Is Chronic Kidney Disease Due to Cadmium Exposure Inevitable and Can It Be Reversed?

Abstract

Cadmium (Cd) is a metal with no nutritional value or physiological role. However, it is found in the body of most people because it is a contaminant of nearly all food types and is readily absorbed. The body burden of Cd is determined principally by its intestinal absorption rate as there is no mechanism for its elimination. Most acquired Cd accumulates within the kidney tubular cells, where its levels increase through to the age of 50 years but decline thereafter due to its release into the urine as the injured tubular cells die. This is associated with progressive kidney disease, which is signified by a sustained decline in the estimated glomerular filtration rate (eGFR) and albuminuria. Generally, reductions in eGFR after Cd exposure are irreversible, and are likely to decline further towards kidney failure if exposure persists. There is no evidence that the elimination of current environmental exposure can reverse these effects and no theoretical reason to believe that such a reversal is possible. This review aims to provide an update on urinary and blood Cd levels that were found to be associated with GFR loss and albuminuria in the general populations. A special emphasis is placed on the mechanisms underlying albumin excretion in Cd-exposed persons, and for an accurate measure of the doses–response relationships between Cd exposure and eGFR, its excretion rate must be normalised to creatinine clearance. The difficult challenge of establishing realistic Cd exposure guidelines such that human health is protected, is discussed.

Modulation of Adverse Health Effects of Environmental Cadmium Exposure by Zinc and Its Transporters

“…Like JECFA, the tolerable ingestion rates for Cd listed in Table 1 assumed the existence of a toxicity threshold level while using the urinary Cd excretion rate, normalized to creatinine excretion to reflect the long-term exposure or body burden of Cd [ 46 , 47 , 48 ]. As reviewed in Satarug, 2024, however, this method of the normalization of urinary Cd excretion created a high degree of statistical uncertainty, which obscured and nullified the quantification of Cd effects [ 53 ]. Consequently, none of the existing guidelines could reliably indicate a dietary intake level that carries a negligible health risk, inferred from the definition for a tolerable intake level of any contaminant.…”