Kuan-Hsing Chen

Dietary leucine supplementation has been explored for the therapeutic intervention of obesity and obesity-induced metabolic dysfunctions. In this study, we aim to examine the effects of dietary leucine supplementation in db/db mice. Mice were treated with or without leucine (1.5% /) in drinking water for 12 weeks. The leucine supplement was found to reduce insulin resistance and hepatic steatosis in db/db mice. Using Nuclear Magnetic Resonance (NMR)-based lipidomics, we found that the reduction of hepatic triglyceride synthesis was correlated with attenuated development of fatty liver. In addition, diabetic nephropathy (DN) was also ameliorated by leucine. Using liquid chromatography⁻time-of-flight mass spectrometry (LC-TOF MS)-based urine metabolomics analysis, we found that the disturbance of the tricarboxylic acid (TCA) cycle was reversed by leucine. The beneficial effects of leucine were probably due to AMP-activated protein kinase (AMPK) activation in the liver and kidneys of d...

Inducing apoptosis to susceptible cells is the major mechanism of most cytotoxic anticancer drugs in current use. Cinnamomum kanehirai Hayata (Lauraceae), a unique and native tree of Taiwan, is the major host for the medicinal fungus Antrodia cinnamomea which exhibits anti-cancer activity. Because of the scarcity of A. cinnamomea, C. kanehirai Hayata instead, is used as fork medicine in liver cancer. Here we observed the C. kanehirai Hayata ethanol extract could inhibit the cellular viability of both HepG2 and HA22T/VGH human hepatoma cell lines in a dose- and time-dependent manner. We found the mode of cell death was apoptosis according to cell morphological changes by Liu's stain, oligonucleosomal DNA fragmentation by gel electrophoresis, externalization of phosphotidyl serine by detecting Annexin V and hypoploid population by cell cycle analysis. Our results showed that the extracts caused cleavage of caspase-3 and increased enzyme activity of caspase-8 and caspase-9. Caspase 3 inhibitor partially reversed the viability inhibition by the extract. Furthermore, the up-regulation of Bax and down-regulation of Bcl-2 were also noted by the extract treatment. In conclusion, C. kanehirai Hayata ethanol extract induced intrinsic pathway of apoptosis through caspase-3 cascade in human hepatoma HA22T/VGH and HepG2 cells, which might shed new light on hepatoma therapy.

A survey of hepatitis B surface antigen (HBSAG) and antibodies against hepatitis C virus (anti-HCV) in 173 patients undergoing hemodialysis in Taiwan revealed that 15 (9%) patients were positive for both HBSAG and anti-HCV, 106 (61%) were positive for anti-HCV alone, and 14 (8%) were positive for HBSAG alone. Most HBSAg positivity was acquired before the onset of hemodialysis. Anti-HCV positivity, however, was mainly acquired via the hemodialysis procedure. Patients with dual markers were younger (43.7 +/- 3.3 years old, p = 0.0274), had the longest period on hemodialysis (6.6 +/- 1.3 years, p < 0.001), and more severe liver dysfunction. When compared with those who were negative for both markers, patients with both HBSAG and anti-HCV had an increased incidence of chronicity (5/15 vs. 2/38; p < 0.05), ultrasonographic cirrhosis (5/15 vs. 1/38; p < 0.05), and clinical decompensation (2/15 vs. 0/38; p < 0.05). Their risk for developing ultrasonographic cirrhosis and clinical decompensation was also greater than that of patients with anti-HCV alone (5/15 vs. 8/106 and 2/15 vs. 2/106; p < 0.05 for both). The presence of HBSAG alone, however, did not increase the incidence of liver dysfunction. The presence of anti-HCV alone was only associated with a greater elevation of serum alanine aminotransferase (44.2 +/- 5.5 vs. 19.1 +/- 2.5 U/l; p < 0.05) and an increased incidence of chronicity (30/106 vs. 2/38; p < 0.05). Our results indicate that a high prevalence of HCV superinfection impose a significant risk on a large population of HBSAG-positive hemodialysis patients in Taiwan. As the coexistence of anti-HCV and HBSAG is associated with more severe liver dysfunction, it is urgent to devise effective methods to prevent HCV circulation in a hemodialysis environment-especially in a hepatitis B virus endemic area such as Taiwan.

Renal fibrosis results from an excessive accumulation of extracellular matrix that occurs in most types of chronic kidney disease. Among the many fibrogenic factors that regulate renal fibrotic processes, transforming growth factor-β1 (TGF-β1) and inflammation after injury play critical roles. Spleen tyrosine kinase (Syk) is important for signaling processes implicated in autoimmune, inflammatory, and allergic diseases. We examined the effects of Syk inhibition on renal fibrosis in vivo and on TGF-β1-induced renal fibroblast activation in vitro. A unilateral ureteral obstruction (UUO) model was induced in male B6 mice. Mice with UUO were administered a Syk inhibitor or saline intraperitoneally 1 day before UUO surgery and daily thereafter. Both kidneys were harvested 7 days after surgery for further analysis. For the in vitro experiments, NRK-49F rat fibroblasts were pre-incubated with a Syk inhibitor before TGF-β1 stimulation. The inhibitory effects of Syk inhibition on signaling pathways down-stream of TGF-β1 were analyzed. In the UUO mouse model, administration of a Syk inhibitor attenuated extracellular matrix protein deposition and expression of α-smooth muscle actin, type I collagen, and fibronectin in a dose-dependent manner. In addition, macrophage infiltration in UUO kidney was reduced by Syk inhibition. Pre-incubation of NRK-49F cells with a Syk inhibitor suppressed TGF-β1-induced myofibroblast activation. Furthermore, inhibitory effects of Syk inhibition on TGF-β1-mediated myofibroblast activation were associated with down-regulation of MAPK-p38. These results suggest that Syk inhibition reduces tubulointerstitial fibrosis in UUO mice and inhibits TGF-β1-induced kidney myofibroblast activation. Syk inhibition could have therapeutic potential for the treatment of renal tubulointerstitial fibrosis.

Determine the effect of the day 1 urinary excretion of cadmium (D1-UE-Cd) on mortality of patients admitted to a coronary care unit (CCU). A total of 323 patients were enrolled in this 6-month study. Urine and blood samples were taken within 24 h after CCU admission. Demographic data, clinical diagnoses, and hospital mortality were recorded. The scores of established systems for prediction of mortality in critically ill patients were calculated. Compared with survivors (n = 289), non-survivors (n = 34) had higher levels of D1-UE-Cd. Stepwise multiple linear regression analysis indicated that D1-UE-Cd was positively associated with pulse rate and level of aspartate aminotransferase, but negatively associated with serum albumin level. Multivariate Cox analysis, with adjustment for other significant variables and measurements from mortality scoring systems, indicated that respiratory rate and D1-UE-Cd were independent and significant predictors of mortality. For each 1 μg/day increase of D1-UE-Cd, the hazard ratio for CCU mortality was 3.160 (95% confidence interval: 1.944-5.136, p < 0.001). The chi-square value of Hosmer-Lemeshow goodness-of-fit test for D1-UE-Cd was 10.869 (p = 0.213). The area under the receiver operating characteristic curve for D1-UE-Cd was 0.87 (95% confidence interval: 0.81-0.93). The D1-UE-Cd, an objective variable with no inter-observer variability, accurately predicted hospital mortality of CCU patients and outperformed other established scoring systems. Further studies are needed to determine the physiological mechanism of the effect of cadmium on mortality in CCU patients.

Previous studies of general populations indicated environmental exposure to low-level cadmium increases mortality. However, the effect of cadmium exposure on maintenance hemodialysis (MHD) patients is unclear.A total of 937 MHD patients from 3 centers in Taiwan were enrolled in this 36-month observational study. Patients were stratified by baseline blood cadmium level (BCL) into 3 groups: high BCL (>0.521 μg/L; n = 312), intermediate BCL (0.286-0.521 μg/L; n = 313), and low BCL (<0.286 μg/L; n = 312). The mortality rates and causes of death were analyzed.The analytic results demonstrated patients in the high BCL group had a significantly higher prevalence of malnutrition and inflammation than patients in the low and intermediate BCL groups. After 3 years of follow-up, 164 (17.5%) patients died and the major cause of death was cardiovascular disease. A Cox multivariate analysis indicated the high BCL group had increased hazard ratios (HRs) for all-cause mortality (HR = 1.72; 95...

Hyponatremia is a common electrolyte abnormality in a variety of medical conditions. Lower predialysis serum sodium concentration is associated with an increased risk of death in oligoanuric patients on hemodialysis. However, whether hyponatremia affects the short-term mortality in chronic peritoneal dialysis (CPD) patients remains unclear. We conducted a cross-sectional and two-year follow-up review retrospectively, and 318 patients with CPD were enrolled in a medical center. Serum sodium levels were measured at baseline and categorized as quartile of Na: quartile 1 (124-135 mEq/L), quartile 2 (136-139), quartile 3 (140-141) and quartile 4 (142-148). Mortality and cause of death were recorded for longitudinal analyses. The patients with higher quartile (higher serum sodium) had a trend of lower age, peritoneal dialysis (PD) duration, co-morbidity index, D/P Cr and white blood cell counts and higher renal Kt/Vurea (Kt/V) and serum albumin level. Stepwise multiple linear regression analysis showed that serum sodium level was positively associated with albumin, residual renal Kt/V and negatively associated with age and PD duration in CPD patients. After two-year follow-up, stepwise multivariate Cox proportional hazards model demonstrated that age, co-morbidity index and serum albumin were the significant risk factors for all-cause two-year mortality, but not serum sodium levels. Serum sodium level in CPD patients is associated with nutritional status, residual renal function and duration of PD. However, baseline serum sodium level is not an independent predictor of two-year mortality in CPD patients.

Deep vein thrombosis is a common disease among Caucasians but is rare in Asia. Venous thrombosis may be fatal, for example by a pulmonary embolism and right or left atrial thrombosis. Alternatively, deep vein thrombosis may follow a benign pattern such as femoral and popliteal vein thrombosis. Theories abound regarding the causes of deep vein thrombosis, with the most common theories being long-term stasis and lack of exercise. Internal jugular vein thrombosis is a rare but potentially fatal disease with various causes. In the pre-antibiotics era, this disease was frequently associated with deep neck infection. Recently however, local trauma, central catheterization, and repeated intravenous injections with drugs have become the leading causes of thrombosis. Spontaneous internal jugular vein thrombosis may occur in connection with a neoplasm, termed Trousseau's syndrome. This investigation reports a case of lung cancer associated with internal jugular vein thrombosis.

Whether environmental lead exposure has a long-term effect on progressive diabetic nephropathy in type II diabetic patients remains unclear. A total of 107 type II diabetic patients with stage 3 diabetic nephropathy (estimated glomerular filtration rate (eGFR) range, 30-60 mL/min/1.73 m(2)) with normal body lead burden (BLB) (<600  μ g/72 hr in EDTA mobilization tests) and no history of exposure to lead were prospectively followed for 2 years. Patients were divided into high-normal BLB (>80  μ g) and low-normal BLB (<80  μ g) groups. The primary outcome was a 2-fold increase in the initial creatinine levels, long-term dialysis, or death. The secondary outcome was a change in eGFR over time. Forty-five patients reached the primary outcome within 2 years. Although there were no differences in baseline data and renal function, progressive nephropathy was slower in the low-normal BLB group than that in the high-normal BLB group. During the study period, we demonstrated that each 100  μ g increment in BLB and each 10  μ g increment in blood lead levels could decrease GFR by 2.2 mL/min/1.72 m(2) and 3.0 mL/min/1.72 m(2) (P = 0.005), respectively, as estimated by generalized equations. Moreover, BLB was associated with increased risk of achieving primary outcome. Environmental exposure to lead may have a long-term effect on progressive diabetic nephropathy in type II diabetic patients.

Activation of interstitial myofibroblasts and excessive production of extracellular matrix proteins are common pathways that contribute to chronic kidney disease. In a number of tissues, AMP-activated kinase (AMPK) activation has been shown to inhibit fibrosis. Here, we examined the inhibitory effect of the AMPK activator, 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR), on renal fibrosis in vivo and TGF-β1-induced renal fibroblasts activation in vitro. A unilateral ureteral obstruction (UUO) model was induced in male BALB/c mice. Mice with UUO were administered AICAR (500 mg/Kg/day) or saline intraperitoneally 1 day before UUO surgery and daily thereafter. Both kidneys were harvested 7 days after surgery for further analysis. For the in vitro studies, NRK-49F rat fibroblasts were pre-incubated with AICAR before TGF-β1 stimulation. The inhibitory effects of AICAR on signaling pathways down-stream of TGF-β1 were analyzed. In UUO model mice, administration of AICAR attenuated e...

Candida parapsilosis is the most prevalent pathogen of fungal peritonitis in peritoneal dialysis (PD). The difference between C. parapsilosis peritonitis and other C. species for clinical outcomes and treatment responses to fungal peritonitis remains unclear. This retrospective study of fungal peritonitis attempts to answer that question. A total 22 patients with fungal peritonitis in 762 PD patients were enrolled in this study. The mean age of the 22 patients, 9 males and 13 females, was 54.7 +/- 12.5 years with a mean PD duration of 39.7 +/- 33.4 months. Candida species accounted for 86% (19 cases) of fungal peritonitis and 41% (9 cases) were C. parapsilosis. Thirteen (59%) patients received fluconazole as monotherapy; others received either amphotericin B alone or in combination with fluconazole. Catheters were removed for all patients. The mean duration from peritonitis onset to catheter removal was 5.8 +/- 4.1 days. Eleven (50%) patients developed severe complications, with abscess formation or persistent peritonitis after catheter removal. C. parapsilosis peritonitis had a higher complication rate than other Candida species (78% versus 20%, p = 0.012). In patients who received fluconazole as monotherapy, the rate of severe complications of C. parapsilosis peritonitis was statistically higher than those of other Candida species (100% versus 29%, p = 0.013). Because of different severity and prognosis, C. parapsilosis peritonitis in PD patients should be treated more aggressively than other Candida species.

This study determines the clinical significance of residual renal function (RRF), defined as residual daily urine volume (RDUV), in maintenance hemodialysis (MHD) patients. This multi-center study enrolled 704 MHD patients. Geographic, hematological, biochemical, and dialysis-related data were obtained. Values for nutritional and inflammatory markers were analyzed together with RDUV. In total, 670 of 704 patients (95.2%) with HD duration greater than 1 year had abnormal RDUV (<500 ml). Patients with higher RRF were younger, had shorter HD duration, higher prevalence of hypertension and levels of serum albumin, high density lipoprotein (HDL), and lower mid-week inter-dialysis body weight increase (MIBWI), cardio-thoracic ratio, levels of intact parathyroid hormone, high sensitivity C-reactive protein (Hs CRP), and KT/V (Daugirdes) values than those with low RRF. Stepwise multiple regression analysis demonstrated that RRF was positively correlated with serum albumin, HDL levels, and presence of hypertension, and negatively correlated with age, HD duration, and MIBWI in MHD patients. Moreover, after adjusting factors that were significantly related to serum albumin or Hs CRP, RRF was still positively correlated with serum albumin (0.000137 +/- 0.000585, p = 0.0197) and negatively correlated with log Hs CRP (-0.000184 +/- 0.000952, p = 0.0533). A one-liter increase in RDUV was associated with a 1.4 g/L increase in serum albumin level in MHD patients. This clinical study first demonstrated that RRF affects nutritional and inflammatory status in MHD patients. Because malnutrition and inflammation can cause high mortality in MHD patients, preserving RRF is important for these patients.

Peritonitis is a serious complication in peritoneal dialysis (PD) patients; however, the clinical outcome of culture-negative peritonitis (CNP) is controversial. This retrospective study of CNP attempts to resolve this controversy. In 813 episodes of peritonitis, 202 episodes of CNP in 152 PD patients were reviewed. Two different methods of effluent culture were utilized during the study period. The incidence of CNP was lower with 50 ml centrifugation culture than 10 ml direct inoculation culture (20.7% vs. 35.7%; p < 0.05). The overall cure rate of CNP was greater than 80% of patients receiving cefamezine and gentamicin as initial therapy. Relapse within 30 days after completion of treatment happened in 9.6% of cases, and antibiotic therapy failed in 8.1% of CNP cases. In comparison with cured patients, patients with relapse or treatment failure are older (62.0 +/- 15.0 years vs. 54.3 +/- 15.3 years; p = 0.007) and have a higher rate of abdominal pain (91.4% vs. 69.3%; p = 0.007) and greater need for salvage therapy (54.3 % vs. 11.0%; p < 0.001). A history of antibiotic use or peritonitis within 30 days before onset of CNP was noted in 23.3% and 12.5% of cases, respectively, but was not associated with clinical outcome. The clinical outcome of CNP was benign in this study. Older age, abdominal pain, and need for salvage therapy were associated with an increased risk for relapse and treatment failure in CNP cases. Moreover, 50 ml centrifugation culture method was better than 10 ml direct inoculation culture in reducing the incidence of CNP.

Initial high peritoneal permeability in peritoneal dialysis (PD) patients was previously thought to be a poor prognostic factor. We aimed to study the factors that determine the initial transport status and prognosis in PD patients. This was an observation cohort study that enrolled 551 fresh uremic patients who commenced PD in a single PD center from January 1994 to December 2004. Patients with different initial peritoneal transport status were analyzed and determinants of the initial peritoneal transport status were evaluated. All patients were followed up to investigate the risks of mortality. At the start of PD, only age and sex were determinants of the initial peritoneal transport status upon multiple linear regression analysis. The average duration of the study follow-up was 45.4 +/- 29.4 months. In the follow-up, a regression toward mean of transport status was found. About 107 patients died during the observation period. Cox-multivariate analysis revealed only age (RR = 1.06, p < 0.001), comorbidity index (RR = 2.31, p < 0.001), serum albumin (RR = 0.58, p = 0.008), and percentage of lean body mass (RR = 0.97, p = 0.008) to be independent predictors of mortality. We observed that the initial peritoneal transport status is not a determinant factor of long-term mortality. The reason may be due to a consequence of regression toward mean of the transport status. Whether the observed longitudinal regression-to-mean phenomenon change represent any physiologic relevance is hard to define. Further studies on the underlying mechanisms are needed.

Inflammatory polyneuropathies represent an important group of neurological disorders. Review of the literature disclosed that glomerulonephritis seems to be not uncommon in acute inflammatory demyelinating polyneuropathy. On the other hand, glomerulonephritis associated with chronic inflammatory demyelinating polyneuropathy (CIDP) appears to be rare. We herein report a 60-year-old man with a clinical history, physical examination and laboratory investigations consistent with CIDP, who also had severe lower limb edema and proteinuria resistant to medical therapy. Renal biopsy showed features consistent with membranous glomerulonephritis. We review the related literature, and the immunological implications are discussed.

Studies on risk factors of mortality in elderly patients with hemodialysis usually focus on comorbidities, nutrition, and inflammation. Discussion on the correlation between living environment and mortality of these patients is limited. A total of 256 elderly hemodialysis patients participated in this 2-year prospective observational study. The subjects were divided into 2 subgroups based on whether they were living in Taipei Basin (n = 63) or not (n = 193). Demographic, hematological, nutritional, inflammatory, biochemical, and dialysis-related data were obtained for cross-sectional analysis. Causes of death and mortality rates were also analyzed for each subgroup. Patients in the basin group had a higher incidence of combined protein-energy wasting and inflammation than those in the around basin group. At the end of the 2-year follow-up, 68 patients had died. Univariate binary logistic regression analysis revealed that a very advanced age, basin group, serum albumin levels, serum creatinine levels, non-anuria, and the complications of stroke and CAD were associated with 2-year mortality. Meanwhile, log high-sensitivity C-reactive protein (hs-CRP) levels were not associated with 2-year mortality. Multivariate Cox regression analysis revealed that basin group, serum albumin levels, and the complications of stroke and CAD were significant risk factors for 2-year mortality in these patients. The results of this study indicate that factors such as living in the Taipei Basin with higher air pollutant levels in elderly hemodialysis patients is associated with protein-energy wasting and inflammation, as well as 2-year mortality. These findings suggest that among this population, living environment is as important as comorbidities and nutrition. Furthermore, air pollution should be getting more attention especially in the overcrowding Basin topography.

Thousands of paraquat (PQ)-poisoned patients continue to die, particularly in developing countries. Although animal studies indicate that hemoperfusion (HP) within 2-4 h after intoxication effectively reduces mortality, the effect of early HP in humans remains unknown. We analyzed the records of all PQ-poisoned patients admitted to 2 hospitals between 2000 and 2009. Patients were grouped according to early or late HP and high-dose (oral cyclophosphamide [CP] and intravenous dexamethasone [DX]) or repeated pulse (intravenous methylprednisolone [MP] and CP, followed by DX and repeated MP and/or CP) PQ therapy. Early HP was defined as HP <4 h, and late HP, as HP ≥ 4 h after PQ ingestion. We evaluated the associations between HP <4 h, <5 h, <6 h, and <7 h after PQ ingestion and the outcomes. Demographic, clinical, laboratory, and mortality data were analyzed. The study included 207 severely PQ-poisoned patients. Forward stepwise multivariate Cox hazard regression analysis showed that early HP <4 h (hazard ratio [HR] = 0.38, 95% confidence interval (CI) 0.16-0.86; P = 0.020) or HP <5 h (HR = 0.60, 95% CI: 0.39-0.92; P = 0.019) significantly decreased the mortality risk. Further analysis showed that early HP reduced the mortality risk only in patients treated with repeated pulse therapy (n = 136), but not high-dose therapy (n = 71). Forward stepwise multivariate Cox hazard regression analysis showed that HP <4.0 h (HR = 0.19, 95% CI: 0.05-0.79; P = 0.022) or <5.0 h (HR = 0.49, 95% CI: 0.24-0.98; P = 0.043) after PQ ingestion significantly decreased the mortality risk in repeated pulse therapy patients, after adjustment for relevant variables. The results showed that early HP after PQ exposure might be effective in reducing mortality in severely poisoned patients, particularly in those treated with repeated pulse therapy.

Clinical outcome of internal carotid artery (ICA) occlusion is highly variable and the reason is uncertain. To study the predictive factors of clinical outcome and stroke recurrence in patients with ischemic stroke associated with unilateral atherosclerosis-related ICA occlusion. Prospective study in neurology department of a single hospital. We prospectively studied 66 patients who suffered from first-ever ischemic stroke associated with unilateral atherosclerosis-related ICA occlusion over a period of two years. The end point was death or stroke recurrence. Chi-square or Fisher's exact test was used to analyze predictors of early functional outcome. Multivariate analysis was used to analyze predictors of death or stroke recurrence within two years. Higher age (>or=70 years) predicted a worse functional outcome (P=0.049). Total anterior circulation syndrome (TACS) was associated with a poor functional outcome (P<0.001), but lacunar syndrome had a better outcome (P=0.001). Stroke in evolution predicted a poor outcome (P=0.001), while those with symptom improvement had a better outcome (P=0.016). Pneumonia predicted a poor outcome (P=0.021). Five patients expired and 22 patients suffered from recurrent stroke in the following 24 months. Previous transient ischemic attack (TIA) and anemia were associated with a higher risk of death or recurrent stroke within two years (P=0.036, P=0.012). High age, TACS, stroke in evolution and pneumonia were predictors for poor functional outcome. Previous TIA and anemia were predictors for death and recurrent stroke within two years.

Cadmium exposure is related to severity of diabetes and diabetes-related organ damage in diabetic patients. Elevated blood cadmium levels (BCLs) are well known in maintenance haemodialysis (MHD) patients but the clinical significance in diabetic MHD patients remains unknown. A total of 212 diabetic MHD patients were enrolled in this 18-month prospective study and were categorized into three equal groups according to the basal BCL: high (> 0.889 μg/L; n = 71), middle (0.373-0.889 μg/L; n = 70) and low (< 0.373 μg/L; n = 71) BCL groups. The mortality and cause of death were recorded and analysed longitudinally. Patients with high BCL had trends of higher white blood cell counts, glycosylated haemoglobin, phosphate and blood lead levels than other group patients. At the end of the follow-up, 31 patients had died. Kaplan-Meier analysis showed that the high BCL group patients had a higher mortality than other group patients (log-rank test, P = 0.036). Cox multivariate analysis demonstrated that logarithmic BCL was associated with increased hazard ratios (HR) for the all-cause mortality (HR = 2.336, 95% confidence intervals [CI] = 1.099-4.964, P = 0.027) in diabetic MHD patients. Similarly, if the low BCL group was the reference, the high BCL was associated with increased HR for all-cause mortality (HR = 2.865, 95% CI = 1.117-7.353, P = 0.043) in these patients. The study results first demonstrated that BCL is associated with increased HR for 18-month all-cause mortality in diabetic MHD patients. Avoiding smoking and high cadmium-containing food may be important in these patients.

Background/Aims: Protein-energy wasting (PEW) is a well-known risk factor of long-term survival in peritoneal dialysis (PD) patients. Serum albumin is a measure of visceral protein, lean body mass is a measure of somatic protein stores and normalized protein nitrogen appearance is a measure of daily protein intake. A protein nutrition index (PNI) that combined these 3 factors was designed and tested as a function of survival in PD patients. Methods: We enrolled 552 PD patients for this study. Demographic, biochemical, nutritional markers, comorbidity and dialysis-related data were obtained. The PNI was calculated. All patients were followed up to investigate the risks for mortality. Results: Patients with probable PEW/low-average nutrition were older and had lower serum creatinine (Cr) and blood urea nitrogen, lower adequacy data and higher D4/P4 Cr compared with patients with high-average/good nutrition. 108 patients (19.6%) died during the observational period. By multivariate analysis, we found only age, comorbidity index and PNI (relative risk = 0.84, confidence interval: 0.76-0.93, p = 0.001) to be independent predictors of mortality. Conclusion: The PNI at the start of PD is associated with all-cause mortality, and each increase by a score of 1 in PNI leads to a 16% decrease in the risk of mortality. Predialysis evaluation of this scoring system is recommended for further research in order to improve outcomes in PD patients.

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. 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. Chi-square analysis showed that the incidence of malnutrition and inflammation was significantly higher in patients with CTR >60% than in patients with CTR <or=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. 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%.

Leukocyte count predicted the risk of first-time myocardial infarction and ischemic stroke. The aim of this study was to determine the role of elevated leukocyte count in non-diabetic patients admitted for acute first-ever ischemic stroke on clinical presentation and 3-year mortality. We studied 462 patients with acute first-ever ischemic stroke without diabetes mellitus or active infection at admission. Patients were classified into 2 groups according to their leukocyte count. A white blood cell (WBC) count ≥ 10,000/μL was defined as an elevated leukocyte count, otherwise as normal. Clinical presentation, risk factors for stroke, laboratory data, co-morbidities, and outcomes were recorded. 64 patients (13.9%) had elevated leukocytes. Multivariate logistic regression showed that an elevated platelet count was positively associated with the elevated leukocyte count, while a low serum sodium level was negatively associated with an elevated leukocyte count (P=0.008, P=0.003, respectively). An elevated leukocyte count was associated with a higher risk of a stroke in evolution (P=0.021). Multivariate Cox regression analysis revealed that an elevated leukocyte count is a significant predictor of 3-year mortality [P=0.010, HR=3.26 (1.33-7.98)]. In conclusion, higher leukocyte counts during the acute stroke stage are associated with increased risk of 3-year mortality in patients with acute, first-ever ischemic stroke.

Hyponatremia is the most common electrolyte disorder in hospitalized patients, and is frequently a marker of a significant underlying disease. The prognostic value of hyponatremia in patients with acute first-ever ischemic stroke is not known. We aimed to analyze whether hyponatremia in the acute stroke stage contributed to the risk of mortality or recurrent stroke in these patients. We studied 925 patients presenting with acute first-ever ischemic stroke between 2002 and 2004. Sodium levels were obtained on arrival at the emergency room within 3 days of acute stroke onset. Hyponatremia was defined as a serum sodium concentration of 134 mmol/l or less. Clinical presentation, stroke risk factors, associated medical disease, and outcome were recorded. All patients were followed for 3 years for survival analysis. A multivariate Cox proportional hazards model was used to identify risk factors for 3-year mortality in these patients. We also constructed Kaplan-Meier survival curves, and compared groups with hyponatremia and normonatremia by means of log rank tests for significant differences. Among the patients with acute first-ever ischemic stroke, 107 (11.6%) were hyponatremic. Among stroke risk factors, the prevalence of diabetes mellitus was significantly higher among hyponatremic patients (p < 0.001). Prevalence of chronic renal insufficiency was also higher in the hyponatremic group (p = 0.002). Clinical presentations, such as the length of acute ward stay, initial impaired consciousness, and clinical course in acute stroke were similar among normo- and hyponatremic patients. Among the complications, pneumonia and urinary tract infection were significantly higher in hyponatremic than in normonatremic patients. After multivariate logistic regression analysis, diabetes mellitus and chronic renal insufficiency were associated with hyponatremia in these patients. Kaplan-Meier analysis indicated that the survival rate was significantly lower in hyponatremic patients than in normonatremic patients (log rank test; p value <0.001). After multivariate Cox proportional hazards model analysis, hyponatremia was a significant predictor of 3-year mortality in these patients after adjustment for related variables (p value = 0.003, hazard ratio = 2.23, 95% confidence interval: 1.30-3.82). Hyponatremia in the acute stroke stage is a predictor of 3-year mortality in patients with acute first-ever ischemic stroke that is independent of other clinical predictors of adverse outcome.

The aim of this study was to assess the relationship between the serum ferritin level and the 1-year outcome in diabetic maintenance hemodialysis (MHD) patients. The prospective clinical study enrolled 187 diabetic MHD patients from a university hospital in Taiwan. All the patients were divided into 3 groups according to their serum ferritin levels: group I (<200 ng/mL; n = 71), group II (200-700 ng/mL; n = 97), and group III (>700 ng/mL; n = 19). A total of 26 demographic, clinical, and laboratory variables were analyzed as predictors of the 1-year mortality. There were no significant differences between these 3 groups except in their erythropoietin usage, hemoglobin, transferrin saturation, and high-sensitive C-reactive protein levels. The 1-year mortality rates were 9.2%, 11.4%, and 46.2% in groups I, II, and III, respectively. Group I and group II patients had a lower 1-year mortality rate than group III patients (log-rank test; chi = 8.807; P = 0.0112). The study suggested that serum ferritin levels predict both all-cause and infection-cause 1-year mortality in diabetic patients on MHD. In such patients, the serum ferritin levels are associated with both iron stores and the inflammation status.

The aim of this study was to investigate clinical significance of impaired fasting glucose (IFG) in nondiabetic patients on maintenance peritoneal dialysis (PD). In total, 362 maintenance PD patients were enrolled and followed up for 2-years. According to 1997 definitions, patients were divided into 3 groups: diabetic (n = 85), nondiabetic with IFG (n = 62) and nondiabetic with normal fasting glucose levels (n = 215). After basal data were collected for cross-sectional analyses, mortality and cause of death were recorded for longitudinal analyses. After adjusting for related variables by multivariate logistic regression analysis, IFG was found to be positively associated with age but negatively associated with normalized protein nitrogen appearance and transferrin saturation in nondiabetic maintenance PD patients. Thirty nondiabetic patients had died after the 2-year follow-up. Cox multivariate analysis showed that age (hazard ratio: 1.037; 95% confidence interval: 1.002-1.073; P = 0.036) and presence of IFG (hazard ratio: 2.719; 95% confidence interval: 1.082-6.833; P = 0.033) were significant risk factors for all-cause 2-year mortality in nondiabetic maintenance PD patients. IFG, a preventable and treatable condition, was associated with all-cause 2-year mortality in nondiabetic maintenance PD patients.

Diabetes mellitus (DM) is characterized by dysregulated energy metabolism. Resveratrol (RSV) has been shown to ameliorate hyperglycemia and hyperlipidemia in diabetic animals. However, its overall in vivo effects on energy metabolism and the underlying mechanism require further investigation. In the present study, electrospray ionization-tandem mass spectrometry was employed to characterize the urine and plasma metabolomes of control, streptozotocin-induced DM and RSV-treated DM rats. Using principal component analysis (PCA) and heat map analysis, we discovered significant differences among control and experimental groups. RSV treatment significantly reduced the metabolic abnormalities in DM rats. Compared with the age-matched control rats, the level of carnitine was lower, and the levels of acetylcarnitine and butyrylcarnitine were higher in the urine and plasma of DM rats. RSV treatment ameliorated the deranged carnitine metabolism in DM rats. In addition, RSV treatment attenuated the diabetic ketoacidosis and muscle protein degradation, as evidenced from the attenuation of elevated urinary methyl-histidine and plasma branched-chain amino acids levels in DM rats. The beneficial effects of RSV in DM rats were correlated with activation of hepatic AMP-activated protein kinase and SIRT1 expression, increase of hepatic and muscular mitochondrial biogenesis and inhibition of muscle NF-κB activities. We concluded that RSV possesses multiple beneficial metabolic effects in insulin-deficient DM rats, particularly in improving energy metabolism and reducing protein wasting.

patients with chronic peritoneal dialysis (CPD) use glucose-based dialysate to maintain their life; however, whether the glycemic status influences outcome of these patients without diabetes remains unknown. we conducted a cross-sectional and 18-month prospective study, and 269 nondiabetic patients with CPD were enrolled in a medical center. Glycated hemoglobin (HbA1c) levels were measured at baseline and categorized in tertiles of HbA1c: high (>5.4%), middle (5.1-5.4%) and low normal (<5.1%). Mortality and cause of death were recorded for longitudinal analyses. the study results showed high HbA1c group patients had a trend of being older and having higher body mass index (BMI) than other group patients. Stepwise multiple linear regression analysis showed HbA1c was positively related to age, BMI and the peritoneal solute transport rate. After 18 months of follow-up, Cox multivariate analysis showed that HbA1c (HR: 4.114; 95% CI: 1.426-11.872; p = 0.009) was the significant risk factor for all-cause mortality after relating variables were adjusted. Moreover, high HbA1c (HR: 3.892; 95% CI: 1.273-11.959; p = 0.026) and low HbA1c (HR: 1.179; 95% CI: 1.160-1.198; p = 0.039), with middle HbA1c group as the reference, also significantly predicted for mortality in these patients. HbA1c levels, or presence of low or high HbA1c, are associated with 18-month all-cause mortality in nondiabetic patients with CPD.

The association between blood lead levels and mortality in patients on maintenance hemodialysis remains unclear. A cross-sectional and 18-month prospective study included 927 patients on maintenance hemodialysis. Baseline variables and blood lead levels were measured before hemodialysis and categorized as 3 equal groups: high (>12.64 μg/dL), middle (8.51-12.64 μg/dL), and low (<8.51 μg/dL). Mortality and cause of death were recoded for longitudinal analyses. At baseline, after related variables were adjusted, logarithmic transformation of blood lead level was negatively related to log ferritin and positively related to the vintage of hemodialysis and the percentage of urban area patients. By the end of the follow-up, 59 patients had died. Kaplan-Meier survival analysis showed that the high blood lead level group had greater mortality than the low blood lead level group (log-rank test, P<.001). After adjustment for potential variables, Cox multivariate analysis demonstrated that by using the low blood lead level as the reference, high blood lead levels were associated with increased hazard ratios (HRs) for all-cause (HR 4.70; 95% confidence interval [CI], 1.92-11.49; P=.003), cardiovascular-cause (HR 9.71; 95% CI, 2.11-23.26; P=.005), and infection-cause (HR 5.35; 95% CI, 1.38-20.83; P=.046) 18-month mortality in patients on maintenance hemodialysis. Moreover, there was a significant trend (P=.032) of HRs for all-cause mortality among the 3 study groups. High blood lead level is associated with increased HRs for all-cause, cardiovascular-cause, and infection-cause 18-month mortality in patients on maintenance hemodialysis.