Elsevier

The Lancet

Volume 354, Issue 9189, 30 October 1999, Pages 1508-1513
The Lancet

Articles
Renal effects of low-level environmental cadmium exposure: 5-year follow-up of a subcohort from the Cadmibel study

https://doi.org/10.1016/S0140-6736(99)91145-5Get rights and content

Summary

Background

The clinical relevance of renal effects of cadmium in people exposed in the environment remains uncertain. This study examined the evolution of renal effects observed in a population exposed to cadmium in the environment.

Methods

208 men and 385 women surveyed in 1985–89 (Cadmium in Belgium study [Cadmibel]; baseline) were reexamined on average 5 years later (Public health and environmental exposure to cadmium study [PheeCad]; followup). Urinary and blood cadmium and markers of renal tubular dysfunction and glomerular effects were measured. The association between cadmium body burden and renal factors was examined by multivariate logistic and linear regression.

Findings

In men, mean urinary cadmium excretion and blood cadmium concentration measured at follow-up were 7·5 nmol/24 h (SD 1·9) and 6·1 nmol/L (2·2), reductions of 16% and 35% from baseline, respectively. In women, the corresponding values were 7·6 nmol/24 h (1·9) and 7·8 nmol/L (2·1), reductions of 14% and 28% from baseline. No indication of progressive renal damage was found and the overall results suggest that the effects of low environmental exposure to cadmium on the kidney are weak, stable, or reversible.

Interpretation

Subclinical renal effects that have been reported in Belgium in patients with increased cadmium body burden are not associated with progressive renal dysfunction and most likely represent non-adverse manifestations.

Introduction

The renal toxicity of cadmium has been documented in highly exposed populations in occupational settings.1 Environmental pollution by cadmium may also induce a subclinical renal response with low-molecular-weight proteinuria and calciuria.1 However, whereas there is good evidence indicating that occupational exposure to cadmium can lead to irreversible tubular effects and possibly glomerular dysfunction, the clinical relevance and the course of the renal effects documented in environmentally exposed populations remain uncertain. On the one hand, a few longitudinal investigations suggested that the renal effects induced by environmental cadmium exposure were not only irreversible but also progressive even after cessation of exposure and some cases of chronic renal failure or uraemia associated with environmental cadmium exposure have been reported.2, 3, 4, 5 On the other hand, studies6, 7, 8 on mortality due to renal disease in populations environmentally exposed to cadmium have provided controversial results. A possible explanation for these inconsistencies may be that the results of some studies have been distorted by biases and confounding factors, which may have caused an overestimation of risk of severe kidney damage induced by environmental cadmium exposure.

In a previous study between 1985 and 1989 we surveyed populations environmentally exposed to cadmium in Belgium (Cadmibel9). That study showed an association between cadmium exposure and increased prevalence of abnormal results of kidney function tests (above the 95th centile in the control group). In particular, the urinary excretion of calcium, β2-microglobulin, retinol-binding protein, and N-acetyl-β-D-glucosaminidase (NAG) was significantly associated with the cadmium body burden as assessed by the urinary excretion of the metal. There was a 10% probability of values of these variables being higher than normal when cadmium excretion exceeded 2–4 μg/24 h.

The primary purpose of our investigation was to follow the course of the cadmium-induced renal effects ascertained in the most exposed subgroup from the Cadmibel study. A second purpose was to examine, the relation between indicators of renal tubular effects and cadmium body burden and the possible development of glomerular dysfunction.

Section snippets

Study population

The design of the study has already been described.10 Briefly, the first study took place in four areas defined by urbanisation grade and environmental cadmium pollution level. The study population was recruited to have equal numbers of individuals in six subgroups stratified by sex and age (20–39 years, 40–59 years, 60–79 years) and drawn from a random sample of households. 2327 of 4532 eligible individuals took part. After this first survey (Cadmibel study, 1985–89, baseline values9) the

Results

The median duration of follow-up was 5·2 years (range 4·6–6·1). The characteristics of the individuals who took part in both examinations are presented in table 1. Urinary cadmium excretion and blood cadmium concentrations decreased slightly in both sexes during follow-up. Overall, mean values of renal variables and prevalence of higher than normal values decreased, suggesting reversibility of the effects of cadmium on the kidney. Microalbuminuria (30–300 mg/24 h) was present in 13 (6·5%) men

Discussion

The main finding of this study is that no sign of glomerular dysfunction or progression of cadmiuminduced renal damage was found in this population with environmental exposure to cadmium and followed up over 5 years.

The strengths of this study are the size of the cohort, the random selection of households, quality control over the whole study period, a well-documented exposure assessment (cadmium, lead, copper, zinc, arsenic)12, 18 and the consideration of several confounding factors (table 2).

References (29)

  • T Kido et al.

    Progress of renal dysfunction infants environmentally exposed to cadmium

    Arch Environ Health

    (1988)
  • M Nishijo et al.

    Mortality of inhabitants in an area polluted by cadmium: 15 year follow up

    Occup Environ Med

    (1995)
  • R Lauwerys et al.

    Health effects of environment exposure to cadmium: objectives, design and organization of the Cadmibel study: a cross-sectional morbidity study carried out in Belgium from 1985 to 1989

    Environ Health Perspect

    (1990)
  • J Staessen et al.

    Blood pressure, the prevalence of cardiovascular diseases, and exposure to cadmium: a population study

    Am J Epidemiol

    (1991)
  • Cited by (131)

    • Renal effects of exposure to metals

      2021, Handbook on the Toxicology of Metals: Fifth Edition
    • Cadmium

      2021, Handbook on the Toxicology of Metals: Fifth Edition
    • Normal variability of 22 elements in 24-hour urine samples – Results from a biobank from healthy non-smoking adults

      2021, International Journal of Hygiene and Environmental Health
      Citation Excerpt :

      Some studies on multiple elements in 24 h urine have focused on occupationally exposed groups, and some on samples from the patients or general population samples, e.g. in Japan (Araki et al., 1986), US (Komaromy-Hiller et al., 2000), the UK (Sieniawska et al., 2012), Belgium (Smolders et al., 2014), and China (Wang et al., 2016). In addition, there are some studies on 24 h urine excretion of single elements such as zinc (Henderson et al., 1996; Ilich et al., 2009), cadmium (Hotz et al., 1999; Uno et al., 2005; Lampe et al., 2008; Akerstrom et al., 2013, 2014), mercury (Akerstrom et al., 2017), chromium (Nomiyama et al., 1980), sulphur (Magee et al., 2004) and phosphorus (Palomino et al., 2013). Older studies may have used analytical methods with limited sensitivity.

    • Renal effects of exposure to metals

      2021, Handbook on the Toxicology of Metals: Volume I: General Considerations
    View all citing articles on Scopus
    View full text