Liang et al. residents continued to consume locally grown vegetables, Cd intake was minimal com- pared with their previous intake from rice. In Nanbaixiang, the moderately polluted area, consumption of locally produced rice ended in the late 1990s because of rapid industrial and economic development in the Wenzhou region. Residents of Yantou, an area with similar living habits and socioeconomic con- ditions located about 40 km away from the contaminated areas, were also recruited into the study. Renal function of individuals from all three areas was assessed in 1995 (Nordberg et al. 1997) and 1998 (Jin et al. 2002). In late 2006 we followed up participants in the studies mentioned above. The Cd content of rice produced in the highly polluted area was as high as 3.7 mg Cd/kg in 1995 (Nordberg et al. 1997), and thus we considered the consumption of rice grown locally as the most important determinant of Cd exposure. The ChinaCad study (Jin et al. 1999, 2002, 2004a, 2004b) showed that in 1998 most of the examined residents in the highly polluted area had BCd > 5 μg/L and UCd > 5 μg/g creatinine, despite being advised by local health authorities to consume rice from nonpolluted areas beginning in 1996. Cd exposure was associated with renal damage manifested by excessive excretion of urinary β2-microglobulin, albumin, NAG, and retinol-binding protein. A total of 790 residents (488 women, 302 men) ≥ 35 years of age were surveyed in 1998, and 497 of them were followed up in 2006 (Chen et al. 2009a, 2009b). Among those who did not participate in the 2006 sur- vey, 60 were dead, 9 were unavailable because of work outside the study areas, 57 had moved out of the study areas, and 167 declined to participate. After excluding individuals who were > 80 years old, had systolic blood pres- sure > 170 mmHg, or were on any physician- prescribed medication, a total of 412 subjects were available for the present study. Sample collection and bioanalysis. Consistent with the same strict sampling protocol used in the 1998 study (Jin et al. 1999, 2002, 2004a, 2004b), blood and urine samples were collected and frozen at –20°C in the local laboratory on the same day. After all samples were collected, they were transported to Fudan University and stored at –80°C until analysis. BCd and UCd were measured by graphite- furnace atomic absorption spectrometry using standard addition, as described by Jin et al. (2002). β2-Microglobulin and albumin were measured by enzyme-linked immunosorbent assay (ELISA). Urinary NAG was analyzed as previously described by Tucker et al. (1975). Creatinine in serum (available only in 2006) and urine were determined by the Jaffe reac- tion method (Hare 1950). To adjust the urine spot samples for dilution, all urine param- eters were standardized to the concentration of creatinine in urine [for details of analyti- cal performance, see Supplemental Material (http://dx.doi.org/10.1289/ehp.1103699)]. Glomerular filtration rate (GFR; in milliliters per minute per 1.73 m2) was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation (Levey et al. 2009). Definition of cut points for kidney effect markers. Impaired kidney function was defined as having NAG, β2-microglobulin, or albumin above the 95th percentile for the study population in the nonpolluted Yantou area. We could not use the same cut points for 1998 and 2006 because the individuals were Table 1. Age distribution (%) by area among the residents followed up in 2006 (n = 412). Age group (years) in 1998 35–44 45–54 55–64 ≥ 65 Characteristic or indicator n (% male) Median age (years) in 1998 BCd (μg/L) UCd (μg/g creatinine) NAG (U/g creatinine) β2-Microglobulin (mg/g creatinine) Albumin (mg/g creatinine) Serum creatinine [μmol/L; median (range)] eGFR [mL/min/1.73 m2; median (range)] Prevalence of hypertension (%)a 224 Nonpolluted (n = 91) 24.2 30.8 28.6 16.5 1998 91 (36.8) 53.0 1.31 (0.75–2.19) 1.79 (1.07–3.63) 1.80 (0.89–3.99) 0.12 (0.07–0.24) 3.08 (1.40–6.40) Moderately polluted (n = 131) 49.6 26.7 19.8 3.8 2006 0.87 (0.57–1.46)* 2.31 (1.42–3.84) 7.92 (5.65–10.7)* 0.16 (0.09–0.26) 2.84 (1.13–4.71)* 65 (39–105) 92 (59–119) 45.0 Table 2. Exposure levels and renal indicators in 1998 and 2006 among residents in study areas (n = 412). Nonpolluted area Moderately polluted area Highly polluted area Values for BCd, UCd, NAG, β2‑microglobulin, and albumin are reported as GM (IQR). aIndividuals with systolic pressure ≥ 140 mmHg or/and diastolic pressure ≥ 90 mmHg were classified as having hypertension. *p < 0.05 compared with 1998, by Wilcoxon signed‑ rank test. **p < 0.05 compared with residents of the nonpolluted area, by Mann‑Whitney U‑test. Highly polluted (n = 190) 45.8 34.7 13.7 5.8 1998 131 (33.6) 46.0 3.78 (2.50–6.50) 3.62 (2.52–6.05) 4.12 (2.02–11.3) 0.16 (0.10–0.31) 4.47 (2.10–9.30) 2006 1.80 (1.27–2.75)* 3.79 (2.66–6.13) 8.15 (5.77–10.7)* 0.28 (0.17–0.44)* 3.83 (1.33–9.44) 66 (45–111) 93 (46–118) 40.4 1998 190 (33.0) 46.5 8.90 (4.97–13.6) 11.6 (7.61–18.7) 7.64 (4.44–14.2) 0.28 (0.14–0.50) 5.38 (2.48–11.9) 2006 3.31 (2.25–5.15)* 8.97 (5.87–13.1)* 11.8 (7.25–17.8)* 0.42 (0.20–0.79)* 3.22 (1.28–7.22)* 70 (31–130)** 92 (38–121) 43.1 ovlume 120 | number 2 | February 2012 • Environmental Health Perspectives 8 years older in 2006 and renal markers are related to age. Therefore, we established dif- ferent cut points for 1998 and 2006. Because the age distribution for the nonpolluted area differed from that of the two polluted areas (Table 1), we adjusted the distributions for all three biomarkers to the age distribution of the whole study group: Data were stratified into four age groups, and weights for each age group in the nonpolluted area were calculated by dividing the total proportion of individuals in an age group (all three areas) by the pro- portion of individuals in the nonpolluted area in that age group. In this way, a data set was created based on the nonpolluted area but with the same age distribution as the whole study group, which was used to establish the cut points for the kidney markers in 1998 and 2006. The weighted cut points for uri- nary NAG, β2-microglobulin, and albumin were 9.8 U/g creatinine, 0.890 mg/g creati- nine, and 14.6 mg/g creatinine, respectively, in 1998; and 16.6 U/g creatinine, 1.028 mg/g creatinine, and 21.7 mg/g creatinine in 2006. Levels of these markers above the cut points were regarded as “elevated.” Values below the cut points were considered “normal.” Statistical methods. Biochemical param- eters that were not normally distributed were expressed as GMs with interquartile ranges (IQRs). We used the Wilcoxon signed-rank test to compare levels of biomarker values in 1998 with those in 2006, and the Mann-Whitney U-test to compare baseline characteristics of participants followed in 2006 and those lost to follow-up. Log-linear models were used to model the relation between prevalence of kid- ney damage (elevated NAG, β2-microglobulin, and albumin) and exposure (UCd in 1998). Pairwise comparisons were made between the prevalence of kidney damage in 1998 and 2006 in each exposure group. p-Values ≤ 0.05 were considered significant. All statistical analyses were performed using R, version 2.9.0 (http:// www.r-project.org). Ethical considerations. We complied with all applicable requirements of the interna- tional regulations during the study. Surveys