A Follow-Up Study After Reduction in an Excessive Intake of Cadmium from Rice on Changes in Blood and Urinary Cadmium Levels and Renal Tubular Function Among Female Farmers in Cadmium-Polluted Areas in Northern Japan

There have been several cadmium-polluted areas in the vicinity of mines or smelters in Japan, where local inhabitants are at risk of overexposure to cadmium, which can induce renal tubular dysfunction. As part of the Japanese multi-centered environmental toxicant study (JMETS), we performed health examinations on female farmers in two adjacent cadmium (Cd)-polluted areas in Akita prefecture, northern Japan. Health examinations were conducted in area A in 2001–2002 and in area B in 2003–2004. The level of Cd pollution was higher in area B than in area A. After the initiation of the flooding of paddy fields to reduce rice Cd concentrations in 2002, we conducted a follow-up study in 2006 and 2008 on the same farmers in areas A and B, respectively. Among the 725 and 438 farmers who participated in the first health examinations, 534 and 356 participated in the follow-up, with follow-up rates of 73.7 and 81.3% in areas A and B, respectively. Of these, we selected 763 eligible female farmers aged 34–83 years in the follow-up for analysis. Cd concentrations in the farmers’ home-harvested rice markedly decreased, indicating a reduction in their Cd intake from rice. However, blood Cd levels did not change because the decrease in Cd intake may have been too small to affect high baseline blood Cd levels. On the other hand, urinary Cd levels increased and decreased from the lower and higher baseline levels of urinary Cd levels, respectively. Renal tubular function, indicated by urinary α1-microglobulin and ß2-microglobulin levels, remained unchanged; however, farmers ≥70 years with a baseline urinary Cd level ≥7 µg/g cr. had elevated urinary α1-microglobulin and ß2-microglobulin levels, indicating the deterioration of renal tubular function. Among them, 3 farmers had Cd nephropathy, presenting with rapid and marked increases in urinary ß2-microglobulin levels during the follow-up period. Collectively, these results provide a temporal picture of the sequential development of Cd nephropathy: an individual exposed to a high level of Cd for a long time develops renal tubular dysfunction gradually when older than 70 years, and Cd nephropathy then suddenly occurs and rapidly progresses.