Mechanisms of Cadmium-Induced Proximal Tubule Injury: New Insights with Implications for Biomonitoring and Therapeutic Interventions
- 5 June 2012
- journal article
- review article
- Published by American Society for Pharmacology & Experimental Therapeutics (ASPET) in The Journal of pharmacology and experimental therapeutics
- Vol. 343 (1), 2-12
- https://doi.org/10.1124/jpet.110.166769
Abstract
Cadmium is an important industrial agent and environmental pollutant that is a major cause of kidney disease. With chronic exposure, cadmium accumulates in the epithelial cells of the proximal tubule, resulting in a generalized reabsorptive dysfunction characterized by polyuria and low-molecular-weight proteinuria. The traditional view has been that as cadmium accumulates in proximal tubule cells, it produces a variety of relatively nonspecific toxic effects that result in the death of renal epithelial cells through necrotic or apoptotic mechanisms. However, a growing volume of evidence suggests that rather than merely being a consequence of cell death, the early stages of cadmium-induced proximal tubule injury may involve much more specific changes in cell-cell adhesion, cellular signaling pathways, and autophagic responses that occur well before the onset of necrosis or apoptosis. In this commentary, we summarize these recent findings, and we offer our own perspectives as to how they relate to the toxic actions of cadmium in the kidney. In addition, we highlight recent findings, suggesting that it may be possible to detect the early stages of cadmium toxicity through the use of improved biomarkers. Finally, some of the therapeutic implications of these findings will be considered. Because cadmium is, in many respects, a model cumulative nephrotoxicant, these insights may have broader implications regarding the general mechanisms through which a variety of drugs and toxic chemicals damage the kidney.This publication has 67 references indexed in Scilit:
- Blood Cadmium and Lead and Chronic Kidney Disease in US Adults: A Joint AnalysisAmerican Journal of Epidemiology, 2009
- Current status of cadmium as an environmental health problemToxicology and Applied Pharmacology, 2009
- Metallothionein protection of cadmium toxicityToxicology and Applied Pharmacology, 2009
- Cadmium — A metallohormone?Toxicology and Applied Pharmacology, 2009
- Discovery of ZIP transporters that participate in cadmium damage to testis and kidneyToxicology and Applied Pharmacology, 2009
- Expression of kidney injury molecule-1 (Kim-1) in relation to necrosis and apoptosis during the early stages of Cd-induced proximal tubule injuryToxicology and Applied Pharmacology, 2009
- Preclinical evaluation of novel urinary biomarkers of cadmium nephrotoxicityToxicology and Applied Pharmacology, 2009
- Biomarkers of Acute Kidney InjuryAnnual Review of Pharmacology and Toxicology, 2008
- Kidney injury molecule-1 is an early biomarker of cadmium nephrotoxicityKidney International, 2007
- Cell adhesion molecules in chemically-induced renal injuryPharmacology & Therapeutics, 2007