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Open AccessArticle

The Source and Pathophysiologic Significance of Excreted Cadmium

1
Kidney Disease Research Collaborative, The University of Queensland Faculty of Medicine and Translational Research Institute, Woolloongabba, Brisbane 4102, Australia
2
Department of Nephrology, Princess Alexandra Hospital, Brisbane 4075, Australia
3
Division of Toxicology, Department of Forensic Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
4
Department of Public Health, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan
5
School of Biomedical Sciences, The University of Queensland, Brisbane 4072, Australia
6
NHMRC Centre of Research Excellence for CKD.QLD, UQ Health Sciences, Royal Brisbane and Women’s Hospital, Brisbane 4029, Australia
7
Stratton Veterans’ Affairs Medical Center and Albany Medical College, Albany, NY 12208, USA
*
Author to whom correspondence should be addressed.
Toxics 2019, 7(4), 55; https://doi.org/10.3390/toxics7040055
Received: 10 August 2019 / Revised: 10 October 2019 / Accepted: 16 October 2019 / Published: 18 October 2019
(This article belongs to the Special Issue Toxic Metals, Chronic Diseases and Related Cancers)
In theory, the identification of the source of excreted cadmium (Cd) might elucidate the pathogenesis of Cd-induced chronic kidney disease (CKD). With that possibility in mind, we studied Thai subjects with low, moderate, and high Cd exposure. We measured urine concentrations of Cd, ([Cd]u); N-acetyl-β-d-glucosaminidase, a marker of cellular damage ([NAG]u); and β2-microglobulin, an indicator of reabsorptive dysfunction ([β2MG]u). To relate excretion rates of these substances to existing nephron mass, we normalized the rates to creatinine clearance, an approximation of the glomerular filtration rate (GFR) (ECd/Ccr, ENAG/Ccr, and Eβ2MG/Ccr). To link the loss of intact nephrons to Cd-induced tubular injury, we examined linear and quadratic regressions of estimated GFR (eGFR) on ECd/Ccr, eGFR on ENAG/Ccr, and ENAG/Ccr on ECd/Ccr. Estimated GFR varied inversely with both ratios, and ENAG/Ccr varied directly with ECd/Ccr. Linear and quadratic regressions of Eβ2MG/Ccr on ECd/Ccr and ENAG/Ccr were significant in moderate and high Cd-exposure groups. The association of ENAG/Ccr with ECd/Ccr implies that both ratios depicted cellular damage per surviving nephron. Consequently, we infer that excreted Cd emanated from injured tubular cells, and we attribute the reduction of eGFR to the injury. We suggest that ECd/Ccr, ENAG/Ccr, and eGFR were associated with one another because each parameter was determined by the tubular burden of Cd. View Full-Text
Keywords: β2-microglobulin; cadmium; creatinine clearance; glomerular filtration; N-acetyl-β-d-glucosaminidase; nephron mass; nephrotoxicity β2-microglobulin; cadmium; creatinine clearance; glomerular filtration; N-acetyl-β-d-glucosaminidase; nephron mass; nephrotoxicity
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Satarug, S.; Vesey, D.A.; Ruangyuttikarn, W.; Nishijo, M.; Gobe, G.C.; Phelps, K.R. The Source and Pathophysiologic Significance of Excreted Cadmium. Toxics 2019, 7, 55.

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