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.     

Prognostic Value of Obesity on Both Overall Mortality and Cardiovascular Disease in the General Population

Background

Obesity represents an important health problem and its association with cardiovascular risk factors is well-known. The aim of this work was to assess the correlation between obesity and mortality (both, all-cause mortality and the combined variable of all-cause mortality plus the appearance of a non-fatal first cardiovascular event) in a general population sample from the south-east of Spain.

Materials and Methods

This prospective cohort study used stratified and randomized two-stage sampling. Obesity [body mass index (BMI) ≥30 kg/m²] as a predictive variable of mortality and cardiovascular events was assessed after controlling for age, sex, cardiovascular disease history, high blood pressure, diabetes mellitus, hypercholesterolemia, high-density lipoprotein/triglycerides ratio, total cholesterol and smoking with the Cox regression model.

Results

The mean follow-up time of the 1,248 participants was 10.6 years. The incidence of all-cause mortality during this period was 97 deaths for every 10,000 person/years (95% CI: 80–113) and the incidence of all-cause mortality+cardiovascular morbidity was 143 cases for every 10,000 person/years (95% CI: 124–163). A BMI ≥35 kg/m² yielded a hazard ratio for all-cause mortality of 1.94 (95% CI: 1.11–3.42) in comparison to non-obese subjects (BMI <30 kg/m²). For the combination of cardiovascular morbidity plus all-cause mortality, a BMI ≥35 kg/m² had a hazard ratio of 1.84 (95% CI: 1.15–2.93) compared to non-obese subjects.

Conclusions

A BMI ≥35 kg/m² is an important predictor of both overall mortality and of the combination of cardiovascular morbidity plus all-cause mortality.     

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.     

Hyperphosphatemia Is an Independent Risk Factor for Mortality in Critically Ill Patients: Results from a Cross-Sectional Study

Background

Phosphate imbalances or disorders have a high risk of morbidity and mortality in patients with chronic kidney disease. It is unknown if this finding extends to mortality in patients presenting at an emergency room with or without normal kidney function.

Methods and Patients

This cross sectional analysis included all emergency room patients between 2010 and 2011 at the Inselspital Bern, Switzerland. A multivariable cox regression model was applied to assess the association between phosphate levels and in-hospital mortality up to 28 days.

Results

22,239 subjects were screened for the study. Plasma phosphate concentrations were measured in 2,390 patients on hospital admission and were included in the analysis. 3.5% of the 480 patients with hypophosphatemia and 10.7% of the 215 patients with hyperphosphatemia died. In univariate analysis, phosphate levels were associated with mortality, age, diuretic therapy and kidney function (all p<0.001). In a multivariate Cox regression model, hyperphosphatemia (OR 3.29, p<0.001) was a strong independent risk factor for mortality. Hypophosphatemia was not associated with mortality (p>0.05).

Conclusion

Hyperphosphatemia is associated with 28-day in-hospital mortality in an unselected cohort of patients presenting in an emergency room.     

Body Mass Index,High-Sensitivity C-Reactive Protein and Mortality in Chinese with Coronary Artery Disease

Background

To investigate single and joint associations of body mass index (BMI) and serum high-sensitivity C-reactive protein (hsCRP) with death.

Methods

The study included 1871 coronary artery disease (CAD) patients aged 40–85 year-old recruited from 2008 to 2011. Cox regression models were used to estimate the association of BMI and hsCRP with mortality. The data was analyzed in 2014.

Results

During 3.1 years follow-up, 141 deaths were recorded, 110 died of cardiovascular disease (CVD). After adjustment of major CVD risk factors, there was a J-shaped association between BMI and all-cause and CVD mortality, and a positive association between hsCRP and mortality. The J-shaped association of BMI with mortality was present among patients who never smoked or with elevated hsCRP (≥3.0 mg/L). Compared with overweight (BMI 24–27.9 kg/m²) patients with normal hsCRP (<3.0 mg/L), obese patients (BMI≥28 kg/m²) with elevated hsCRP had a 3.41-fold risk of all-cause mortality (95% CI 1.49–7.80) and a 3.50-fold risk of CVD mortality (1.40–8.75), lean patients (BMI<24 kg/m²) with elevated hsCRP concentration had a 2.54-fold risk of all-cause mortality (1.36–4.74) and a 2.36-fold risk of CVD mortality (1.19–4.70).

Conclusions

The association pattern between baseline BMI and mortality changed among different baseline hsCRP concentrations, indicating that low-grade inflammation may be related to BMI and secondary prognosis of CAD.     

Association between Body Mass Index,Asymmetric Dimethylarginine and Risk of Cardiovascular Events and Mortality in Norwegian Patients with Suspected Stable Angina Pectoris

Background

Asymmetric dimethylarginine (ADMA) is associated with increased risk of atherosclerotic cardiovascular disease and mortality through inhibition of nitrogen oxide (NO) synthesis. As positive correlations between serum concentrations of NO and body mass index (BMI) have been observed, we aimed to explore whether the potential associations between plasma ADMA levels and the risk of acute myocardial infarction (AMI) and mortality were modified by BMI.

Methods

Multivariable Cox proportional hazard models were used to estimate the hazard ratios (HR) for AMI, cardiovascular death and all-cause mortality according to baseline plasma ADMA levels in 4122 patients with suspected stable angina pectoris. Analyses were subsequently repeated in patients with BMI below (low BMI) or above (high BMI) median.

Results

A total of 2982 patients (72%) were men. Median (range) age, plasma ADMA level and BMI were 62 (21–88) years, 0.54 (0.10–1.25) μmol/L and 26.3 (18.5–54.3) kg/m², respectively. During a mean (standard deviation) follow-up time of 4.7 (1.4) years, 337 (8%) patients suffered from an AMI, 300 (7%) died, whereof 165 (55%) due to cardiovascular disease. Each 0.1 μmol/L increment in plasma ADMA level was associated with an increased risk of AMI (HR (95% CI) 1.21 (1.08, 1.35) and cardiovascular death 1.30 (1.13, 1.49) in participants with low BMI only. Interactions were significant for AMI (p = 0.04) and CV death (p = 0.03). BMI did not modify the association between plasma ADMA levels and all-cause mortality.

Conclusion

Plasma ADMA levels were associated with risk of AMI and cardiovascular death among patients with low BMI only.     

Inflammatory Cytokines in General and Central Obesity and Modulating Effects of Physical Activity

Context

Chronic systemic inflammation in obesity originates from local immune responses in visceral adipose tissue. However, assessment of a broad range of inflammation-mediating cytokines and their relationship to physical activity and adipometrics has scarcely been reported to date.

Objective

To characterize the profile of a broad range of pro- and anti-inflammatory cytokines and the impact of physical activity and energy expenditure in individuals with general obesity, central obesity, and non-obese subjects.

Design, Setting, and Participants

A cross-sectional study comprising 117 obese patients (body mass index (BMI) ≥ 30) and 83 non-obese community-based volunteers.

Main Outcomes Measures

Serum levels of interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12, IL-13, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon (IFN)-γ and tumor necrosis factor (TNF)-α were measured. Physical activity and energy expenditure (MET) were assessed with actigraphy. Adipometrics comprised BMI, weight, abdominal-, waist- and hip-circumference, waist to hip ratio (WHR), and waist-to-height-ratio (WHtR).

Results

General obesity was associated with significantly elevated levels of IL-5, IL-10, IL-12, IL-13, IFN-γ and TNF-α, central obesity with significantly elevated IL-5, IL-10, IL-12, IL-13 and IFN-γ-levels. In participants with general obesity, levels of IL-4, IL-10 and IL-13 were significantly elevated in participants with low physical activity, even when controlled for BMI which was negatively associated with physical acitivity. Cytokines significantly correlated with adipometrics, particularly in obese participants.

Conclusions

Results confirm up-regulation of certain pro- and anti-inflammatory cytokines in obesity. In obese subjects, physical activity may lower levels and thus reduce pro-inflammatory effects of cytokines that may link obesity, insulin resistance and diabetes.     

Free Levels of Selected Organic Solutes and Cardiovascular Morbidity and Mortality in Hemodialysis Patients: Results from the Retained Organic Solutes and Clinical Outcomes (ROSCO) Investigators

Background and Objectives

Numerous substances accumulate in the body in uremia but those contributing to cardiovascular morbidity and mortality in dialysis patients are still undefined. We examined the association of baseline free levels of four organic solutes that are secreted in the native kidney — p-cresol sulfate, indoxyl sulfate, hippurate and phenylacetylglutamine — with outcomes in hemodialysis patients.

Design, Setting, Participants and Measurements

We measured these solutes in stored specimens from 394 participants of a US national prospective cohort study of incident dialysis patients. We examined the relation of each solute and a combined solute index to cardiovascular mortality and morbidity (first cardiovascular event) using Cox proportional hazards regression adjusted for demographics, comorbidities, clinical factors and laboratory tests including Kt/V_UREA.

Results

Mean age of the patients was 57 years, 65% were white and 55% were male. In fully adjusted models, a higher p-cresol sulfate level was associated with a greater risk (HR per SD increase; 95% CI) of cardiovascular mortality (1.62; 1.17–2.25; p=0.004) and first cardiovascular event (1.60; 1.23–2.08; p<0.001). A higher phenylacetylglutamine level was associated with a greater risk of first cardiovascular event (1.37; 1.18–1.58; p<0.001). Patients in the highest quintile of the combined solute index had a 96% greater risk of cardiovascular mortality (1.96; 1.05–3.68; p=0.04) and 62% greater risk of first cardiovascular event (1.62; 1.12–2.35; p=0.01) compared with patients in the lowest quintile. Results were robust in sensitivity analyses.

Conclusions

Free levels of uremic solutes that are secreted by the native kidney are associated with a higher risk of cardiovascular morbidity and mortality in incident hemodialysis patients.     

Increased Risks of Mortality and Atherosclerotic Complications in Incident Hemodialysis Patients Subsequently with Bone Fractures: A Nationwide Case-Matched Cohort Study

Background

Hemodialysis (HD) patients with bone fractures have an increased risk for death. However, the risks for mortality and atherosclerotic complications in incident HD patients subsequently with bone fractures are unknown.

Methods

Data derived from the Taiwan National Health Institute Research Database between January 1997 and December 2008 was analyzed. The enrolled patients included 3,008 incident HD patients subsequently with a single long bone fracture (LB Fx) and 2,070 incident HD patients subsequently with a single non-long bone fracture (NLB Fx). These patients were matched (1:5 ratio) for age, sex, and same duration of HD with incident HD patients who had no fractures and outcomes were measured over a 3-year follow-up.

Results

After demographic and co-morbidity adjustment, LB Fx increased the risk for overall mortality (HR = 1.59, p < 0.001) and stroke (HR = 1.09, p = 0.028) in incident HD patients. NLB Fx increased the risk for overall mortality (HR = 1.52, p < 0.001), stroke (HR = 1.19, p < 0.001), coronary artery disease (CAD), (HR = 1.13, p = 0.003), and peripheral arterial occlusive disease (PAOD), (HR = 1.41, p < 0.001) in incident HD patients. Moreover, incident patients subsequently with NLB Fx had significantly higher risks of CAD and PAOD than those subsequently with LB Fx.

Conclusions

The rates of mortality and stroke were significantly higher in incident HD patients subsequently with bone fractures than in matched patients without bone fractures. Incident HD patients subsequently with NLB Fx had significantly higher risks of CAD and PAOD than those subsequently with LB Fx and without bone fractures. Thus, incident HD patients subsequently with bone fractures should be closely followed for a higher mortality and possible development of atherosclerotic complications.     

Serum Oxidized Albumin and Cardiovascular Mortality in Normoalbuminemic Hemodialysis Patients: A Cohort Study

Background

Substantial evidence suggests that increased oxidative stress in hemodialysis (HD) patients may contribute to cardiovascular complications. Oxidative modifications of human serum albumin (HSA), the largest thiol pool in plasma, alter its biological properties and may affect its antioxidant potential in HD patients.

Methods

We conducted a long-term follow-up study in a cohort of normoalbuminemic HD patients to examine the impact of redox state of serum albumin on patients’ survival by measuring the human nonmercaptoalbumin (HNA) fraction of HSA.

Results

After adjusting for potential demographic, anthropometric, and clinical confounders, a positive association of HNA level with the risk of death from cardiovascular disease (CVD) and all-cause mortality was observed in normoalbuminemic HD patients. Using stratified analysis, we found a stronger association between HNA level and the risk of death from CVD and all-cause mortality in patients with pre-existing CVD.

Conclusions

Serum HNA level is a positive predictor of mortality in normoalbuminemic HD patients, especially among those with pre-existing CVD. Increased oxidative stress resulting from biological changes in serum albumin levels could contribute to accelerated atherosclerosis and the development of cardiovascular disease in HD patients.     

Care Needs and Clinical Outcomes of Older People with Dementia: A Population-Based Propensity Score-Matched Cohort Study

Objective

To explore the healthcare resource utilization, psychotropic drug use and mortality of older people with dementia.

Design

A nationwide propensity score-matched cohort study.

Setting

National Health Insurance Research database.

Participants

A total of 32,649 elderly people with dementia and their propensity-score matched controls (n=32,649).

Measurements

Outpatient visits, inpatient care, psychotropic drug use, in-hospital mortality and all-cause mortality at 90 and 365 days.

Results

Compared to the non-dementia group, a higher proportion of patients with dementia used inpatient services (1 year after index date: 20.91% vs. 9.55%), and the dementia group had more outpatient visits (median [standard deviation]: 7.00 [8.87] vs. 3.00 [8.30]). Furthermore, dementia cases with acute admission had the highest psychotropic drug utilization both at baseline and at the post-index dates (difference-in-differences: all <0.001). Dementia was associated with an increased risk of all-cause mortality (90 days, Odds ratio (OR)=1.85 [95%CI 1.67-2.05], p<0.001; 365 days, OR=1.59 [1.50-1.69], p<0.001) and in-hospital mortality (90 days, OR=1.97 [1.71-2.27], p<0.001; 365 days, OR=1.82 [1.61-2.05], p<0.001) compared to matched controls.

Conclusions

When older people with dementia are admitted for acute illnesses, they may increase their use of psychotropic agents and their risk of death, particularly in-hospital mortality.     

Annual Hospital Volume of High Dose Interleukin-2 and Inpatient Mortality in Melanoma and Renal Cell Carcinoma Patients

Background

Immunotherapy using high dose interleukin-2 (HD IL2) in patients with renal cell carcinoma (RCC) and melanoma is associated with severe toxicities. The association between annual hospital volume of HD IL2 and inpatient mortality is not well studied. In this study we aim to quantify the impact of annual hospital volume of HD IL2 on inpatient mortality using National Inpatient Sample (NIS) data.

Methods

We did a cross-sectional study using NIS, one of the largest inpatient datasets in United States, from 2003 to 2011. Patients with melanoma and RCC receiving HD IL2 were identified by ICD9 procedure code 00.15. The primary outcome was inpatient mortality. Using Joinpoint regression, which detects change in trend of inpatient mortality with change in annual volume, the hospitals were classified in three volume categories (low: 1–40, medium: 41–120, high: >120). Multivariate logistic regression was used to identify predictors of inpatient mortality controlling for confounders.

Results

From 2003 to 2011, 29,532 patients with RCC or melanoma who received HD IL2 were identified, and 124 died during the hospitalization (0.4%). The hospitals with low, medium and high annual volume had significant difference in inpatient mortality (0.83%, 0.29% and 0.13% respectively, p = 0.0003). On multivariate analysis, low volume hospitals were associated with significantly higher odds of inpatient mortality (OR 6.1, 95% CI 1.6–23.2, p = 0.003) as compared to high volume hospitals. Additionally, the hospitals with annual volume of 1–20 had even higher rates (1.31% vs. 0.13%, p<0.0001) and multivariate odds (OR 8.9, 95% CI 2.4–33.2, p = 0.0006) of inpatient mortality as compared to high volume hospitals.

Conclusions

Lower annual hospital volume of HD IL2 is associated with worse outcomes. Annual hospital volume of 1–40 and 1–20 treatments per year is associated with 6 and 9 times higher odds of inpatient mortality respectively as compared to high volume hospitals. Our findings provide preliminary evidence for a volume-outcome relationship for RCC and melanoma patients undergoing HD IL2 treatment. They support future volume-outcome analyses in relation to other anti-cancer therapies that require special training and expertise.     

Risk Score to Predict 1-Year Mortality after Haemodialysis Initiation in Patients with Stage 5 Chronic Kidney Disease under Predialysis Nephrology Care

Background

Few risk scores are available for predicting mortality in chronic kidney disease (CKD) patients undergoing predialysis nephrology care. Here, we developed a risk score using predialysis nephrology practice data to predict 1-year mortality following the initiation of haemodialysis (HD) for CKD patients.

Methods

This was a multicenter cohort study involving CKD patients who started HD between April 2006 and March 2011 at 21 institutions with nephrology care services. Patients who had not received predialysis nephrology care at an estimated glomerular filtration rate (eGFR) of approximately 10 mL/min per 1.73 m² were excluded. Twenty-nine candidate predictors were selected, and the final model for 1-year mortality was developed via multivariate logistic regression and was internally validated by a bootstrapping technique.

Results

A total of 688 patients were enrolled, and 62 (9.0%) patients died within one year of HD initiation. The following variables were retained in the final model: eGFR, serum albumin, calcium, Charlson Comorbidity Index excluding diabetes and renal disease (modified CCI), performance status (PS), and usage of erythropoiesis-stimulating agent (ESA). Their β-coefficients were transformed into integer scores: three points were assigned to modified CCI≥3 and PS 3–4; two to calcium>8.5 mg/dL, modified CCI 1–2, and no use of ESA; and one to albumin<3.5 g/dL, eGFR>7 mL/min per 1.73 m², and PS 1–2. Predicted 1-year mortality risk was 2.5% (score 0–4), 5.5% (score 5–6), 15.2% (score 7–8), and 28.9% (score 9–12). The area under the receiver operating characteristic curve was 0.83 (95% confidence interval, 0.79–0.89).

Conclusions

We developed a simple 6-item risk score predicting 1-year mortality after the initiation of HD that might help nephrologists make a shared decision with patients and families regarding the initiation of HD.     

Precedent Fluctuation of Serum hs-CRP to Albumin Ratios and Mortality Risk of Clinically Stable Hemodialysis Patients

Background

A high sensitivity C-reactive protein to albumin ratio (hs-CRP/Alb) predicts mortality risk in patients with acute kidney injury. However, it varies dynamically. This study was conducted to evaluate whether a variation of this marker was associated with long-term outcome in clinically stable hemodialysis (HD) patients.

Methods

hs-CRP/Alb was checked bimonthly in 284 clinically stable HD outpatients throughout all of 2008. Based on the “slope” of trend equation derived from 5–6 hs-CRP/alb ratios for each patient, the total number of patients was divided into quartiles—Group 1: β≦ −0.13, n = 71; group 2: β>-0.13≦0.003; n = 71, group 3: β>0.003≦0.20; and group 4: β>0.20, n = 71. The observation period was from January 1, 2009 to August 31, 2012.

Results

Group 1+4 showed a worse long-term survival (p = 0.04) and a longer 5-year hospitalization stay than Group 2+3 (38.7±44.4 vs. 16.7±22.4 days, p<0.001). Group 1+4 were associated with older age (OR = 1.03, 95% CI = 1.01–1.05) and a high prevalence of congestive heart failure (OR = 2.02, 95% CI = 1.00–4.11). Standard deviation (SD) of hs-CRP/Alb was associated with male sex (β = 0.17, p = 0.003), higher Davies co-morbidity score (β = 0.16, p = 0.03), and baseline hs-CRP (β = 0.39, p<0.001). Patients with lower baseline and stable trend of hs-CRP/Alb had a better prognosis. By multivariate Cox proportional methods, SD of hs-CRP/alb (HR: 1.05, 95% CI: 1.01–1.08) rather than baseline hs-CRP/Alb was an independent predictive factor for long-term mortality after adjusting for sex and HD vintage.

Conclusion

Clinically stable HD patients with a fluctuating variation of hs-CRP/Alb are characterized by old age, and more co-morbidity, and they tend to have longer subsequent hospitalization stay and higher mortality risk.     

Weight Loss and Decrease of Body Mass Index during Allogeneic Stem Cell Transplantation Are Common Events with Limited Clinical Impact

Purpose

Weight loss in cancer patients has been attributed with significant morbidity and mortality. During allogeneic stem cell transplantation (SCT), oral nutrition is often hampered and hence total parenteral nutrition (TPN) is necessary. We therefore investigated the course of weight during stem cell transplantation and the clinical consequences of weight change.

Methods

180 consecutive patients who received allogeneic SCT between January 2010 and December 2011 at our center were analyzed for weight loss, laboratory and clinical parameters.

Results

During SCT, a median decrease of 6.6% of body mass index (BMI) was observed for the whole population (from 25.3 at admission to 23.6 at discharge), and a 1.6fold increase of malnutrition despite use of TPN (28.3% to 45.0%). 55.6% of patients experienced a significant weight loss of ≥5% with a median decrease of 9.2% in BMI. Serum levels of albumin, total protein and cholesterol rapidly decreased during conditioning therapy. After a median of 2.4 years, the median BMI was still only 23.4 (not different from discharge). However, we did not observe a meaningful difference in side effects and survival between patients that did or did not lose weight.

Conclusion

Weight loss is commonly observed during allogeneic SCT despite TPN, but the clinical consequences thereof seem limited: we observed no significant impact on patients with a decrease ≥ 5% in BMI on transplant outcome, side effects or survival.     

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.     

Hyponatremia Predicts New-Onset Cardiovascular Events in Peritoneal Dialysis Patients

Background and Aim

Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients on peritoneal dialysis (PD). Hyponatremia was recently shown to be a modifiable factor that is strongly associated with increased mortality in PD patients. However, the clinical impact of hyponatremia on CV outcomes in these patients is unclear.

Methods

To determine whether a low serum sodium level predicts the development of CV disease, we carried out a prospective observational study of 441 incident patients who started PD between January 2000 and December 2005. Time-averaged serum sodium (TA-Na) levels were determined to investigate the ability of hyponatremia to predict newly developed CV events in these patients.

Results

During a mean follow-up of 43.2 months, 106 (24.0%) patients developed new CV events. The cumulative incidence of new-onset CV events after the initiation of PD was significantly higher in patients with TA-Na levels ≤ 138 mEq/L than in those with a TA-Na > 138 mEq/L. After adjustment for multiple potentially confounding covariates, an increase in TA-Na level was found to be associated with a significantly lower risk of CV events (subdistribution hazard ratio per 1 mEq/L increase, 0.90; 95% confidence interval, 0.83–0.96; p = 0.003). Patients with a TA-Na ≤ 138 mEq/L had a 2.31-fold higher risk of suffering a CV event.

Conclusions

These results provide evidence of a clear association between low serum sodium and new-onset CV events after dialysis initiation in PD patients. Whether the correction of hyponatremia for this indication provides additional protection for the development of CV disease in these patients remains to be addressed in interventional studies.     

Body Mass Index,Mortality, and Gender Difference in Advanced Chronic Kidney Disease

Background and Aim

A higher body mass index (BMI) appears to be reversely associated with mortality in dialysis patients. Moreover, although women have better survival in chronic kidney disease (CKD), this survival advantage is cancelled in dialysis. The association between BMI and mortality and the gender difference remain controversial in advanced CKD.

Methods

This study enrolled 3,320 patients (1,938 men and 1,382 women) from southern Taiwan who had CKD stages 3–5 with a BMI of 15.0–35.0 kg/m².

Results

During a median 2.9-year follow-up, there were 328 (16.9%) all-cause mortality and 319 (16.5%) cardiovascular (CV) events and death in male patients, 213 (15.4%) all-cause mortality and 224 (16.2%) CV events and death in female patients. Compared with the reference BMI of 27.6–30.0 kg/m² in an adjusted Cox model, lower-BMI groups in men, BMI 15.0–20.0 kg/m² and 20.1–22.5 kg/m², were associated with higher risks of all-cause mortality: hazard ratios (HRs) 3.19 (95% confidence interval [CI], 1.97–5.18) and 2.01 (95% CI, 1.29–3.14), respectively. Higher-BMI group in men, BMI 30.1–35.0 kg/m², was associated with a higher risk of all-cause mortality: HR 1.72 (95% CI, 1.02–2.96). Likewise, lower- and higher-BMI groups in men were associated with a higher risk of CV events and death. In women, these associations between BMI and poor outcomes were not observed.

Conclusions

In advanced CKD, there was a reverse J-shaped association between BMI and all-cause mortality, and a U-shaped association between BMI and CV outcomes in men. Neutral associations between BMI and poor outcomes were detected in women. Gender could modify the effect of BMI on mortality in patients with CKD.     

Combining Serum Cystatin C with Total Bilirubin Improves Short-Term Mortality Prediction in Patients with HBV-Related Acute-On-Chronic Liver Failure

Background & Aims

HBV-related acute-on-chronic liver failure (HBV-ACLF) is a severe liver disease which results in a high mortality in China. To early predict the prognosis of the patients may prevent the complications and improve the survival. This study was aimed to develop a new prognostic index to estimate the survival related to HBV-ACLF.

Methods

Consecutive patients with HBV-ACLF were included in a prospective observational study. Serum Cystatin C concentrations were measured by using the particle-enhanced immunonephelometry assay. All of the patients were followed for at least 3 months. Cox regression analysis was carried out to identify which factors were predictive of mortality. The area under the receiver operating characteristic curve (AUC) was used to evaluate the efficacy of the variates for early predicting mortality.

Results

Seventy-two patients with HBV-ACLF were recruited between January 2012 and January 2013. Thirty patients died (41.7%) during 3-months followed up. Cox multivariate regression analysis identified serum cystatin C (CysC) and total bilirubin (TBil) were independent factors significantly (P < 0.01) associated with survival. Our results further showed that new prognostic index (PI) combining serum CysC with TBil was a good indicator for predicting the mortality of patients with HBV-ACLF. Specifically, the PI had a higher accuracy than the CTP, MELD, or MELD-Na scoring for early prediction short-term survival of HBV-ACLF patients with normal levels of serum creatinine (Cr). The survival rate in low risk group (PI < 3.91) was 94.3%, which was markedly higher than those in the high-risk group (PI ≥ 3.91) (17.4%, P < 0.001).

Conclusion

We developed a new prognostic index combining serum CysC with TBil which early predicted the short-term mortality of HBV-ACLF patients.     

Predictive Power of a Body Shape Index for Development of Diabetes,Hypertension, and Dyslipidemia in Japanese Adults: A Retrospective Cohort Study

Background/Objectives

Recently, a body shape index (ABSI) was reported to predict all-cause mortality independently of body mass index (BMI) in Americans. This study aimed to evaluate whether ABSI is applicable to Japanese adults as a predictor for development of diabetes, hypertension, and dyslipidemia.

Subjects/Methods

We evaluated the predictive power of ABSI in a retrospective cohort study using annual health examination data from Chiba City Hall in Japan, for the period 2008 to 2012. Subjects included 37,581 without diabetes, 23,090 without hypertension, and 20,776 without dyslipidemia at baseline who were monitored for disease incidence for 4 years. We examined the associations of standardized ABSI, BMI, and waist circumference (WC) at baseline with disease incidence by logistic regression analyses. Furthermore, we conducted a case-matched study using the propensity score matching method.

Results

Elevated BMI, WC, and ABSI increased the risks of diabetes and dyslipidemia [BMI-diabetes: odds ratio (OR) = 1.26, 95% confidence interval (95%CI) = 1.20−1.32; BMI-dyslipidemia: OR = 1.15, 95%CI = 1.12−1.19; WC-diabetes: OR = 1.24, 95%CI = 1.18−1.31; WC-dyslipidemia: OR = 1.15, 95%CI = 1.11−1.19; ABSI-diabetes: OR = 1.06, 95%CI = 1.01−1.11; ABSI-dyslipidemia: OR = 1.04, 95%CI = 1.01−1.07]. Elevated BMI and WC, but not higher ABSI, also increased the risk of hypertension [BMI: OR = 1.32, 95%CI = 1.27−1.37; WC: OR = 1.22, 95%CI = 1.18−1.26; ABSI: OR = 1.00, 95%CI = 0.97−1.02]. Areas under the curve (AUCs) in regression models with ABSI were significantly smaller than in models with BMI or WC for all three diseases. In case-matched subgroups, the power of ABSI was weaker than that of BMI and WC for predicting the incidence of diabetes, hypertension, and dyslipidemia.

Conclusions

Compared with BMI or WC, ABSI was not a better predictor of diabetes, hypertension, and dyslipidemia in Japanese adults.