Urinary neutrophil gelatinase-associated lipocalin is associated with heavy metal exposure in welding workers

Abstract

Metals cause nephrotoxicity with acute and/or chronic exposure; however, few epidemiological studies have examined impacts of exposure to metal fumes on renal injury in welding workers. In total, 66 welding workers and 12 office workers were recruited from a shipyard located in southern Taiwan. Urine samples from each subject were collected at the beginning (baseline) and end of the work week (1-week exposure). Personal exposure to PM2.5 was measured. The 8-h mean PM2.5 was 50.3 μg/m(3) for welding workers and 27.4 μg/m(3) for office workers. iTRAQs coupled with LC-MS/MS were used to discover the pathways in response to welding PM2.5 in the urine, suggesting that extracellular matrix (ECM)-receptor interactions are a critical mechanism. ECM-receptor interaction-related biomarkers for renal injury, kidney injury molecule (KIM)-1 and neutrophil gelatinase-associated lipocalin (NGAL), were significantly elevated in welding workers post-exposure, as well as were urinary Al, Cr, Mn, Fe, Co, and Ni levels. NGAL was more significantly associated with Al (r = 0.737, p < 0.001), Cr (r = 0.705, p < 0.001), Fe (r = 0.709, p < 0.001), and Ni (r = 0.657, p < 0.001) than was KIM-1, suggesting that NGAL may be a urinary biomarker for welding PM2.5 exposure. Nephrotoxicity (e.g., renal tubular injury) may be an emerging concern in occupational health.

Figure 1. Physicochemical analyses of particles collected from the office and welding place.

The particles were collected using two Micro-Orifice Uniform Deposit Impactors (MOUDI; MSP Inc., USA). The samples in the size between 1 μm and 1.8 μm were analysed using SEM and EDX. C, O, F, Al, Si, V, Cr, Mn, Fe, Co, Ni, Cu and Cd were determined in the blank, office and welding samples.

Figure 2. Pathways associated with the downregulation and upregulation of protein responses in post-exposure office workers, pre-exposure welding workers, and post-exposure welding workers were determined using a DAVID analysis.

An enhanced score [−log(p value)] of ≥1.3 threshold (red line) was considered significant.

Figure 3. Urinary kidney injury molecule (KIM)-1 and neutrophil gelatinase-associated lipocalin (NGAL) levels after adjustment by urinary creatinine (uCr) in pre- and post-exposure office workers and welding workers.

NGAL levels (adjusted by uCr) in post-exposure office workers and post-exposure welding workers were significantly higher than those in the pre-exposure groups, respectively (*p < 0.05).

Figure 4. Urinary Al, Cr, Mn, Fe, Co, and Ni levels after adjustment by urinary creatinine (uCr) in pre-exposure office workers, post-exposure office workers, pre-exposure welding workers, and post-exposure welding workers.

Al, Cr, Mn, Fe, Co, and Ni levels had significantly increased in post-exposure office workers and post-exposure welding workers compared to their pre-exposure levels. (*p < 0.05).