Dan-Tzu Lin-Tan

Environmental Exposure to Lead and Progression of Chronic Renal Diseases: A Four-Year Prospective Longitudinal Study

Previous retrospective research suggests that low-level environmental lead exposure is associated with an acceleration of age-related impairment of renal function. For elucidating the long-term relationship between low-level environmental lead exposure and progression of chronic renal diseases in patients without diabetes, 121 patients who had chronic renal insufficiency, a normal body lead burden (BLB), and no history of exposure to lead were observed prospectively for 48 mo. Associations of both BLB and blood lead level (BLL) with renal function were evaluated, with reference to other covariates. The primary end point was an increase in the serum creatinine level to double the baseline value. Sixty-three patients had BLB > or =80 microg and < 600 microg (high-normal group), and 58 patients had BLB < 80 microg (low-normal group). The primary end point occurred in 17 patients. Fifteen of them had high-normal BLB, whereas two patients had low-normal BLB (hazard ratio [95% confidence interval]: 1.01 [1.00 to 1.01] for each increment of 1 microg; P = 0.002). The BLB and BLL at baseline were the most important risk factors to predict progression of renal insufficiency. Each increase of 10 microg in the BLB or 1 microg/dl in the BLL reduced the GFR by 1.3 (P = 0.002) or 4.0 ml/min (P = 0.01) during the study period. In conclusion, low-level environmental lead exposure is associated with accelerated deterioration of renal insufficiency. Even at levels far below the normal ranges, both increased BLL and BLB predict accelerated progression of chronic renal diseases.

Food safety involving ingestion of foods and beverages prepared with phthalate-plasticizer-containing clouding agents

In May 2011, the illegal use of the phthalate plasticizer di(2-ethylhexyl) phthalate in clouding agents for use in foods and beverages was reported in Taiwan. This food scandal has caused shock and panic among the majority of Taiwanese people and has attracted international attention. Phthalate exposure is assessed by ambient monitoring or human biomonitoring. Ambient monitoring relies on measuring chemicals in environmental media, foodstuff and consumer products. Human biomonitoring determines body burden by measuring the chemicals, their metabolites or specific reaction products in human specimens. In mammalian development, the fetus is set to develop into a female. Because the female phenotype is the default, impairment of testosterone production or action before the late phase may lead to feminizing characteristics. Phthalates disrupt the development of androgen-dependent structures by inhibiting fetal testicular testosterone biosynthesis. The spectrum of effects obtained following perinatal exposure of male rats to phthalates has remarkable similarities with the human testicular dysgenesis syndrome. Epidemiological studies have suggested associations between phthalate exposure and shorter gestational age, shorter anogenital distance, shorter penis, incomplete testicular descent, sex hormone alteration, precocious puberty, pubertal gynecomastia, premature thelarche, rhinitis, eczema, asthma, low birth weight, attention deficit hyperactivity disorder, low intelligence quotient, thyroid hormone alteration, and hypospadias in infants and children. Furthermore, many studies have suggested associations between phthalate exposure and increased sperm DNA damage, decreased proportion of sperm with normal morphology, decreased sperm concentration, decreased sperm morphology, sex hormone alteration, decreased pulmonary function, endometriosis, uterine leiomyomas, breast cancer, obesity, hyperprolactinemia, and thyroid hormone alteration in adults. Finally, the number of phthalate-related scientific publications from Taiwan has increased greatly over the past 5 years, which may reflect the health effects from the illegal addition of phthalate plasticizer to clouding agent in foodstuff over the past two decades.

Cadmium level in seminal plasma may affect the pregnancy rate for patients undergoing infertility evaluation and treatment

This study evaluated the relationship between pregnancy rate and semen cadmium concentration. This prospective and nonrandomized clinical study analyzed 341 male partners of infertile couples undergoing infertility evaluation and management. Semen samples were collected to analyze semen quality and cadmium concentrations. The main outcome was pregnancy during 60-day infertility treatment. Simple linear regression analysis revealed an association between semen cadmium concentration NS sperm count (r=-0.150, P=0.0416) in nonsmoking subjects (n=184). In both smokers and nonsmokers, semen cadmium concentrations were significantly higher in non-pregnant patients than in pregnant patients. In nonsmokers, Cox multi-variable fertility ratio analysis demonstrated an association between semen cadmium concentration and fertility (fertility ratio of log semen cadmium=0.24; 95% confidence intervals (CI)=0.12-0.47, P<0.0001) after adjusting for related variables. Each tenfold increase in semen cadmium concentration was associated with a 4.17-fold increase in infertility ratio in nonsmoking patients. In smokers, Cox multi-variable fertility ratio analysis demonstrated that sperm count and semen cadmium concentration are associated with fertility (fertility ratio of log semen cadmium=0.17; 95% CI=0.04-0.63, P=0.0085) after adjusting for related variables. In smokers, each tenfold increase in semen cadmium concentration was associated with a 5.88-fold increase in infertility ratio. In conclusion, low levels of cadmium accumulation in semen may contribute to male infertility by reducing sperm quality.

Spectrum of toxic hepatitis following intentional paraquat ingestion: analysis of 187 cases

This retrospective observational study examined the clinical features, the degrees of toxic hepatitis, physiological markers and clinical outcomes after intentional paraquat poisoning and sought to determine what association, if any, might exist between these findings.

Sequential organ failure assessment score can predict mortality in patients with paraquat intoxication.

Introduction Paraquat poisoning is characterized by multi-organ failure and pulmonary fibrosis with respiratory failure, resulting in high mortality and morbidity. The objective of this study was to identify predictors of mortality in cases of paraquat poisoning. Furthermore, we sought to determine the association between these parameters. Methods A total of 187 patients were referred for management of intentional paraquat ingestion between January 2000 and December 2010. Demographic, clinical, and laboratory data were recorded. Sequential organ failure assessment (SOFA) and acute kidney injury network (AKIN) scores were collected, and predictors of mortality were analyzed. Results Overall hospital mortality for the entire population was 54% (101/187). Using a multivariate logistic regression model, it was found that age, time to hospitalization, blood paraquat level, estimated glomerular filtration rate at admission (eGFR first day), and the SOFA48-h score, but not the AKIN48-h score, were significant predictors of mortality. For predicting the in-hospital mortality, SOFA48-h scores displayed a good area under the receiver operating characteristic curve (AUROC) (0.795±0.033, P<0.001). The cumulative survival rate differed significantly between patients with SOFA48-h scores <3 and those ≥3 (P<0.001). A modified SOFA (mSOFA) score was further developed by using the blood paraquat level, and this new score also demonstrated a better AUROC (0.848±0.029, P<0.001) than the original SOFA score. Finally, the cumulative survival rate also differed significantly between patients with mSOFA scores <4 and ≥4 (P<0.001). Conclusion The analytical data demonstrate that SOFA and mSOFA scores, which are based on the extent of organ function or rate of organ failure, help to predict mortality after intentional paraquat poisoning.

Association Between Body Mass and Mortality in Maintenance Hemodialysis Patients

A total of 959 Taiwanese patients undergoing maintenance hemodialysis—102 underweight (BMI < 18.5 kg/m2), 492 normal weight (BMI 18.5–22.9 kg/m2), 187 overweight (BMI 23.0–24.9 kg/m2), and 178 obese (BMI ≥ 25 kg/m2) were recruited into this three‐year, multicenter longitudinal study. It was found initially that the underweight group had more females, longer hemodialysis durations, less use of a biocompatible membrane (BCM) dialyzer, higher erythropoietin doses and Kt/Vurea, and lower white blood cell counts, hemoglobin, serum creatinine and phosphate, and high sensitivity C‐reactive protein (hsCRP) than other groups (P < 0.001). Furthermore, a χ2‐test demonstrated that underweight patients had poorer nutrition (P = 0.023), but less systemic inflammation (P < 0.001) than other groups. A stepwise multiple linear regression analysis established that age, sex, diabetes mellitus, hemodialysis duration, use of BCM dialyzer, Kt/Vurea, creatinine, high‐density lipoprotein cholesterol, and hsCRP were significant risk factors associated with BMI (P < 0.001–0.002). After three years, 149 (15.5%) patients had died, including 22 of 102 (21.6%) underweight patients, 64 of 492 (13.0%) normal weight patients, 38 of 187 (20.3%) overweight patients, and 25 of 178 (15.5%) obese patients. The primary causes of mortality were cardiovascular (52.3%) and infection (39.6%). A multivariate Cox regression analysis revealed that age, diabetes mellitus, BMI, albumin, hsCRP, and cardiothoracic ratio were significant risk factors associated with all‐cause mortality over three years (P < 0.001–0.022). Finally, Kaplan–Meier analysis confirmed that underweight patients suffer higher mortality than other groups (Log rank, P = 0.0392); therefore, the data have demonstrated a survival disadvantage of low BMI in Taiwanese patients undergoing maintenance hemodialysis.

Fasting Glucose Levels in Predicting 1-Year All-Cause Mortality in Patients Who Do Not Have Diabetes and Are on Maintenance Hemodialysis

Chronic inflammation and malnutrition relate to increased risks for cardiovascular death. This study compared fasting glucose levels (FGL) and impaired fasting glucose (IFG) with malnutrition and inflammation in nondiabetic maintenance hemodialysis (MHD) patients to investigate the adverse affects and risks for mortality. In total, 693 MHD patients were enrolled in this study and followed up for 1 yr. Geographic, hematologic, biochemical, and dialysis-related data were collected. According to 1997 and 2003 definitions, all patients were classified into three groups: Diabetic, nondiabetic with IFG, and nondiabetic with normal FGL. More diabetic and nondiabetic with IFG group patients were malnourished (chi(2) = 24.55, P < 0.0001) and had inflammatory changes (chi(2) = 9.32, P = 0.0095) than those with normal FGL. The IFG group had higher high-sensitivity C-reactive protein and ferritin and lower serum albumin, creatinine levels, and normalized protein catabolic rate than the normal FGL group. Age and parameters of nutrition and inflammation were associated with FGL. Stepwise multiple regression analysis demonstrated that FGL were negatively associated with serum albumin (P = 0.0026) and positively correlated with Log high-sensitivity C-reactive protein (P = 0.0004) in nondiabetic MHD patients. In addition, after 1 yr of follow-up, Cox multivariate analysis demonstrated that, after adjustment for other significant related factors, FGL (relative risk 1.049; 95% confidence interval 1.007 to 1.093; P = 0.0232) or presence of IFG (relative risk 3.798; 95% confidence interval 1.168 to 12.344; P = 0.0265) was a significant risk factor for 1-yr all-cause mortality of these patients. On the basis of these findings, basal FGL or presence of IFG, a preventive and treatable status, plays an important role in inflammation, malnutrition, and short-term mortality of nondiabetic MHD patients.

Cardiothoracic ratio, malnutrition, inflammation, and two-year mortality in non-diabetic patients on maintenance hemodialysis.

Background/Aims: Cardiothoracic ratio (CTR) is associated with left ventricular mass, left ventricular systolic dysfunction and mortality in patients with hypertension or chronic cardiovascular disease. The clinical significance of CTR in non-diabetic maintenance hemodialysis (MHD) patients remains unclear. Methods: 468 non-diabetic MHD patients were enrolled. Geographic, hematological, biochemical and dialysis-related data were obtained. The patients were analyzed for nutritional and inflammatory markers as well as CTR. All patients were followed up for 2 years to investigate the risks for mortality. Results: Chi-square analysis showed that the incidence of malnutrition and inflammation was significantly higher in patients with CTR >60% than in patients with CTR ≤60%. CTR positively correlated with high-sensitivity C-reactive protein (hsCRP) levels but negatively correlated with albumin levels. 29 patients (6.2%) had expired by the end of the study. Cox multivariate analysis revealed that CTR significantly predicts both all-cause and cardiovascular-cause 2-year mortality in non-diabetic MHD patients. Conclusion: CTR is an indicator of inflammation and nutritional status in non-diabetic MHD patients and can predict 2-year mortality in these patients. The analytical results of this study support continued efforts to reduce CTR and treat underlying causes in patients with CTR >50%.

Lead level in seminal plasma may affect semen quality for men without occupational exposure to lead

BackgroundInfertility affects approximately 10–15% of reproductive-age couples. Poor semen quality contributes to about 25% of infertile cases. Resulting from the direct effect on testicular function or hormonal alterations, heavy metals exposure has been related to impaired semen quality. The objective of this study was to assess the level of lead in the seminal plasma in men without occupational exposure to lead, and to determine the relationship between semen quality and lead concentration in the semen.MethodsThis is a prospective and nonrandomized clinical study conducted in University infertility clinic and academic research laboratory. Three hundred and forty-one male partners of infertile couples undergoing infertility evaluation and management were recruited to the study. Semen samples collected for the analyses of semen quality were also used for the measurement of lead concentrations. Semen samples were evaluated according to the WHO standards.ResultsAll subjects were married and from infertile couples without occupational exposure to lead. There is a significant inverse correlation between the lead concentration in seminal plasma and sperm count. A higher semen lead concentration was correlated with lower sperm count, but not with semen volume, sperm motility or sperm morphology as assessed by simple linear regression.ConclusionsWe found that semen lead concentration was significantly higher among the patients with lower sperm count. To our knowledge, this is the first study to demonstrate that a high level of lead accumulation in semen may reduce the sperm count contributing to infertility of men without occupational exposure to lead.

Association of environmental cadmium exposure with inflammation and malnutrition in maintenance haemodialysis patients

BACKGROUND Chronic inflammation and malnutrition are associated with increased risk of cardiovascular death, and may cause protein-energy wasting in individuals with chronic kidney disease. Raised blood cadmium (Cd) levels were observed in maintenance haemodialysis (HD) patients in previous studies. However, the correlation of Cd exposure with inflammation and malnutrition remains uncertain. This study examined the possible adverse effects of environmental Cd exposure in maintenance HD patients. METHODS A total of 954 maintenance HD patients were enrolled and divided into four equal-sized groups based on blood Cd levels. Geographic, haematological, biochemical and dialysis-related data were obtained. The analysis included values for nutritional and inflammatory markers. RESULTS Abnormal blood Cd levels (> or =1 microg/L) were exhibited in 26.8% (256/954) of studied subjects. More subjects in the highest quartile group were malnourished (chi- square = 23.27; P < 0.0001) and had inflammatory changes (chi-square = 13.99; P = 0.0029) than in the lowest quartile group. Stepwise multiple regression analysis revealed a significant inverse correlation between serum albumin and blood Cd levels. Notably, a 10-fold increase in blood Cd levels was associated with a 0.06 g/dL decrease in serum albumin levels (P = 0.0060). Multivariate regression analysis also demonstrated a positive correlation between inflammatory risk (high-sensitivity C-reactive protein >3 mg/L) and blood Cd levels. The risk ratio of inflammation with a 10-fold increase in blood Cd levels was 1.388 (95% CI: 1.025-1.825, P = 0.0336). CONCLUSIONS Environmental Cd exposure is significantly associated with malnutrition, inflammation and even protein-energy wasting in maintenance HD patients. It is important for this population to avoid diets with high Cd concentrations and smoking.