Tohoku J. Exp. Med., 2017 January, 241(1), 65-87.

Invited Review

Kidney Cadmium Toxicity, Diabetes and High Blood Pressure: The Perfect Storm


1Centre for Kidney Disease Research, Translational Research Institute and The University of Queensland Diamantina Institute, Woolloongabba, Brisbane, Queensland, Australia

Cadmium (Cd) is an environmental toxicant of widespread exposure and pervasive toxicity. Absorption, systemic transport and uptake of Cd are mediated by metal transporters that the body uses for acquisition of physiologically-essential elements, notably of iron, zinc and calcium. Currently, human exposure to Cd is known to damage the kidneys, especially the proximal tubular cells that actively reabsorb Cd along with zinc, glucose and amino acids in the glomerular filtrate. Severe kidney damage, glycosuria and proteinuria are known outcomes after high dietary Cd intake (> 200 μg/day). Dietary Cd intake of 10-30 μg/day has been linked with reduced tubular reabsorption, chronic kidney disease, hypertension, coronary arterial and peripheral arterial diseases, macular degeneration, obesity-independent diabetes, and cancer. The links between diabetes, hypertension and end stage kidney disease (ESKD) are indisputable. ESKD requires dialysis or kidney transplant, an immense health care cost. This review adds to these connections by presenting the synergism of kidney Cd toxicity on blood pressure control and glucose homeostasis. Blood pressure control is mediated at least in part by cytochrome P450 (CYP) enzymes such as CYP4A11 and CYP4F2 that produce 20-hydroxyeicosatetraenoic acid (20-HETE), involved in salt balance in the kidney, and all are known to be altered during Cd exposure. The potential effects of Cd exposure on glucose reabsorption, inflammation, oxidative stress, and heme oxygenase activity are highlighted. The information presented offers strategies for mitigation of toxic effects of Cd through minimization of the food-chain transfer of Cd, and modulation of mechanistic pathways altered by Cd exposure.

Key words —— cadmium; diabetes; end stage kidney disease; hypertension; 20-HETE


Tohoku J. Exp. Med., 2017, 241, 65-87