ESA Hyporesponsiveness Is Associated with Adverse Events in Maintenance Hemodialysis (MHD) Patients,But Not with Iron Storage

Objective

It has been reported that hyporesponsiveness to erythropoiesis-stimulating agent (ESA) is associated with adverse events in patients on maintenance hemodialysis (MHD). However, it has not been determined whether higher iron storage is associated with an improved response, including better survival, to ESA.

Design and Method

We measured serum ferritin, hemoglobin (Hb), and transferrin saturation (TSAT) levels every three months for two years in 1,095 MHD patients. The weekly dose of ESA to Hb ratio was also calculated as an index of ESA responsiveness (ERI).

Results

A significant correlation (p<0.001, R = 0.89) between ferritin and Hb was only observed in the patients with ferritin levels <50 ng/mL. High-dose (≥50 mg/week) intravenous iron administration, female sex, low serum albumin, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use were significant predictors of a high ERI value (>280); however, serum ferritin and TSAT levels did not predict a higher ERI. In the time-dependent Cox hazard model, the risk for a composite event in the patients with a high ERI (≥280) and a high ferritin level (≥100 ng/mL) was significantly greater (hazard ratio [HR], 2.09, P = 0.033) than that for patients with a high ERI and a low ferritin (<100 ng/mL) level.

Conclusion

Hb was dependent upon ferritin levels in patients with ferritin levels <50 ng/mL but not in patients with ferritin levels ≥50 ng/mL. Patients with hyporesponsiveness to ESA had a greater risk of composite events, but ERI was unrelated to iron storage.     

The Korean Clinical Research Center for End-Stage Renal Disease Study Validates the Association of Hemoglobin and Erythropoiesis-Stimulating Agent Dose with Mortality in Hemodialysis Patients

Background

Anemia is an important risk factor for mortality in hemodialysis (HD) patients. However, higher hemoglobin (Hb) is not necessarily better, as seen in several studies. This study aimed to validate the clinical use of an Hb target of 10–11 g/dL in Korean HD patients.

Methods

A total of 1,276 HD patients from the Clinical Research Center (CRC) for End-Stage Renal Disease (ESRD) were investigated in a prospective observational study. Cox proportional hazard analysis was conducted for each category of time-dependent Hb level and erythropoiesis-stimulating agent (ESA) dose, with subgroup analysis stratified by age and diabetes status.

Results

Using a reference Hb level of 10–11 g/dL, the hazard ratios (HRs) of death were 5.12 (95% confidence interval [CI], 2.62–10.02, P <0.05) for Hb level <9.0 g/dL, and 2.03 (CI, 1.16–3.69, P <0.05) for Hb level 9.0–10.0 g/dL, after adjustment for multiple clinical variables. However, an Hb level ≥11 g/dL was not associated with decreased mortality risk. In an adjusted model categorized by Hb and ESA dose, the risk of death at an Hb level <10 g/dL and a higher dose of ESA (≥126 U/kg/week) had an HR of 2.25 (CI, 1.03–4.92, P <0.05), as compared to Hb level 10–11 g/dL and a lower dose of ESA. In subgroup analysis, those older than 65 years or who were diabetic had greater risk for mortality only in Hb category <9.0 g/dL. However, there was no significant interaction between age or diabetes status and Hb.

Conclusion

Using CRC-ESRD data, we validated the association between Hb and ESA dose and mortality in Korean HD patients. The clinical practice target of an Hb of 10–11 g/dL before the new KDIGO guideline era seems reasonable considering its survival benefit in HD patients.     

Vitamin D Deficiency—Prognostic Marker or Mortality Risk Factor in End Stage Renal Disease Patients with Diabetes Mellitus Treated with Hemodialysis—A Prospective Multicenter Study

BackgroundEnd stage renal disease (ESRD) patients on renal replacement therapy (RRT) with diabetes mellitus (DM) have a higher mortality rate and an increase prevalence of vitamin D deficiency compared to those without DM. It is still debated if vitamin D deficiency is a risk factor or a prognostic marker for mortality in these patients. This study investigated the prevalence of vitamin D deficiency and its impact on all-cause mortality in HD patients with DM.MethodsOur prospective non-interventional cohort study included 600 patients on hemodialysis therapy (HD) (median aged 56, interquartile range (19) years, 332 (55.3%) males) recruited from 7 HD centers, from all main geographical regions of Romania. The prevalence of DM was 15.3%. They were then followed regarding: dialysis duration, dialysis efficiency, renal anemia, CKD-MBD, inflammatory status and comorbidities: coronary artery disease (CAD), peripheral vascular disease (PVD) and stroke. The deficiency of 25-OH vitamin D was defined as a value lower than12 ng/mL.ResultsPatients were followed for 3 years. The overall 3 year mortality was 25.5% (153 individuals), being higher in patients with DM as compared to those without DM (33.7% vs. 24.0%; P = 0.049). The time-related prognosis was also influenced by the presence of DM, at the survival analysis resulting in a HR of 1.52 [1.03 to 2.26] 95% CI, P = 0.037, for death in dialyzed patients with DM. In DM patients, 25-OH vitamin D deficiency was significantly higher (37.0% compared to 24.0%, P = 0.009). Furthermore, in patients with DM we observed a shorter dialysis duration (2 vs. 3 years, P<0.001) and a lower intact parathyroid hormone (iPTH) (258.0 pg/ml vs. 441.9 pg/ml, P = 0.002). Regarding the presence of comorbidities at the inclusion in the study, the presence of diabetes in dialyzed patients was associated with increased prevalence of CAD (87.0% vs. 58.1%, P<0.001), PVD (67.4% vs. 17.3%, P<0.001) and history of stroke (29.3% vs. 14.0%, P<0.001). In patients with DM the presence of 25-OH vitamin D deficiency increased the probability of death (50.0% vs. 24.1%; P = 0.011). In multiple Cox proportional hazards analysis, vitamin D deficiency remained an independent predictor for mortality in dialysis patients with DM (HR = 1.71, 95% CI 1.21 to 2.43, P = 0.003). In the same time, multiple Cox proportional hazards analysis showed that age (HR = 1.02 per one year increase, P = 0.004), CAD (HR = 1.55, P = 0.046) and PVD (HR = 1.50, P = 0.029) were independent predictors for mortality in dialysis patients with DM.ConclusionsESRD patients with DM treated with HD have a higher overall mortality than non-DM patients. Vitamin D deficiency is significantly more prevalent in HD patients with DM. Low 25-OH vitamin D levels were associated with increased all-cause mortality in these patients. According to our data, in HD patients with DM, screening for vitamin D deficiency (and its correction) should be mandatory for an optimal risk reduction strategy.     

Serum Gamma-Glutamyltransferase Levels Predict Clinical Outcomes in Hemodialysis Patients

Background

Gamma-glutamyltransferase (GGT) is a biomarker of liver injury. GGT has also been reported to be a marker of oxidative stress and a predictor of mortality in the general population. Hemodialysis (HD) patients suffer from oxidative stress. The aim of our study was to investigate the relationship between serum GGT levels and clinical outcomes in HD patients.

Methods

A total of 1,634 HD patients were enrolled from the Clinical Research Center registry for end-stage renal disease, a prospective cohort in Korea. Patients were categorized into three groups by tertiles of serum GGT levels. The primary outcome was all-cause, cardiovascular, or infection-related mortality and hospitalization.

Results

During the median follow-up period of 30 months, the highest tertile of serum GGT levels had a significantly higher risk for all-cause mortality (hazard ratio (HR) 2.39, 95% confidence interval (CI), 1.55–3.69, P<0.001), cardiovascular mortality (HR 2.14, 95% CI, 1.07–4.26, P = 0.031) and infection-related mortality (HR 3.07, 95% CI, 1.30–7.25, P = 0.011) using tertile 1 as the reference group after adjusting for clinical variables including liver diseases. The highest tertile also had a significantly higher risk for first hospitalization (HR 1.22, 95% CI, 1.00–1.48, P = 0.048) and cardiovascular hospitalization (HR 1.42, 95% CI, 1.06–1.92, P = 0.028).

Conclusions

Our data demonstrate that high serum GGT levels were an independent risk factor for all-cause, cardiovascular, and infection-related mortality, as well as cardiovascular hospitalization in HD patients. These findings suggest that serum GGT levels might be a useful biomarker to predict clinical outcomes in HD patients.     

Sagittal Abdominal Diameter Is an Independent Predictor of All-Cause and Cardiovascular Mortality in Incident Peritoneal Dialysis Patients

Backgrounds and Aims

Visceral fat has a crucial role in the development and progression of cardiovascular disease, the major cause of death in end-stage renal disease (ESRD). Although sagittal abdominal diameter (SAD), as an index of visceral fat, significantly correlated with mortality in the general population, the impact of SAD on clinical outcomes has never been explored in ESRD patients. Therefore, we sought to elucidate the prognostic value of SAD in incident peritoneal dialysis (PD) patients.

Methods

We prospectively determined SAD by lateral abdominal X-ray at PD initiation, and evaluated the association of SAD with all-cause and cardiovascular mortality in 418 incident PD patients.

Results

The mean SAD was 24.5±4.3 cm, and during a mean follow-up of 39.4 months, 97 patients (23.2%) died, and 49.4% of them died due to cardiovascular disease. SAD was a significant independent predictor of all-cause [3rd versus 1st tertile, HR (hazard ratio): 3.333, 95% CI (confidence interval): 1.514–7.388, P = 0.01; per 1 cm increase, HR: 1.071, 95% CI: 1.005–1.141, P = 0.03] and cardiovascular mortality (3rd versus 1st tertile, HR: 8.021, 95% CI: 1.994–32.273, P = 0.01; per 1 cm increase, HR: 1.106, 95% CI: 1.007–1.214, P = 0.03). Multivariate fractional polynomial analysis also showed that all-cause and cardiovascular mortality risk increased steadily with higher SAD values. In addition, SAD provided higher predictive value for all-cause (AUC: 0.691 vs. 0.547, P<0.001) and cardiovascular mortality (AUC: 0.644 vs. 0.483, P<0.001) than body mass index (BMI). Subgroup analysis revealed higher SAD (≥24.2 cm) was significantly associated with all-cause mortality in men, women, younger patients (<65 years), and patients with lower BMI (<22.3 kg/m²).

Conclusions

SAD determined by lateral abdominal X-ray at PD initiation was a significant independent predictor of all-cause and cardiovascular mortality in incident PD patients. Estimating visceral fat by SAD could be useful to stratify mortality risk in these patients.     

Resistance to Erythropoiesis Stimulating Agents in Patients Treated with Online Hemodiafiltration and Ultrapure Low-Flux Hemodialysis: Results from a Randomized Controlled Trial (CONTRAST)

Resistance to erythropoiesis stimulating agents (ESA) is common in patients undergoing chronic hemodialysis (HD) treatment. ESA responsiveness might be improved by enhanced clearance of uremic toxins of middle molecular weight, as can be obtained by hemodiafiltration (HDF). In this analysis of the randomized controlled CONvective TRAnsport STudy (CONTRAST; {"type":"clinical-trial","attrs":{"text":"NCT00205556","term_id":"NCT00205556"}}NCT00205556), the effect of online HDF on ESA resistance and iron parameters was studied. This was a pre-specified secondary endpoint of the main trial. A 12 months'' analysis of 714 patients randomized to either treatment with online post-dilution HDF or continuation of low-flux HD was performed. Both groups were treated with ultrapure dialysis fluids. ESA resistance, measured every three months, was expressed as the ESA index (weight adjusted weekly ESA dose in daily defined doses [DDD]/hematocrit). The mean ESA index during 12 months was not different between patients treated with HDF or HD (mean difference HDF versus HD over time 0.029 DDD/kg/Hct/week [−0.024 to 0.081]; P = 0.29). Mean transferrin saturation ratio and ferritin levels during the study tended to be lower in patients treated with HDF (−2.52% [−4.72 to −0.31]; P = 0.02 and −49 ng/mL [−103 to 4]; P = 0.06 respectively), although there was a trend for those patients to receive slightly more iron supplementation (7.1 mg/week [−0.4 to 14.5]; P = 0.06).In conclusion, compared to low-flux HD with ultrapure dialysis fluid, treatment with online HDF did not result in a decrease in ESA resistance.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00205556","term_id":"NCT00205556"}}NCT00205556     

Serum Magnesium and Sudden Death in European Hemodialysis Patients

Despite suggestions that higher serum magnesium (Mg) levels are associated with improved outcome, the association with mortality in European hemodialysis (HD) patients has only scarcely been investigated. Furthermore, data on the association between serum Mg and sudden death in this patient group is limited. Therefore, we evaluated Mg in a post-hoc analysis using pooled data from the CONvective TRAnsport STudy (CONTRAST, NCT00205556), a randomized controlled trial (RCT) evaluating the survival risk in dialysis patients on hemodiafiltration (HDF) compared to HD with a mean follow-up of 3.1 years. Serum Mg was measured at baseline and 6, 12, 24 and 36 months thereafter. Cox proportional hazards models, adjusted for confounders using inverse probability weighting, were used to estimate hazard ratios (HRs) of baseline serum Mg on all-cause mortality, cardiovascular mortality, non-cardiovascular mortality and sudden death. A generalized linear mixed model was used to investigate Mg levels over time. Out of 714 randomized patients, a representative subset of 365 (51%) were analyzed in the present study. For every increase in baseline serum Mg of 0.1 mmol/L, the HR for all-cause mortality was 0.85 (95% CI 0.77–94), the HR for cardiovascular mortality 0.73 (95% CI 0.62–0.85) and for sudden death 0.76 (95% CI 0.62–0.93). These findings did not alter after extensive correction for potential confounders, including treatment modality. Importantly, no interaction was found between serum phosphate and serum Mg. Baseline serum Mg was not related to non-cardiovascular mortality. Mg decreased slightly but statistically significant over time (Δ -0.011 mmol/L/year, 95% CI -0.017 to -0.009, p = 0.03). In short, serum Mg has a strong, independent association with all-cause mortality, cardiovascular mortality and sudden death in European HD patients. Serum Mg levels decrease slightly over time.     

Treatment with Oral Active Vitamin D Is Associated with Decreased Risk of Peritonitis and Improved Survival in Patients on Peritoneal Dialysis

Peritonitis is a major complication of peritoneal dialysis (PD) being associated with hospitalization, catheter loss, technique failure, and increased mortality. Data on incidence rates and risk factors for peritonitis episodes vary between centers. In seven Austrian PD units clinical and laboratory data on each peritonitis episode were collected from all patients (n = 726) who performed PD between January 2000 and December 2009. The peritonitis incidence rate was 0.32 episodes/patient-year. In a multivariate analysis the risk of peritonitis was decreased by 57% in patients treated with oral active vitamin D (HR 0.43; 95% CI 0.28–0.64). Renal disease classified as “other or unknown” (HR 1.65; 95% CI 1.08–2.53) and serum albumin <3500 mg/dl (HR 1.49; 95% CI 1.04–2.15) were also associated with an increased risk of peritonitis. Albumin levels <3500 mg/dl (HR 1.89; 95% CI 1.13–3.17), age (HR 1.06 per year; 95% CI 1.03–1.09), and cardiomyopathy (HR 3.01; 95% CI 1.62–5.59) were associated with increased mortality, whereas treatment with oral active vitamin D was associated with a significantly lower risk of death (HR 0.46; 95% CI 0.27–0.81). In this retrospective multi-center study we identified several factors being related to increased risk of peritonitis in PD patients. Treatment with oral active vitamin D was identified as being independently associated with decreased risk of peritonitis, and decreased all-cause mortality in PD patients.     

The Different Association between Serum Ferritin and Mortality in Hemodialysis and Peritoneal Dialysis Patients Using Japanese Nationwide Dialysis Registry

Background/Aims

Monitoring of serum ferritin levels is widely recommended in the management of anemia among patients on dialysis. However, associations between serum ferritin and mortality are unclear and there have been no investigations among patients undergoing peritoneal dialysis (PD).

Methods

Baseline data of 191,902 patients on dialysis (age, 65 ± 13 years; male, 61.1%; median dialysis duration, 62 months) were extracted from a nationwide dialysis registry in Japan at the end of 2007. Outcomes, such as one-year mortality, were then evaluated using the registry at the end of 2008.

Results

Within one year, a total of 15,284 (8.0%) patients had died, including 6,210 (3.2%) cardiovascular and 2,707 (1.4%) infection-related causes. Higher baseline serum ferritin levels were associated with higher mortality rates among patients undergoing hemodialysis (HD). In contrast, there were no clear associations between serum ferritin levels and mortality among PD patients. Multivariate Cox regression analysis of HD patients showed that those in the highest serum ferritin decile group had higher rates of all-cause and cardiovascular mortality than those in the lowest decile group (hazard ratio [HR], 1.54; 95% confidence interval [CI], 1.31–1.81 and HR, 1.44; 95% CI, 1.13–1.84, respectively), whereas associations with infection-related mortality became non-significant (HR, 1.14; 95% CI, 0.79–1.65).

Conclusions

Using Japanese nationwide dialysis registry, higher serum ferritin values were associated with mortality not in PD patients but in HD patients.     

Pneumonia and Mortality Risk in Continuous Ambulatory Peritoneal Dialysis Patients with Diabetic Nephropathy

Background

Although clinical experience suggests that patients with diabetes mellitus are more susceptible to several types of infections, the overall scope of pneumonia in continuous ambulatory peritoneal dialysis (CAPD) patients with diabetic nephropathy (DN) has received little attention.

Methods

This was a prospective observational cohort study in CAPD patients in which prognostic risks of pneumonia were evaluated in DN and non-DN patients by Cox regression analysis. Hazard ratios of pneumonia events, all-cause and pneumonia-related mortality were calculated by Kaplan-Meier curves and the Cox proportional hazards model for DN versus non-DN patients.

Results

A total of 1148 patients (58.6% male, 48.34±15.78 years) had a median follow-up of 23.8 months and a maximum follow-up of 72.0 months. The pneumonia incidence rate of 62.3/1,000 patient-years in CAPD patients with DN was significantly higher than that of 28.5/1,000 patient-years in non-DN patients. On multivariate analysis, independent predictors of pneumonia occurrence in CAPD patients with DN were high body mass index (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.01–1.31; P = 0.037) and low serum albumin level (HR, 0.87; 95% CI, 0.78–0.98; P = 0.014). Older age (HR, 1.63; 95% CI, 1.35–1.96; P<0.001) was an independent risk factor for the presence of pneumonia in non-DN patients. CAPD patients with DN had higher pneumonia-related mortality (HR, 4.424; 95% CI, 1.871–10.461; P<0.001) and all-cause mortality (HR, 2.608; 95% CI, 1.890–3.599; P<0.001) hazards than their non-DN counterparts, even when extensive demographics, comorbidities, and lab adjustments were made.

Conclusions

The pneumonia and all-cause mortality risks were strikingly higher in CAPD patients with DN than in non-DN counterparts, which may warrant further investigation and therapeutic care intensification.     

Perioperative Blood Transfusion Promotes Worse Outcomes of Bladder Cancer after Radical Cystectomy: A Systematic Review and Meta-Analysis

Background

Multiple studies have investigated the effect of perioperative blood transfusion (PBT) for patients with radical cystectomy (RC), but the results have been inconsistent. We conducted a systematic review and meta-analysis to investigate the relationship between PBT and the clinical outcomes of RC patients.

Methods

We searched MEDLINE, EMBASE, the Cochrane library and BIOSIS previews to identify relevant literature for studies that focused on the relationship of PBT and outcomes of patients undergoing RC. A fixed or random effects model was used in this meta-analysis to calculate the pooled hazard ratio (HR) with 95% confidence intervals (CIs).

Results

A total of 7080 patients in 6 studies matched the selection criteria. Aggregation of the data suggested that PBT in patients who underwent RC correlated with increased all-cause mortality, cancer-specific mortality and cancer recurrence. The combined HRs were 1.19 (n = 6 studies, 95% CI: 1.11–1.27, Z = 4.71, P<0.00001), 1.17 (n = 4 studies, 95% CI: 1.06–1.30, Z = 3.06, P = 0.002), 1.14 (n = 3 studies, 95% CI: 1.03–1.27, Z = 2.50, P = 0.01), respectively. The all-cause mortality associated with PBT did not vary by the characteristics of the study, including number of study participants, follow-up period and the median blood transfusion ratio of the study.

Conclusion

Our data showed that PBT significantly increased the risks of all-cause mortality, cancer-specific mortality and cancer recurrence in patients undergoing RC for bladder cancer.     

The Association between Body Mass Index and Mortality in Incident Dialysis Patients

Objectives

To study the body mass index (BMI) trajectory in patients with incident end-stage kidney disease and its association with all-cause mortality.

Methods

This longitudinal cohort study included 17022 adult patients commencing hemodialysis [HD] (n = 10860) or peritoneal dialysis [PD] (n = 6162) between 2001 and 2008 and had ≥6-month follow-up and ≥2 weight measurements, using the Australia and New Zealand Dialysis and Transplant Registry data. The association of time-varying BMI with all-cause mortality was explored using multivariate Cox regression models.

Results

The median follow-up was 2.3 years. There was a non-linear change in the mean BMI (kg/m²) over time, with an initial decrease from 27.6 (95% confidence interval [CI]: 27.5, 27.7) to 26.7 (95% CI: 26.6, 26.9) at 3-month, followed by increments to 27.1 (95% CI: 27, 27.2) at 1-year and 27.2 (95% CI: 26.8, 27.1) at 3-year, and a gradual decrease subsequently. The BMI trajectory was significantly lower in HD patients who died than those who survived, although this pattern was not observed in PD patients. Compared to the reference time-varying BMI category of 25.1–28 kg/m², the mortality risks of both HD and PD patients were greater in all categories of time-varying BMI <25 kg/m². The mortality risks were significantly lower in all categories of time-varying BMI >28.1 kg/m² among HD patients, but only in the category 28.1–31 kg/m² among PD patients.

Conclusions

BMI changed over time in a non-linear fashion in incident dialysis patients. Time-varying measures of BMI were significantly associated with mortality risk in both HD and PD patients.     

Association of healthy lifestyle including a healthy sleep pattern with incident type 2 diabetes mellitus among individuals with hypertension

Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic disease and independently affects the development of cardiovascular (CV) disease. We investigated whether hepatic steatosis and/or fibrosis are associated with the development of incident heart failure (iHF), hospitalized HF (hHF), mortality, and CV death in both the general population and HF patients. We analyzed 778,739 individuals without HF and 7445 patients with pre-existing HF aged 40 to 80 years who underwent a national health check-up from January 2009 to December 2012. The presence of hepatic steatosis and advanced hepatic fibrosis was determined using cutoff values for fatty liver index (FLI) and BARD score. We evaluated the association of FLI or BARD score with the development of iHF, hHF, mortality and CV death using multivariable-adjusted Cox regression models. A total of 28,524 (3.7%) individuals in the general population and 1422 (19.1%) pre-existing HF patients developed iHF and hHF respectively. In the multivariable-adjusted model, participants with an FLI ≥ 60 were at increased risk for iHF (hazard ratio [HR], 95% confidence interval [CI], 1.30, 1.24–1.36), hHF (HR 1.54, 95% CI 1.44–1.66), all-cause mortality (HR 1.62, 95% CI 1.54–1.70), and CV mortality (HR 1.41 95% CI 1.22–1.63) in the general population and hHF (HR 1.26, 95% CI 1.21–1.54) and all-cause mortality (HR 1.54 95% CI 1.24–1.92) in the HF patient group compared with an FLI < 20. Among participants with NAFLD, advanced liver fibrosis was associated with increased risk for iHF, hHF, and all-cause mortality in the general population and all-cause mortality and CV mortality in the HF patient group (all p < 0.05). Hepatic steatosis and/or advanced fibrosis as assessed by FLI and BARD score was significantly associated with the risk of HF and mortality.     

Progression of Aortic Arch Calcification Over 1 Year Is an Independent Predictor of Mortality in Incident Peritoneal Dialysis Patients

Backgrounds and Aims

The presence and progression of vascular calcification have been demonstrated as important risk factors for mortality in dialysis patients. However, since the majority of subjects included in most previous studies were hemodialysis patients, limited information was available in peritoneal dialysis (PD) patients. Therefore, the aim of this study was to investigate the prevalence of aortic arch calcification (AoAC) and prognostic value of AoAC progression in PD patients.

Methods

We prospectively determined AoAC by chest X-ray at PD start and after 12 months, and evaluated the impact of AoAC progression on mortality in 415 incident PD patients.

Results

Of 415 patients, 169 patients (40.7%) had AoAC at baseline with a mean of 18.1±11.2%. The presence of baseline AoAC was an independent predictor of all-cause [Hazard ratio (HR): 2.181, 95% confidence interval (CI): 1.336–3.561, P = 0.002] and cardiovascular mortality (HR: 3.582, 95% CI: 1.577–8.132, P = 0.002). Among 363 patients with follow-up chest X-rays at 12 months after PD start, the proportion of patients with AoAC progression was significantly higher in patients with baseline AoAC (64.2 vs. 5.3%, P<0.001). Moreover, all-cause and cardiovascular death rates were significantly higher in the progression groups than in the non-progression group (P<0.001). Multivariate Cox analysis revealed that AoAC progression was an independent predictor for all-cause (HR: 2.625, 95% CI: 1.150–5.991, P = 0.022) and cardiovascular mortality (HR: 4.008, 95% CI: 1.079–14.890, P = 0.038) in patients with AoAC at baseline.

Conclusions

The presence and progression of AoAC assessed by chest X-ray were independently associated with unfavorable outcomes in incident PD patients. Regular follow-up by chest X-ray could be a simple and useful method to stratify mortality risk in these patients.     

Monocyte-to-albumin ratio as a novel predictor of long-term adverse outcomes in patients after percutaneous coronary intervention

Background: Monocyte count and serum albumin (Alb) have been proven to be involved in the process of systemic inflammation. Therefore, we investigated the prognostic value of monocyte-to-albumin ratio (MAR) in patients who underwent percutaneous coronary intervention (PCI).Methods: We enrolled a total of 3561 patients in the present study from January 2013 to December 2017. They were divided into two groups according to MAR cut-off value (MAR < 0.014, n=2220; MAR ≥ 0.014, n=1119) as evaluated by receiver operating characteristic (ROC) curve. The average follow-up time was 37.59 ± 22.24 months.Results: The two groups differed significantly in the incidences of all-cause mortality (ACM; P<0.001), cardiac mortality (CM; P<0.001), major adverse cardiovascular events (MACEs; P=0.038), and major adverse cardiovascular and cerebrovascular events (MACCEs; P=0.037). Multivariate Cox regression analyses revealed MAR as an independent prognostic factor for ACM and CM. The incidence of ACM increased by 56.5% (hazard ratio [HR] = 1.565; 95% confidence interval [CI], 1.086–2.256; P=0.016) and that of CM increased by 76.3% (HR = 1.763; 95% CI, 1.106–2.810; P=0.017) in patients in the higher-MAR group. Kaplan–Meier survival analysis suggested that patients with higher MAR tended to have an increased accumulated risk of ACM (Log-rank P<0.001) and CM (Log-rank P<0.001).Conclusion: The findings of the present study suggested that MAR was a novel independent predictor of long-term mortality in patients who underwent PCI.     

The Association between Continuity of Care and All-Cause Mortality in Patients with Newly Diagnosed Obstructive Pulmonary Disease: A Population-Based Retrospective Cohort Study, 2005-2012

BackgroundThe disease burden is increasing for chronic obstructive pulmonary disease (COPD) due to increasing of the growth rate of prevalence and mortality. But the empirical researches are a little for COPD that studied the association between continuity of care and death and about predictors effect on mortality.ObjectiveTo investigate the association between continuity of care (COC) and chronic obstructive pulmonary disease (COPD) mortality and to identify other mortality-related factors in COPD patients.MethodsWe conducted a longitudinal, population-based retrospective cohort study in adult patients with COPD from 2002 to 2012 using a nationwide health insurance claims database. The study sample included individuals aged 40 years and over who developed COPD in 2005 and survived until 2006. We performed a Cox proportional hazard regression analysis with COC analyzed as a time-dependent covariate.ResultsOf the 3,090 participants, 60.8% died before the end of study (N = 1,879). The median years of survival for individuals with high COC (COC index≥0.75) was 3.92, and that for patients with low COC (COC index<0.75) was 2.58 in a Kaplan Meier analysis. In a multivariate, time-dependent analysis, low COC was associated with a 22% increased risk of all-cause mortality (HR, 1.22; 95% CI, 1.09–1.36). Not receiving oxygen therapy at home was associated with a 23% increased risk of all-cause mortality (HR, 1.23; 95% CI, 1.01–1.49). Moreover, the risk of all-cause mortality for individuals who admitted one time increased 38% (HR, 1.38; 95% CI, 1.21–1.59), two times was 63% (HR, 1.63; 95% CI, 1.34–1.99) and 3+ times was 96% (HR, 1.96; 95% CI, 1.63–2.36) relative to the reference group (no admission).ConclusionsHigh COC was associated with a decreased risk of all-cause mortality. In addition, home oxygen therapy and number of hospital admissions may predict mortality in patients with COPD.     

Association of Adiponectin with High-Sensitivity C-Reactive Protein and Clinical Outcomes in Peritoneal Dialysis Patients: A 3.5-Year Follow-Up Study

Introduction

Adiponectin (ADPN), one of most abundant fat-derived biologically active substances, plays an important role in anti-atherosclerotic process. There are conflicting results about the impact of ADPN on cardiovascular (CV) outcomes and mortality, particularly in patients undergoing peritoneal dialysis (PD). Moreover, the relationship between ADPN and inflammatory mediators has been seldom explored in this population. Therefore, we examined the relationship between ADPN and longitudinal high-sensitivity C-reactive protein (hs-CRP) changes and investigated whether ADPN or hs-CRP levels could predict CV outcomes and mortality in prevalent PD patients after comprehensive adjustment of possible confounders.

Methods

In this prospective cohort study, 78 PD patients were enrolled and followed from February 2009 to August 2012. During follow-up, CV events and all-cause mortality were recorded.

Results

The mean baseline ADPN value was 29.46±18.01 μg/ml and duration of PD treatment was 37.76±36.96 months. In multiple linear regression analysis, plasma ADPN levels positively correlated with high-density lipoprotein and negatively associated with hs-CRP, body mass index, D4/D0 glucose, triglyceride, and duration of PD treatment. After stratified by genders, the inverse association between baseline ADPN and hs-CRP was more significant in the female group. The hs-CRP levels were followed up annually and remained significantly lower in the high ADPN group in the first 2 years. Patients were then stratified into two groups according to the median ADPN value (23.8 μg/ml). The results of Kaplan-Meier survival analysis demonstrated less CV events and better survival in high ADPN group. On multivariate Cox regression analysis, only ADPN level (HR: 0.93, 95% CI: 0.88–0.98, p = 0.02), age and history of CV diseases were independent risk factors for future CV events. Furthermore, hs-CRP (HR: 1.11, 95% CI:1.001–1.22, p = 0.04) was identified as independent predictor of all-cause mortality.

Conclusions

Serum hs-CRP levels were consistently lower in the high ADPN group during 2-year follow-up. We also demonstrated the importance of ADPN and hs-CRP in predicting CV events and all-cause mortality in PD population during 3.5-year follow-up.     

Angiopoietin-2 as a Prognostic Biomarker of Major Adverse Cardiovascular Events and All-Cause Mortality in Chronic Kidney Disease

Background

Chronic kidney disease (CKD) patients have higher prevalence of major adverse cardiovascular events (MACE) and all-cause mortality. Endothelial damage and dysfunction have been regarded as early portents of MACE in CKD patients. Angiopoietin-2 (Ang-2) impairs endothelial function and promotes aberrant neovascularization. The aim of the study was to assess the relationship between circulating Ang-2 and MACE or all-cause mortality in a CKD cohort.

Methods

A total of 621 pre-dialysis stage 3–5 CKD patients were enrolled from January 2006 to December 2011 and were followed up till October 2014. Plasma Ang-2 was measured in duplicate using commercial enzyme-linked immunosorbent assays (ELISA). Clinical outcomes included MACE or all-cause mortality

Results

Of all patients, 122 (19.8%) reached MACE or all-cause mortality. Seventy-two had MACE, 79 died, and 29 had both MACE and all-cause mortality during the follow-up period of 41.5±28.3 months. Ang-2 quintile was divided at 1405.0, 1730.0, 2160.9, and 2829.9 pg/ml. The adjusted HR of MACE or all-cause mortality for every single higher log Ang-2 was 5.69 (95% CI: 2.00–16.20, P = 0.001). The adjusted HR of MACE or all-cause mortality was 2.48 (95% CI: 1.25–4.90) for patients of quintile 5 compared with those of quintile 1. A longitudinal association between MACE or all-cause mortality and stepwise increases in Ang-2 levels was found (P-trend = 0.008).

Conclusions

Ang-2 is an independent predictor of MACE or all-cause mortality in CKD patients. Additional study is necessary in order to explore the mechanism of the association of Ang-2 with adverse outcomes in patients with CKD.     

Prevalence and Impact on Stroke in Patients Receiving Maintenance Hemodialysis versus Peritoneal Dialysis: A Prospective Observational Study

Background

Patients undergoing maintenance dialysis are at increased risk of stroke, however, less is known about the prevalence and impact on stroke in the patients.

Methods

In this prospective cohort study, 590 patients undergoing hemodialysis (HD; n = 285) or peritoneal dialysis (PD; n = 305) from January 1, 2008 to December 31, 2012 were recruited. Baseline demographic, clinical, and laboratory data were collected. Timeline incidence data were analyzed using a Poisson model. The Cox proportional hazards regression assessed adjusted differences in stroke risk, a multivariate analysis was also performed.

Results

62 strokes occurred during 1258 total patient-years of follow-up. Stroke occurred at a rate of 49.2/1,000 patient-years with a predominance in HD patients compared with PD patients (74.0 vs. 31.8/1,000 patient-years). The cumulative hazard of developing stroke was significantly higher in HD patients (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.15–3.62; p = 0.046) after adjusting for potential confounders. HD patients had an increased risk of ischemic stroke (HR, 2.62; 95% CI, 1.56–4.58; p = 0.002). The risk of hemorrhagic stroke was not significantly different between PD and HD patients. On multivariate Cox analysis, risk factors of stroke in both HD and PD patients were older age, diabetes, and cardiovascular disease. Other independent risk factors of stroke were lower albumin-corrected calcium in HD patients and higher triglycerides in PD patients.

Conclusions

Patients undergoing PD were less likely to develop ischemic stroke than those undergoing HD. Comprehensive control of diabetes, cardiovascular disease, calcium-phosphorus metabolism, and triglyceride levels may be useful preventive strategies for stroke in dialysis patients.     

Arm exercise stress perfusion imaging predicts clinical outcome

Treadmill exercise capacity in resting metabolic equivalents (METs) and stress hemodynamic, electrocardiographic (ECG), and myocardial perfusion imaging (MPI) responses are independently predictive of adverse clinical events. However, limited data exist for arm ergometer stress testing (AXT) in patients who cannot perform leg exercise because of lower extremity disabilities. We sought to determine the extent to which AXT METs, hemodynamic, ECG, and MPI responses to arm exercise add independent incremental value to demographic and clinical variables for prediction of all-cause mortality, myocardial infarction (MI), or late coronary revascularization, individually or as a composite. A prospective cohort of 186 patients aged 64 ± 10 (SD) yr, unable to perform lower extremity exercise, underwent AXT MPI for clinical reasons between 1997 and 2002, and were followed for 62 ± 23 mo, to an endpoint of death or 12/31/2006. Average annual rates were 5.4% for mortality, 2.2% for MI, 2.5% for late coronary revascularization, and 8.0% for combined events. After adjustment for age and clinical variables, AXT METs [P < 0.05; hazard ratio (HR) = 0.59; confidence interval (CI) = 0.35-0.84] and abnormal MPI (P < 0.01; HR = 2.48; CI = 2.15-2.81) were independently predictive of mortality. A positive AXT ECG (P < 0.05; HR = 2.61; CI = 2.13-3.10) was predictive of MI. Death and MI combined were prognosticated by METs (P < 0.05; HR = 0.63; CI = 0.41-0.85), MPI (P < 0.05; HR = 1.77; CI = 1.49-2.05), and a positive AXT ECG (P < 0.05; HR = 1.86; CI = 1.55-2.17). In conclusion, for high risk older patients who cannot perform leg exercise because of lower extremity disabilities, AXT METs are as important as MPI for prediction of mortality alone and death and MI combined, and a positive AXT ECG prognosticates MI alone and death and MI combined.