Association and Interaction between Heavy Metals and Hyperuricemia in a Taiwanese Population.

The prevalence of hyperuricemia in Taiwan is high, and hyperuricemia has been associated with a risk of developing several diseases. Although the traditional risk factors for hyperuricemia are well known, the relationship between heavy metals and hyperuricemia is still undefined. Therefore, the aim of this study was to investigate the relationship between hyperuricemia and heavy metals. A total of 2447 participants (977 males and 1470 females) residing in southern Taiwan were enrolled, and levels of the following heavy metals were measured: lead in blood, and nickel, chromium, manganese, arsenic (As), copper, and cadmium in urine. Hyperuricemia was defined as a serum uric acid level greater than 7.0 mg/dL (416.5 µmol/L) in men and 6.0 mg/dL (357 µmol/L) in women. The participants were divided into two groups: those without hyperuricemia (n = 1821; 74.4%) and those with hyperuricemia (n = 626; 25.6%). Multivariate analysis showed that only high urine As (log per 1 µg/g creatinine; odds ratio, 1.965; 95% confidence interval, 1.449 to 2.664; p < 0.001), young age, male sex, high body mass index, high hemoglobin, high triglycerides, and low estimated glomerular filtration rate were significantly associated with hyperuricemia. In addition, the interactions between Pb × Cd (p = 0.010), Ni × Cu (p = 0.002), and Cr × Cd (p = 0.001) on hyperuricemia were statistically significant. Increasing levels of Pb and Cr yielded an increased prevalence of hyperuricemia, and the effect was progressively greater for increasing Cd. Moreover, increasing levels of Ni yielded an increased prevalence of hyperuricemia, and the effect was progressively greater for increasing Cu. In conclusion, our results show that high urine As is associated with hyperuricemia, and some interactions of heavy metals on hyperuricemia are noted. We also found that young age, male sex, high BMI, high hemoglobin, high triglycerides, and low eGFR were significantly associated with hyperuricemia.

Sex Difference in the Associations among Hyperuricemia with New-Onset Chronic Kidney Disease in a Large Taiwanese Population Follow-Up Study.

The global prevalence and incidence of chronic kidney disease (CKD) continue to increase. Whether hyperuricemia is an independent risk factor for renal progression and whether there are sex differences in the relationships between serum uric acid (UA) and a decline in renal function are unclear. Therefore, in this longitudinal study, we aimed to explore these relationships in a large cohort of around 27,000 Taiwanese participants in the Taiwan Biobank (TWB), and also to identify serum UA cutoff levels in men and women to predict new-onset CKD. A total of 26,942 participants with a median 4 years of complete follow-up data were enrolled from the TWB. We excluded those with CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2) at baseline (n = 297), and the remaining 26,645 participants (males: 9356; females: 17,289) were analyzed. The participants who developed CKD during follow-up were defined as having incident new-onset CKD, and those with a serum UA level >7 mg/dL in males and >6 mg/dL in females were classified as having hyperuricemia. After multivariable analysis, hyperuricemia (odds ratio [OR], 2.541; 95% confidence interval [CI], 1.970−3.276; p < 0.001) was significantly associated with new-onset CKD. Furthermore, in the male participants (n = 9356), hyperuricemia (OR, 1.989; 95% CI, 1.440−2.747; p < 0.001), and quartile 4 of UA (vs. quartile 1; OR, 2.279; 95% CI, 1.464−3.547; p < 0.001) were significantly associated with new-onset CKD, while in the female participants (n = 17,289), hyperuricemia (OR, 3.813; 95% CI, 2.500−5.815; p < 0.001), quartile 3 of UA (vs. quartile 1; OR, 3.741; 95% CI, 1.250−11.915; p = 0.018), and quartile 4 of UA (vs. quartile 1; OR, 12.114; 95% CI, 14.278−34.305; p < 0.001) were significantly associated with new-onset CKD. There were significant interactions between hyperuricemia and sex (p = 0.024), and quartiles of serum UA and sex (p = 0.010) on new-onset CKD. Hyperuricemia was associated with new-onset CKD in the enrolled participants, and the interactions between hyperuricemia and sex were statistically significant. Hyperuricemia was more strongly associated with new-onset CKD in the women than in the men.

Association of Heavy Metals with Overall Mortality in a Taiwanese Population.

Previous studies have shown links between heavy metals and many health issues. However, data on the association between heavy metals and mortality in the general population are still limited. Therefore, the aim of this study was to investigate the relationship between heavy metals and overall mortality in the general population. We enrolled 2497 participants (1001 males and 1496 females) living in southern Taiwan, and measured levels of seven heavy metals: lead (Pb) in blood and cadmium (Cd), nickel (Ni), copper (Cu), chromium (Cr), manganese (Mn) and arsenic (As) in urine. The median follow-up period was 41.8 (4-50) months, during which 40 (1.6%) patients died. Compared to the participants who survived, those who died had higher urine Cd, higher urine Cu and lower urine Mn levels. Multivariate analysis showed that high urine Cd (per 1 µg/L; hazard ratio [HR], 1.352; 95% confidence interval [CI], 1.089-1.680; p = 0.006), high urine Cu (per 1 µg/dL; HR, 1.350; 95% CI, 1.151-1.583; p < 0.001), and low urine Mn (per 1 µg/L; HR, 0.717; 95% CI, 0.557-0.923; p = 0.010) were associated with increased overall mortality. In conclusion, our results demonstrated that high levels of urine Cd and Cu and low urine Mn level were associated with increased overall mortality in the general population.

Associations among Heavy Metals and Proteinuria and Chronic Kidney Disease.

BACKGROUND: The prevalence of chronic kidney disease (CKD) is increasing annually in Taiwan. In addition to traditional risk factors, heavy metals contribute to the development of CKD. The aim of this study was to investigate associations among heavy metals and proteinuria and CKD in the general population in Southern Taiwan. We also explored the interaction and synergetic effects among heavy metals on proteinuria. METHODS: We conducted a health survey in the general population living in Southern Taiwan between June 2016 and September 2018. Seven heavy metals were measured: blood lead (Pb) and urine nickel (Ni), chromium (Cr), manganese (Mn), arsenic (As), copper (Cu), and cadmium (Cd). Proteinuria was measured using reagent strips. CKD was defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2. RESULTS: The mean age of the 2447 participants was 55.1 ± 13.2 years and included 977 males and 1470 females. Participants with high blood Pb and high urine Ni, Mn, Cu, and Cd were significantly associated with proteinuria. Interactions between blood Pb and urine Cr, and between urine Cd and Cu, had significant effects on proteinuria. The participants with high blood Pb and high urine Cu were significantly associated with an eGFR of <60 mL/min/1.73 m2. CONCLUSION: High blood Pb and high urine Cu may be associated with proteinuria and an eGFR of <60 mL/min/1.73 m2. High urine Ni, Mn, and Cd were significantly associated with proteinuria. Co-exposure to Cd and Cu, and Pb and Cr, may have synergistic effects on proteinuria.

Significant association between blood lead (Pb) level and haemoglobin A1c in non-diabetic population.

Although many heavy metals are necessary for normal biological function, a subset of heavy metals have no role in human physiology, such as lead (Pb) and arsenic (As). Such elements have deleterious effects on physiology and be associated with the incidence of diabetes and related metabolic syndromes. Haemoglobin A1c (HbA1c) is not only a useful diagnostic and prognostic parameter in patients with diabetes, but it is also helpful in prediction of future diabetic risk in non-diabetic patients. However, no studies have evaluated the relationship between heavy metal concentration and HbA1c in non-diabetic patients. Therefore, the present study was designed to address this issue. We performed surveys for general populations living in southern Taiwan from June 2016 to September 2018. All participants received face-to-face interviews, laboratory tests, and measurements of weight and height, waist circumference, heart rate, and systolic and diastolic blood pressures. HbA1c was positively associated with Log blood Pb, after adjustments for age, body mass index, fasting blood glucose, total cholesterol, and triglyceride. Additionally, a Log 1 µg/dL increase in Pb was associated with a small (0.819 mmol/mol, 95% confidence interval = 0.072-1.566) increase in HbA1c (P = 0.032). No association with HbA1c was observed for urine nickel, chromium, manganese, As, copper, and cadmium in the multivariable analysis. In conclusion, after adjusting for important clinical parameters, Log blood Pb was positively associated with HbA1c in our non-diabetic population. This finding implies that high blood Pb might have the potential to predict future diabetic risk in non-diabetic populations. Further prospective studies are necessary to validate this issue.