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.     

Elevated Plasma Levels of PAI-1 Predict Cardiovascular Events and Cardiovascular Mortality in Prevalent Peritoneal Dialysis Patients

Background. Elevated plasminogen activator inhibitor-1 (PAI-1) levels are associated with increased cardiovascular (CV) risk in the general population. It has been shown that peritoneal dialysis (PD) patients have increased plasma levels of PAI-1. The aim of this study was to investigate whether PAI-1 independently predicted CV outcome in PD patients. Material and Methods. Seventy-two PD patients (53% females, mean age 49.9 ± 16.1 years) were studied. Twelve patients who underwent kidney transplantation and 14 patients who transferred to hemodialysis during follow-up were excluded from the analysis. The remaining 46 patients (54% female, mean age 54 ± 16 years, dialytic age 42 ± 30 months) were followed a mean time of 45.4 ± 19.4 months (range 8–71 months). Baseline PAI-1, clinical, and laboratory parameters were assessed in all patients. Survival analyses were made with Kaplan-Meier and Cox regression analysis, with all-cause mortality and CV mortality and CV events (CVEs) as clinical end points. Results. During the follow-up, 29 patients died (17 from CV causes), and 28 fatal and non-fatal CVEs were recorded. The patients were divided according to plasma PAI-1 levels (i.e., ≤ or >41 ng/mL). The significant independent predictors of all-cause of mortality were age (60 years; p = 0.018), CRP (5 mg/L; p = 0.015), and serum albumin (<3.5 g/L; p = 0.011). Multivariable Cox regression analysis showed that plasma PAI-1 41 ng/mL was independently predictive of higher CV mortality (p = 0.021) and CVEs (p = 0.001). The only other independent predictor of CV mortality was only CRP (5 mg/L; p = 0.008). Conclusions. Plasma levels of PAI-1 41 ng/mL is a significant predictor of CV mortality and CVEs in PD patients.     

Zinc-α2-Glycoprotein: Is There Association between This New Adipokine and Body Composition in Hemodialysis Patients?

Peptides involved in the regulation of body composition are of interest in hemodialysis (HD) patients because protein wasting associated with high fat mass (FM) is present in these patients. Zinc-α2-glycoprotein (ZAG), a new adipokine, is involved in the regulation of lipid metabolism, adiposity, and energy balance. The purpose of this study was to evaluate ZAG levels and its relationship with body composition and dietary intake in HD patients. Forty-nine HD patients (28 men, 53.1 ± 12.5 years, and BMI 24.0 ± 4.3 kg/m²) were studied and compared with 20 healthy subjects (9 men, 49.5 ± 15.2 years, and BMI 25.6 ± 4.1 kg/m²). Plasma ZAG levels were measured using the ELISA methods and body composition was evaluated through anthropometric data. Dietary intake was assessed 3 days by 24-hour food recall. Although most of the HD patients (59.2%) were eutrophic according to BMI, 92.3% presented high percentage of body fat (BF), and 43.5%, reduced fat-free mass according to midarm muscle circumference values. ZAG levels were ～2.5-fold higher in HD patients (135.9 ± 40.9 mg/L) compared with healthy individuals (54.6 ± 23.0 mg/L) (p < 0.0001). Circulating ZAG was not associated with dietary intake; however, this peptide was negatively correlated with %BF and, for each 1% reduction in BF, ZAG levels increased by 2.4 mg/L (p = 0.02). In summary, circulating ZAG is increased and inversely correlated with adiposity in HD patients; however, in spite of its higher plasma levels, the majority of HD patients did not show low BF.     

An Association Between Inflammatory State and Left Ventricular Hypertrophy in Hemodialysis Patients

This study was performed to investigate the potential relationship between left ventricular hypertrophy (LVH) and proinflammatory cytokines in hemodialysis (HD) patients and the effect of HD on cytokine production. Serum interleukin 1 beta (IL-1 β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) measurements and echocardiographic studies were performed in 35 stable HD patients. A variety of probable risk factors for LVH including age, HD duration, blood pressure (BP), body mass index, lipid profile, hemoglobin, albumin, parathormone and homocysteine levels were also investigated. Additionally, the effect of HD procedure on cytokine levels was evaluated. Predialysis serum levels of IL-1β, IL-6, TNF-α, and homocysteine in HD patients were compared with 12 healthy subjects. Left ventricular hypertrophy was demonstrated in 20 (57%) of HD patients by echocardiography. Left ventricular mass index (LVMI) was correlated positively with systolic BP (r = 0.556, p = 0.001), diastolic BP (r = 0.474, p = 0.004), and serum levels of TNF-α (r = 0.446, p = 0.009).Multiple regression analysis showed that systolic BP and TNF-α levels were significant independent predictors of LVH. No relationship was observed between LVH and other parameters. The mean predialysis serum level of IL-6 was significantly higher in HD patients compared to healthy controls (15.7 ± 8.7 vs. 7.3 ± 0.7 pg/mL, p = 0.001). Predialysis serum levels of TNF-α in HD patients were higher when compared to healthy subjects, but the difference was not statistically significant (8.3 ± 3 vs. 7 ± 1.45 pg/mL, respectively, p > 0.05). However, serum levels of IL-6 and TNF-α significantly elevated after HD, when compared to predialysis levels (from 15.7 ± 8.7 to 17.8 ± 9.5 pg/mL, p = 0.001 and from 8.3 ± 3.0 to 9.9 ± 3.5 pg/mL p = 0.004, respectively). As a conclusion, in addition to BP, proinflammatory cytokines, TNF-α in particular, seem to be associated with LVH in ESRD patients.     

RELATIONS BETWEEN OXIDATIVE STRESS,HEPATOCYTE GROWTH FACTOR,AND LIVER DISEASE IN HEMODIALYSIS PATIENTS

Background: Hepatocyte growth factor (HGF) and copper/zinc superoxide dismutase (Cu/Zn SOD) protect against tissue injury, including that due to oxidative stress (SOX). We studied whether they could be associated with each other, SOX markers, prevalence of viral hepatitis, and cardiovascular disease (CVD) and their laboratory surrogates in maintenance hemodialysis (HD) patients. Methods: In 24 patients, pre-dialysis serum HGF, plasma Cu/Zn SOD, total lipid peroxides, and serum autoantibodies against oxidized LDL were measured by ELISAs. Viral hepatitis B and C markers were determined by third generation microparticle ELISAs, and CVD was identified on a clinical basis. Results: In HD patients, circulating HGF, Cu/Zn SOD, and the other SOX markers were higher than in healthy controls, and HGF directly correlated with Cu/Zn SOD levels (P = 0.0006). Both HGF (P = 0.021) and Cu/Zn SOD (P = 0.017) were positively associated with prevalence of viral hepatitis and serum alanine aminotransferase activity (P = 0.021 and P = 0.040, respectively). Presence of CVD directly correlated with HGF (P = 0.001) but not with Cu/Zn SOD levels (P = 0.087). Circulating HGF positively related to serum C-reactive protein (P = 0.043). In patients without viral hepatitis and CVD, both HGF and Cu/Zn SOD were lower than in those with, and higher than in healthy controls. CVD (P = 0.003) and viral hepatitis (P = 0.024) were independent predictors of increased HGF, while positive viral hepatitis marker predicted increased Cu/Zn SOD levels (P = 0.019) in HD patients. There were no associations between HGF and the SOX markers in controls. Conclusions: In maintenance HD patients, circulating Cu/Zn SOD and HGF levels are increased, likely as a part of the reparatory reaction against liver damage. Viral hepatitis status and liver function should be considered in further studies of Cu/Zn SOD in these subjects.     

Impact of serum albumin and body-mass index on survival in hemodialysis patients

A low body mass index (BMI) and serum albumin are associated with increased risk of mortality in patients with chronic kidney disease (CKD). The purpose of this study was to evaluate BMI and serum albumin as predictors of all-cause and cardiovascular (CV) mortality in hemodialysed (HD) patients. We describe the results of a five-year retrospective observational study with 187 HD patients (54.9 ± 15.6 years old, 54% men, and 46% suffering from diabetes) from RenalCor Clinic in Rio de Janeiro, Brazil. The influence of serum albumin levels and BMI (determined every three months) over all-cause mortality was examined using a Cox model, while the influence of the same factors over CV mortality among all-cause mortality was modeled through a logistic regression. During the five years, 26.7% of the patients died, 62% of which due to CV disease (CVD). Analysis by the Cox model showed that low serum albumin and low BMI were significant predictors of mortality. Patients with higher BMI had a lower hazard of death for all-cause mortality (hazard ratio [HR] = 0.92; P = 0.035) and a 1 g/l increase in serum albumin was associated with significantly lower hazard of death (hazard ratio = 0.9679; P < 0.001). The highest BMI value (>30 kg/m²) was significantly associated with an increase of odds of CV mortality (odds ratio = 1.22, P = 0.03). We confirm here in a Brazilian cohort of hemodialysis patients that both low BMI (<19 kg/m²) and hypoalbuminemia are strong predictors of death.     

Correlation of Serum Lead Levels with Inflammation,Nutritional Status,and Clinical Complications in Hemodialysis Patients

The aim of this study was to determine blood lead level (BLL) in hemodialysis (HD) patients and their relation with high-sensitivity C-reactive protein (hsCRP) and albumin which are inflammatory and nutritional biomarkers, respectively, and clinical complications. A total of 93 patients, who were dialyzed at least for 3 months, were included in the study. Blood samples were collected before HD and BLL was measured and categorized as three equal groups: low normal (BLL < 8 μg/dL), middle normal (BLL = 8–10.6 μg/dL), and high normal (BLL > 10.6 μg/dL). All patients had normal BLL, 9.7 ± 3.4 g/dL. Patients with abnormal hsCRP level (>3 mg/L) had higher BLL than other patients (16.4 ± 0.8 vs. 11.5 ± 2.7 mg/L, p = 0.003). Patients with BLL > 10.6 μg/dL had significantly lower hemoglobin, ferritin, iron, and albumin levels and higher hsCRP and intact parathyroid hormone (iPTH) levels than the patients with BLL < 8 μg/dL. In addition, BLL revealed a significant positive correlation with duration of dialysis. We concluded that BLL associated to inflammation, malnutritional status, iron-deficiency condition, and high iPTH level in HD patients.     

Low Plasma Dehydroepiandrosterone Sulfate Level and its Relationship to Adiponectin in Hemodialysis Patients

The aim of the present study was to assess the relationship between plasma DHEA-S and adiponectin concentrations in hemodialyses patients (HD). Plasma adiponectin, DHEA-S, cholesterol, and albumin levels were estimated in 94 HD and 46 healthy subjects (HS). In HD, a significantly lower plasma DHEA-S concentration (2.5±0.2 vs. 4.7±0.4 μmol/L respectively; p?=?0.002) but significantly higher plasma adiponectin level (15.0±0.7 vs. 8.7±0.8 μg/mL respectively; p?=?0.004) than in HS were found. Only in uremic patients was a significant negative correlation found between plasma adiponectin and DHEA-S concentrations (tau?=?–0.210; p?=?0.001). Decreased plasma DHEA-S level is associated with increased adiponectinemia in uremic patients.     

Anorexia,fatigue, and plasma interleukin-6 levels in chronic hemodialysis patients

This study aimed at evaluating the possible relationship between anorexia and fatigue in hemodialysis (HD) patients and at measuring the plasma levels of interleukin-6 (IL-6) and C-reactive protein (CRP) in HD patients with or without anorexia and/or fatigue. The first question of the Hemodialysis Study Appetite questionnaire was used to assess the appetite of the HD patients and the vitality scale of the SF-36 to assess fatigue. The Charlson Comorbidity Index was assessed in each patient. Seventy-six HD patients were studied. Forty-four were males and 32 females. Thirty-two were classified as not-anorexic and not-fatigued, 12 as not-anorexic but fatigued, 6 as anorexic and not-fatigued, and 26 as anorexic and fatigued. Plasma IL-6 levels (pg/mL) were significantly higher in anorexic and fatigued patients (10.9 ± 11.9) than in not-anorexic and not-fatigued (1.6 ± 0.6) (p < 0.001) and in anorexic but not-fatigued patients (1.8 ± 1.7) (p < 0.01). With respect to not-anorexic but fatigued patients (3.1 ± 1.5), the difference was not statistically significant (p = 0.058). The plasma CRP levels (mg/dL) also were significantly higher in anorexic and fatigued patients (9.2 ± 6.3) than in not-anorexic and not-fatigued patients (4.1 ± 4.5), in anorexic but not-fatigued patients (2.5 ± 1.6), and in not-anorexic but fatigued patients (4.1 ± 4.4) (p = 0.001). The presence of both anorexia and fatigue in chronic HD patients is associated with significantly higher levels of plasma IL-6 and CRP and a higher frequency of comorbidities.     

SARS-CoV-2 spike protein antibody titers 6 months after SARS-CoV-2 mRNA vaccination among patients undergoing hemodialysis in Japan

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is shown to prevent severe illness and death in hemodialysis (HD) patients, but the immune response to vaccines is reduced in this population. This study compared SARS-CoV-2 spike protein antibody titers between HD patients and healthy controls in Japan for up to 6 months following vaccination.

Methods

A multi-institutional retrospective study at five clinics in Japan was conducted using 412 HD patients and 156 healthy controls who received two doses of the BNT162b2 (Pfizer-BioNTech) mRNA vaccine. Anti-SARS-CoV-2 spike protein S1 IgG antibody titers were measured at 1, 3, and 6 months after the second dose. The attenuation speed was calculated as slope (i.e., –β) using a linear mixed-effects model toward the log-transformed antibody titers.

Results

The HD group had significantly lower month 1 antibody titers (Ab-titer-1) than the controls, and these remained lower through month 6 (95% CI: 2617.1 (1296.7, 5240.8) vs. 7285.4 (4403.9, 11,000.0) AU/mL at Ab-titer-1, and 353.4 (178.4, 656.3) vs. 812.0 (498.3, 1342.7) AU/mL at Ab-titer-6 (p?<?0.001, respectively)). Lower log Ab-titer-1 levels in the HD group were significantly associated with a lower log Ab-titer–6 (0.90 [0.83, 0.97], p?<?0.001). The –β values in the HD patients and healthy controls were –4.7?±?1.1 and –4.7?±?1.4 (year^?1), respectively.

Conclusion

SARS-CoV-2 spike protein antibody titers were significantly lower in HD patients than in healthy controls at 1 (peak) and 6 months after the second vaccination. Low peak antibody titers contributed to low 6-month antibody titers.

     

Nutritional and inflammatory status influence darbepoetin dose in pre-dialysis elderly patients

Anaemia is a common finding in elderly patients particularly in those with chronic kidney disease. Effective correction of anaemia improves survival and quality of life. The association between anaemia and a poor nutritional status as well as the presence of inflammation has already been documented. The aim of our study was to assess the impact of the nutritional and inflammatory status on darbepoetin dose requirements of elderly patients followed in a “Chronic Kidney Disease” outpatient clinic. We included 71 elderly patients (age ≥ 65 years) in a “Chronic Kidney Disease” outpatient clinic. Creatinine Clearance (CrCl) was estimated according to the Cockroft–Gault equation. Nutritional status was evaluated by biochemical and anthropometric parameters. Tumour Necrosis Factor-alpha (TNF-α), Interleukin-6 (IL-6) and high sensitivity C-reactive protein (hs-CRP) were used as biomarkers of inflammation. Our patients (56% males) with a mean age of 76.2 ± 6.6 years were followed for 33.1 ± 43.6 months. Mean eCrCl was 13.5 ± 7.2 ml/mn/1.73 m². All patients were under supplemental iron therapy and 74.7% needed darbepoietin (0.762 ± 0.6 (μg/kg/week) to correct anaemia. Among the several variables regressed on darbepoietin dose, in a multiple regression model, only Hb, IL-6 and TNF-α levels and SGA score predicted the need for higher doses of darbepoietin. (r = 0.677; r ² = 0.459). In Conclusion, in our pre-dialysis elderly patients, markers of a poor nutritional status (SGA and albumin) and inflammation (IL-6 and TNF-α) independently predicted the use of higher doses of darbepoietin to correct anaemia.     

The Prevalence of Insulin Resistance and Its Relationship Between Anemia,Secondary Hyperparathyroidism,Inflammation, and Cardiac Parameters in Chronic Hemodialysis Patients

Background: Insulin resistance (IR) frequently accompanies end-stage renal disease (ESRD). There is a positive correlation between IR and cardiovascular pathologies that plays a role in mortality and morbidity on patients with ESRD. We aim to research the prevalence and evaluability of homeostasis model assessment–insulin resistance (HOMA-IR) in hemodialysis (HD) patients and also to evaluate the relationship of this value with various clinical parameters. Material and Methods: 57 ESRD patients, regularly undergoing HD were enrolled in the study. Obese patients (BMI > 25 kg/m²) and ESRD patients with diabetic etiology were excluded. Twenty-nine patients were men (50.9%), and 28 patients were women (48.1%); the mean age was 45.9 ± 13.6 years. Results were recorded after evaluated by HOMA-IR. In addition to calculating the HOMA index, anthropometrical parameters, plasma levels of total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), hematocrit (hct), parathyroid hormone (PTH), calcium (Ca), phosphorus (P), C-reactive protein (CRP), fasting glucose, and insulin plasma levels were measured by standard methods in all subjects. The systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure were recorded, and left ventricle posterior wall thickness was measured by echocardiography. All patients completed the study. The minimum HOMA-IR value was 0.11, maximum value was 5.18, and the cut-off point was 1.23. According to this value, the patients were classified into two groups: HOMA-IR positive that were equal or higher than 1.23 (group 1), and HOMA-IR negative that were under this value (group 2). Results: We established that 18 of 57 (31.6%) patients were HOMA-IR positive and 39 of 57 (68.4%) patients were negative. In group 2, hct levels were higher than in group 1 and the weekly requiring dose of rHuEpo was significantly low in group 2 compared with group 1 (p< 0.05). Interestingly, the Ca × P products ( ≥ 55 mg/dL) were significantly higher in group 2 than in group 1 (p< 0.05). There was not any significant correlation between HOMA-IR and anthropometrics measurements, hemodialysis adequacy, plasma PTH level, cardiac parameters, and inflammation markers. We established the prevalence of IR as 31.6% in our HD patients' cohort. Conclusions: There was a positive correlation between low HOMA-IR value with target hct levels and administration of the rHuEpo. Because insulin resistance is an independent risk factor of cardiovascular mortality in ESRD patients, it was accepted that being able to correct the insulin resistance could be a novel therapeutic approach in this cohort.     

Hemodialysis with Regenerated Cellulosic Membranes Does Not Reduce Plasma Selenium Levels in Chronic Uremic Patients

Abstract: Selenium (Se) is considered an essential and very important trace element for humans. Se blood levels are frequently low in end-stage renal disease (ESRD) patients, but very little has been established concerning the mechanisms that could modify Se status in uremia, including a supposed dialysis-mediated Se depletion. In order to verify whether hemodialysis (HD) can induce a loss of Se, thereby leading or contributing to a low plasma Se concentration, we investigated the effect of HD procedure with the most commonly used regenerated cellulosic membrane (Cuprophan) on plasma Se levels in 20 uremic patients on HD for 62.5 ± 49.4 months. Plasma Se levels were also determined in 15 chronic renal failure (CRF) nondialyzed patients and in 28 age-matched healthy controls. Se concentration was determined by atomic absorption spectrophotometry. Plasma Se levels of both HD patients (61.3 ± 8.5 μ/L) and CRF nondialyzed patients (56.4 ± 10.1 μg/L) were significantly lower than in normal subjects (78.3 ± 9.7 μg/L, p < 0.001). In CRF nondia-lyzed patients, a significant (p < 0.05) negative correlation was found between the plasma Se concentration versus serum creatinine values. Within the HD group, plasma Se levels significantly increased after the HD procedure (72.8 ± 17.2 μg/L, p < 0.02) together with hemat-ocrit and total plasma protein values (p < 0.05 and p < 0.001, respectively). In the hollow fiber dialyzer during an HD session, the Se concentration increased but not significantly from the blood inflow site (64.6 ± 12.5 μg/L) to the outflow site (72.6 ± 17 μg/L) and decreased, again not significantly, from the dialysate entrance (5 ± 1.9 μg/L) to the outlet (4.8 ± 2.5 μ?.). In HD with low-flux regenerated cellulosic dialyzer, very likely due to the high molecular weight of Se-binding proteins, the replacement treatment did not induce a Se loss in chronic uremic patients with a low plasma Se concentration.     

Acute Effects of Intermittent Hemodialysis and Sustained Low-Efficiency Hemodialysis (SLED) on the Pulmonary Function of Patients under Mechanical Ventilation

The effects of hemodialysis (HD) on pulmonary function are still controversial. The objective of this study was to evaluate the effect of intermittent hemodialysis (IHD) and sustained low-efficiency dialysis (SLED) on the respiratory mechanics of ICU patients under invasive mechanical ventilation. We prospectively studied 31 patients. Laboratory and respiratory evaluation (static and dynamic compliance and resistance) was performed pre- and post-HD. Forty HD sessions were studied and grouped in: SLED (n?=?17; Qa?=?200–250 mL/min, Qd?=?300 mL/min) and IHD (n?=?23; Qa =?250–300 mL/min, Qd?=?500 mL/min). There was no difference between the groups according to age, gender, comorbidities, APACHE II, and cause of mechanical ventilation, but pre-HD, patients in the IHD group had higher levels of plasma creatinine (5.4 ± 2.0 vs. 4.2 ± 1.3 mg/dL, p = 0.048) and platelets (286 ± 186 vs. 174 ± 95 10³/mm², p = 0.032) and lower arterial pH (7.37 ± 0.07 vs. 7.42 ± 0.05, p = 0.02). The efficiency of the treatment was similar (p > 0.05) with both types of HD regarding fluid removal, urea reduction rate, and decrease in plasma creatinine. Pre-HD, the ventilatory conditions of both groups were similar (p > 0.05) except for pressure support ventilation and airflow resistance. There were no changes (pre- versus post-HD p > 0.05) induced either by IHD or SLED in the ratio PaO₂/FiO₂ or in any measured ventilatory parameter. In conclusion, neither IHD nor SLED modifies the pulmonary function of patients under mechanical ventilation.     

The Association between Serum Adiponectin Levels and Nutritional Status of Hemodialysis Patients

Adiponectin plays an important role in the regulation of body weight, insulin sensitivity, lipid metabolism, and the inflammatory response. Adiponectin is elevated in hemodialysis patients. We investigated the association between altered serum adiponectin levels and the nutritional–inflammation status of hemodialysis patients. Forty-four hemodialysis patients (21 men and 23 women; mean age 53.9 ± 9.2 years) were enrolled and 32 healthy volunteers were included as the control group. Serum adiponectin was measured using a commercial radioimmunoassay kit. Serum albumin, cholesterol, triglyceride, high-sensitivity C-reactive protein, urea, creatinine, transferrin, lean body mass, fat mass, body mass index (BMI), the subjective global assessment (SGA) score, and the malnutrition–inflammation score (MIS) were measured in all patients. Adiponectin levels were significantly elevated in the hemodialysis patients compared with the healthy subjects (24.8 ± 10.4 μg/mL and 6.8 ± 4.2 μg/mL, respectively, p < 0.0001). Serum adiponectin correlated positively with SGA (r = 0.47) and MIS (r = 0.38), and negatively with BMI (r = ?0.34), triglyceride (r = ?0.53), and glucose levels (r = ?0.42). Serum adiponectin levels were significantly higher in malnourished patients than in well-nourished patients when assessed with SGA (20.5 ± 10.4 μg/mL and 29.0 ± 8.7 μg/mL, respectively, p = 0.005). In conclusion, serum adiponectin levels reflect the nutritional–inflammation status of hemodialysis patients. Adiponectin may also be associated with insulin resistance, dyslipidemia, and the inflammatory response in these patients.     

Effects of resistance exercise training on acyl-ghrelin and obestatin levels in hemodialysis patients

Abstract

Background: Patients undergoing hemodialysis (HD) present altered levels of appetite hormones such as acyl-ghrelin (orexigenic) and obestatin (anorexigenic), which may contribute to anorexia. Physical exercise may affect these hormones and improve appetite in these patients. Objectives: The objective of this study is to evaluate the effects of a resistance exercise program in appetite hormones, body composition, and nutritional status in HD patients. Design: Intervention study with the control group. Subjects: Fifty-two patients on regular HD program were enrolled into two groups: 37 patients performed exercises (56.7% male, 45?±?12.8 years, 57 (9–192) months on HD) and 15 patients comprised the control group (66.7% men, 50?±?10.6 years, 57 (11–153) months on HD). Measurements: Exercise program (performed with elastic bands and ankle cuffs in both lower limbs) was supervised three times a week during 6 months (72 sessions). Patients had their blood drawn in a regular HD day after overnight fasting, before and after 6 months of exercise program. Obestatin, acyl-ghrelin, routine biochemical parameters, quality of life, and anthropometric data were collected and analyzed before and after 6 months. Results: After 6 months of exercise, obestatin levels reduced [from 3.0?ng/mL (2.3–3.4) to 1.9?ng/mL (0.6–3.4)] and acyl-ghrelin levels increased [from 21.5?pg/mL (1.3–77.7) to 37.2?pg/mL (16.7–94.1)] and the control group presented no significant differences in both plasma levels of hormones. Body composition and physical functional assessed by SF-36 and albumin levels (3.7?±?0.3 to 3.9?±?0.2, p?<?0.05) improved after exercises. Conclusion: Six months of resistance exercises contributed to changes in plasma appetite hormones, body composition, and nutritional status in hemodialysis patients.     

Prevalence and Risk Factors of Myocardial Remodeling in Hemodialysis Patients

Background. Left ventricular hypertrophy (LVH) is an independent risk factor for morbidity/mortality in patients with end stage renal disease (ESRD). Our study aimed to identify prevalence as well as independent risk factors that contribute to the development of LV geometric remodeling in our HD patients. Methods. The left ventricles of 116 HD patients were classified echocardiographically into four different geometric patterns on the basis of LV mass and relative wall thickness. Furthermore, we measured inferior vena cava (IVC) diameter and its collapsibility index (CI) by echocardiography. Finally, we modeled a stepwise multiple regression analysis to determine the predictors of LV geometry.?Results. Our study provides evidence that HD patients had a prevalence of abnormal LV geometry in 92% and LVH in 81%. We found all four geometric models of LV. Most dominant were eccentric LVH. Concentric LVH was observed in 37, normal geometry (NG) in 9, and concentric remodeling (CR) in 13 of HD patients. Mean arterial blood pressure was significantly higher in the cLVH group (95 ± 10 mmHg) than in the NG and CR groups (81.6 ± 12.3 and 80 ± 11.8, respectively, p < 0.001). The cLVH and eCLVH groups had significantly lower mean hemoglobin (10.3 ± 1.4g/dL and 10.6 ± 1g/dL, respectively) compared with the NG group (11.9 ± 1.4g/dL), p < 0.001. Furthermore, interdialytic weight gain (kg) was significantly higher in eCLVH group (3.13 ± 0.8) than in NG group (2.3 ± 1.1), p < 0.001. Mean IVC index of the eLVH group (10.83 ± 2.07 mm/m²) was significantly higher than corresponding indexes of NG (10.83 ± 2.07 mm/m²), CR (8.31 ± 1.32 mm/m²) and cLVH (8.12 ± 2.06 mm/m²) groups (p < 0.001 for each comparisons). Conclusion. Mean arterial pressure, hemoglobin, IVC index, and interdialytic weight gain were found to be independent predictors of LV geometry (R² = 0.147; p < 0.001) in HD patients.     

Impact of Gastric Banding on Plasma Adiponectin Levels

Background: Several endocrine abnormalities are reported in obesity. In an earlier study, we found that the changes in BMI following laparoscopic adjustable gastric banding (LAGB) were associated with changes in hormone profiles such as insulin and proinsulin. In the current study, we explored the changes in plasma adiponectin levels in morbidly obese subjects who lost abundant weight following LAGB. Methods: 23 adult morbidly obese patients (15 females), aged 21-56 years, were studied. Blood samples were collected before, and 6 and 14 months after LAGB. The plasma adiponectin levels were determined by commercial kit (B-Bridge International, Inc). Statistical analysis was based on one-way repeated measures ANOVA, followed by Student-NewmanKeuls post-hoc test. Regression model was used to look for predictors of adiponectin change after LAGB. Results: Mean BMI before surgery was 46.04±4.44 kg/m², and decreased significantly by 18% 6 months after surgery to 37.67±4.47 kg/m². BMI further decreased by 32% 14 months after surgery to a mean of 31.30±4.65 kg/m² (P =.000). The mean adiponectin level before surgery was 3997±1766 μg/ml, and increased significantly by 16% to 4763±1776 μg/ml 6 months after surgery, and to 6336±3292 μg/ml (37%) 14 months after surgery. Although BMI persistently decreased, while adiponectin persistently increased, BMI did not correlate with adiponectin. Conclusion: In morbidly obese patients who underwent LAGB, adiponectin levels persistently increased, probably due to the reduction of visceral fat mass. Adiponectin plasma increase was correlated with proinsulin levels prior to the surgery. The interaction between adiponectin, proinsulin and BMI change in morbid obesity merits further investigation.     

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.     

Assessment of the relationship between serum paraoxonase activity and epicardial adipose tissue in hemodialysis patients

Purpose

Paraoxonase-1 (PON-1) is a high-density lipoprotein-associated (HDL) enzyme, which has been shown to reduce susceptibility to low-density lipoprotein (LDL) peroxidation. Epicardial adipose tissue (EAT) is a marker of atherosclerosis. The aim of this study was to determine the relationship between PON-1 activity and EAT in hemodialysis (HD) patients.

Methods

This is a cross-sectional study conducted on 72 (43 males) HD patients with end-stage renal disease. Serum levels for lipid profiles, C-reactive protein, calcium, phosphate, and parathyroid hormone were measured. PON-1 activity was also measured and compared to the rate of enzymatic hydrolysis of paraoxon to p-nitrophenol. Echocardiography was used to measure EAT thickness (EATT). The correlation between PON-1 and EATT was assessed, while independent predictors of EATT in HD patients were similarly assessed using multivariate regression analysis.

Results

There was a significant low mean value of PON-1 activity in HD patients compared with the control group (82.1 ± 31.6 vs. 164.3 ± 61.5 U/l, p = 0.0001) and significant high mean value of EATT in HD patients, compared with controls (6.2 ± 1.7 vs. 3.9 ± 1.1 mm, p = 0.0001). In addition, there was a significant negative correlation between PON-1 activity and EATT (r = ?0.484, p = 0.0001) and a significant positive correlation between PON-1 activity and HDL-C (r = 0.417, p = 0.0003). PON-1, total cholesterol, triglycerides, LDL, HDL, age, and body mass index were found to be independent predictors of EATT.

Conclusion

Our study demonstrated that PON-1 activity was significantly lower in HD patients compared with healthy controls and that PON-1 activity was inversely correlated with EATT in this population.