Heavy Metal Intoxication: A Key-Player in Chronic Kidney Disease (A Review)

Abstract

Heavy metals gain entry into biological systems mainly via inhalation and ingestion, and also via radiation or radio-therapeutic measures. The accumulation of these heavy metals in biological systems overtime may cause several deleterious health challenges such as liver, kidney and brain damages amongst others. Intoxication with heavy metals may either be acute or chronic, and because the kidney has the ability to reabsorb and accumulate divalent metals, it happens to be the primary target organ for heavy metal toxicity, inducing renal damage. The extent of this damage depends on the dose, nature, route and duration of exposure to the metal. Chronic kidney disease (CKD) is characterized by a permanent loss of nephrons accompanied by an eventual decline in glomerular filtration rate (GFR); this (to a greater extent) maybe due to heavy metal intoxication and the renal reabsorption of these heavy metals. Although 70 percent of the heavy metals are reabsorbed in the proximal tubule, all segments of the nephrons are involved in the reabsorption of these metals, where several transporters such as the Divalent Metal Transporter (DMT)-1, Na+/amino acid co-transporter, Zinc Transporter (ZnT)-1 and stretch-activated cation channels (SAC) facilitate the reabsorption. In the nephrons of each kidney, heavy metals are primarily reabsorbed via the apical membrane and accumulate at the basolateral membrane; these heavy metals do not readily exit the basolateral membrane, which overtime may result in chronic inflammation of the nephrons, fibrosis and kidney failure. However, the loss of nephrons and decline in GFR in CKD are compensated by certain changes (glomerular and cellular, enhanced renal blood flow, enhanced single nephron glomerular filtration rate and tubular hypertrophy) in the remaining functional nephrons. These changes help to deliver solutes to the remaining functional nephrons for uptake by the epithelial cells of the renal tubules. Also, because the luminal and basolateral surfaces of tubular epithelial cells of the remaining healthy nephrons are also potentially exposed to higher levels of metabolic wastes, xenobiotics, heavy metals and other nephrotoxicants, renal injury, tubular or glomerulosclerosis, and death of these nephrons occur. These compensatory changes become insufficient once about 75 percent of the nephrons are no longer functional and incapable of maintaining homeostasis and renal function. This results in the accumulation of metabolic wastes in the blood, and induction of metabolic disturbances and/or organ intoxication.