Plasma Ghrelin Levels Are Associated with Coronary Microvascular and Endothelial Dysfunction in Peritoneal Dialysis Patients

Cardiovascular (CV) disease is the main cause of death in peritoneal dialysis (PD) patients, and endothelial dysfunction (ED) is an early sign of vascular pathology. Ghrelin, a gastric peptide with CV actions, has been shown to inhibit proatherogenic changes in experimental models. However, another peptide hormone, leptin, may mediate deleterious effects on the CV system. The aim of this study is to evaluate the relationship between plasma ghrelin and leptin levels, and their association with coronary microvascular and endothelial functions in PD patients. Twenty-four (14 females and 10 males; mean age 44 ± 12 yr) nondiabetic PD patients, between 18 and 70 years of age, were enrolled. In addition to demographic, clinical, and laboratory parameters, plasma concentrations of ghrelin and leptin were evaluated. Endothelial functions of the coronary arteries were determined by coronary flow reserve (CFR) measurement using transthoracic Doppler echocardiography (TTDE). A CFR value of < 2 was used as an evidence for ED. When the study group was divided according to CFR measurements as CFR < 2 and ≥ 2, there were no significant differences considering age, gender, etiology of renal disease, body mass index (BMI), duration of dialysis, PD modality, PD solution type, history of peritonitis, mean arterial pressure, ejection fraction, and biochemical parameters between the two subgroups. Plasma ghrelin levels (129.4 ± 82.1 pg/mL) in patients with CFR ≥ 2 were significantly higher than those in patients with CFR< 2 (63.3 ± 35.8 pg/mL) (p = 0.03). However, no significant differences in plasma leptin levels were found between these groups [31.39 ± 37.81 ng/mL vs. 63.95 ± 72.83 ng/mL (p = 0.28)]. No correlation existed between plasma ghrelin levels and age, BMI, duration of dialysis, mean arterial pressure, ejection fraction, plasma leptin levels, and biochemical parameters. Decreased plasma ghrelin levels may contribute to the development of atherosclerosis in PD patients by causing ED.     

Reduced Plasma Zinc Levels,Lipid Peroxidation,and Inflammation Biomarkers Levels in Hemodialysis Patients: Implications to Cardiovascular Mortality

Despite the fact that low plasma zinc (Zn) levels play important roles in the oxidative stress, the relationships between lipid peroxidation and inflammation biomarkers with low plasma Zn levels have not been investigated in chronic kidney disease (CKD) patients. The aim of this study was to evaluate the Zn plasma levels, electronegative LDL [LDL(–)] levels, and inflammation markers as predictors of cardiovascular (CV) mortality in hemodialysis (HD) patients. Forty-five HD patients (28 men, 54.2 ± 12.7 years, 62.2 ± 51.4 months on dialysis and BMI 24.3 ± 4.1 kg/m²) were studied and compared to 20 healthy individuals (9 men, 51.6 ± 15.6 years, BMI 25.2 ± 3.9 kg/m²) and followed for 24 months to investigate the risks for CV mortality. LDL(–) levels were measured by ELISA, plasma Zn levels by atomic absorption spectrophotometry, C-reactive protein (CRP) level by immunoturbidimetric method, and tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and plasminogen activator inhibitor-1 (PAI-1) levels by a multiplex assay kit. HD patients presented low plasma Zn levels (54.9 ± 16.1 μg/dL) and high-LDL(–) (0.18 ± 0.12 U/L) and TNF-α (5.5 ± 2.2 pg/mL) levels when compared to healthy subjects (78.8 ± 9.4μ g/dL, 0.10 ± 0.08U/L, 2.4 ± 1.1 pg/mL, respectively, p < 0.05). Zn plasma levels were negatively correlated to TNF-α (r = –0.49; p = 0.0001) and LDL(–) (r = –0.33; p = 0.008). During the 2 years, 24.4% of the patients died, all due to CV disease. Analysis by the Cox model showed that high CRP, TNF-α, IL-6 levels, and long duration of HD were significant predictors of mortality. In conclusion, reduced Zn levels were associated with lipid peroxidation and inflammation, and we confirm here in a Brazilian cohort of HD patients that inflammation markers are strong predictors of CV death.     

Intraindividual Interleukin-6 Variations on the Cardiovascular Prognosis of Patients with Chronic Renal Disease

In chronic kidney disease (CKD) patients on dialysis, plasma interleukin (IL)-6 levels predict mortality better than other markers. Impact of intraindividual changes of inflammatory markers on cardiovascular (CV) events in CKD patients is unknown. The aim of this study is to demonstrate the relation between CV outcomes and variations of C-reactive protein (CRP), IL-6, IL-1β, and tumor necrosis factor (TNF)-α in CKD. Ninety patients (mean age: 68.5 ± 12.8 years) at different stages (1–4) of CKD were evaluated. Serum CRP, IL-6, IL-1β, and TNF-α were measured basally and after taking statins or angiotensin II receptor blockers. Three patterns were defined for each marker (baseline, mean of two measurements, and variation of the marker: increase or decrease after 6 months). During follow-up (mean time: 72.7 ± 19.8 months), 14 patients died, 11 were included on dialysis program, and 29 suffered a CV event. Patients with persistently elevated IL-6 values had higher risk to develop CV events [OR = 1.21 (1.11–1.32), p = 0.001]. Mean of two measurements of IL-6 was a better predictor for events than a single measurement of IL-6, CRP, TNF-α, and IL-1β. A mean of two determinations of plasma IL-6 greater than 6 pg/mL and previous peripheral vascular disease was related to an increased risk for CV events [2.34 (1.05–5.22), p = 0.037 and 2.95 (1.27–6.93), p = 0.011, respectively] in an adjusted Cox regression model. IL-6 is a better inflammatory marker than CRP, TNF-α, and IL1β at predicting CV events in CKD nondialysis patients. Mean of two measurements is better than simple determinations at predicting CV outcome.     

Clinical characteristics of sepsis-induced acute kidney injury in patients undergoing continuous renal replacement therapy

Objective: The aim of this study was to investigate the clinical characteristics of sepsis-induced acute kidney injury (AKI) in patients undergoing continuous renal replacement therapy (CRRT).

Methods: From 2011 to 2015, we enrolled 340 patients who were treated with CRRT for sepsis at the Presbyterian Medical Center. In all patients, CRRT was performed using the PRISMA platform. We divided these patients into two groups (survivors and non-survivors) according to the 28-day all-cause mortality. We compared clinical characteristics and analyzed the predictors of mortality.

Results: The 28-day all-cause mortality was 62%. Survivors were younger than non-survivors and had higher platelet counts (178?±?101?×?10³/mL vs. 134?±?84?×?10³/mL, p?p?p?p?0.05?mL/kg/h (66% vs. 86%, p?=?.001) in the first day. In a multivariate logistic regression analysis, age, platelet count, RDW score, APACHE II score, serum creatinine level, and a urine output of <0.05?mL/kg/h the first day were prognostic factors for the 28-day all-cause mortality.

Conclusion: Age, platelet count, APACHE II score, RDW score, serum creatinine level, and urine output the first day are useful predictors for the 28-day all-cause mortality in sepsis patients requiring CRRT.     

High mobility group box 1 and tumor growth factor β: useful biomarkers in pediatric patients receiving peritoneal dialysis

Background: Peritonitis, the most important limitation of peritoneal dialysis (PD), could be detected by biomarkers in dialysate effluent, representing a noninvasive method to indirectly assess the peritoneum status. The aim of our study was to test high mobility group box 1 (HMGB1) in PD patients, evaluating its role as precocious marker of peritoneum damage during peritonitis. Transforming growth factor (TGF)-β was correlated with peritoneal transport characteristics.

Methods: Six patients, treated by ambulatory PD, were enrolled. Samples were collected at the onset of peritonitis (T1) and every day until its resolution (T-end). Serum (s) and peritoneal (p) white blood cell (WBC) count was also evaluated. Peritoneal Equilibration Test evaluated the filter activity of peritoneum.

Results: In patients with acute peritonitis, the highest serum and peritoneal HMGB1 values (64?±?3.6 and 70?±?5.3?ng/mL, respectively) were assessed, with a progressive decrease of their levels at the resolution time (T-end: sHMGB1:36?±?2.5; pHMGB1:30.5?±?7.0?ng/mL). While no differences of sWBC and pWBC were observed between baseline and T-end values, pHMGB1 levels remained higher at T-end than those observed at T0 (pHMGB1:30.5?±?7.0 versus 6.9?±?3.6; p?p?=?0.01). An inverse correlation was found between TGF-β levels and dialysate/plasmatic creatinine values (r = ?0.83; p?=?0.03).

Conclusion: HMGB1 represents a useful biomarker for peritoneum evaluation in PD patients. A prognostic role of this alarmin, as a marker of response to therapy, could be hypothesized. TGF-β could predict the peritoneal transport status and dialysis technique adequacy.     

High soluble vascular cell adhesion molecule-1 concentrations predict long-term mortality in hemodialysis patients

Purpose

Soluble vascular cell adhesion molecule-1 (sVCAM-1) has a strong association with cardiovascular deaths in patients with coronary artery disease. The aim of this study is to explore the association between sVCAM-1 and cardiovascular mortality in maintenance hemodialysis (MHD) patients.

Methods

Eighty-three clinically stable MHD patients (mean age of 59.4 ± 13.7 years) at a single hospital-based dialysis facility were included. sVCAM-1, soluble intercellular adhesion molecule-1 (sICAM-1), and soluble E-selectin (sE-selectin) were determined at study baseline. The study cohort was divided into higher and lower concentration groups by the median value. The all-cause and cardiovascular mortality of this cohort were followed for 7 years.

Results

The mean concentrations of sVCAM-1, sICAM-1, and sE-selectin were 1,393.08 ± 300.96, 230.16 ± 84.86, and 60.01 ± 42.00 ng/mL, respectively. The higher concentration groups of sVCAM-1 and sICAM-1 had higher all-cause mortality by Kaplan–Meier analysis (p = 0.002 and p = 0.030, respectively). Higher sVCAM-1 concentrations had a higher risk of all-cause and cardiovascular mortality (p = 0.006 p = 0.046, respectively) in Cox proportional hazards model analysis.

Conclusion

In MHD patients, higher sVCAM-1 concentrations independently predict all-cause and cardiovascular mortality. This biomarker may be used as a valid surrogate marker for predicting outcomes.     

Aortic pulse wave velocity is a strong predictor of all – cause and cardiovascular mortality in chronic dialysis patients

Background/Aims: The aim of this study was to investigate all-cause and cardiovascular mortality in chronic hemodialysis patients (CHP) and to identify the determinants of mortality predictors. Methods: In this study with 3 years of follow-up period, we studied a cohort of 80 CHPs. Mean age at entry was 59.3?±?11.8 years (duration of dialysis 5.47?±?5.16 years). At entry, together with standard clinical and biochemical analyses, pulse wave velocity (PWV) was determined from time diversity propagation of the common carotid artery and common femoral artery flow signals by Doppler ultrasound. Results: The mean PWV (m/s) was presented at entry: in survived (12.5?±?2.01) and deceased (13.13?±?1.70) patients. The PWV cutoff point (by ROC curves) was 11.8. The regression coefficients (b) and Exp (b) hazard ratio coefficients of covariates in Cox-regression survival analysis in all-cause and CV outcomes was: PWV (b?=?0.2617, Exp[b]?=?1.2992, p?=?0.0027; b?=?0.3569, Exp[b]?=?1.4289, p?=?0.0005), CRP (b?=?0.0776, Exp[b]?=?1.0807, p?=?0.0001; b?=?0.0832, Exp[b]?=?1.0868, p?=?0.0001) and albumin (b?=??0.1302, Exp[b]?=?0.8779, p?=?0.0089; b?=??0.1881, 0.8285, p?=?0.0030), respectively. Relative risk for exposed groups according to all-cause and CV events was 4.2976 (95% CI?=?1.6051–11.5071) and 14.3590 (95% CI?=?1.6051–11.5071), p?=?0.0037, respectively. Conclusions: We conclude that PWV, CRP and serum albumin are strong independent predictors of overall and CV mortality in patients undergoing dialysis.     

Leptin and plasminogen activator inhibitor-1 levels in children on chronic dialysis

Abstract

Purpose: In this study, it is aimed to compare the serum leptin and PAI-1 levels and evaluate their relationship in children on hemodialysis (HD) and peritoneal dialysis (PD). Method: Thirty-six patients on HD (mean age: 15.0?±?2.8 years), 19 patients on PD (mean age: 13.0?±?3.5 years) and 15 healthy subjects (mean age: 14.5?±?2.7 years) were included in the study. Laboratory investigations included blood count, biochemical parameters, serum iron, iron binding capacity, parathormone, erythrocyte sedimentation rate, C-reactive protein (CRP), prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, serum leptin and PAI-1 levels. Results: Serum leptin levels were significantly higher in HD group than in control group when the effects of BMI and sex were controlled, while PD and control groups had similar leptin levels. PAI-1 levels were also significantly higher in HD group than in control group, while there was no statistically significant difference in PAI-1 levels of PD and control group. PAI-1 levels and leptin levels were significantly correlated, which was independent of the effect of BMI in both HD and PD groups when they are evaluated separately. Conclusion: Results of our study showed that HD patients had higher leptin and PAI-1 levels and leptin and PAI-1 levels were correlated significantly in both patient groups. The effect of elevated serum leptin and PAI-1 levels on the cardiovascular complications remains to be established.     

The Relationship of Visfatin Levels with Insulin Resistance and Left Ventricular Hypertrophy in Peritoneal Dialysis Patients

Background/objectives: Cardiovascular abnormalities are common in patients with chronic kidney disease. Visfatin influences lipid metabolism, insulin sensitivity, and cardiovascular health. The aim of this study was to explore the relation of serum visfatin to cardiovascular risk factors in nondiabetic peritoneal dialysis (PD) patients. Patients and methods: Eighty-seven nondiabetic patients (mean age 48 ± 15 years, 39 males) under PD were enrolled. Weight, anthropometric measurements, blood pressure, biochemical parameters, and insulin resistance (homeostatic model assessment-insulin resistance—HOMA-IR) were measured. Visfatin was measured and left ventricular mass index (LVMI) was calculated by echocardiography. Results: LVMI was correlated with body mass index (BMI; r = 0.47, p = 0.01), systolic blood pressure (SBP; r = 0.62, p = 0.04), and serum visfatin levels (r = 0.49, p = 0.03). According to HOMA-IR levels patients were grouped as insulin-resistant (IR) (HOMA-IR ≥2.0, n = 35) and noninsulin-resistant (non-IR) (HOMA-IR <2.0, n = 52) groups. The IR group had longer PD duration and higher BMI, total cholesterol, uric acid, and serum visfatin levels (p < 0.05). The study patients were divided into three groups according to their serum visfatin levels. Group 1 (≤34 ng/mL, n = 22) was considered as the lowest tertile of low visfatin and group 2 (35–42 ng/mL, n = 43) and group 3 (≥43 ng/mL, n = 22) in the upper tertile. Considering the visfatin groups, group 3 patients had significantly higher BMI (p = 0.00), total cholesterol (p = 0.03), C-reactive protein (CRP) (p = 0.03), HOMA-IR (p = 0.03), and LVMI (p = 0.02). In regression analysis, SBP (β = 0.19, p < 0.05) and serum visfatin levels (β = 0.74, p < 0.05) were independent variables affecting LVMI. Conclusion: Serum visfatin might be a sensitive marker than HOMA-IR evaluations for cardiac performance in nondiabetic PD patients.     

Brain Natriuretic Peptide and Its Relationship to Left Ventricular Hypertrophy in Patients on Peritoneal Dialysis or Hemodialysis Less Than 3 Years

An increase of brain natriuretic peptide (BNP) levels is commonly observed in patients on dialysis. Increased circulating levels of BNP are related to future cardiac events and associated with shorter survival in patients on chronic hemodialysis (HD). During the first 1 or 2 years on dialysis, patients on peritoneal dialysis (PD) have been shown to have an improvement in left ventricular hypertrophy, blood pressure, and volume status. This study compares BNP levels and cardiac status of PD and HD patients without cardiovascular disease and on dialysis for less than 36 months. The correlation between plasma BNP concentration and findings of echocardiography before HD scans were examined and compared with findings of PD. Twenty-two HD patients (15 men, 7 women; mean age, 52.5 ± 13.9 years) and 19 PD patients (10 men, 9 women; mean age, 47.6 ± 11.3 years) were studied. There were no significant differences between HD and PD patients with regard to age, gender, duration of dialysis, left ventricular mass, left ventricular mass index (p > 0.05). Plasma BNP levels were markedly greater in HD patients (467.8 ± 466.5 pg/mL) than those of PD patients (143.1 ± 165.2 pg/mL). Urine output was significantly higher in PD patients compared with HD patients (p < 0.05). A positive correlation between systolic blood pressure, diastolic blood pressure, and plasma BNP in HD patients (r: 0.653, p: 0.001; r: 0.493, p: 0.023, respectively) was detected. Additional studies are needed to investigate whether lower BNP level in PD patients is an advantage.     

Proton pump inhibitor usage is associated with higher all-cause mortality and CV events in peritoneal dialysis patients

ObjectivesA long period of inappropriate proton pump inhibitors (PPI) treatment has been proved to be associated with adverse prognosis in general population and hemodialysis patients. This study was conducted to clarify the impact of PPI usage on mortality and adverse cardiovascular (CV) events in peritoneal dialysis (PD) patients.Methods and designThis is a retrospective study. A total of 905 patients were enrolled from two PD centers, including 211 patients on PPI treatment and 618 patients not on PPIs. Kaplan–Meier curves were used to identify the incidence of adverse outcomes. Multivariate Cox regression models and inverse probability of treatment weighting (IPTW) were applied to analyze hazard ratios (HRs) for adverse outcomes.ResultsDuring follow-up, 162 deaths and 102 CV events were recorded. Kaplan–Meier curve demonstrated all-cause mortality (log-rank test p = .018) and CV events (log-rank test p = .024) were significantly higher in PPI usage group. Multivariate Cox regression models and IPTW showed that PPI usage was an indicator for all-cause mortality (HR = 1.35, 95%CI = 1.09–1.67, p = .006) and CV events (HR = 1.78, 95%CI = 1.35–2.32, p < .001).ConclusionsPPI usage is associated with higher all-cause mortality and CV events in PD patients. Clinicians are supposed to be more careful when using PPI and need to master the indications more rigorously in patients receiving PD treatment.     

Does high sensitive CRP improve cardiovascular risk prediction in metabolic syndrome among the aged?

Abstract

Objectives. To analyze whether an elevated level of high hsCRP has an additive effect on metabolic syndrome (MetS) in predicting future cardiovascular events (CVEs) as well as on all-cause mortality among the aged subjects. Design. A prospective, population-based study with a 9-year follow-up. The study population consisted of persons aged 64 and above in 1998–99 without vascular disease and CRP less than 10 mg/l at baseline (n = 733). Adjusted hazard ratios (HRs) and their 95% confidence intervals (CIs) for CVEs and all-cause mortality predicted by baseline MetS (defined by both International Diabetes Federation (IDF) and World Health Organization (WHO)) and hsCRP-level were estimated. Results. During the 9-year follow-up, a total of 142 CVEs and 206 deaths occurred. After multivariable adjustment, no significant interactions were found between hsCRP and MetS in CVEs (IDF: p = 0.828; WHO: p = 0.572) or in all-cause mortality (IDF: p = 0.113; WHO: p = 0.374). HsCRP was not associated with the occurrence of CVEs (IDF: HR = 1.10, 95% CI = 0.92–1.32, p = 0.281; WHO: HR = 1.10, 95% CI = 0.93–1.32, p = 0.247) or with all-cause mortality (IDF: HR = 1.12, 95% CI = 0.97–1.29, p = 0.134; WHO: HR = 1.11, 95% CI = 0.96–1.28, p = 0.146). Conclusions. It seems that hsCRP does not give any extra value in evaluation of CVE risk or all-cause mortality of older subjects with MetS.     

Van Buchem disease: Clinical,biochemical, and densitometric features of patients and disease carriers

Van Buchem disease (VBD) is a rare bone sclerosing dysplasia caused by the lack of a regulatory element of the SOST gene, which encodes for sclerostin, an osteocyte‐derived negative regulator of bone formation. We studied the demographic, clinical, biochemical, and densitometric features of 15 patients with VBD (12 adults and 3 children) and 28 related carriers of the gene mutation. The most common clinical findings in patients were facial palsy (100%) and various degrees of hearing impairment (93%); raised intracranial pressure had been documented in 20%. The clinical course of the disease appeared to stabilize in adulthood, with the majority of patients reporting no progression of symptoms or development of complications with time. Carriers of the disease had none of the clinical features or complications of the disease. Sclerostin could be detected in the serum in all but 1 VBD patients (mean 8.0 pg/mL; 95% confidence interval [CI], 4.9–11.0 pg/mL), and were lower than those of carriers (mean 28.7 pg/mL; 95% CI, 24.5–32.9 pg/mL; p < 0.001) and healthy controls (mean 40.0 pg/mL; 95% CI, 34.5–41.0 pg/mL; p < 0.). Serum procollagen type 1 amino‐terminal propeptide (P1NP) levels were also significantly higher in adult patients (mean 96.0; 95% CI, 54.6–137.4 ng/mL versus mean 47.8; 95% CI, 39.4–56.2 ng/mL, p = 0.003 in carriers and mean 37.8; 95% CI, 34.5–41.0 ng/mL, p = 0.028 in healthy controls) and declined with age. Bone mineral density (BMD) was markedly increased in all patients (mean Z‐score 8.7 ± 2.1 and 9.5 ± 1.9 at the femoral neck and spine, respectively); BMD of carriers was significantly lower than that of patients but varied widely (mean Z‐scores 0.9 ± 1.0 and 1.3 ± 1.5 at the femoral neck and spine, respectively). Serum sclerostin levels were inversely correlated with serum P1NP levels (r = –0.39, p = 0.018) and BMD values (femoral neck r = –0.69, p < 0.001; lumbar spine r = –0.78, p < 0.001). Our results show that there is a gene‐dose effect of the VBD deletion on circulating sclerostin and provide further in vivo evidence of the role of sclerostin in bone formation in humans. The small amounts of sclerostin produced by patients with VBD may explain their milder phenotype compared to that of patients with sclerosteosis, in whom serum sclerostin is undetectable. © 2013 American Society for Bone and Mineral Research.     

Association of plasminogen activator inhibitor-1 gene polymorphism and type 2 diabetic nephropathy

Background: We investigated the relationship between plasminogen activator inhibitor-1 (PAI-1) 4G/5G insertion/deletion polymorphism and prevalence of diabetic nephropathy (DN) in Chinese patients. Methods: A total of 107 patients with type 2 diabetes were randomly recruited in the study, and 102 healthy subjects were selected as Control. Patients were divided into three groups according to their urinary albumin–creatinine ratio (UACR). Group A (n?=?44), had patients without DN (serum creatinine <106?µmol/L and UACR <30?µg/mg); Group B (n?=?30), had patients with micro-albuminuria (UACR 30–299?µg/mg), and Group C (n?=?33), had patients with macro-albuminuria (UACR ≥300?µg/mg and creatinine <200?µmol/L). Plasma level of PAI-1 was measured by ELISA. PAI-1 polymorphism was determined by a polymerase chain reaction (PCR) method and DNA sequencing. Results: (1) The plasma PAI-1 levels of group A (60.39?±?17.01?ng/L), group B (68.76?±?17.81?ng/L) and group C and (68.63?±?18.30?ng/L) are higher than that of controls (46.26?±?26.04?ng/L); (2) Patients with genotype 4G/4G tended to exhibit higher PAI-1 level; (3) The distribution frequency of genotype 4G/4G in group C was significantly higher than in group A (42.4% vs. 28.7%, p?Conclusions: (1) Plasma PAI-1 level was elevated in Type 2 diabetic patients; (2) The level of plasma PAI-1 is closely related to PAI-1 gene 4G/5G polymorphism and (3) PAI-1 4G/5G polymorphism is associated with the development and progression of predominant proteinuria diabetes nephropathy.     

Serum T3 Level Can Predict Cardiovascular Events and All-Cause Mortality Rates in CKD Patients with Proteinuria

Background: Patients with proteinuria frequently show changes in thyroid hormone levels. Serum T3 depression predicts a negative outcome in chronic kidney disease (CKD) patients and may be associated with cardiovascular complications or chronic inflammation. Few studies have explored the relationship between thyroid hormone dysregulation and clinical outcome in patients with proteinuria. Methods: We reviewed thyroid function test results obtained from 211 patients with 24 h urinary protein excretion greater than 150 mg/day and found a correlation of thyroid hormone level with cardiovascular events and mortality. Results: T3 decreased with age (p = 0.001) and 24 h urine albumin (p = 0.028). Free T4 decreased in accordance with 24 h urine protein and serum creatinine (p = 0.034 and p = 0.033, respectively). In the Kaplan–Meier survival analysis, lower cumulative survival, higher cardiovascular events, and mortality were found in the low T3 group compared with the normal T3 group (p = 0.000, p = 0.013, and p = 0.001, respectively). In Cox regression analysis, we observed that, with low T3, decreased sodium, and old age, the incidence of cardiovascular complications (p = 0.000, p = 0.016, and p = 0.000, respectively), cardiovascular mortality (p = 0.000, p = 0.048, and p = 0.001, respectively), and all-cause mortality (p = 0.000, p = 0.017, and p = 0.000, respectively) increased. Conclusion: In CKD patients with proteinuria, low T3 concentration predicted all-cause mortality and cardiovascular event independently of the severity of proteinuria.     

Decreased Serotonin Levels and Serotonin‐Mediated Osteoblastic Inhibitory Signaling in Patients With Ankylosing Spondylitis

Evidence suggests that serotonin is an inhibitor of bone formation. We aimed to assess: 1) serum serotonin levels in patients with ankylosing spondylitis (AS), a prototype bone‐forming disease, compared with patients with rheumatoid arthritis (RA) and healthy subjects; 2) the effect(s) of TNFα blockers on serum serotonin levels in patients with AS and RA; and 3) the effect(s) of serum of AS patients on serotonin signaling. Serum serotonin levels were measured in 47 patients with AS, 28 patients with RA, and 40 healthy subjects by radioimmunoassay; t test was used to assess differences between groups. The effect of serum on serotonin signaling was assessed using the human osteoblastic cell line Saos2, evaluating levels of phospho‐CREB by Western immunoblots. Serotonin serum levels were significantly lower in patients with AS compared with healthy subjects (mean ± SEM ng/mL 122.9 ± 11.6 versus 177.4 ± 24.58, p = 0.038) and patients with RA (mean ± SEM ng/mL 244.8 ± 37.5, p = 0.0004). Patients with AS receiving TNFα blockers had significantly lower serotonin levels compared with patients with AS not on such treatment (mean ± SEM ng/mL 95.8 ± 14.9 versus 149.2 ± 16.0, p = 0.019). Serotonin serum levels were inversely correlated with pCREB induction in osteoblast‐like Saos‐2 cells. Serotonin levels are low in patients with AS and decrease even further during anti‐TNFα treatment. Differences in serotonin levels are shown to have a functional impact on osteoblast‐like Saos‐2 cells. Therefore, serotonin may be involved in new bone formation in AS. © 2015 American Society for Bone and Mineral Research.     

Neutrophil reactive oxygen formation,bacterial infections and mortality in malnourished hemodialysis patients: Evaluation of clinical outcomes

Introduction

Patients with end stage kidney disease undergoing maintenance hemodialysis (MHD) are prone to malnutrition and infections.

Objective

The objective of this study was to evaluate the effect of polymorphonuclear (PMN) cell dysfunction on clinical outcomes of MHD patients, in association with nutritional status.

Methods

This prospective study investigated 39 MHD patients by evaluating the oxidative activity of their PMN cells using Phorbol 12-Myristate-13-Acetate (PMA) stimulation. Blood samples were taken from each participant at dialysis initiation. Demographics, laboratory data, and clinical outcomes during a 24-month follow-up period were obtained from electronic medical records.

Results

Phagocytic activity was described in percentiles of mean fluorescence intensity (MFI) of PMA levels. There were no differences in comorbidities between patients with low or high MFI-PMA percentiles. Patients in the lowest (25th) MFI-PMA percentile (N = 10) had poorer nutritional status and more frequent severe infections compared to the other 29 patients (4.3 ± 3.4 events versus 2 ± 2.2 events, p = 0.017). Furthermore, they had more frequent hospitalizations (>3) due to infections (70% versus 41%, p = 0.073) and their mortality rate was higher (80% versus 31%, p = 0.007). The odds ratio for all-cause mortality was 8.85. In multivariate analysis, the MFI-PMA percentile and ischemic heart disease were the strongest predictors of all-cause mortality (p = 0.02 and p = 0.005, respectively).

Conclusions

Low MFI-PMA levels were associated with poor nutritional status and adverse clinical outcomes and might serve as a prognostic biomarker, predicting severe infections and mortality among malnourished MHD patients.     

Optimal targets of chronic kidney disease-mineral and bone disorder markers for Chinese patients with maintenance peritoneal dialysis: a single-center retrospective cohort study

BackgroundThe chronic kidney disease-mineral and bone disorder（CKD-MBD) is known to be associated with increased mortality in dialysis patients, but whether current global guidelines for CKD-MBD, which were primarily developed from hemodialysis, are suitable for peritoneal dialysis (PD) patients practice require further investigation.MethodsThis is a single-center retrospective cohort study. In total 491 prevalent PD patients (median follow-ups: 34 months) from Peking Union Medical College Hospital (PUMCH) from January 2004 to December 2017 were included and followed until 30 June 2018. In the first dialysis year, the average levels of serum calcium, albumin-corrected calcium (CorCa), phosphorus, and parathyroid hormone (PTH) levels were the interested predictors in Cox proportional regression model.ResultsOf these PD patients (age 58 ± 17 years), 52% were male and 36% had diabetic nephropathy. In Cox regression over first-year mean parameters, PTH <100 pg/mL (HR = 1.97, 95% CI 1.32 to 2.94, p < 0.001) and ≥300 pg/mL (HR = 2.24, 95% CI 1.32 to 3.81, p = 0.003) were associated with increased all-cause mortality than that of PTH 100–200 pg/mL. Patients with albumin-corrected serum calcium level < 2.13 mmol/L also had higher risk of death than patients with level of 2.13 to 2.38 mmol/L (HR = 2.06, 95% CI 1.06 to 4.01, p = 0.02). Serum phosphorus ≥1.45 mmol/L were associated with increased all-cause mortality. However, lacking of data on 25-hydroxy vitamin D, alkaline phosphatase, and activated vitamin-D are limitations of our analysis.ConclusionsAs one of the largest PD cohort study focusing on CKD-MBD, we demonstrated that the level of CKD-MBD markers in the first PD year are independent predictors of all-cause mortality. PTH 100–300 pg/mL might be the best target for Chinese PD patients.     

Determinants of Coronary Artery Disease in Nondiabetic Hemodialysis Patients: A Matched Case-Control Study

Background/Aims. The aim of this matched case-control study was to evaluate the determinants of coronary artery disease (CAD) other than conventional risk factors in nondiabetic hemodialysis (HD) patients. Methods. Among 312 consecutive patients on regular HD, 26 nondiabetic patients with angiographically defined coronary artery disease (20 men, 6 women; mean age 57.0 ± 13 years) constituted the case group (group 1). A subject group of the same gender, smoking status, and hypertension with similar ages and body mass indexes who had normal electrocardiography and myocardial perfusion scintigraphy served as controls (20 men, 6 women; mean age 54.1±12 years, group 2). Demographics, high sensitivity C-reactive protein (hs-CRP), erythrocytes dimentation rate (ESR), hematocrit-corrected ESR, beta-2 microglobulin, cardiac troponin I, parathyroid hormone, albumin, calcium (Ca), phosphorus (P), Ca × P, and lipid profiles were compared between the groups. Results. Patients in group 1 had higher hs-CRP and troponin I (18.0±12 vs. 7.2±5 mg/L, p < 0.001; 0.36±0.16 vs. 0.22±0.05 ng/mL, p < 0.001, respectively) and lower HDL cholesterol levels than group 2 (37.0±10mg/dL vs. 46.3±17mg/dL, p = 0.02). Backwards stepwise logistic regression analysis revealed that high hs-CRP and troponin I levels (p = 0.03 and p = 0.01) and low HDL cholesterol levels (p = 0.02) were independently related with CAD. Conclusion. According to these results, in nondiabetic patients on regular hemodialysis, high hs-CRP, troponin I levels and low HDL-cholesterol were the determinants of CAD.