A
Roels
H
H
Deschodt-Lanckman
M
M
Gueuning
C
C
Lauwerys
R
R
D000118:Acetylglucosaminidase / Q000652:urine; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D015415:Biomarkers / Q000652:urine; D002104:Cadmium / Q000652:urine*; D003404:Creatinine / Q000652:urine; D006801:Humans; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000652:urine*; D016273:Occupational Exposure; D011506:Proteins / Q000378:metabolism; D012044:Regression Analysis; D012177:Retinol-Binding Proteins / Q000652:urine; D012907:Smoking / Q000378:metabolism / Q000652:urine*; D014598:Uteroglobin; D001613:beta 2-Microglobulin / Q000652:urine
D015415:Biomarkers; D011506:Proteins; D012177:Retinol-Binding Proteins; C556389:SCGB1A1 protein, human; D001613:beta 2-Microglobulin; D002104:Cadmium; D014598:Uteroglobin; D003404:Creatinine; D000118:Acetylglucosaminidase; D015260:Neprilysin