Yu-Chung Lien

Clinical Outcomes and Predictors for ESRD and Mortality in Primary GN

BACKGROUND AND OBJECTIVES Relatively little is known about the long-term outcomes of different histologic types of primary glomerulonephritis in Asian populations. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS From 1993 to 2006, 987 patients undergoing renal biopsy were studied, and 580 patients (mean age=44.4 years, male=58.5%) with the four most common forms of glomerulonephritis (membranous nephropathy, focal and segmental glomerulosclerosis, IgA nephropathy, and minimal change disease) were selected for analysis. Median follow-up period was 5.9 (interquartile range=5.7) years. RESULTS The focal and segmental glomerulosclerosis group displayed the highest incidence of ESRD (25.8%) and the fastest decline of estimated GFR (4.6 ml/min per 1.73 m(2) per year). The IgA nephropathy group also had a higher rate of ESRD than the membranous nephropathy patients (19.2% versus 4.3%, P<0.001). In contrast, the membranous nephropathy group exhibited an overall death rate similar to the focal and segmental glomerulosclerosis group (17.2% versus 14.4%) but higher than the IgA nephropathy and minimal change disease patients (4.6% and 3.7%, respectively, P<0.001). The most powerful predictor for ESRD was focal and segmental glomerulosclerosis, whereas the strongest predictor for all-cause mortality was membranous nephropathy with higher proteinuria. Protectors against ESRD included male sex and higher hemoglobin. CONCLUSIONS Most predictors for ESRD and overall mortality found in this ethnic Chinese cohort were similar to other studies. However, some risk factors linked with distinct glomerular pathologies displayed differential clinical outcomes.

Lean Body Mass Predicts Long-Term Survival in Chinese Patients on Peritoneal Dialysis

Background Reduced lean body mass (LBM) is one of the main indicators in malnutrition inflammation syndrome among patients on dialysis. However, the influence of LBM on peritoneal dialysis (PD) patients’ outcomes and the factors related to increasing LBM are seldom reported. Methods We enrolled 103 incident PD patients between 2002 and 2003, and followed them until December 2011. Clinical characteristics, PD-associated parameters, residual renal function, and serum chemistry profiles of each patient were collected at 1 month and 1 year after initiating PD. LBM was estimated using creatinine index corrected with body weight. Multiple linear regression analysis, Kaplan–Meier survival analysis, and Cox regression proportional hazard analysis were used to define independent variables and compare survival between groups. Results Using the median LBM value (70% for men and 64% for women), patients were divided into group 1 (n = 52; low LBM) and group 2 (n = 51; high LBM). Group 1 patients had higher rates of peritonitis (1.6 vs. 1.1/100 patient months; p<0.05) and hospitalization (14.6 vs. 9.7/100 patient months; p<0.05). Group 1 patients also had shorter overall survival and technique survival (p<0.01). Each percentage point increase in LBM reduced the hazard ratio for mortality by 8% after adjustment for diabetes, age, sex, and body mass index (BMI). Changes in residual renal function and protein catabolic rate were independently associated with changes in LBM in the first year of PD. Conclusions LBM serves as a good parameter in addition to BMI to predict the survival of patients on PD. Preserving residual renal function and increasing protein intake can increase LBM.

Accumulation of epicardial fat rather than visceral fat is an independent risk factor for left ventricular diastolic dysfunction in patients undergoing peritoneal dialysis

BackgroundSymptoms of heart failure with preserved left ventricular systolic function are common among patients undergoing peritoneal dialysis (PD). Epicardial fat (EpF) is an ectopic fat depot with possible paracrine or mechanical effects on myocardial function. The aim of our current study is to assess the association between EpF and Left ventricular diastolic dysfunction (LVDD) in patients undergoing PD and to clarify the relationships among EpF, inflammation, and LVDD in this population.MethodsThis was a cross-sectional study of 149 patients with preserved left ventricular systolic function who were undergoing PD. LVDD was diagnosed (according to the European Society of Cardiology guidelines) and EpF thickness measured by echocardiography. The patients without LVDD were used as controls. The serum inflammatory biomarker high-sensitivity C-reactive protein (hsCRP) was measured. The location and amount of adipose tissue were assessed by computed tomography (CT) at the level of the fourth lumbar vertebra.ResultsSubjects with LVDD had higher levels of hsCRP, more visceral and peritoneal fat, and thicker EpF (all p < 0.001) than controls. Visceral adipose tissue, hsCRP, and EpF all correlated significantly (p < 0.05) with LVDD. Multivariate regression analysis rendered the relationship between visceral adipose tissue and LVDD insignificant, whereas EpF was the most powerful determinant of LVDD (odds ratio = 2.41, 95% confidence interval = 1.43–4.08, p < 0.01). EpF thickness also correlated significantly with the ratio of transmitral Doppler early filling velocity to tissue Doppler early diastolic mitral annular velocity (E/e’; r = 0.27, p < 0.01).ConclusionEpF thickness is significantly independently associated with LVDD in patients undergoing PD and may be involved in its pathogenesis.

Differential association of proinflammatory cytokines with left ventricular diastolic dysfunction in subjects with and without continuous ambulatory peritoneal dialysis

BACKGROUND AND AIMS The association between inflammation and left ventricular (LV) diastolic dysfunction in continuous ambulatory peritoneal dialysis (CAPD) and non-CAPD patients is not established. The objective of this study was to test the above association and whether inflammation interacts with CAPD to increase LV diastolic dysfunction risks. METHODS AND RESULTS 120 subjects with normal creatinine levels and 101 CAPD patients were recruited. Echocardiographic parameters were assessed in all patients. The participants were classified as having LV diastolic dysfunction by echocardiographic findings including mitral inflow E/A ratio < 1, deceleration time > 220 cm/s, or decreased peak annular early diastolic velocity in tissue Doppler imaging. Blood was sampled at the baseline for measurement of inflammation markers, including tissue necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Subjects with LV diastolic dysfunction had higher proinflammation cytokines levels in both groups. Inflamed markers correlated significantly with echocardiography parameters for LV diastolic dysfunction in patients receiving CAPD. In a multivariate regression analysis adjusting for all the factors associated with LV diastolic dysfunction, inflammation is still significantly associated with left ventricular diastolic dysfunction (TNF-alpha, OR: 2.6, 95% CI: 2.0-3.35, p < 0.001; IL-6, OR: 1.26, 95% CI: 1.25-1.26, p = 0.01). In addition, the interaction of CAPD and inflammation significantly contributed to the development of LV diastolic dysfunction (CAPD∗ TNF-α: OR: 1.45, 95% CI: 1.13-1.79, P = 0.004). CONCLUSION We found inflammation plays a vital role for LV diastolic dysfunction especially in CAPD patients. A synergistic effect between CAPD and inflammation, especially TNF-α, would further aggravate LV diastolic dysfunction.

Tamoxifen Downregulates Connective Tissue Growth Factor to Ameliorate Peritoneal Fibrosis

Peritoneal fibrosis (PF), including simple sclerosis and encapsulating peritoneal sclerosis (EPS), is a serious complication in patients on long-term peritoneal dialysis. Tamoxifen has successfully been used in treating EPS; however, the mechanism of tamoxifen in treating EPS fibrosis disorders remains unclear. This study demonstrates a possible antifibrotic mechanism of tamoxifen. A bleach-induced PF rat model was applied as the in vivo treatment target. Tamoxifen was intraperitoneally injected daily to treat PF. The PF scores and thickness of the submesothelial zone over the liver surface were measured as indicators for the severity of PF. Human peritoneal mesothelial cells (HPMC) were used as an in vitro model to test the antifibrotic effect of tamoxifen. Gene expressions of transforming growth factors-β (TGF-β), connective tissue growth factor (CTGF) and collagen were investigated using quantitative polymerase chain reactions. In HPMC, tamoxifen showed paradoxical effects between collagen I and TGF-β. Tamoxifen also inhibited TGF-β-induced collagen and CTGF. The possible antifibrotic effect of tamoxifen is through inhibiting CTGF to block collagen synthesis, although it enhances TGF-β which increases fibrosis. These results provide a possible molecular mechanism for tamoxifen.

Osteoprotegerin, inflammation and dyslipidemia are associated with abdominal aortic calcification in non-diabetic patients on peritoneal dialysis

BACKGROUND AND AIMS Abdominal aortic calcification (AC) has been reported to be associated with cardiovascular disease (CVD) in hemodialysis patients but is rarely discussed in peritoneal dialysis (PD) patients. We examined the independent predictors and predictive power for survival of AC in prevalent PD patients. METHODS AND RESULTS AC was detected by computed tomography (CT) and represented as the percentage of the total aortic cross-section area affected by AC (%AC). The predictors of %AC ≥ 15 were examined by multiple logistic regression analysis. Cox proportional hazard analysis was used to determine the hazard ratios associated with high %AC. A total of 183 PD patients were recruited to receive CT scans and divided into group 1 (%AC < 15, n = 97), group 2 (%AC ≥ 15, n = 41), and group 3 (diabetic patients, n = 45). Group 1 patients had lower osteoprotegerin (OPG) levels than group 2 patients (798 ± 378 vs. 1308 ± 1350 pg/mL, p < 0.05). The independent predictors for %AC ≥ 15 included the atherogenic index, OPG, and C-reactive protein (CRP). The age-adjusted hazard ratios associated with %AC ≥ 15 were 3.46 (p = 0.043) for mortality and 1.90 (p = 0.007) for hospitalization. CONCLUSIONS %AC can predict mortality and morbidity in non-diabetic PD patients, and 15% is a good cut-off value for such predictions. There are complex associations among mineral metabolism, inflammation, and dyslipidemia in the pathogenesis of AC.

Dissecting the Mechanisms of Left Ventricular Diastolic Dysfunction and Inflammation in Peritoneal Dialysis Patients

Objective Patients with symptoms of heart failure and preserved left ventricular (LV) systolic function are commonly encountered in clinical practice especially in peritoneal dialysis (PD) patients. We hypothesized that adiposity might influence LV diastolic function through systemic inflammation in this specific group. Methods We designed a cross-sectional study in 173 prevalent PD patients. LV diastolic dysfunction was diagnosed by echocardiography. PD patient without LV diastolic dysfunction served as the control group. Serum inflammatory biomarkers were examined including tissue necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). The location and amount of adipose tissue were assessed by computerized tomography (CT) at the level of the fourth lumbar vertebra. Results Subjects with LV diastolic dysfunction had higher levels of the pro-inflammation cytokines and more visceral and peritoneal fat (all P<0.001) than control subjects. A significant correlation was found between visceral adipose tissue and pro-inflammatory cytokines (r = 0.70; P<0.001). Multivariable regression analysis found that the relationship between visceral adipose tissue and LV diastolic dysfunction became insignificant when either TNF-α or IL-6 were introduced into the model, although TNF-α and IL-6 were both significantly associated with LV diastolic dysfunction even after adjusting for visceral fat (OR = 1.51; 95% CI = 1.09–2.02; P = 0.033 and OR = 1.62; 95% CI = 1.09–1.82; P = 0.031, respectively). Conclusions Larger amounts of adipose tissue were associated with higher serum pro–inflammatory levels in PD patients, which might be related to the development of LV diastolic dysfunction. Modulating inflammatory reactions in PD patients can be a useful therapeutic approach for managing LV diastolic dysfunction.

High Peritoneal KT/V and Peritonitis Rates Are Associated with Peritoneal Calcification

Background Peritoneal calcification (PC) is a specific finding in patients undergoing peritoneal dialysis (PD), but its prevalence, risk factors, and impacts in PD patients remain unclear. The present study investigated these issues and provided information useful for the management of PC. Methods The study included 183 PD patients. The severity of PC was determined using abdominal computed tomography (CT), and we summed up all scores from slices obtained from the diaphragm to the pelvic floor normalized to body surface area. We analyzed the associations between PC and demographic and clinical characteristics, and between PC and levels of biomarkers, including C-reactive protein (CRP), osteoprotegrin and fetuin-A. The determinants of PC were examined using multiple regression analysis. Results Patients were categorized into group 1 (without PC, n = 133) and group 2 (with PC, n = 50). Group 2 patients showed different degrees of PC with a mean of 160±769 mm2/m2. Group 1 patients had higher fetuin-A levels than group 2 patients (861±309 vs. 760±210 µg/mL; p = 0.021). The independent risk factors for the presence of PC included male gender, previous peritonitis, and PD adequacy (KT/V). Further analysis performed in group 2 patients showed that the dosage of vitamin D, serum levels of CRP, and dialysate calcium load were the independent determinants of PC. However, the presence of PC did not affect patients’ technique survival, peritonitis incidence, or mortality in the mean follow up period of 28±12 months. Conclusions The presence and severity of PC were associated with inflammation, peritoneal KT/V, and mineral metabolism. The impact of PC on the outcomes of PD patients requires further study with a longer follow-up.

Self-powered wireless temperature sensor with piezoelectric energy harvester fabricated with metal-MEMS process

This paper presents a self-powered wireless temperature sensor powered with a micro piezoelectric energy harvester. The piezoelectric energy harvester is a cantilever beam design fabricated with metal-MEMS process on stainless steel substrates. The energy harvester is tuned to have resonant frequency around 120Hz and the bimorph version can generate more than 400μW power output when driven with vibration levels of 1.5g acceleration at resonance. A shaker simulated the vibrations of motors general seen in air conditioning system with a vibration level around 0.5g is used to drive the piezoelectric energy harvesters and has a power output around 50μW power. An interfacing circuit with energy buffer is used to accumulate electrical energy in a capacitor and then turn on the Bluetooth wireless module to send temperature readings measured from internal temperature sensor to a smartphone intermittently. The Bluetooth module can be turn on for around 1 second to send the readings to a smartphone for every 1.5 minutes.