The relationship between cadmium in kidney and cadmium in urine and blood in an environmentally exposed population

Abstract

Introduction

Cadmium (Cd) is toxic to the kidney and a major part of the body burden occurs here. Cd in urine (U-Cd) and blood (B-Cd) are widely-used biomarkers for assessing Cd exposure or body burden. However, empirical general population data on the relationship between Cd in kidney (K-Cd), urine, and blood are scarce. Our objectives were to determine the relationship between cadmium in kidney, urine, and blood, and calculate the elimination half-time of Cd from the kidney.

Methods

Kidney cortex biopsies, urine, and blood samples were collected from 109 living kidney donors. Cd concentrations were determined and the relationships between K-Cd, U-Cd, and B-Cd were investigated in regression models. The half-time of K-Cd was estimated from the elimination constant.

Results

There was a strong association between K-Cd and U-Cd adjusted for creatinine (r_p = 0.70, p < 0.001), while the association with B-Cd was weaker (r_p = 0.44, p < 0.001). The relationship between K-Cd and U-Cd was nonlinear, with slower elimination of Cd at high K-Cd. Estimates of the K-Cd half-time varied between 18 and 44 years. A K-Cd of 25 μg/g corresponds to U-Cd of 0.42 μg/g creatinine in overnight urine (U-Cd/K-Cd ratio: about 1:60). Multivariate models showed Cd in blood and urinary albumin as determinants for U-Cd excretion.

Discussion

In healthy individuals with low-level Cd exposure, there was a strong correlation between Cd in kidney and urine, especially after adjustment for creatinine. Urinary Cd was also affected by Cd in blood and urinary albumin. Previous estimates of the U-Cd/K-Cd ratio may underestimate K-Cd at low U-Cd.

Introduction

Cadmium (Cd) is a serious environmental contaminant which accumulates in the kidney and can potentially affect human health at relatively low concentrations. It is toxic to the kidney, especially the proximal tubular cells, but can also cause bone demineralization (EFSA, 2009, Ferraro et al., 2010, Jarup and Akesson, 2009, Jarup et al., 1998, Nawrot et al., 2010, Nordberg et al., 2007, Prozialeck and Edwards, 2010, Satarug et al., 2010). Soil and water are contaminated through airborne deposition, and soil concentrations are further increased by the use of fertilizers or sewage sludge on agricultural farm fields (EFSA, 2009, Nawrot et al., 2010, Nordberg et al., 2007, Prozialeck and Edwards, 2010, Satarug et al., 2010). Cadmium from the soil is accumulated in the crops, and diet is the main source of Cd exposure in the general population. For smokers, tobacco consumption is also an important route of exposure. Gastrointestinal Cd absorption in humans from dietary exposure is 3–5%, while Cd absorption from inhalation is 10–50% (EFSA, 2009, Nawrot et al., 2010, Nordberg et al., 2007, Prozialeck and Edwards, 2010, Satarug et al., 2010). When absorbed, Cd binds to proteins in the blood and is transported to the liver where it is bound to metallothionein. The Cd-metallothionein complex is filtered in the renal glomerulus, reabsorbed in the tubular cells, and accumulated in the kidney with a biological half-time ranging from 10 to 30 years (EFSA, 2009, Jarup and Akesson, 2009, Nawrot et al., 2010, Nordberg et al., 2007). Approximately 50% of the total Cd body burden is accumulated in the kidney. Absorbed Cd is excreted in urine and feces (EFSA, 2009, Jarup and Akesson, 2009, Nordberg et al., 2007).

Urinary Cd (U-Cd) and blood Cd (B-Cd) are widely used as biomarkers to assess exposure or body burden of Cd in the general population (Jarup et al., 1998). U-Cd is considered to reflect the kidney burden and body burden of Cd, while B-Cd is considered to be the most valid marker of recent exposure (EFSA, 2009, Jarup et al., 1998, Nordberg et al., 2007). Close relationships between the concentrations of Cd in the kidney, urine, and blood are anticipated at steady state. If a linear relationship between K-Cd and U-Cd is assumed, a U-Cd concentration of 2.5 μg/g creatinine corresponds to a concentration of about 50 μg/g in the kidney, giving a U-Cd/K-Cd ratio of about 1:20 (EFSA, 2009, Jarup et al., 1998, Nordberg et al., 2007).

Until now, information about the relationship between K-Cd, U-Cd, and B-Cd has mainly been collected by in vivo measurements using X-ray fluorescence (XRF) (Borjesson and Mattsson, 1995, Borjesson et al., 1997, Borjesson et al., 2001, Christoffersson et al., 1987, Nilsson et al., 1995, Nilsson et al., 2000) or neutron activation (Ellis et al., 1983, Mason et al., 1999, Roels et al., 1981), or by autopsy studies (Orlowski et al., 1998, Satarug et al., 2002). However, most in vivo studies have been performed in occupationally exposed workers, and the techniques are not sensitive enough for investigating the relationship between K-Cd and biomarkers of Cd at the low-level exposure occurring in the general population (Nilsson et al., 1995, Nilsson et al., 2000). Autopsy cases may not be representative of the healthy part of the population, and Cd levels in urine and blood may change post mortem. Moreover, data concerning diet and smoking habits may be uncertain in autopsy studies.

Our study is the first to provide empirical data on Cd levels in the kidney cortex, urine, and blood of healthy individuals from the general population with low-level Cd exposure, using analytical methods which can precisely quantify kidney Cd at very low concentrations. Our aims for this study were to determine the relationship between Cd in kidney and Cd in urine, and thereby estimate the elimination half-time of Cd in kidney, and to investigate factors affecting U-Cd excretion and the relationships between Cd in kidney, urine, and blood.