Chih-Hsien Wang

Increased risk of cancer in chronic dialysis patients: a population-based cohort study in Taiwan

BACKGROUND An increased incidence of cancer in chronic dialysis patients has not been confirmed in the Chinese population. The aim of this population-based study was to examine the risk of various types of cancers in chronic dialysis patients in Taiwan. METHODS Data of 92 348 chronic dialysis patients extracted from the National Health Institutes Research Database during 1997-2008 were analyzed. Patients newly diagnosed with end-stage renal disease, free of cancer and receiving dialysis for >3 months were eligible for inclusion in the study. RESULTS After a mean follow-up of 4.4 years, a new cancer was diagnosed in 4328 chronic dialysis patients. The standardized incidence ratio (SIR) of chronic dialysis patients was 1.4 [95% confidence interval (CI): 1.3-1.4] and annual incidence of cancer was 1.1%. A trend of an increased SIR of cancer was observed in young patients and within the first year of dialysis. Bladder cancer carried the highest SIR (SIR: 8.2, 95% CI: 6.7-9.9) and had the highest frequency (21.2%). Importantly, the frequency (15.3%) of liver cancer was the second highest and the SIR (SIR: 1.4, 95% CI: 1.2-1.5) of liver cancer in chronic dialysis patients was higher than that of their healthy counterparts. Unexpectedly, chronic dialysis patients had a significantly reduced risk of developing lung cancer. CONCLUSION Increased risk of cancer in chronic dialysis patients is confirmed in the Taiwanese population and it is necessary to develop different strategies for cancer screening in chronic dialysis patients among different ethnicities.

Fasting Serum Total Ghrelin Level Inversely Correlates with Metabolic Syndrome in Hemodialysis Patients

BACKGROUND Metabolic syndrome (MS) is a significant risk factor for cardiovascular disease and predicts hospitalization in patients undergoing hemodialysis. An inverse association between circulating ghrelin and MS has been observed in adults. However, no data are available on the relationship between MS and serum total ghrelin levels in hemodialysis patients. METHODS Fasting blood samples were obtained from 52 hemodialysis patients. MS and its components were defined using diagnostic criteria from the International Diabetes Federation. Total ghrelin levels were measured using a commercial enzyme-linked immunosorbent assay kit. RESULTS Of the 52 hemodialysis patients, 30 (58%) had MS. Fasting total ghrelin level inversely correlated with MS among these hemodialysis patients (p<0.001). There was a tendency for the fasting total ghrelin level to decrease as the number of diagnostic criteria for MS in patients increased. Univariate linear regression analysis showed that the pre-hemodialysis body weight (r=-0.401; p=0.007), waist circumference (r=-0.554; p<0.001), triglyceride level (r=-0.317; p=0.022), and insulin level (r=-0.353; p=0.015) were negatively correlated with total ghrelin levels, whereas high-density lipoprotein (HDL) (r=0.506; p<0.001) and growth hormone (r=0.305; p<0.040) levels were positively correlated with the total ghrelin level. Multivariate forward stepwise linear regression analysis of the significant variables showed that waist circumference (R(2) change=0.297, p<0.001) was an independent predictor of the total ghrelin among the hemodialysis patients and explained 29.7% of the variance. CONCLUSIONS We observed an inverse association between the circulating fasting total ghrelin level and MS among hemodialysis patients. There was a tendency for the total ghrelin level to decrease as the number of diagnostic criteria for MS in patients increased. Waist circumference was an independent predictor of the total ghrelin level among hemodialysis patients.

A Cohort Study of Subjective Global Assessment and Mortality in Taiwanese Hemodialysis Patients

Many patients with end-stage renal disease are malnourished, and cross-sectional studies have shown that markers of malnutrition may predict death. In this study, we investigated the possible association of Subjective Global Assessment and mortality in a small cohort of Taiwanese hemodialysis patients. Fifty hemodialysis patients at a hemodialysis center in eastern Taiwan were enrolled in June 2002. Height and weight were used to determine the body mass index. Bioelectrical impedance analysis of body fat mass was performed before and after a mid-week dialysis session. Biochemical indexes of the nutritional status included serum albumin, creatinine, transferrin, cholesterol, and the normalized protein catabolic rate. Mortality data during 42 months after enrollment were obtained. Twenty-six hemodialysis patients were classified as well-nourished and twenty-four as malnourished based on Subjective Global Assessment. Decreased body mass index (p = 0.006), increased body fat mass (p = 0.019 before hemodialysis; p = 0.007 after hemodialysis), decreased serum albumin (p = 0.011), and decreased serum creatinine (p = 0.006) were significantly higher in the malnourished group. Older age (p = 0.042), decreased serum albumin (p = 0.028), decreased serum transferrin (p = 0.041), and malnourishment (p = 0.004) were significantly higher in the mortality group. Multivariate forward stepwise linear regression analysis of mortality and nutrition profiles show that Subjective Global Assessment is the independent predictor of mortality (R2 = 0.20). Malnourished hemodialysis patients had a higher mortality rate than well-nourished hemodialysis patients in Taiwan. Subjective Global Assessment of the nutritional status appears to be a simple tool for assessing the nutritional status of hemodialysis patients in long-term care. This assessment tool is also beneficial for hemodialysis patients who are at a greater risk of nutritional-associated mortality.

Use of cardio-ankle vascular index in chronic dialysis patients

Eur J Clin Invest 2010; 41 (1): 45–51

Fasting serum adiponectin level inversely correlates with metabolic syndrome in peritoneal dialysis patients.

Background:Metabolic syndrome is a significant risk factor for cardiovascular disease and predicts hospitalization in peritoneal dialysis (PD) patients. An inverse association between circulating adiponectin and metabolic syndrome has been observed in humans. However, no data are available on the relationship between metabolic syndrome and serum adiponectin levels in PD patients. Method: Fasting blood samples were obtained from 47 PD patients and 47 subjects in an outpatient department were enrolled as a control group. Metabolic syndrome and its components were defined using diagnostic criteria from the International Diabetes Federation. Adiponectin levels were measured using a commercial enzyme immunoassay kit. Results: Twenty-seven of 47 PD patients (57.5%) had metabolic syndrome. PD patients had lower serum albumin (p < 0.001) and higher serum adiponectin levels (p = 0.016), high-sensitivity C-reactive protein (p = 0.008), creatinine (p < 0.001) and metabolic syndrome (p < 0.001) than controls. The fasting adiponectin level inversely correlated with the metabolic syndrome in these PD patients (p = 0.006). Univariate linear regression analysis showed that the waist circumference (r = –0.304; p = 0.038), body mass index (r = –0.347; p = 0.017), body fat mass (r = –0.305; p = 0.037), white blood count (r = –0.631; p < 0.001), triglyceride (TG; r = –0.526; p < 0.001), and fasting glucose (r = –0.394; p = 0.006) were negatively correlated with the fasting serum adiponectin levels, while high-density lipoprotein-cholesterol (r = 0.443; p = 0.002) was positively correlated with the fasting serum adiponectin levels among the PD patients. Multivariate forward stepwise linear regression analysis of the significant variables showed that white blood count (R2 change = 0.398, p < 0.001), and TG (R2 change = 0.118, p = 0.002) were the independent predictors of fasting serum adiponectin levels and explained 51.6% of variance. Conclusions: We observed that PD patients had higher metabolic syndrome than the general population and an inverse association was found between the circulating fasting adiponectin level and metabolic syndrome in PD patients. White blood count and TG were independent predictors of the serum adiponectin level among PD patients.

Increased risks of mortality and atherosclerotic complications in incident hemodialysis patients subsequently with bone fractures: A nationwide case-matched cohort study

Background Hemodialysis (HD) patients with bone fractures have an increased risk for death. However, the risks for mortality and atherosclerotic complications in incident HD patients subsequently with bone fractures are unknown. Methods Data derived from the Taiwan National Health Institute Research Database between January 1997 and December 2008 was analyzed. The enrolled patients included 3,008 incident HD patients subsequently with a single long bone fracture (LB Fx) and 2,070 incident HD patients subsequently with a single non-long bone fracture (NLB Fx). These patients were matched (1:5 ratio) for age, sex, and same duration of HD with incident HD patients who had no fractures and outcomes were measured over a 3-year follow-up. Results After demographic and co-morbidity adjustment, LB Fx increased the risk for overall mortality (HR = 1.59, p < 0.001) and stroke (HR = 1.09, p = 0.028) in incident HD patients. NLB Fx increased the risk for overall mortality (HR = 1.52, p < 0.001), stroke (HR = 1.19, p < 0.001), coronary artery disease (CAD), (HR = 1.13, p = 0.003), and peripheral arterial occlusive disease (PAOD), (HR = 1.41, p < 0.001) in incident HD patients. Moreover, incident patients subsequently with NLB Fx had significantly higher risks of CAD and PAOD than those subsequently with LB Fx. Conclusions The rates of mortality and stroke were significantly higher in incident HD patients subsequently with bone fractures than in matched patients without bone fractures. Incident HD patients subsequently with NLB Fx had significantly higher risks of CAD and PAOD than those subsequently with LB Fx and without bone fractures. Thus, incident HD patients subsequently with bone fractures should be closely followed for a higher mortality and possible development of atherosclerotic complications.

Fasting Serum Leptin Level Correlates With Mid‐Arm Fat Area in Peritoneal Dialysis Patients

Leptin correlates with body fat content and plays a pivotal role in inflammatory response. This study aimed to investigate the relationships of fasting serum leptin levels and the anthropometric fat components among peritoneal dialysis (PD) patients. Fasting blood samples were obtained from 40 PD patients. Leptin levels were measured using a commercial enzyme‐linked immunosorbent assay kit. Body weight (r = 0.424; P = 0.006), waist circumference (r = 0.352; P = 0.026), body mass index (BMI; r = 0.483; P = 0.002), body fat mass (r = 0.352; P = 0.026), high sensitivity C‐reactive protein (hs‐CRP; r = 0.494; P = 0.001), triceps skinfold thickness (TSF; r = 0.505; P = 0.001), mid‐arm circumference (MAC; r = 0.471; P = 0.002), and mid‐arm fat area (MAFA; r = 0.564; P < 0.001) were positively correlated, while high density lipoprotein (HDL)‐cholesterol (r = −0.345; P = 0.028) was negatively correlated with fasting serum leptin levels among the PD patients. Multivariate forward stepwise linear regression analysis showed that MAFA (R2 = 0.318, P = 0.011) was the independent predictor of fasting serum leptin levels among the PD patients. In conclusion, fasting leptin level was positively associated with body fat composition (body weight, waist circumference, BMI, body fat mass, TSF, MAC, and MAFA) and hs‐CRP among PD patients, and MAFA was the independent predictor of fasting serum leptin levels among the PD patients.

The Association of Serum Osteoprotegerin and Osteoporosis in Postmenopausal Hemodialysis Patients: A Pilot Study

AIM Osteoprotegerin (OPG) is a potent inhibitor of osteoclasts and plays an important role in bone metabolism. Relatively high serum levels of OPG have been observed in postmenopausal women with osteoporosis compared with age-matched controls. No data, however, are available on the relationship between low bone density and serum OPG levels in postmenopausal hemodialysis (HD) patients. METHODS The enrolled subjects included 28 postmenopausal HD patients and 28 age-matched postmenopausal women with normal renal function as controls. Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry (DEXA) in both hips. Low BMD was defined as femoral neck T-score <-2.5. Serum OPG levels were measured using a commercial enzyme-linked immunosorbent assay (ELISA) kit. RESULTS Eight of the age-matched postmenopausal controls (28.6%) and 12 of the postmenopausal HD patients (42.9%) had low BMD. There was no statistically significant difference in low BMD between postmenopausal HD patients and age-matched postmenopausal patients (p = 0.263). The serum OPG level was significantly higher in the postmenopausal HD group (p < 0.001). Increased serum OPG (p = 0.017) and decreased serum albumin (p = 0.021) were significantly correlated with low BMD in postmenopausal HD patients. Univariate linear regression analysis showed that serum albumin (r = -0.455, p = 0.015) was negatively correlated, whereas age (r = 0.423, p = 0.025) and the length of time since menopause (r = 0.397, p = 0.036) were positively correlated with the serum OPG level in postmenopausal HD patients. Multivariate forward stepwise linear regression analysis showed that serum OPG (adjusted R(2) = 0.262, p = 0.003) was an independent predictor of low BMD in postmenopausal HD patients and explained 26.2% of the variance. CONCLUSIONS Serum OPG is associated with low BMD in postmenopausal HD patients.

Risk of Mortality and of Atherosclerotic Events Among Patients Who Underwent Hemodialysis and Subsequently Developed Retinal Vascular Occlusion: A Taiwanese Retrospective Cohort Study

IMPORTANCE Retinal vascular occlusion is considered a risk factor for cardiovascular diseases in the general population. However, the long-term outcomes of patients who undergo incident hemodialysis and subsequently develop retinal vascular occlusion have not been examined. OBJECTIVE To determine the mortality rate and subsequent prevalence of systemic vascular diseases associated with retinal vascular occlusion among patients undergoing hemodialysis in Taiwan. DESIGN, SETTING, AND PARTICIPANTS Data from the Taiwan National Health Institutes research database were used, and we identified 105,956 patients undergoing hemodialysis during the period from January 1997 to December 2008. In total, 113 patients with retinal artery occlusion and 463 patients with retinal vein occlusion were enrolled and matched for age, sex, and the duration of hemodialysis (at a 1:5 ratio) with patients without ocular disorders. MAIN OUTCOMES AND MEASURES Mortality and atherosclerotic events. A multivariate Cox regression model for mortality and a competing risk regression model for atherosclerotic events were used for this population-based retrospective cohort study. RESULTS Of 113 patients with retinal artery occlusion and 463 patients with retinal vein occlusion, 66 (58.4%) and 245 (52.9%) were females, respectively (ranging in age from ≤40 to 80 years). Our study showed there was a significant risk of mortality among patients undergoing hemodialysis who subsequently developed retinal artery occlusion or retinal vein occlusion compared with patients undergoing hemodialysis without ocular disorders. Patients with retinal artery occlusion had higher risks of ischemic stroke (adjusted hazard ratio [HR], 3.35 [95% CI, 2.00-5.59]; P < .001), coronary artery disease (adjusted HR, 1.70 [95% CI, 1.23-2.36]; P = .001), acute coronary syndrome (adjusted HR, 2.03 [95% CI, 1.24-3.33]; P = .002), and peripheral arterial occlusive disease (adjusted HR, 2.15 [95% CI, 1.26-3.66]; P = .002) than did patients without ocular disorders. Patients with retinal vein occlusion had higher risks of hemorrhagic stroke (adjusted HR, 2.54 [95% CI, 1.50-4.30]; P = .001), coronary artery disease (adjusted HR, 1.55 [95% CI, 1.31-1.83]; P < .001), and acute coronary syndrome (adjusted HR, 1.53 [95% CI, 1.14-2.06]; P = .002) than did patients without ocular disorders. CONCLUSIONS AND RELEVANCE Our data demonstrate that the risks of mortality and atherosclerotic events were increased among patients undergoing incident hemodialysis who subsequently developed retinal vascular occlusion.

A Clinical Study of Prognosis and Glucocorticoid Pulse Treatment in Patients with Acute Paraquat Intoxication

Objective: Paraquat is a highly toxic herbicide that binds strongly to tissue and causes high mortality rates due to pesticide intoxication in Taiwan. In this study, we evaluated the usefulness of methylprednisolone pulse therapy and calculation of the severity index of paraquat poisoning (SIPP) to predict the prognosis in patients with oral paraquat intoxication. Materials and Methods: Thirty-two patients with paraquat poisoning from January 2003 to April 2005 were enrolled into this study at a medical center in eastern Taiwan. All 32 patients had history of oral intake of paraquat and urine paraquat was positive at the emergency department. Time of oral intake of paraquat and serum paraquat levels were assayed at the emergency department for calculating SIPP (hour×mg/L) level. Sixteen patients with oral paraquat poisoning were treated with intravenous methylprednisolone 1 g/day and charcoal hemoperfusion for 3 days (MP group), and 16 patients with oral paraquat poisoning were treated with charcoal hemoperfusion only for 3 days (control group). Results: The mortality rate of the patients with oral paraquat poisoning was high (87.5%). There were no statistically significant differences in death (p=1.000), age (p=0.706), sex (p=0.069), serum blood urea nitrogen (p=0.104), creatinine (p=0.174), aspartate aminotransferase (p=0.083), alanine aminotransferase (p=0.365), plasma level of paraquat (p=0.880) and SIPP level (p=0.734) between the MP group and control group. Young age (p=0.030), lower initial plasma paraquat level (p=0.002), lower serum creatinine (p=0.009), female sex (p=0.033), lower elapsed time from ingestion of paraquat to arrival at hospital (p=0.035) and SIPP level less than 10 (p＜0.001) were associated with survival in patients with oral paraquat poisoning. Multivariate forward stepwise linear regression analysis of deaths showed that SIPP＞10 (hour×mg/L) (p＜0.001) was an independent predictor of death in patients with oral paraquat poisoning and explained 77.1% of the variance (R^2=0.771). Conclusion: Treatment with methylprednisolone pulse therapy did not show better results in patients with acute oral paraquat poisoning. SIPP was an independent predictor of death in patients with oral paraquat poisoning.