Abstract
Background: Cadmium (Cd) is abundantly documented as a metal mainly affecting tubular function both in workers and in the general population indirectly exposed via the environment. Results from epidemiological studies linking Cd exposure and risk of progression to chronic kidney disease (CKD) are, however, conflicting. Objectives: To perform a systematic review of the association between Cd exposure and CKD. Methods: A systematic appraisal of publications found in MEDLINE (1946–2014), EMBASE (1974–2012) and an in-house database (1986–2013) was conducted. Additional studies were searched for by contacting experts and checking reference lists. Search terms used key and text words. No language restriction was applied. Cohort, case–control and case-series with follow-up including individual and objective assessment of occupational or environmental exposure were eligible. Studies were selected and data extracted by two independent reviewers using predefined forms. Study characteristics and results were extracted to structured tables. Synthesis was qualitative and results appraised with causality criteria. Results: Thirty-four exposed groups, totaling more than 3000 participants, were eligible. Overall, results disclosed no convincing evidence supporting a risk of progression to CKD in populations exposed to Cd. Lack of information about methods, risk of bias and heterogeneity were identified as limitations and precluded conducting a meta-analysis. Publication bias did not appear as a major problem. Conclusions: This qualitative systematic review does not support the contention that human exposure to Cd leads to progressive CKD.
Acknowledgements
We wish to thank Mrs. C. Fardo for the management of the literature, Mr. C. Ochsner, Mrs. S. Hilfiker, and Dr. M. Egli, for help and advice regarding translations, and Dr. M. Gosteli for checking the MEDLINE literature search and adapting it for EMBASE. We are very grateful to the four anonymous reviewers for the value of their comments in improving the manuscript. The first evaluation of the epidemiological literature on Cd and CKD (Verougstraete Citation2005) was conducted for the Ministry of Social Affairs, Public Health and Environment (Belgium) within the scope of the EC Council Regulation (EC) 793/93 requiring the risk assessment of existing substances.
Declaration of interest
Affiliations for the authors are shown on the cover page. The authors declare that they have no actual or potential competing financial interest. Part of this work has been conducted by order of the Ministry of Social Affairs, Public Health and Environment (Belgium), within the scope of the EC Council Regulation (EC)793/93, requiring the risk assessment of existing substances. The funding source played no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report or approval of the manuscript, and in the decision to submit the paper for publication. The review strategy, the conduct of the review and the interpretation and synthesis of the findings were exclusively the work of the authors. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication. P. Hotz, D. Lison, K. Byber, and V. Verougstraete devised the conceptual framework of the study. K. Byber and P. Hotz did the data analysis and wrote the first draft of the manuscript. All investigators contributed to the interpretation of the data and to the writing of the article.