Cadmium and Lead Exposure, Nephrotoxicity, and Mortality

Abstract

The present review aims to provide an update on health risks associated with the low-to-moderate levels of environmental cadmium (Cd) and lead (Pb) to which most populations are exposed. Epidemiological studies examining the adverse effects of coexposure to Cd and Pb have shown that Pb may enhance the nephrotoxicity of Cd and vice versa. Herein, the existing tolerable intake levels of Cd and Pb are discussed together with the conventional urinary Cd threshold limit of 5.24 μg/g creatinine. Dietary sources of Cd and Pb and the intake levels reported for average consumers in the U.S., Spain, Korea, Germany and China are summarized. The utility of urine, whole blood, plasma/serum, and erythrocytes to quantify exposure levels of Cd and Pb are discussed. Epidemiological studies that linked one of these measurements to risks of chronic kidney disease (CKD) and mortality from common ailments are reviewed. A Cd intake level of 23.2 μg/day, which is less than half the safe intake stated by the guidelines, may increase the risk of CKD by 73%, and urinary Cd levels one-tenth of the threshold limit, defined by excessive ß2-microglobulin excretion, were associated with increased risk of CKD, mortality from heart disease, cancer of any site and Alzheimer’s disease. These findings indicate that the current tolerable intake of Cd and the conventional urinary Cd threshold limit do not provide adequate health protection. Any excessive Cd excretion is probably indicative of tubular injury. In light of the evolving realization of the interaction between Cd and Pb, actions to minimize environmental exposure to these toxic metals are imperative.

The Effect of Cadmium on GFR Is Clarified by Normalization of Excretion Rates to Creatinine Clearance

“…If this inference is correct, then E Cd , like E NAG , is an indicator of Cd-induced tubular injury [ 15 ]. Tubulointerstitial nephritis, destruction of nephrons, and a reduction in GFR are logical sequelae of such injury [ 3 , 31 ].…”

“…If urinary Cd and NAG emanate from tubules, then we should expect the excretion of these substances to vary directly with the number of intact nephrons and the severity of cellular injury. In the absence of renal hypoperfusion, we assume a proportional relationship between GFR and nephron number [ 3 ]. Consequently, to focus on the severity of injury as a determinant of eGFR, we nullify the simultaneous contribution of nephron number to E Cd and E NAG by normalizing these excretion rates to C cr .…”

“…After Cd is separated from MT in lysosomes of tubular cells, it induces in situ synthesis of MT, which mitigates the toxicity of the free metal. Nevertheless, a small amount of unbound Cd inflicts injury that may eventuate in nephron loss and a reduction in the glomerular filtration rate (GFR) [ 2 , 3 ].…”

“…However, in contrast to E x /E cr , E x /C cr is also unaffected by muscle mass because [cr] p varies in proportion to E cr at a given C cr . Moreover, if x emanates from tubular cells, E x may fall because of nephron loss; in that circumstance, E x /C cr depicts the excretion of x per surviving nephron because C cr falls simultaneously [ 2 , 3 ].…”

Assessment of Pb(II), Cd(II), and Al(III) Removal Capacity of Bacteria from Food and Gut Ecological Niches: Insights into Biodiversity to Limit Intestinal Biodisponibility of Toxic Metals

“…It has also been suggested that Cd is involved in metabolic diseases and susceptibility to respiratory tract infections [ 12 , 13 ]. A Cd intake of 23.2 μg/day (less than half the safe intake, according to current guidelines) might increase the risk of chronic kidney disease, mortality from heart disease, cancer at any site, and Alzheimer’s disease [ 14 ]. Moreover, epidemiological studies of co-exposure to Cd and Pb have shown that each metal enhances the nephrotoxicity of the other.…”