Hyperhomocysteinemia predicts cardiovascular outcomes in hemodialysis patients

BACKGROUND: We prospectively tested the prediction power of homocysteinemia for all-cause and cardiovascular outcomes in a cohort of 175 hemodialysis patients followed for 29 +/- 12 months. METHODS: Survival analysis was performed by the Cox's proportional hazard model and data were expressed as hazard ratio and 95% confidence interval (CI). RESULTS: During the follow-up period 51 patients died, 31 of them (61%) of cardiovascular causes and 16 patients developed non-fatal atherothrombotic complications. Plasma total homocysteine was an independent predictor of cardiovascular mortality (P=0.01). Combined analysis of fatal and non-fatal atherothrombotic events showed that homocysteine was a strong and independent predictor of these outcomes because the risk of these events was 8.2 times higher (95% CI 1.9 to 32.2) in patients in the third homocysteine tertile than in those in the first tertile (P=0.005). CONCLUSIONS: There is a clear association between hyperhomocysteinemia and incident cardiovascular mortality and atherothrombotic events in hemodialysis patients. Intervention studies are needed to determine whether the accumulation of this substance has a causal role in the pathogenesis of cardiovascular damage in patients undergoing hemodialysis.     

Influence of hypertension on cardiovascular outcomes in hemodialysis patients

Cardiovascular disease is a leading cause of morbidity and mortality in chronic hemodialysis patients. Most patients with chronic kidney disease have hypertension and its prevalence remains high following renal replacement therapy. Early studies suggested that hypertension was a risk factor for total and cardiovascular mortality in chronic hemodialysis patients, but the results of more recent studies have caused experts to question these assertions. Systolic hypertension, widened pulse pressure, and nondipping may be better predictors of mortality compared to diastolic hypertension or increased mean arterial pressure. Hypertension in hemodialysis patients is a risk factor for left ventricular hypertrophy (LVH), diastolic dysfunction, and congestive heart failure; good blood pressure control may promote its regression. Atherosclerosis and ventricular arrhythmias may also be linked to hypertension. Thus blood pressure control with a focus on systolic pressure appears to be a prudent strategy to improve cardiovascular outcomes in hemodialysis patients.     

The study of cardiovascular disease and survival among maintenance hemodialysis patients

Objective To evaluate the associated factors about cardiovascular disease and survival among maintenance hemodialysis patients. Methods The newly diagnosed patients with ESRD in the 44th hospital of People's Liberation Army and Changzheng hospital during the period of 2008-2012 were analyzed retrospectively. The baseline variables and laboratory results were collected. Cardiovascular disease and survival were recorded. Logistic regression and multivariate COX regression were used to detect the relative factors. Results A total of 158 patients were included in the study. The mean age was 54.61±16.98. Cardiovascular complications were recorded in 40 cases. Heart and coronary artery disease were recorded 24 cases, strokes were recorded in 16 cases. Cox proportional hazards regression model showed thatage (HR=1.051, 95%CI:1.023-1.081), male (HR=6.025, 95%CI:2.571-14.121), increased neutrophile granulocyte(%) (HR=1.073, 95%CI:1.028-1.121), increased LDL (HR=1.562, 95%CI:1.058-2.305), high calcium concentration dialysate (HR=5.025, 95%CI:1.163-21.739) were risk factors for cardiovascular disease. Compared to conventional hemodialysis, in-center nocturnal hemodialysis was a protective factor (HR=0.288, 95%CI:0.090-0.924). In our study, 7 patients died. After adjusted to multiple variances, we found diabetes was a risk factor for survival (HR=15.385, 95%CI：1.692-145.851). Compared to conventional hemodialysis, hemodiafiltration may reduce the risk of CVD(HR=0.145, 95%CI:0.021-1.016, P=0.052). Conclusions To maintenance hemodialysis patients, age, male gender, the percent of neutrophile granulocyte, LDL, high calcium concentration dialysate are risk factors for CVD. In-center nocturnal hemodialysis reduces the risk ofCVD. Diabetes increase the risk of death, while hemodiafiltration may reduce the risk of death.     

Associations among time-average mineral values,mortality and cardiovascular events in hemodialysis patients

Abstract

Mineral and bone disease (CKD-MBD), disorders of mineral metabolism, is associated with mortality and cardiovascular disease in dialysis patients. However, the associations among time average mineral values (P, Ca and PTH) and clinical outcomes are not well investigated. Objectives: This study examines the associations among mineral values and clinical outcomes from a single medical center. Methods: Adult patients who initiate hemodialysis in Taoyuan General Hospital from 2008 to 2013 were enrolled. We examined these associations using baseline and time-average model. The clinical outcomes included mortality, major adverse cardiovascular events (MACE) and cardiovascular events. We also examined the association between achieve K/DOQI guidelines’ targets and clinical outcomes. Results: From a total of 284 hemodialysis patients, none of the baseline mineral values is associated with mortality and cardiovascular event, except hyperphosphatemia. Compared to patients achieved K/DOQI guidelines’ targets, time average hyperphosphatemia is associated with MACE and first cardiovascular event [the adjusted hazard ratios (AHRs) are 6.343 and 3.278); whereas time average hypercalcemia is associated with MACE marginally (the AHR is 5.964). None of above clinical outcomes is related to hyperparathyroidism. The AHRs for mortality in those who only met PTH targets and none of the mineral value targets are 1.73 and 1.74, whereas the AHRs for cardiovascular events in those who met only Ca, only PTH, and none of the targets are 1.73, 1.81 and 2.54 (all ps?<?0.05). Conclusion: Time-average phosphate is associated with cardiovascular events after initiation of dialysis. Among mineral values, serum phosphate is still the strongest predictor for mortality and cardiovascular events.     

Adiponectin, metabolic risk factors, and cardiovascular events among patients with end-stage renal disease.

Adiponectin (ADPN), which is a secretory protein of adipose tissue, attenuates endothelial inflammatory responses in vitro. Among human subjects, plasma ADPN concentrations are reduced among patients with atherosclerotic complications but are substantially increased among patients with advanced renal failure. The clinical and biochemical correlates of plasma ADPN levels were investigated and the predictive power of ADPN levels with respect to survival rates and cardiovascular events was prospectively tested in a cohort of 227 hemodialysis patients, who were monitored for 31 +/- 13 mo. Plasma ADPN levels were 2.5 times higher (P < 0.0001) among dialysis patients (15.0 +/- 7.7 microg/ml) than among healthy subjects (6.3 +/- 2.0 microg/ml), were independent of age, and were higher (P = 0.03) among women (15.2 +/- 7.9 microg/ml) than among men (14.0 +/- 7.4 microg/ml). For both genders, plasma ADPN levels were inversely related to body mass index values, plasma leptin levels, insulin levels, serum triglyceride levels, and homeostatic model assessment index values. Furthermore, plasma ADPN levels were directly related to HDL cholesterol levels and inversely related to von Willebrand factor levels. Plasma ADPN levels were lower (P < 0.05) among patients who experienced new cardiovascular events (13.7 +/- 7.3 microg/ml) than among event-free patients (15.8 +/- 7.8 microg/ml). There was a 3% risk reduction for each 1 microg/ml increase in plasma ADPN levels, and the relative risk of adverse cardiovascular events was 1.56 times (95% confidence interval, 1.12 to 1.99 times) higher among patients in the first ADPN tertile, compared with those in the third tertile. Plasma ADPN levels are an inverse predictor of cardiovascular outcomes among patients with end-stage renal disease. Furthermore, ADPN is related to several metabolic risk factors in a manner consistent with the hypothesis that this protein acts as a protective factor for the cardiovascular system.     

Association of short-term blood pressure variability with cardiovascular mortality among incident hemodialysis patients

Objective: To investigate the association of short-term blood pressure variability (BPV) with cardiovascular mortality in hemodialysis (HD) patients, using a reliable index called average real variability (ARV), and to assess the factors associated with ARV in incident HD population.

Methods: A total of 103?HD patients were recruited, with 44-h ambulatory blood pressure monitoring performed after the midweek HD session. Systolic BPV was assessed by SD, coefficient of variation (CV), and ARV, respectively. Laboratory data were obtained from blood samples before the midweek HD. All patients were followed up for 24 months.

Results: According to the median of BPV indices, the comparisons between patients with the low and high values were conducted. Kaplan–Meier analysis showed the survival curves corresponding to median of SD and CV exhibit similar performance for the low and high groups (p?=?.647, p?=?.098, respectively). In contrast, patients with higher ARV had a lower survival rate than those with lower ARV (77.8% vs. 98.0%, p?=?.002). After adjustment for demographics and clinical factors, ARV (HR: 1.143; 95% CI: 1.022–1.279, p?=?.019) and high-sensitivity C-reactive protein (HR: 1.394; 95% CI: 1.025–1.363, p?=?.021) were associated with increased risk of cardiovascular mortality in HD patients. Age and interdialytic weight gain (IDWG) were related factors for ARV (β?=?0.065, p?=?.005; β?=?0.825, p?=?.003, respectively).

Conclusions: Greater ARV was independently associated with increased risk of cardiovascular mortality in HD patients. Age and IDWG were independent related factors for ARV.     

Iron administration and clinical outcomes in hemodialysis patients

To evaluate the impact of parenteral iron administration on the survival and rate of hospitalization of US hemodialysis patients, a nonconcurrent cohort study of 10,169 hemodialysis patients in the United States in 1994 was conducted. The main outcome measures were patient survival and rate of hospitalization. After adjusting for 23 demographic and comorbidity characteristics among 5833 patients included in multivariable analysis, bills for 10 vials showed a statistically significant elevated rate of death (adjusted RR = 1.11; 95% CI, 1.00 to 1.24; P = 0.05). Bills for 10 vials showed statistically significant elevated risk (adjusted RR = 1.12; 95% CI, 1.01 to 1.25; P = 0.03). Prescribing iron in quantities of 10 vials (1000 mg) of iron dextran over a period of 6 mo.     

Erectile dysfunction among hemodialysis patients

Objective  

Erectile dysfunction (ED) is a distressing problem in hemodialysis patients. A combination of organic and psychological factors has been reported to take part in the pathophysiology of this condition. The aim of this study is to determine the prevalence of sexual dysfunction among hemodialysis patients.     

Body composition and cardiovascular risk in hemodialysis patients.

Death rate is unacceptably elevated in end-stage renal disease patients treated with hemodialysis. Excessive body fat, or obesity, is the well-known risk factor for cardiovascular disease and other health problems in the general population. However, hemodialysis patients with a higher body mass index (BMI) have a lower risk of death, as shown by many studies. There are several explanations for the paradox of BMI in dialysis patients. First, although body mass is composed of fat mass and fat-free mass (lean mass), it is unknown which is more important, fat mass or lean mass, in predicting outcome of hemodialysis patients. Second, it is also possible that functions of adipose tissue are altered in renal failure so that accumulation of body fat leads to less atherogenicity and beneficial properties become predominant. Third, an increased fat mass may be protective against death after harmful events. In this article, we explore these possibilities using either the data of our own cohort of hemodialysis patients or the existing registry data of Japan. We conclude that in hemodialysis patients, fat mass rather than lean mass plays a protective role against mortality, that the fat mass-adipocytokine relationship is altered, and that a low BMI is associated with increased risk of fatality after cardiovascular events rather than the risk of occurrence of such events.     

Intensity of care and better outcomes among hemodialysis patients: a role for the Medical Director

The Medical Director is responsible for all levels of quality patient care in the facility as mandated by the 2008 revision of the Medicare Conditions for Coverage of dialysis facilities. He/she is the leader and primary individual tasked with ensuring that facility processes are in place to meet or exceed key quality goals or adopt new ones and prioritize them appropriately-all to drive improved facility performance, particularly the ultimate outcomes of morbidity and mortality rates. Management of vascular access, dialysis dose, mineral metabolism, acid-base balance, sodium and fluid management, anemia, among other aspects of care, have representative intermediate clinical outcomes that are often called "surrogate" or "process" measures-because they may reflect the quality of care delivery while impacting "primary" outcomes such as death and hospitalization. The proportion of dialysis patients within a dialysis facility meeting a selected group among these goals has become the standard "care process" metric since the 1990s. Evidence supports its use, in that graded improvements in the facility patients' primary outcomes have been documented as more patients in a facility achieved a greater number of these "process" goals. A caveat: these process measures do not represent overall quality by themselves because nonclinical processes also influence primary outcomes. Nevertheless, process improvement in meeting facility goals should be led by the Medical Director, particularly those with the strongest links to primary outcomes such as reduction of hemodialysis catheter exposure, forming the cornerstone of quality improvement efforts. Specific recommendations on how to effectively lead a care team to achieve these goals are discussed.     

Atherosclerotic cardiovascular disease risks in chronic hemodialysis patients

BACKGROUND: Cardiovascular diseases are the most common causes of death among chronic hemodialysis patients, yet the risk factors for these events have not been well established. METHODS: In this cross-sectional study, we examined the relationship between several traditional cardiovascular disease risk factors and the presence or history of cardiovascular events in 936 hemodialysis patients enrolled in the baseline phase of the Hemodialysis Study sponsored by the U.S. National Institutes of Health. The adjusted odds ratios for each of the selected risk factors were estimated using a multivariable logistic regression model, controlling for the remaining risk factors, clinical center, and years on dialysis. RESULTS: Forty percent of the patients had coronary heart disease. Nineteen percent had cerebrovascular disease, and 23% had peripheral vascular disease. As expected, diabetes and smoking were strongly associated with cardiovascular diseases. Increasing age was also an important contributor, especially in the group less than 55 years and in nondiabetic patients. Black race was associated with a lower risk of cardiovascular diseases than non-blacks. Interestingly, neither serum total cholesterol nor predialysis systolic blood pressure was associated with coronary heart disease, cerebrovascular disease, or peripheral vascular disease. Further estimation of the coronary risks in our cohort using the Framingham coronary point score suggests that traditional risk factors are inadequate predictors of coronary heart disease in hemodialysis patients. CONCLUSIONS: Some of the traditional coronary risk factors in the general population appear to be also applicable to the hemodialysis population, while other factors did not correlate with atherosclerotic cardiovascular diseases in this cross-sectional study. Nontraditional risk factors, including the uremic milieu and perhaps the hemodialysis procedure itself, are likely to be contributory. Further studies are necessary to define the cardiovascular risk factors in order to devise preventive and interventional strategies for the chronic hemodialysis population.     

Long-term clinical outcomes of nocturnal hemodialysis patients compared with conventional hemodialysis patients post-renal transplantation

Abstract:  Nocturnal home hemodialysis (NHD) is a novel dialysis strategy associated with multiple advantages over conventional hemodialysis (CHD). Short- and long-term clinical outcomes of NHD patients after kidney transplantation are unknown. We hypothesized that the incidence of delayed graft function (DGF), patient and graft survival, and post-transplant estimated glomerular filtration rate (eGFR) is better among CHD-transplanted individuals than among those having received NHD. Of 231 NHD patients, 36 underwent renal transplantation between 1994 and 2006 and were matched to 68 transplanted CHD patients with a maximum follow-up of 11.7 yr. The incidence of DGF was not different between the two groups [NHD: 15/35 (42.9%) vs. CHD: 25/68 (36.8%) p = 0.43]. In modeling eGFR pre-transplant weight, donor age and recipient race were most predictive. Dialysis modality prior to transplantation influenced neither the level of eGFR post-transplantation (p = 0.34), nor the rate of eGFR decline. Patient survival was comparable between NHD and CHD groups (log-rank p = 0.91). Based on this analysis, it appeared that the incidence of DGF was similar between NHD- and CHD-transplanted patients and that pre-transplant modality did not impact on the level or rate of deterioration of post-transplant eGFR.     

High doses of epoetin do not lower mortality and cardiovascular risk among elderly hemodialysis patients with diabetes

A randomized trial had suggested that high doses of erythropoiesis-stimulating agents (ESAs) might increase the risk of cardiovascular outcomes in predialysis diabetic patients. To evaluate this risk in diabetic patients receiving dialysis, we used data from 35,593 elderly Medicare patients on hemodialysis in the US Renal Data System of whom 19,034 were diabetic. A pooled logistic model was used to estimate the monthly probability of mortality and a composite cardiovascular end point. Inverse probability weighting was used to adjust for measured time-dependent confounding by indication, estimated separately for diabetic and non-diabetic cohorts. The adjusted 9-month mortality risk, significantly different between an ESA dose of 45,000 and 15,000?U/week, was 13% among diabetics and 5% among non-diabetics. In diabetic patients, the hazard ratio (HR) for more than 40,000?U/week was 1.32 for all-cause mortality and 1.26 for a composite end point of death and cardiovascular events compared with patients receiving 20,000 to 30,000?U/week. The corresponding HRs in non-diabetic patients were 1.06 and 1.10, respectively. A smaller effect of dose was found in non-diabetic patients. Thus, higher ESA doses, which are often necessary to achieve high hemoglobin levels, are not beneficial, and possibly harmful, to diabetic patients receiving dialysis. Our findings support a Food and Drug Administration advisory recommending that the lowest possible ESA dose be used to treat hemodialysis patients.     

血液透析与腹膜透析患者微炎症反应比较及其与营养状况、心血管疾病关系的研究

目的 研究血液透析、腹膜透析两种透析方式对慢性肾衰尿毒症患者微炎症状态的影响,探讨微炎症状态与营养状况、心血管疾病的关系.方法 选择2011年1月至2012年6月沈阳市红十字会医院肾内科住院的尿毒症患者64例(血液透析30例、腹膜透析34例)及健康对照者30例,检测C反应蛋白、白介素6、尿素氮、肌酐、白蛋白、前白蛋白、血红蛋白,计算体重指数.根据主观综合性营养评价将患者分为营养良好组、营养不良组.记录透析处方和心血管并发症.结果 本组尿毒症患者C反应蛋白、白介素6较对照组显著升高(P＜0.01),血液透析组C反应蛋白、白介素6显著高于腹膜透析组(P＜0.05).尿毒症各组内营养良好组C反应蛋白、白介素6较营养不良组显著升高(P＜0.05),合并慢性心衰组C反应蛋白、白介素6较无心衰并发症组显著升高(P＜0.05).C反应蛋白与白蛋白、前白蛋白呈显著负相关,与尿素氮、肌酐、血红蛋白无显著相关性.结论 血液透析患者微炎症状态比腹膜透析患者严重,尿毒症患者微炎症状态与营养不良及心血管疾病密切相关.     

Posttransplant outcomes of peritoneal dialysis versus hemodialysis patients

The impact of dialysis modality on posttransplant outcomes remains controversial. The authors have compared primary failure, delayed graft function (DGF), acute rejection episodes as well as patient and allograft survivals among patients undergoing renal transplantation between 2004 and 2009, according to the modality of hemodialysis (HD) versus peritoneal dialysis (PD). We studied 306 patients (268 HD and 38 PD) with a mean follow-up of 29 ± 16 months. The PD cohort included a predominance of females (68.4% vs 36.2%; P = .001), lower age at transplantation (38 ± 14 vs 46 ± 12 years; P = .004), shorter time on dialysis (33 ± 49 vs 59 ± 157 months; P = .043), and higher rate of living donor grafts (PD 31.6% vs HD 13.1%; P = .003). Donor age (PD 43 ± 13 vs HD 45 ± 14 years; P = .30), human leukocyte antigen mismatch (P = .17), panel reactive antibody values (HD 11 ± 22 vs PD 13 ± 26; P = .55), and hyperimunized patients (HD 3.73%; PD 7.89%; P = .23) were not different. Primary graft failure (3.4% vs 0%; P = .025) and DGF (37.1% vs 13.1%; P = .037) were more frequent among HD patients, but incidences of acute rejection episodes were similar (HD 10.5% vs PD 5.3%; P = 0.19). Neither recipient survival at 1 (97% in PD and HD) or 3 years (HD 90% vs PD 94%; P = .657) nor allograft survival at 1 year (HD 94% vs PD 95%; P = .80) or 3 years: (HD 70%, vs PD 81%; P = .73) were different. Graft function was similar at 1 (HD 64.2 ± 25 vs PD 56.4 ± 24 mL/min; P = .17) and 3 years (HD 62.3 ± 21 vs PD 46 ± 23 mL/min; P = .16). In our study, HD patients showed an higher incidence of DGF and primary allograft failure, but there was no difference in acute rejection episodes, long-term survivals, or renal function.     

骨硬化蛋白与维持性血液透析患者冠状动脉钙化的关系

Objective To evaluate the potential association of serum sclerostin with the development of coronary artery calcifications(CAC)in maintenance hemodialysis (MHD) patients. Methods Ninety-two patients who were on MHD between Jan 2014 and Jan 2015 in the dialysis center were enrolled prospectively. Serum sclerostin was tested. CAC was measured by multi-slice computed tomography (MSCT) scanning, and the CAC score (CACs) was calculated. Logistic regression analysis was used to determine the risk factor of CAC in MHD patients. The diagnostic value of serum sclerostin for CAC was assessed using receiver operator characteristic curve (ROC). Results CAC (Agatston score>100) was present in 65.2% (60/92) patients, the median CAC score was 446 (26, 1 000). The median of serum sclerostin levels was 37.05 (29.99, 49.04) ng/L. The serum sclerostin levels were significantly elevated in the group of CACs＞400 compared to that in the group of CACs＜100 [40.71(36.69, 74.21) ng/L vs 28.16 (25.27, 33.64) ng/L, P＜0.05]. Multivariate logistic regression analysis showed that serum sclerostin level was independent risk factor for CAC (OR=1.292, 95%CI 1.017-1.641, P＜0.05). The area under the ROC curve (AUC) of serum sclerostin for CAC was 0.846 (95%CI 0.717-0.975, P=0.001), sensitivity was 0.826, and specificity was 0.769 for a cutoff value of 35.165 ng/L. Conclusions Serum sclerostin level is associated with CAC. Serum sclerostin level may have a diagnostic value for CAC in MHD patients.