[show abstract][hide abstract] ABSTRACT: Since the pioneering studies by Eschbach et al in 1987, erythropoiesis-stimulating agents (ESAs) have become the mainstay of anemia therapy in chronic kidney disease (CKD) patients. The introduction of ESAs 25 years ago markedly improved the lives of many patients with CKD, who until then had severe, often transfusion-dependent anemia. However, randomized controlled trials demonstrate an increased risk for cardiovascular events such as stroke, thrombosis, and death at nearly normal hemoglobin concentrations and higher ESA doses in CKD. By contrast, kidney transplant recipients may represent a unique population of CKD patients who may benefit from ESA therapy. This review discusses potential mechanisms involving the erythropoietic and nonerythropoietic effects of ESA treatment and ESA resistance. Further research aimed at elucidating the causal pathways is strongly recommended. Given current knowledge, however, clinical practice should avoid disproportionately high dosages of ESAs to achieve recommended hemoglobin targets, particularly in those with significant cardiovascular morbidity or ESA resistance. The key to CKD anemia management will be individualization of the potential benefits of reducing blood transfusions and anemia-related symptoms against the risks of harm.
Journal of the Formosan Medical Association 09/2013; · 1.00 Impact Factor
[show abstract][hide abstract] ABSTRACT: Elevated aldosterone is associated with increased mortality in the general population. In patients on dialysis, however, the association is reversed. This paradox may be explained by volume overload, which is associated with lower aldosterone and higher mortality.
We evaluated the relationship between aldosterone and outcomes in a prospective cohort of 328 hemodialysis patients stratified by the presence or absence of volume overload (defined as extracellular water/total body water >48%, as measured with bioimpedance). Baseline plasma aldosterone was measured before dialysis and categorized as low (<140 pg/mL), middle (140 to 280 pg/mL) and high (>280 pg/mL).
Overall, 36% (n = 119) of the hemodialysis patients had evidence of volume overload. Baseline aldosterone was significantly lower in the presence of volume overload than in its absence. During a median follow-up of 54 months, 83 deaths and 70 cardiovascular events occurred. Cox multivariate analysis showed that by using the low aldosterone as the reference, high aldosterone was inversely associated with decreased hazard ratios for mortality (0.49; 95% confidence interval, 0.25-0.76) and first cardiovascular event (0.70; 95% confidence interval, 0.33-0.78) in the presence of volume overload. In contrast, high aldosterone was associated with an increased risk for mortality (1.97; 95% confidence interval, 1.69-3.75) and first cardiovascular event (2.01; 95% confidence interval, 1.28-4.15) in the absence of volume overload.
The inverse association of aldosterone with adverse outcomes in hemodialysis patients is due to the confounding effect of volume overload. These findings support treatment of hyperaldosteronemia in hemodialysis patients who have achieved strict volume control.
PLoS ONE 01/2013; 8(2):e57511. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Normotension has been hold to be the goal of hemodialysis. It remains obscure which cardiovascular parameter determines the prognosis in these normotensive hemodialysis patients. METHODS: We prospectively enrolled 145 hemodialysis patients, who had attained normotension without anti-hypertensive medications, and followed them for 72.6 +/- 28.5 months. Important cardiovascular parameters were obtained at enrollment. Predictors for all-cause and cardiovascular mortalities were identified with the Cox model. RESULTS: There were 45 (18 cardiovascular/27 non-cardiovascular) deaths occurred during follow-up. Age, diabetes, left ventricular mass index (LVMI), left ventricular ejection fraction (LVEF), carotid intima-media thickness (CIMT), and aortic pulse wave velocity (PWV) were significant predictors for all-cause and cardiovascular mortalities. After adjustment for age and diabetes, only LVEF was significantly associated with all-cause mortality. LVEF was significantly associated with cardiovascular mortality. LVEF remained as a significant independent predictor of cardiovascular death after adjusting for age, diabetes, LVMI, CIMT, or PWV, respectively. CONCLUSION: LVEF is the independent predictor for all-cause and cardiovascular mortalities in the normotensive hemodialysis patients.
[show abstract][hide abstract] ABSTRACT: Inflammation is closely associated with cardiovascular disease, the leading cause of mortality in patients with CKD. Serum decoy receptor 3 (DcR3) is a member of the TNF receptor superfamily. CKD patients have higher levels of DcR3 than the general population, but whether DcR3 predicts mortality in CKD patients on hemodialysis has not been explored.
DcR3 levels were measured in 316 prevalent hemodialysis patients who were followed up from November 1, 2004, to June 30, 2009, for cardiovascular and all-cause mortality.
The baseline DcR3 concentration showed a strong positive correlation with inflammatory markers including high-sensitivity C-reactive protein, IL-6, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1). During a follow-up period of 54 months, 90 patients died (34 cardiovascular deaths). Kaplan-Meier survival analysis showed higher cardiovascular and all-cause mortality in patients with higher DcR3 levels. The hazard ratios (95% confidence intervals) of the highest versus lowest tertiles of DcR3 were 2.8 (1.1-7.3; P for trend=0.04) for cardiovascular mortality and 2.1 (1.1-3.7; P for trend=0.02) for all-cause mortality, respectively. Based on the minimal increase in the area under the receiver operating characteristic curve from 0.79 to 0.80, the addition of DcR3 to established risk factors including VCAM-1, albumin, and IL-6 does not improve the prediction of mortality.
Higher DcR3 levels strongly correlate with inflammation and independently predict cardiovascular and all-cause mortality in CKD patients on hemodialysis.
Clinical Journal of the American Society of Nephrology 05/2012; 7(8):1257-65. · 5.07 Impact Factor
[show abstract][hide abstract] ABSTRACT: The blood pressure (BP) of a proportion of chronic hemodialysis (HD) patients rises after HD. We investigated the influence of postdialysis BP rise on long-term outcomes.
A total of 115 prevalent HD patients were enrolled. Because of the fluctuating nature of predialysis and postdialysis BP, systolic BP (SBP) and diastolic BP before and after HD were recorded from 25 consecutive HD sessions during a 2-month period. Patients were followed for 4 years or until death or withdrawal.
Kaplan-Meier estimates revealed that patients with average postdialysis SBP rise of more than 5 mmHg were at the highest risk of both cardiovascular and all-cause mortality as compared to those with an average postdialysis SBP change between -5 to 5 mmHg and those with an average postdialysis SBP drop of more than 5 mmHg. Furthermore, multivariate Cox regression analysis indicated that both postdialysis SBP rise of more than 5 mmHg (HR, 3.925 [95% CI, 1.410-10.846], p = 0.008) and high cardiothoracic (CT) ratio of more than 50% (HR, 7.560 [95% CI, 2.048-27.912], p = 0.002) independently predicted all-cause mortality. We also found that patients with an average postdialysis SBP rise were associated with subclinical volume overload, as evidenced by the significantly higher CT ratio (p = 0.008).
A postdialysis SBP rise in HD patients independently predicted 4-year cardiovascular and all-cause mortality. Considering postdialysis SBP rise was associated with higher CT ratio, intensive evaluation of cardiac and volume status should be performed in patients with postdialysis SBP rise.
[show abstract][hide abstract] ABSTRACT: The association between intravenous (IV) iron administration and outcomes in hemodialysis (HD) patients is still debated. Therefore, this study was aimed to assess the relationship between the IV administration of ferric chloride hexahydrate (Atofen®) and cardiovascular (CV) outcome and the interaction between iron-induced oxidative stress and endothelial dysfunction in chronic HD patients.
A cohort of 1239 chronic HD patients was recruited. In a follow-up of 12 months, Kaplan-Meier survival curves showed that higher doses of IV Atofen associated with higher risks for CV events and deaths in HD patients. In multivariate Cox models, compared to no iron supplementation, IV Atofen administration was an independent predictor for CV events and overall mortality. However, the nature of the observational cohort study possibly bears selection bias. We further found that IV Atofen enhanced the superoxide production of mononuclear cells (MNCs), the levels of circulating soluble adhesion molecules, and the adhesion of MNCs to human aortic endothelial cells (HAECs). In vitro experiments showed that Atofen increased the expression of intracellular cell adhesion molecule-1 and vascular cell adhesion molecule-1 in HAECs and aggravated the endothelial adhesiveness in a dose-dependent manner. These iron-induced changes were significantly attenuated by the co-treatment of HAECs with N-acetylcysteine and inhibitors of NADPH oxidase, nuclear factor κB, and activator protein-1.
A cumulative dose of IV Atofen >800 mg within 6 months was associated with an adverse CV outcome and a higher mortality among chronic HD patients. The detrimental effects of IV iron supplementation were partly due to the increased oxidative stress and induction of MNC adhesion to endothelial cells, a pivotal index of early atherogenesis.
PLoS ONE 01/2012; 7(12):e50295. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Elevated levels of serum pancreatic enzymes are frequently observed in hemodialysis (HD) patients. The complex hemodynamic, biochemical, and physiological alterations in uremia were speculated to cause excessive release of pancreatic enzymes beyond decreased renal clearance. However, hemodynamic factors are seldom explored in this aspect. We performed the study to evaluate the association between intradialytic hemodynamic change and elevated serum pancreatic amylase (SPA). Eighty-three prevalent HD patients without any clinical evidence of acute pancreatitis underwent pre-HD and post-HD blood sampling for serum pancreatic enzyme levels. Demographic, biochemical, and hematological data were collected from patient record review. Hemodialysis information including intradialytic blood pressure changes and ultrafiltration (UF) amount were collected and averaged for 1 month before the blood sampling day. Patients with elevated SPA during the HD session had greater mean systolic blood pressure and mean arterial pressure reduction, greater UF volume, greater pre-HD blood urea nitrogen and serum creatinine, higher serum phosphorus, lower pre-HD serum total CO(2) , and lower left ventricle ejection fraction (LVEF). Using multivariate linear and logistic regression analysis, the independent predictors of elevated SPA were determined to be mean arterial pressure reduction during HD, mean UF amount, pre-HD serum total CO(2) , and LVEF. Greater blood pressure reduction during HD, greater UF volume, lower pre-HD serum total CO(2) , and lower LVEF were significantly associated with elevated SPA during HD. This suggests that hemodynamic factors contribute to elevated serum pancreatic enzymes in HD patients.
Hemodialysis International 01/2011; · 1.44 Impact Factor
[show abstract][hide abstract] ABSTRACT: In healthy, normotensive individuals, age-related changes in carotid augmentation index (AI) are more prominent in younger individuals (< 50 years), whereas changes in aortic pulse wave velocity (PWV) are more marked in older individuals (> 50 years). We investigated whether the differential effects of age on AI and PWV also existed in end-stage renal disease (ESRD) patients.
Two hundred and fifty-seven patients (50% male; mean age, 53.9 +/- 15.0 years) with ESRD and 260 normal controls (52% male; mean age, 51.4 +/- 17.8 years) received a comprehensive evaluation of cardiovascular structure and function.
The percent differences in PWV between the younger and older subjects were similar in both ESRD patients (+46.2%) and normal controls (+52.5%). The percent differences in PWV between normal controls and ESRD patients were also similar in both younger (+28.2%) and older (+22.9%) subjects. In contrast, the differences in AI between the younger and older subjects were small in ESRD patients (7.3%) but large in normal controls (19.7%). Furthermore, there was a large difference in AI between normal controls and ESRD patients in the younger (+13.3%) subjects, but no difference in the older subjects (+0.8%) (interaction between study groups and age: p < 0.001).
Markedly differential effects of age on AI and PWV were observed in ESRD patients. PWV increased with age similarly in both ESRD patients and normal controls, whereas AI increased markedly in the younger but only slightly in the older ESRD patients.
Journal of the Chinese Medical Association 04/2008; 71(4):166-73. · 0.75 Impact Factor
[show abstract][hide abstract] ABSTRACT: A 42-year-old woman underwent hemodialysis secondary to diabetic nephropathy. Total parathyroidectomy with forearm autograft was performed due to secondary hyperparathyroidism (HPT) complicated with calciphylaxis. Rapidly progressive enlargement of autograft with unusual "gourd-shape" developed, and then it was removed. Pathologic examination of the autograft disclosed multinodular hyperplasia. Residual parathyroid gland in the retrothyroid region was found later. Rapidly recurrent HPT originating from both the residual parathyroid tissues and the enlarged autograft within such short time after parathyroidectomy is rare in the literature. The multinodular hyperplasia pattern of the parathyroid gland may be a major factor for such rapid recurrence. In addition to good control of calcium and phosphate, regular follow-up of parathyroid hormone level and imaging studies of not only autografted gland at the forearm but also possibly residual parathyroid tissues at the neck are important for monitoring recurrence in maintenance hemodialysis patients after parathyroidectomy with forearm autograft, especially in those with pathologic type of nodular hyperplasia and calciphylaxis.
The American Journal of the Medical Sciences 06/2006; 331(5):284-7. · 1.33 Impact Factor
[show abstract][hide abstract] ABSTRACT: Normotensive hemodialysis patients may still have left ventricular hypertrophy in the absence of significant pressure or volume overload. We examined the hypothesis that treatment with an angiotensin-converting enzyme inhibitor could be beneficial in the reversal of left ventricular hypertrophy in these patients.
Forty-six normotensive patients with end-stage renal disease on regular hemodialysis therapy were randomly assigned to administration of ramipril, 2.5 mg 3 times/wk, or placebo for 1 year. Left ventricular mass index and parameters of cardiovascular structure and function were evaluated noninvasively by means of echocardiography and arterial tonometry at baseline, 6 and 12 months after treatment, and 1 month after washout.
In the ramipril group, blood pressure decreased significantly at 6 and 12 months after treatment. There were no significant within-group or between-group differences in left ventricular mass index at entry, 6 and 12 months after treatment, and 1 month after washout. There were no significant differences in left atrial dimension, left ventricular size and wall thickness, left ventricular ejection fraction, aortic dimension, intima-media thickness, elastic modulus and augmentation index of the common carotid artery, and aortic pulse wave velocity between the ramipril and placebo groups at entry, 6 and 12 months after treatment, and 1 month after washout.
A 12-month treatment with ramipril did not cause significant regression of left ventricular hypertrophy in normotensive hemodialysis patients. Results may suggest that the renin-angiotensin system has little role in the pathogenesis of mild left ventricular hypertrophy in these patients.
American Journal of Kidney Diseases 04/2006; 47(3):478-84. · 5.29 Impact Factor
[show abstract][hide abstract] ABSTRACT: A total of 32 patients without regional wall motion abnormality of the left ventricle underwent sequential tissue Doppler echocardiography and cardiac catheterization. Peak velocities of systolic (Sa), early diastolic (Ea), and late diastolic (Aa) motion of the mitral annulus were measured. Normal references for Sa, Ea and Aa were obtained from 138 volunteers. Indices of left ventricular (LV) systolic and diastolic function were evaluated using high-fidelity LV pressure and volume signals. By multivariate analysis, Sa, Ea and As were significantly and independently related to the maximum of the first derivative of pressure over time (dP/dt(max)), LV relaxation time constant (tau), and LV ejection fraction (EF), respectively. Using the fifth percentiles of the age-stratified normal references as cut-offs, low Sa, low Ea and low Aa identified declined dP/dt(max), prolonged tau and reduced EF, respectively, with good sensitivities and specificities. In conclusion, mitral annulus velocities by tissue Doppler echocardiography can be used to identify patients with declined dP/dt(max), prolonged tau and reduced EF.
Ultrasound in Medicine & Biology 02/2005; 31(1):23-30. · 2.46 Impact Factor
[show abstract][hide abstract] ABSTRACT: Left ventricular (LV) relaxation time constant (Tau) is a relatively load-independent index of diastolic function in the evaluation of heart failure. However, the requirement of high-fidelity intraventricular pressure recording limits its clinical utility. In the present study, we investigated whether Tau could be estimated noninvasively.
Thirty-seven patients indicated for cardiac catheterization were recruited for study. Echocardiography and cardiac catheterization with high-fidelity LV pressure recording were performed sequentially within 1 hour. The non-invasive TauDopp was derived from the formula: TauDopp = IVRT(Dopp)/[ln(Ps) - ln(10)], where IVRT is the isovolumic relaxation time measured by Doppler echocardiography and Ps is systolic blood pressure measured during the echocardiographic examination. The invasive TauLM was determined by non-linear least-square parameter estimate technique, using the exponential equation: Pv = Poe(-t/Tau) + b, where Pv is the instantaneous LV pressure, P0 is LV pressure at minimal dP/dt, and b is the theoretical asymptote. The difference between TauDopp and TauLM was compared using paired t-test, and their relation was evaluated using simple correlation and intra-class correlation coefficient.
IVRT(Dopp) was significantly correlated with the invasively derived IVRT (r = 0.42, p = 0.012). The completely non-invasive TauDopp was significantly correlated with the direct curve-fitted TauLM (r = 0.41;p = 0.013), and the intraclass correlation coefficient was 0.29 (p = 0.04). In addition, TauDopp was significantly smaller than TauLM (36+/-6 ms vs. 57+/-15 ms, p < 0.001).
Tau can be estimated noninvasively by transthoracic Doppler echocardiographic method with limited accuracy. The clinical utility of TauDopp remains to be determined.
Journal of the Chinese Medical Association 08/2004; 67(7):317-22. · 0.75 Impact Factor
[show abstract][hide abstract] ABSTRACT: In end-stage renal disease (ESRD) patients undergoing regular haemodialysis (HD), the maintenance of fluid status within an optimal range is critical. We therefore examined the role of Doppler echocardiographic parameters in the assessment of fluid status in these patients.
Three study groups were enrolled: 40 healthy volunteers (NTNR), 40 HD patients who were normotensive without receiving antihypertensive agents (NTHD) and 38 HD patients who had remained hypertensive (HTHD) despite antihypertensive treatment. Measurements of Doppler echocardiographic parameters from pulmonary vein (PV) and mitral inflow (Mi) were performed on a non-dialysis day. Extracellular water as a percentage of body weight (ECW%) and pre-dialysis mean blood pressure (BDMBP) were references for fluid status. The best Doppler parameter for fluid status assessment identified from the study groups was then tested in another validation groups (38 NTHD and 38 HTHD).
Among all of the PV and Mi parameters, the S/D ratio (peak systolic velocity divided by peak diastolic velocity) was correlated with fluid status parameters best (with ECW%, r = -0.49, P<0.001; with BDMBP, r = -0.51, P<0.001). The correlations were independent of age, sex and Mi parameters. The receiver operating characteristics curve analysis demonstrated that an S/D ratio >1.33 had a sensitivity of 90% and a specificity of 77% in identifying NTHD patients. When the same criterion was applied to the validation groups, the positive predictive value was 64% and the negative predictive value was 86%.
The Doppler-derived S/D ratio is a potentially useful marker for the assessment of fluid status in HD patients.
[show abstract][hide abstract] ABSTRACT: Large-artery derangement is a major risk factor for cardiovascular and all-cause mortality in patients with end-stage renal disease (ESRD). It is not clear how body fluid distribution affects large-artery structure and function in patients with ESRD.
One hundred fifty-seven hemodialysis (HD) patients (mean age, 55.9 +/- 15.1 years; 76 men, 81 women) were enrolled. Influence of the extracellular fluid (ECF)-to-intracellular fluid (ICF) ratio derived from bioimpedance spectroscopy on the structure and function of the common carotid artery (CCA) and aorta was analyzed. One hundred forty-four healthy subjects were examined to obtain normal reference values for body fluid compartments. Based on ECF-ICF ratio, 2 groups were identified: ECF-ICF ratio in the 95th percentile or less and ECF-ICF ratio greater than the 95th percentile of age- and sex-stratified normal reference values.
ECF-ICF ratio was significantly related to CCA diameter (r2 = 0.26; P < 0.001), CCA incremental modulus (E(inc); r2 = 0.15; P < 0.001), carotid augmentation index (AGI; r2 = 0.10; P < 0.001), and aortic pulse wave velocity (aPWV; r2 = 0.21; P < 0.001). ECF-ICF ratio remained a significant independent determinant for CCA diameter (model r2 = 0.47; P < 0.001), E(inc) (r2 = 0.29; P < 0.001), aPWV (r2 = 0.51; P < 0.001), and AGI (r2 = 0.40; P < 0.001) when age, sex, mean blood pressure, anthropometrical parameters, HD duration, and status of diabetes mellitus were accounted for. HD patients with an ECF-ICF ratio greater than the 95th percentile had a greater CCA diameter, E(inc), aPWV, and AGI than their counterparts.
ECF-ICF ratio is associated with large-artery structure and function in HD patients. Patients with ESRD with a high ECF-ICF ratio are characterized by significant large-artery derangement.
American Journal of Kidney Diseases 11/2003; 42(5):990-9. · 5.29 Impact Factor