Associations between apolipoprotein E gene polymorphism and plasminogen activator inhibitor-1 and atherogenic lipid profile in dialysis patients

BACKGROUND: Apolipoprotein-E (ApoE) gene polymorphism has an important role in lipoprotein metabolism and could participate in the development of cardiovascular diseases (CVD). Plasminogen activator inhibitor-1 (PAI-1) is also regarded as a risk factor for CVD. The aim of the present study is to further investigate the possible link(s) between ApoE gene polymorphism and plasma PAI-1 antigen and serum lipid profile in peritoneal dialysis (PD) and hemodialysis (HD) patients. MATERIAL AND METHODS: We studied 72 PD patients (38 female, mean age 49.9 +/- 16.1 years), 72 HD patients (22 female, mean age 57.4 +/- 14.6 years), and 42 healthy subjects (21 female, mean age 50.1 +/- 18.6 years). Serum lipid parameters, plasma PAI-1 levels, and ApoE genotypes were determined in all subjects. RESULTS: The distribution of ApoE genotypes and alleles frequencies was similar in dialysis patients and healthy controls. In PD patients, total cholesterol (TC), low-density lipoprotein (LDL)-C, and ApoB levels were significantly higher than that of HD patients. HD patients with E3/4 genotype had elevated TC, LDL-C and ApoB levels compared with E3/3 genotype. TC and triglyceride levels were also higher in E3/4 genotype than that of E2/3 genotype. PD and HD patients showed a significantly increased PAI-1 levels compared with controls, whereas PAI-1 levels were highest in HD patients. There was no significant relation between ApoE genotypes and PAI-1 levels. CONCLUSIONS: The present study suggests that ApoE polymorphism significantly affects serum lipid profile in HD patients and epsilon4 allele carriers are more susceptible to have atherogenic lipid profile.     

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.     

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.     

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.     

Increased Body Mass Index Is Not a Reliable Marker of Good Nutrition in Hemodialysis Patients

Objective. The aim of the study was to assess the body fat (BF) composition in hemodialysis (HD) patients using anthropometry and bioelectrical impedance analysis (BIA) and investigate relationships between BIA-determined BF composition and nutritional parameters in different weight groupings. Design. Cross-sectional study. Setting. A tertiary-care university hospital. Methods. 164 HD patients (M/F: 89/75, mean age: 48.4 ± 15.8 years, mean HD duration: 58.2 ± 42.6 months) were divided into three groups according to body mass index (BMI): normal weight (NW: BMI 18.5–24.9), overweight (OW: BMI 25–29.9), obese (OB, BMI ≥ 30). Biochemical parameters and BF composition using anthropometry and foot-to-foot BIA were compared between three groups. Results. Ninety-six (59%) patients were NW, 40 (24%) were OW, and 28 (17%) were OB. Average mean skinfold thickness (p = 0.005), mid-arm circumference (p = 0.001), BF% (p = 0.001), and fat-free mass (FFM) (p = 0.03) were all significantly greater in the OB group than in the NW group. Compared to the NW patients, the OB group had significantly higher serum levels of glucose (p = 0.03), total cholesterol (p = 0.02), and triglycerides (p = 0.02), but significantly lower serum albumin (p = 0.05) and blood urea nitrogen (p = 0.05). The OB group also had significantly higher white blood cell count (p?=?0.002) and serum CRP (p = 0.001) than the NW group. Conclusions. The results suggest that BIA-determined BF composition is correlated with body mass index. In addition, obesity is associated with elevated CRP and white blood cell count and lower serum albumin level in HD patients.     

Influence of long-term recombinant human erythropoietin (rHuEpo) therapy on plasma leptin and neuropeptide Y concentration in haemodialysed uraemic patients

Background: In patients with chronic renal failure, rHuEpo therapy ameliorates anaemia and improves wellbeing, exercise tolerance, and appetite. Both leptin and neuropeptide Y play an important role in regulation of appetite and energy balance in humans. Methods: The present study aimed to assess the influence of 12 months rHuEpo therapy on plasma leptin and neuropeptide Y concentrations in 15 haemodialysed patients (HDP) (6F, 9M; mean age 4.8±2.9 years; mean BMI 23.6±1.1 kg/m²; mean duration of HD 3.3±0.6 months) (Epo group). A second group (no-Epo group) consisted of 17 HDP (9F, 8M; mean age 44±3.2 years; mean BMI 24.3±1.0 kg/m²; mean duration of HD 2.5±0.4 months not treated with rHuEpo for 12 months. Basal plasma leptin and neuropeptide Y concentrations were estimated by RIA at the beginning and after 3, 6, 9 and 12 months of rHuEpo therapy (Epo group) or clinical observation (No-Epo group). The control group consisted of 30 healthy subjects (15 females, 15 males, mean age-38.2±1.7 years, mean BMI 24.7±0.7 kg/m²). Results: Baseline plasma leptin concentrations in HDP were higher, although statistically not significant than leptinaemia in healthy subjects. After 3, 6, and 12 months of rHuEpo therapy plasma leptin concentrations were significantly lower than at the beginning of the study. Baseline plasma neuropeptide Y concentrations in HDP did not differ significantly from controls. After 3 and 6 months of the study period plasma neuropeptide Y concentrations increased significantly in patients of both the Epo and No-Epo group. This increase was, however significantly higher in rHuEpo-treated than in untreated patients. Conclusions: (1) rHuEpo treatment in haemodialysed patients with chronic renal failure is followed by a significant decline of leptinaemia and disappearance of the physiological positive BMI/leptinaemia relationship. (2) Suppression of leptinaemia induced by rHuEpo may be of clinical relevance in haemodialysed patients with chronic renal failure.     

Atherosclerosis is associated with plasminogen activator inhibitor type-1 in chronic haemodialysis patients

Aim: The aim of the present report was to investigate the probable association of circulating levels of PAI-1 and expression of PAI-1 in internal iliac artery walls with atherosclerotic disease in chronic haemodialysis (HD) patients. Methods: Sixty-eight non-diabetic HD patients and 50 age- and sex-matched healthy normotensive controls participated in the study. Atherosclerotic disease in both groups was assessed by measuring intima-media thickness (IMT) and plaque score of the common carotid arteries using an ultrasound scanner. Levels of serum PAI-1, C-reactive protein (CRP), interleukin (IL)-6 and lipids profile were measured. Internal iliac artery samples were obtained at the time of renal transplantation. Quantitative expression of PAI-1 in internal iliac artery walls was assessed by positive unit (pu) value using an immunohistochemical method. In addition, the IMT and carotid plaque score were analyzed in relation to circulating levels of PAI-1 and expression of PAI-1 in internal iliac artery walls. Results: Compared with control subjects, HD patients had significantly increased common carotid artery (CCA)-IMT (P = 0.002). Atherosclerotic plaques were detected in 42 (61.76%) of HD patients and in two (4%) controls. The above ultrasonographic indices were correlated with age in HD patients (P < 0.001). A significant relationship was observed between IMT and systolic blood pressure (BP), low-density lipoprotein in HD patients (P < 0.001 and P < 0.001, respectively). In HD patients, IMT was significantly correlated with CRP and IL-6 (P < 0.001 and P < 0.001, respectively). In HD patients, a close correlation was found between serum PAI-1 level, CRP and IL-6 (P < 0.01 and P < 0.01, respectively). A close correlation was also found between PAI-1 pu value, CRP and IL-6 (P < 0.01 and P < 0.01 respectively). Serum PAI-1 level is highly correlated to PAI-1 pu value (P < 0.01). In HD patients, CCA-IMT and plaque score were correlated significantly with circulating levels of PAI-1(P < 0.01 and P < 0.05, respectively) and expression of PAI-1 in internal iliac artery walls (P < 0.01 and P < 0.05, respectively). Multivariate analysis showed that log CRP values were a strong independent contributor to CCA-IMT and plaque score (P = 0.03 and P = 0.04, respectively). Multivariate analysis showed that serum PAI-1 concentration was a strong independent correlate of CCA-IMT and carotid plaque score (P = 0.004 and P = 0.009, respectively). Multivariate analysis also showed that expression of PAI-1 in internal iliac artery walls was a strong independent correlate of CCA-IMT and carotid plaque score (P = 0.008 and P = 0.005, respectively). Conclusion: The circulating levels of PAI-1 and expression of PAI-1 in internal iliac artery walls were statistically associated with CRP, IL-6 and low-density lipoprotein cholesterol. Moreover, in HD patients, CCA-IMT and plaque score were correlated significantly with circulating levels of PAI-1 and expression of PAI-1 in internal iliac artery walls and the circulating levels of PAI-1 and expression of PAI-1 in internal iliac artery walls were independent predictors of carotid atherosclerosis including CCA-IMT and carotid plaque score. The correlations may suggest that increased circulating PAI-1 level and upregulated expression of PAI-1 in the vasculature could indicate a chronic endothelium activated state and PAI-1 may more precisely identify the risk of atherothrombosis and be useful as a target for anti-inflammatory treatment strategies.     

Discrepancies in Serum Albumin Measurements Vary by Dialysis Modality

Background.?Serum albumin level is an important prognostic marker in patients with chronic renal failure. However there are discrepancies in the methods of estimation of serum albumin. The objective of this study is to evaluate the magnitude of the discrepancy in the serum albumin levels as measured by Bromcresol Green (BCG) and Bromcresol Purple (BCP) dye methods in patients on hemodialysis (HD) and peritoneal dialysis (PD) and to ascertain the clinical determinants of the discrepancy (ΔSA = BCG-BCP; g/dL) in each of the modalities. Method.?We measured serum and plasma albumin levels by BCG and BCP methods in 19 adult HD patients and 18 adult PD patients treated in the dialysis units of the University of Colorado Health Sciences Center. Similar measurements were performed in 10 normal adult subjects. In all groups, paired blood samples were taken to estimate the albumin in both serum and plasma. Nephelometry (NM) was subsequently performed on the serum of 13 of the HD patients, 14 of the PD patients, and each of the 10 normal subjects. Results.?We found that for both the dye methods serum and plasma albumin levels are almost identical in each of the three subject groups. In the normal subjects serum albumin estimated by BCP is in good agreement with NM values but BCG overestimates the albumin levels. In the PD group the discrepancy between the BCG and BCP (ΔSA) is statistically significant with the BCG averaging 0.59 ± 0.12 g/dL more than the BCP. The BCG values are closer to those obtained by the “gold standard”, NM. In the HD group the ΔSA is significantly (p<0.001) less than in the PD group (0.34 ± 0.11 g/dL). As for PD, BCG values are closer to NM values. Increasing age, female gender, and higher dialysis adequacy are associated with higher ΔSA in the HD but not in the PD group. Utilizing linear regression analysis we developed equations for each dialysis modality to convert albumin measurements from one method to the other. Conclusion.?We confirm that a discrepancy exists between the commonly used dye methods (BCG and BCP) for serum albumin estimation. This discrepancy is significantly lower in HD patients than in PD patients. Nephrologists should be aware of this discrepancy and appropriate corrections should be made during quality improvement analysis.     

Correlation of Serum Leptin Concentrations with Body Composition and Gender in Taiwanese Hemodialysis Patients without Diabetes

Objective.?(1) To evaluate the impact of body composition and gender on serum leptin concentration in hemodialysis patients. (2) To study which marker of adiposity is most appropriate in Taiwanese hemodialysis patients without diabetes. (3) To compare the nutrition status between nonlean and lean subjects. Patients and Methods.?Serum leptin concentrations were measured by radioimmunoassay collected in 88 hemodialysis patients without diabetes. Bioimpedance analysis was performed to determine percent fat mass (%FM), lean body mass (LM), and total body water (TBW). Body mass index (BMI) was calculated as weight/height². Albumin and transferrin were measured by standard laboratory methods. Results.?Serum leptin levels were more correlated with percent fat mass (r = 0.697; P<0.001) than with body fat mass (r = 0.672; P<0.001) or with BMI (r = 0.594; P<0.001) in the group as a whole and in each subgroup when analyzed separately by gender. The mean (±SD) serum leptin levels were 32.5 ± 34.3 ng mL^?1 in women subjects and 13.6 ± 15.5 ng mL^?1 in men subjects (P<0.001). Multiple regression analysis in all subjects revealed that serum leptin levels were independently affected by percent fat mass and gender. Adiposity corrected serum leptin, such as leptin/BMI, leptin/percent fat mass, and leptin/body fat mass was significantly different between sexes (P<0.001). The significantly higher serum leptin concentrations in women than in men were observed in obese subjects with BMI >25 kg/m² (P<0.001) as well as nonobese subjects with BMI<25 kg/m² (P<0.05). There were no differences in lean mass and albumin between nonlean and lean subjects. Conclusion.?Gender and adiposity had impact on serum leptin levels in hemodialysis patients without diabetes. In terms of adiposity, serum leptin levels had stronger correlation with percent fat mass than with body fat mass (FM) or BMI in Taiwanese hemodialysis patients. Steady-state serum leptin levels could serve as valuable clinical markers for the body adiposity in stable hemodialysis patients without diabetes. Protein malnutrition markers and lean mass should be checked in lean subjects for the evaluation of the protein stores of hemodialysis patients.     

Leptin and resistin levels and their relationships with glucose metabolism in children with chronic renal insufficiency and undergoing dialysis

AIM: The aim of the present study is: (i) to evaluate the serum concentrations of leptin and resistin in the paediatric patients with chronic renal impairment (CRI), on haemodialysis (HD) and on peritoneal dialysis (PD) treatment; (ii) to examine the relationship between these hormones; and (iii) to investigate the possible influence of these hormones on the insulin resistance and sensitivity indexes as well as on serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) levels. METHODS: In total, 52 patients (15 patients with CRI, 24 PD patients and 13 HD patients) and 23 healthy age- and sex-matched control subjects were included in the present study. RESULTS: Homeostasis model assessment of insulin resistance (HOMA-IR) was higher than 2.5 in 47.1% of the patients. IGF-1 levels of patients with CRI, PD and HD patients were significantly lower than those in the controls (P < 0.001, P < 0.001, P < 0.001, respectively). The leptin levels of patients with CRI and on PD and HD treatment were significantly higher than the control group (P = 0.038, P = 0.002, P = 0.006, respectively). Similarly, serum resistin levels of patients with CRI and those of PD and HD patients were higher when compared with healthy controls (P = 0.037, P < 0.001, P = 0.005, respectively). CONCLUSION: Leptin and resistin levels were increased in the children with CRF; however, this elevation was not found to be associated with hyperinsulinism. Further studies to explain the mechanisms and consequences of the accumulation of these hormones in CRF may provide the therapeutical approach aiming to normalize their circulating levels.     

Relationship between geriatric nutritional risk index and subpopulation lymphocyte counts in patients undergoing hemodialysis and peritoneal dialysis

We investigated the relationship between geriatric nutritional risk index (GNRI) and subpopulation lymphocyte counts (SLCs) in hemodialysis (HD) and peritoneal dialysis (PD) patients and evaluated whether they can be helpful in the diagnosis of malnutrition in these patients. We examined the GNRI and SLCs of 50 HD patients (mean: 55.8?±?12.7 years; 28 men and 22 women) and 16 Continuous Ambulatory Peritoneal Dialysis (CAPD) patients (mean: 49.8?±?14.5 years; 10 men and six women). The GNRI is calculated based on the serum albumin level, dry weight, and ideal body weight and uses the following equation: GNRI?=?[14.89?×?albumin (g/dL)]?+?[41.7?×?(weight/ideal body weight)]. SLCs were evaluated using flow cytometry. T-tests and χ² tests were performed to compare the two groups. Logistic regression analysis was performed for predicting malnutrition in dialysis patients. The average GNRI value was 100.1?±?8.4 in HD patients and 99.2?±?8.1 in PD patients, and no significant differences in GNRI or SLC were observed between the two groups. SLCs were higher in patients with higher GNRI (GNRI?≥?100) although there was no statistical difference. Logistic regression for predicting malnutrition according to GNRI revealed that age, female sex, and CD19 counts predicted malnutrition in HD and PD patients. These results suggest that GNRI and SLCs (especially CD19 count) may be significant nutritional markers in these patients.     

Changes in Leptin,Plasminogen Activator Factor and Oxidative Stress in Morbidly Obese Patients following Open and Laparoscopic Swedish Adjustable Gastric Banding

Background: Oxidative stress is increased in obesity, leading to endothelial dysfunction, atherogenesis, and platelet aggregation. The purpose of this study was to determine the effects of weight loss after bariatric surgery on serum lipids, malondialdehyde (MDA, a marker of oxidative stress), oxidized low-density lipoprotein (oxLDL, which is increased in obesity and causes endothelial dysfunction), paraoxonase (PON-1, which inhibits lipid peroxidation), leptin and plasminogen activator inhibitor type-1 (PAI-1, which contributes to a thrombotic state). Methods: 40 morbidly obese patients had insertion of a Swedish adjustable gastric band (SAGB). A lipid profile, MDA, oxLDL, PON-1, leptin and PAI-1 levels were drawn before and 6 months after the operation. 20 patients underwent open (Group 1) and 20 laparoscopic (Group 2) SAGB, to compare the systemic inflammatory response of the two approaches. Results: Patient demographics, indications for surgery, and postoperative results were no different between the groups. Postoperative BMI and concentrations of lipid, MDA, oxLDL, leptin and PAI-1 decreased significantly in both groups. PON-1 activity increased and was negatively correlated with BMI (r=-0.618, P< 0.01), MDA (r=-0.735, P<0.001), oxLDL (r=-0.701, P< 0.01), leptin (r=-0.626, P<0.01) and PAI-1 (r=-0.461, P<0.05). There was a correlation between BMI and MDA (r=0.790, P <0.001), and also leptin (r=0.900, P<0.001) and PAI-1 (r=0.888, P=0.001). There was no correlation between BMI and oxLDL. Conclusion: These findings support the hypothesis that in morbid obesity, weight loss after surgery has positive effects on fibrinolytic function, oxidative stress and antioxidant activity. Both operative approaches had similar effects in this study.     

Female Sexual Dysfunction in Peritoneal Dialysis and Hemodialysis Patients

Background. Sexual dysfunction (SD) is a common problem in end-stage renal disease (ESRD). In contrast to basic and clinical research in the field of male SD, the sexual problems of women have received relatively little attention and are often under-treated. We evaluated sexual function in female ESRD patients using the validated Female Sexual Function Index (FSFI) and relation with QOL, depression, and some laboratory parameters. Methods. 117 ESRD patients (85 peritoneal dialysis [PD], 32 hemodialysis [HD], mean age 48.5 ± 13.9 years) were enrolled. All patients had been dialyzed (PD or HD) for more than three months. In addition, an age-matched married control group of 48 subjects (mean age 47.1 ± 12.7 years) were enrolled in the study. All patients were asked to complete three questionnaires of the FSFI, Beck Depression Index (BDI) and SF-36. Results. Female sexual dysfunction was found in 80 of the 85 peritoneal dialysis patients (94.1%) and all of the HD patients (100%), but in only 22 subjects of the control group (45.8%). A significant negative correlation was found between total FSFI score and age (r = ?0.288, p = 0.002), BDI score (r = ?0.471, p < 0.001), mental-physical component score of QOL (r = ?0.463, p < 0.001 and r = ?0.491, p < 0.001, respectively) in PD and HD patients. The rates of depression were 75.3, 43.8, and 4.2% in the PD and HD patients and control subjects, respectively. Conclusion. Female sexual dysfunction is common problem ESRD. This problem especially related with depression and QOL. Thus, sexual function should be evaluated in female subjects to determine its impact on quality of life.     

Apelin and nutritional status in children on dialysis

Background: We aimed to evaluate whether serum apelin could reflect the nutritional status of children on dialysis. Methods: Twelve patients on peritoneal dialysis (PD) and 20 patients on hemodialysis (HD) were enrolled. Patients received individualized diet for six months. Anthropometric and laboratory indices were measured at onset and the end of the study. Results: The anthropometric indices were all significantly lower in patients than in controls whereas similar in PD and HD patients. The protein catabolic rate (nPCR), height, mid-arm circumference (MAC), triceps skinfold thickness (TSF), arm muscle area (AMA) and arm fat area (AFA) z scores were significantly increased in dialysis patients after nutritional intervention. Weight z scores statistically increased in HD group whereas did not statistically change in PD group. Serum albumin levels were significantly improved in PD and HD patients. Apelin levels were similar in PD, HD and control groups. Post nutritional apelin values did not differ in each dialysis groups. On multivariate analysis, apelin was independently associated with age, weight, ESR and TG. Conclusions: Apelin seems to be not a useful indicator for monitoring the nutritional status in children on dialysis. However, the close link of apelin with inflammatory and lipid parameters suggested that apelin might be a novel target for slowing the atherogenic process in pediatric dialysis patients.     

C-reactive protein but not hepcidin,NGAL and transferrin determines the ESA resistance in hemodialysis patients

Background: Erythropoiesis-stimulating agents (ESA) are commonly used for the treatment of anemia in hemodialysis (HD) patients, however, 5–10% of these patients have resistance to ESA treatment. Hepcidin and neutrophil-gelatinase associated lipocalin (NGAL) are induced by inflammation and these proteins may take role in ESA resistance. Herein, we aimed to investigate the effects of serum hepcidin, NGAL, transferrin and C-reactive protein (CRP) levels on ESA resistance in HD patients. Methods: A total of 63 chronic HD patients (6.0?±?17?years, M/F:44/19) and 20 healthy controls (6.0?±?4?years, M/F:14/6) were enrolled. ESA resistance index (ERI) was calculated as weekly ESA dose (IU)/body weight (kg)/hemoglobin level (g/dL). Patients on ESA treatment were divided into two groups depending on the median ERI value as low and high ERI groups. Results: Serum ferritin, hepcidin and NGAL levels were significantly higher in HD patients compared with controls. Serum transferrin levels were lower in high ESA index group compared with patients without ESA treatment and healthy controls. ERI was significantly correlated with serum CRP levels (r?=?0.55, p?r?=?0.55, p?r?=?0.27, p?=?0.03). Dose of ESA was significantly associated with serum CRP (r?=?0.34, p?=?0.02), total protein (r?=??0.34, p?=?0.01), transferrin (r?=??0.28, p?=?0.04) and ferritin (r?=?0.31, p?=?0.02). In linear regression analysis to predict ERI, age, gender, serum CRP, hepcidin, NGAL, albumin, ferritin and BMI were included (Model R?=?0.62, R²?=?0.38, p?=?0.02). Serum CRP was the only significant factor predicting ERI. Conclusion: CRP was the only predictor of ESA resistance index in HD patients. Hepcidin, NGAL and transferrin were not found to be markers of ESA resistance.     

Clinical morbidity in pediatric dialysis patients: data from the Network 1 Clinical Indicators Project

The Health Care Financing Administration (HCFA) has gathered clinical data on end stage renal disease (ESRD) patients since 1994, but details are only available on patients ≥18 years. In this report, we present morbidity data collected prospectively over 12 months from all children (1–18 years) maintained on either hemodialysis (HD) or peritoneal dialysis (PD) within the six-state New England area. During this year, 17 observations were recorded on 14 HD patients (age 13.4± 11.3 years) and 36 observations were made on 25 PD patients (age 11.5±4.8 years; mean ± SD). These patients were generally highly functional, attending school at least part time in nearly all cases. Dialysis adequacy index (DAI), defined as the delivered KT/V divided by DOQI guideline values, indicated that patients were well dialyzed (HD 1.41±0.1 and PD 1.10±0.1; mean ± SE). When all dialysis patients were grouped and analyzed, the DAI did not correlate with number of hospitalizations, degree of anemia, serum albumin, or type of dialysis. The number of hospitalizations were greater the younger the patient (P<0.01). The need for antihypertensive medications was higher in the children maintained on HD (94%) compared to children on PD (58%) (P<0.01). Lastly, while serum ferritin did not correlate with serum iron, hematocrit or Epo dosage, it was inversely related to serum albumin (P<0.03). We conclude that, in children, (1) exceeding suggested dialysis adequacy may not improve patient morbidity, (2) the need for antihypertensive medications appears greater in children maintained on HD, and (3) inflammation may play a role in determining serum albumin independent of nutrition. Received: 3 April 2001 / Revised: 26 June 2001 / Accepted: 10 July 2001     

Role of leptin in legg–calvé–perthes disease

Obesity is considered a clinical risk sign for Legg–Calvé–Perthes disease (LCPD). Leptin is primarily secreted by adipocytes, and it regulates adipose tissue mass and body weight. Furthermore, obesity is clearly associated with increased leptin levels. We investigated the roles of leptin and the soluble leptin receptor (sOB‐R) in LCPD. This matched case–control study included 38 male and 3 female patients with LCPD, and an equal number of age—(range was 4–12) and sex‐matched control patients with healthy fractures. Serum leptin and sOB‐R levels were quantified with ELISA. The free leptin index (FLI) was defined as the ratio of leptin to sOB‐R levels. Serum leptin levels, sOB‐R, and FLI were compared between groups. The relationship between leptin, disease severity, and treatment outcomes were analyzed in the LCPD group. There were no significant differences between groups in terms of age, sex, and body mass index (BMI) percentile. Mean leptin levels (p = 0.042), sOB‐R levels (p = 0.003), and FLI (p = 0.013) differed significantly between groups. In the LCPD group, the serum leptin levels, sOB‐R levels, and FLI differed significantly between the lateral pillar and Stulberg classification groups (p < 0.05). Also, the leptin levels and FLI increased significantly according to the lateral pillar and Stulberg classifications even after adjusting for age and BMI percentile (p < 0.05). Circulating leptin and FLI were significantly higher in the LCPD group. Furthermore, leptin, disease severity, and treatment outcomes were associated. This correlation suggests that leptin might play an important role in LCPD pathogenesis. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1605‐1610, 2013     

Impact of rHuEPO therapy initiation on soluble adhesion molecule levels in haemodialysis patients

Background: Increased levels of soluble adhesion molecules have been reported in haemodialysis (HD) patients. Recent studies have shown that recombinant human erythropoietin (rHuEPO) elicits proliferation and migration of endothelial cells and modifies endothelial function. The present study was design to explore the effects of rHuEPO on serum levels of soluble adhesion molecules in HD patients. Methods: Soluble serum levels of E‐selectin (sE‐selectin), intracellular adhesion molecule‐1 (sICAM‐1) and vascular cell adhesion molecule‐1 (sVCAM‐1) were measured by ELISA in 29 rHuEPO naïve HD patients (20 males, 9 females) and 10 control subjects at baseline and second month. The HD patients with a haemoglobin level lower than 10.0 mg/dL (n = 19) were administered rHuEPO therapy and other HD patients (n = 10) were followed as a placebo group. Results: Serum levels of soluble adhesion molecules were significantly higher in HD patients compared with the control group. A significant rise from the baseline in sE‐selectin levels (77 ± 70 vs 100 ± 86 ng/mL, P < 0.05) was observed 2 months after rHuEPO initiation, while sICAM‐1 and sVCAM‐1 levels decreased (271 ± 261 vs 197 ± 89 and 1043 ± 243 vs 990 ± 236 ng/mL, respectively, P < 0.05). Conclusions: The present data indicate that rHuEPO could have an important action on serum levels of soluble adhesion molecules in HD patients. rHuEPO might modify the expression of adhesion molecules from endothelial cells either. However, the exact mechanism responsible for the serum elevation of these molecules in HD patients is yet to be fully elucidated.     

Serum indoleamine 2,3 dioxygenase and tryptophan and kynurenine ratio using the UPLC-MS/MS method,in patients undergoing peritoneal dialysis,hemodialysis, and kidney transplantation

Background: The level and activity of indoleamine 2,3-dioxygenase (IDO) and the concentrations of L-tryptophan and its metabolite L-kynurenine were determined in association with various renal diseases. However, there have been no data regarding these parameters in patients on peritoneal dialysis compared to those undergoing hemodialysis or kidney transplantation.

Methods: This study investigated the level and activity of IDO and determined oxidative balance by calculating the total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI). We enrolled 60 kidney disease patients, including 20 on peritoneal dialysis (PD group), 19 on hemodialysis (HD group), and 21 with kidney transplantation (KT group), as well as 21 control group.

Results: IDO levels were increased in the PD, HD, and KT groups compared to the control group. The concentration of kynurenine was significantly increased in the PD group compared to the other groups (p?p?p?Conclusion: The results showed that IDO levels were increased in peritoneal dialysis and hemodialysis patients and in renal transplant recipients, while oxidative stress was found to be related to IDO activity and was most increased in the patients on peritoneal dialysis.     

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.