Chronic Kidney Disease and Exposure to Nephrotoxic Metals

Sarah E Orr, Christy C Bridges, Sarah E Orr, Christy C Bridges

Abstract

Chronic kidney disease (CKD) is a common progressive disease that is typically characterized by the permanent loss of functional nephrons. As injured nephrons become sclerotic and die, the remaining healthy nephrons undergo numerous structural, molecular, and functional changes in an attempt to compensate for the loss of diseased nephrons. These compensatory changes enable the kidney to maintain fluid and solute homeostasis until approximately 75% of nephrons are lost. As CKD continues to progress, glomerular filtration rate decreases, and remaining nephrons are unable to effectively eliminate metabolic wastes and environmental toxicants from the body. This inability may enhance mortality and/or morbidity of an individual. Environmental toxicants of particular concern are arsenic, cadmium, lead, and mercury. Since these metals are present throughout the environment and exposure to one or more of these metals is unavoidable, it is important that the way in which these metals are handled by target organs in normal and disease states is understood completely.

Keywords: arsenic; cadmium; chronic kidney disease; lead, mercury.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Histological sections of kidneys from Sham or 75% nephrectomized Wistar rats. Normal glomeruli (arrows) and tubules from the renal cortex are shown in panel (A) while panel (B) shows normal tubules (arrowheads) from the outer stripe of the outer medulla. Sections of renal cortex (C) and outer stripe of outer medulla (D) from a 75% nephrectomized rat are also shown. A 75% nephrectomized rat is considered to be an appropriate model of chronic kidney disease. Glomeruli (arrows (C)) from a 75% nephrectomized rat appear to be hypertrophied as a compensatory response to a reduction in renal mass. Similarly, the tubules in the outer stripe of the outer medulla (D) of the 75% nephrectomized rat also appear to be hypertrophied (arrowheads). In contrast, some tubules (*) display signs of necrosis, which is likely due to the reduced perfusion of blood to those nephrons. Magnification, 100×.
Figure 2
Figure 2
Histological sections of kidneys from Sham or 75% nephrectomized Wistar rats exposed to 2.5 μmol kg−1 HgCl2. Panel (A) shows a representative section of kidney from Sham rats exposed to2.5 μmol kg−1 HgCl2. This section displays a normal glomerulus (arrow) and a mix of normal and injured tubules (*). In addition, there is an infiltration of lymphocytes, which is likely one of the first responses to the inflammation caused by exposure to mercury. Panel (B) shows a representative section of kidney from 75% nephrectomized rats exposed to 2.5 μmol kg−1 HgCl2. Glomeruli (arrows) were hypertrophied and tubular necrosis (*) was widespread. The degree of injury in the 75% nephrectomized rats was significantly greater than that in corresponding Sham rats, suggesting that rats with reduced renal mass may be more sensitive to the nephrotoxicants such as mercury, than rats with normal renal mass. Magnification, 100×.
Figure 2
Figure 2
Histological sections of kidneys from Sham or 75% nephrectomized Wistar rats exposed to 2.5 μmol kg−1 HgCl2. Panel (A) shows a representative section of kidney from Sham rats exposed to2.5 μmol kg−1 HgCl2. This section displays a normal glomerulus (arrow) and a mix of normal and injured tubules (*). In addition, there is an infiltration of lymphocytes, which is likely one of the first responses to the inflammation caused by exposure to mercury. Panel (B) shows a representative section of kidney from 75% nephrectomized rats exposed to 2.5 μmol kg−1 HgCl2. Glomeruli (arrows) were hypertrophied and tubular necrosis (*) was widespread. The degree of injury in the 75% nephrectomized rats was significantly greater than that in corresponding Sham rats, suggesting that rats with reduced renal mass may be more sensitive to the nephrotoxicants such as mercury, than rats with normal renal mass. Magnification, 100×.

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