Association of the circulating adiponectin concentration with coronary in-stent restenosis in haemodialysis patients.

BACKGROUND: Success of coronary stenting is limited by in-stent restenosis. We aimed to determine whether circulating levels of the cytokines, which have anti-inflammatory properties such as adiponectin or interleukin-10, could be associated with the occurrence of coronary in-stent restenosis in patients with end-stage renal disease (ESRD). METHODS: We enrolled 71 consecutive ESRD patients undergoing haemodialysis (mean age: 64.9+/-8.9 years; 19 women, 52 men; mean haemodialysis duration: 78.2+/-87.5 months), who received stenting for a single coronary lesion. Plasma concentrations of adiponectin and IL-10 were measured within one week before coronary stenting. RESULTS: Of the 71 patients who had received stenting, in-stent restenosis occurred in 37 patients (52.1%) within 6 months after stenting. In univariate logistic analysis, the homeostasis model assessment index of insulin resistance, blood haemoglobin, serum concentrations of high density lipoprotein-cholesterol or triglycerides and plasma concentrations of insulin or adiponectin were significantly associated with coronary in-stent restenosis. In a multiple logistic regression analysis among these variables, however, only the plasma adiponectin concentration was associated with the coronary in-stent restenosis: the odds ratio of the increase in 1 microg/ml of plasma adiponectin concentration for having restenosis was 0.651 (P = 0.001, 95% confidence interval: 0.506-0.839). Patients with restenosis had lower plasma adiponectin concentrations than those without [6.2+/-2.2 microg/ml (2.1-10.4 microg/ml; n = 37) vs 27.2+/-10.8 microg/ml (17.9-79.8 microg/ml; n = 34); P = 0.0001]. CONCLUSIONS: Circulating adiponectin concentrations may be associated with the occurrence of coronary in-stent restenosis in ESRD patients undergoing maintenance haemodialysis.     

Plasma adiponectin concentration before and after successful kidney transplantation

BACKGROUND: Adiponectin, a protein secreted exclusively by adipocytes, is presumed to be involved in the pathogenesis of atherosclerosis and insulin resistance. An elevated plasma adiponectin concentration was found in ESRD patients on hemodialysis (HD). However, the role of kidneys in adiponectin biodegradation/elimination is unknown. Therefore, we assessed plasma adiponectin concentrations in ESRD patients before and after successful kidney transplantation. METHODS: Among 44 hemodialyzed patients (29 men, 15 women; mean age 39 +/- 11 years; mean body mass index [BMI] 23.6 +/- 3.5 kg/m(2); mean duration of HD treatment before kidney transplantation 27 +/- 26 months), plasma adiponectin concentrations and insulin resistance indices (HOMA-R) were measured twice: immediately before kidney transplantation (Tx) and 1-2 days before patient discharge from the hospital with stable kidney transplant function (mean serum creatinine level 191 +/- 105 micromol/L). The control group consisted of 22 normotensive healthy subjects (12 men, 10 women). RESULTS: Among uremic patients, before Tx, plasma adiponectin concentrations were significantly higher than in healthy subjects (20.8 +/- 8.3 vs 8.7 +/- 4.8 microg/mL; P <.001) After successful Tx, plasma adiponectin concentrations decreased significantly (20.8 +/- 8.3 vs 15.7 +/- 7.0 microg/mL before and after Tx, respectively; P <.001). Simultaneously, after successful kidney transplantation, an increase in HOMA-R was observed (1.01 +/- 0.61 vs 1.43 +/- 0.83; P =.002). However, changes in adiponectinemia did not significantly correlate with serum creatinine or HOMA-R. CONCLUSION: The kidneys seem to play an important role in adiponectin biodegradation and/or elimination.     

Plasma pentraxin 3 is associated with cardiovascular disease in hemodialysis patients

This cross-sectional study evaluates the associations of Pentraxin 3 (PTX3) and cardiovascular disease (CVD) in hemodialysis (HD) patients. Plasma was obtained from 98 maintenance HD patients before and after a session of HD and 50 age-matched healthy subjects. We measured plasma PTX3 levels by enzyme-linked immunosorbent assay. Our results showed that plasma PTX3 levels were significantly higher in HD patients compared with controls (1.87 vs. 1.11 ng/mL, p < 0.001), and increased acutely after a single HD session (post-HD 2.18 ng/mL vs. pre-HD 1.87 ng/mL, p < 0.001). Patients with CVD had higher plasma PTX3 levels than those without CVD (2.18 vs. 1.76 ng/mL, p < 0.05). Plasma PTX3 levels correlated positively with cardiac troponin T (ρ = 0.287, p = 0.007) and carotid artery intima-media thickness (ρ = 0.294, p = 0.043). High plasma PTX3 (>1.87 ng/mL) level was positively and independently associated with CVD (OR = 3.15, p = 0.024). Receiver operator characteristics analysis showed the correlation between PTX3 and CVD more closely than high sensitivity C-reactive protein (hs-CRP) in patients whose hs-CRP were higher than 3 mg/L. The area under the curve for PTX3 and hs-CRP was 0.655 (p = 0.047) and 0.562 (p = 0.458), respectively. Moreover, plasma PTX3 levels correlated negatively with body mass index, hemoglobin, pre-albumin, total cholesterol, triglyceride, and low-density lipoprotein. These data support the main conclusions: PTX3 levels are markedly elevated in HD patients; HD procedure itself induces PTX3 elevation; plasma PTX3 is associated with CVD in maintenance HD patients.     

Adiponectin and cardiovascular remodeling in end-stage renal disease and co-morbid diabetes mellitus

OBJECTIVES AND METHODS: Altered plasma high-sensitivity C-reactive protein (hs-CRP) and adiponectin (ADP) may contribute to increased vascular inflammation and accelerated atherosclerosis in patients with end-stage renal disease (ESRD) and co-morbid diabetes. Common carotid artery intima-media thickness (CCA-IMT) and atherosclerotic plaque occurrence, left-ventricular mass index (LVMI), and pulse wave velocity of the proximal aorta (PWVr) were determined by ultrasound imaging in 120 ESRD (55 diabetic) patients, and 83 age-, sex-, and blood pressure-matched controls. Also, plasma levels of ADP and hs-CRP were determined and their relationships with the above cardiovascular alterations were analyzed. RESULTS: LVMI, PWVr, CCA-IMT and atherosclerotic plaque occurrence were all increased in ESRD patients compared to controls (all p < 0.001). LVMI (p < 0.05), PWVr (p < 0.001), CCA-IMT (p < 0.001) and atherosclerotic plaque occurrence (p < 0.001) were increased in diabetic compared to nondiabetic ESRD patients. Hs-CRP levels were increased and ADP levels were decreased in diabetic compared to nondiabetic ESRD patients (both p < 0.001). ADP levels correlated inversely with hs-CRP (r = -0.473, p < 0.0001) in ESRD patients. Hs-CRP was positively correlated with LVMI (r = 0.365, p < 0.0001), PWVr (r = 0.42, p < 0.0001) and CCA-IMT (r = 0.18, p = 0.047) while ADP inversely correlated with PWVr (r = -0.263, p = 0.0035) and CCA-IMT (r = -0.207, p = 0.022) in ESRD patients. CONCLUSION: The present results indicate diabetic disease-specific alterations in the biochemical parameters of hs-CRP and ADP in ESRD patients. The above biochemical parameters were intimately linked to the cardiovascular measurements of LVMI, PWVr and CCA-IMT in patients with ESRD and co-morbid diabetes mellitus.     

Reduced gene expression of adiponectin in fat tissue from patients with end-stage renal disease

BACKGROUND: Cardiovascular disease (CVD) is the main cause of death in end-stage renal disease (ESRD) patients. It has been suggested that inflammation plays a key role in the development of both atherosclerosis and malnutrition (MIA), a combination of complications associated with poor outcome. Although plasma levels of adiponectin, a recently discovered anti-inflammatory and antiatherogenic adipocytokine, are markedly elevated in ESRD, gene expression of adiponectin (ApM1) has not been analyzed in ESRD patients. METHODS: We analyzed the ApM1 gene expression in adipose tissue from 18 ESRD patients of whom 9 (7 males, 60 +/- 8 years, BMI 24 +/- 6 kg/m(2)) had a high prevalence of MIA complications, and 9 age- (55 +/- 9 years), gender- (7 males) and BMI- (24 +/- 2 kg/m(2)) matched ESRD patients had few MIA complications. The results were compared with age- (59 +/- 11 years), gender- (7 males), and BMI- (24 +/- 6 kg/m(2)) matched healthy control patients. Information on CVD was obtained at the recruitment based on a detailed medical history. Malnutrition was defined as a subjective global assessment (SGA) score >1. Inflammation was defined as CRP >/=10 mg/L. Gene expression analysis was performed using the in situ hybridization technique. RESULTS: Gene expression of ApM1 was lower in ESRD patients compared with healthy control patients (P= 0.001). On the other hand, when comparing the gene expression between ESRD patients with and without MIA complications, respectively, no difference in the ApM1 gene expression was detected. CONCLUSION: Adiponectin gene expression is significantly down-regulated in ESRD patients compared with healthy control patients. We propose that the decrease in expression may be the result of a negative feedback regulation, as a result of elevated levels of circulating adiponectin caused by renal failure.     

Plasma pentosidine is associated with inflammation and malnutrition in end-stage renal disease patients starting on dialysis therapy

Pentosidine is an advanced glycation end-product (AGE), formed by glycosylation and oxidation, that accumulates markedly in end-stage renal disease (ESRD). It has been speculated that AGE and carbonyl stress contributes to long-term complications such as cardiovascular disease (CVD) in ESRD patients. This study determined plasma levels of pentosidine as well as the presence of inflammation (CRP > or = 10 mg/L), clinical CVD (CVD(clin)), and malnutrition (subjective global assessment [SGA] > 1) in a cohort of 191 ESRD patients, median age of 55 yr (range, 23 to 70 yr) and median GFR = 7 ml/min (range, 2 to 17 ml/min), close to start of renal replacement therapy. Fifty-one elderly subjects, median age of 82 yr (range, 71 to 110 yr), with mild renal impairment, median GFR = 67 ml/min (range, 38 to 113 ml/min), were also studied for comparative analysis of plasma pentosidine. The plasma pentosidine content was elevated in all patients compared with the levels in the elderly subjects and were negatively correlated with GFR both in the ESRD patients (Rho = -0.24; P < 0.01; n = 159) and in the elderly subjects (Rho = -0.31; P < 0.05). Moreover, the plasma pentosidine content was correlated with age in the ESRD patients (Rho = 0.26; P < 0.001) and in the elderly subjects (Rho = 0.44; P < 0.001). The 63 malnourished ESRD patients (35%) had a significantly higher (P < 0.05) median plasma pentosidine than the well-nourished patients (39 versus 27 pmol/mg albumin). Similarly, 73 inflamed patients (38%) had a significantly higher (P < 0.001) median pentosidine content compared with 118 non-inflamed patients (37 versus 24 pmol/mg albumin). Also, the plasma pentosidine content showed weak but significant positive correlations with CRP (Rho = 0.28; P < 0.0001), fibrinogen (Rho = 0.23; P < 0.01; n = 126), IL-6 (Rho = 0.22; P < 0.01; n = 169), and soluble vascular cellular adhesion molecule-1 (Rho = 0.38; P < 0.001; n = 74). On the other hand, no significant differences in plasma pentosidine content were noted between the patients with and those without CVD(clin) (32 versus 27 pmol/mg albumin, respectively). Analyses of all-cause mortality, by Kaplan-Meier, showed that mortality was not linked to the plasma pentosidine content. Moreover, survival analysis by the Cox regression model showed that age (P < 0.001), diabetes mellitus (P < 0.01), malnutrition (P < 0.01), and CVD(clin) (P < 0.01) independently predicted poor outcome, whereas an elevated plasma pentosidine content did not. The present study shows that an elevated plasma pentosidine content in ESRD patients is significantly associated with both inflammation and malnutrition and confirms that low residual renal function and high age further contribute to an increased plasma pentosidine content. However, in this small cohort, the plasma pentosidine content did not predict outcome. Thus, accumulation of plasma pentosidine is unlikely to be an appropriate clinically useful marker to predict mortality in ESRD patients.     

Plasma Pentraxin 3 is Associated with Cardiovascular Disease in Hemodialysis Patients

Abstract

This cross-sectional study evaluates the associations of Pentraxin 3 (PTX3) and cardiovascular disease (CVD) in hemodialysis (HD) patients. Plasma was obtained from 98 maintenance HD patients before and after a session of HD and 50 age-matched healthy subjects. We measured plasma PTX3 levels by enzyme-linked immunosorbent assay. Our results showed that plasma PTX3 levels were significantly higher in HD patients compared with controls (1.87 vs. 1.11 ng/mL, p < 0.001), and increased acutely after a single HD session (post-HD 2.18 ng/mL vs. pre-HD 1.87 ng/mL, p < 0.001). Patients with CVD had higher plasma PTX3 levels than those without CVD (2.18 vs. 1.76 ng/mL, p < 0.05). Plasma PTX3 levels correlated positively with cardiac troponin T (ρ = 0.287, p = 0.007) and carotid artery intima-media thickness (ρ = 0.294, p = 0.043). High plasma PTX3 (>1.87 ng/mL) level was positively and independently associated with CVD (OR = 3.15, p = 0.024). Receiver operator characteristics analysis showed the correlation between PTX3 and CVD more closely than high sensitivity C-reactive protein (hs-CRP) in patients whose hs-CRP were higher than 3 mg/L. The area under the curve for PTX3 and hs-CRP was 0.655 (p = 0.047) and 0.562 (p = 0.458), respectively. Moreover, plasma PTX3 levels correlated negatively with body mass index, hemoglobin, pre-albumin, total cholesterol, triglyceride, and low-density lipoprotein. These data support the main conclusions: PTX3 levels are markedly elevated in HD patients; HD procedure itself induces PTX3 elevation; plasma PTX3 is associated with CVD in maintenance HD patients.     

Low fetuin-A levels are associated with cardiovascular death: Impact of variations in the gene encoding fetuin

BACKGROUND: Vascular calcification is common among end-stage renal disease (ESRD) patients and a central characteristic of the atherosclerotic cardiovascular disease observed in dialysis patients. Fetuin-A, a circulating calcium-regulatory glycoprotein that inhibits vascular calcification, is associated with inflammation and outcome in dialysis patients. In the present study, we evaluated the association between fetuin-A, clinical phenotype, and outcome, as well as the impact of fetuin gene (AHSG) polymorphisms on the protein product and outcome. METHODS: In a cohort of 258 (161 males) ESRD patients starting renal replacement therapy [glomerular filtration rate (GFR) 6.8 +/- 0.2 mL/min] aged 52 +/- 1 years the following parameters were studied: presence of malnutrition (subjective global assessment), comorbidity [diabetes mellitus and clinical manifest cardiovascular disease (CVD)], carotid plaques (N= 101), hs-CRP, fetuin-A, S-albumin, interleukin (IL)-6, and single nucleotide polymorphisms (SNPs) in the AHSG gene (N= 215) at amino acid positions Thr248Met (C-->T), Thr256Ser (C-->G), Asp276Asn (G-->A), and Arg317Cys (C-->T). RESULTS: Both all-cause (P < 0.001) and cardiovascular (P < 0.001) mortality were associated with low fetuin-A levels independently of age, smoking, diabetes, S-albumin, CVD, and inflammation (CRP > or =10 mg/L). Inflamed (0.199 vs. 0.247 g/L; P < 0.01) and malnourished (0.207 vs. 0.262 g/L; P < 0.05) patients had significantly lower median fetuin-A than noninflamed and well-nourished ESRD patients, respectively. In a logistic regression model (N= 101), fetuin-A was significantly (P < 0.05) associated with the presence of carotid plaques independently of age, CVD, diabetes, S-albumin, gender, and inflammation. Significant correlations were observed between fetuin-A and both S-albumin (Rho = 0.30; P < 0.0001) and IL-6 (Rho =-0.21; P < 0.01). Patients with the AHSG 256Ser allele had lower serum fetuin-A levels, and higher all-cause and cardiovascular mortality rate if they were inflamed. CONCLUSION: The present study shows that a low fetuin-A level is associated with malnutrition, inflammation, and atherosclerosis (carotid plaques), as well as with increased cardiovascular and all-cause mortality. Because the present study demonstrates an effect of variations in the AHSG gene on both circulating fetuin-A levels and outcome, this indicates that ESRD patients with the AHSG 256Ser allele are at risk of accelerated vascular calcification.     

Total and high molecular weight adiponectin concentrations in plasma of patients with end-stage renal disease before and after peritoneal dialysis

Background: Adiponectin is an antiatherogenic adipocyte‐derived proteins. The level of plasma adiponectin is inversely correlated to cardiovascular risk in patients with end‐stage renal disease (ESRD). The aim of this study was to elucidate the changes of adiponectin concentrations in newly diagnosed ESRD patients after peritoneal dialysis. Methods: In 16 newly diagnosed ESRD patients, total concentrations of adiponectin and high molecular weight (HMW) adiponectin, the HMW ratio (HMWR; ratio of the plasma level of HMW adiponectin to that of total adiponectin), the body mass index (BMI), insulin concentrations, blood glucose and estimation of the insulin sensitivity index by the homeostasis model assessment (HOMR_IR) were compared before and after 1 year of peritoneal dialysis. Results: Plasma total adiponectin was decreased from 15.52 ± 9.35 μg/mL to 11.80 ± 6.84 μg/mL (P = 0.046), HMW adiponectin was decreased from 9.05 ± 6.48 μg/mL to 4.83 ± 4.15 μg/mL (P = 0.009), and HMWR was decreased from 0.51 ± 0.18 to 0.35 ± 0.20 (P = 0.008). Total and HMW adiponectin/BMI ratio was decreased. The BMI was increased from 25.2 ± 5.7 to 25.8 ± 6.2 (P = 0.036). The HOMR_IR, insulin level and lipid profile were not changed. Conclusion: Total adiponectin, HMW adiponectin and HMWR were decreased in newly diagnosed ESRD patients after 1 year of peritoneal dialysis. The factors that influence the decrease of the level of adiponectin should be studied in a larger prospective study.     

Steroid pulse therapy impaired endothelial function while increasing plasma high molecule adiponectin concentration in patients with IgA nephropathy.

BACKGROUND: Decreased plasma adiponectin is associated with impaired endothelial function and, thereby, increased risk for cardiovascular events. Glucocorticoid (GC) affects vascular endothelial cells either favourably or harmfully depending upon the dosages and duration. We examined the effect of GC pulse therapy on vascular endothelial function. METHODS: Fourteen young patients with IgA nephropathy were evaluated for flow-mediated vasodilation (FMD), plasma levels of adiponectin both in high molecular weight (HMW adiponectin) form and in single molecular form (total adiponectin), hepatocyte growth factor (HGF), asymmetric dimethylarginine (ADMA), and high-sensitive C-reactive protein, before and after a course of GC pulse therapy. RESULTS: GC pulse therapy significantly decreased FMD (from 7.2 +/- 2.6 to 5.7 +/- 2.5%, P < 0.01). Meanwhile, plasma adiponectin levels were significantly augmented (total adiponectin: from 10.2 +/- 4.0 to 12.1 +/- 6.3 microg/ml, P < 0.05; HMW: from 6.5 +/- 3.2 to 7.7 +/- 3.3 microg/ml, P < 0.05). In parallel, elevated concentrations of serum HGF (from 0.28 +/- 0.12 to 0.63 +/- 0.38 ng/ml, P < 0.01) and plasma ADMA (from 0.45 +/- 0.07 to 0.53 +/- 0.04 nmol/ml, P < 0.05) were observed. CONCLUSIONS: GC pulse therapy impaired endothelial function while increasing plasma adiponectin levels, which may in turn restore the endothelial function in patients with IgA nephropathy.     

Effect of antihypertensive agents on plasma adiponectin levels in hypertensive patients with metabolic syndrome

AIM: Plasma adiponectin levels are well associated with metabolic syndrome. However, the relationship between hypertension and plasma adiponectin levels is not clear. Also, there is not enough data about the effects of different antihypertensive regimens on plasma adiponectin levels. METHODS: Ninety-six hypertensive patients (48 male, 48 female) who fulfil the diagnostic criteria of metabolic syndrome were enrolled. Patients were treated for 3 months with metoprolol (n = 18, 100 mg/day), amlodipine (n = 20, 10 mg/day), doxazosin (n = 18, 4 mg/day), ramipril (n = 20, 5 mg/day) and valsartan (n = 20, 80 mg/day). Blood biochemistry and plasma adiponectin concentrations were measured both before and after the study. Insulin resistance was measured by homeostasis assessment index (HOMA). RESULTS: Plasma adiponectin levels were correlated with the total cholesterol (r = -0.244, P = 0.017), triglyceride (r = -0.306, P = 0.002), high-density lipoprotein-cholesterol (r = 0.286, P = 0.005), body mass index (r = -374, P < 0.001), systolic (r = -502, P < 0.001) and diastolic blood pressures (r = -235, P = 0.021). The independent predictors of plasma adiponectin levels were HOMA (beta = -0.199, P = 0.02), body mass index (beta = -0.313, P < 0.001) and systolic blood pressures (beta = -0.483, P < 0.001). Ramipril and valsartan increased the plasma adiponectin levels significantly higher than the other regimens (P < 0.05 for both) while metoprolol did not make a significant effect. CONCLUSION: According to the results, plasma adiponectin levels are associated with the arterial blood pressures, body fat content and the lipid parameters in hypertensive patients with metabolic syndrome. The effects of antihypertensive drugs on plasma adiponectin levels are parallel to their effects on blood pressures and insulin sensitivities. The different effects of several regimens on plasma adiponectin levels and insulin sensitivities may account for the diversity of the cardiovascular outcomes in patients with hypertension.     

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 micromol/L respectively; p = 0.002) but significantly higher plasma adiponectin level (15.0+/-0.7 vs. 8.7+/-0.8 microg/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.     

The +276 polymorphism of the APM1 gene, plasma adiponectin concentration, and cardiovascular risk in diabetic men

Recently, the genetic variability at adiponectin locus (APM1) was associated with cardiovascular risk in patients with type 2 diabetes. We sought to examine the associations of five variants of APM1 gene (C-11365G, A-4034C, A-3964G, T45G, and G276T) with the risk of cardiovascular diseases (CVDs) in a larger cohort of diabetic patients. Of 879 diabetic men from the Health Professionals Follow-up Study, 239 participants developed coronary heart disease or stroke during 14 years of follow-up and 640 CVD-negative subjects were used as control subjects. The risk of CVD was significantly lower in TT homozygotes at locus +276 than in other genotypes under a recessive inheritance model after adjusting for age, BMI, smoking, alcohol consumption, physical activity, aspirin use, HbA1c, and history of hypertension or hypercholesterolemia (odds ratio 0.38 [95% CI 0.18-0.79]; P = 0.009). In the CVD-negative control subjects, the allele 276T was associated with significantly higher plasma adiponectin levels in a dose-dependent pattern (GG 14.8, GT 16.2, and TT 18.8 microg/ml) after adjusting for age, BMI, and other variables (P for trend = 0.0019). In conclusion, our study showed significant associations between APM1 G276T and decreased CVD risk and increased plasma adiponectin levels in diabetic men.     

Pattern of Expression of Adiponectin Receptors in Human Liver and its Relation to Nonalcoholic Steatohepatitis

BACKGROUND: Adiponectin has antisteatosis-anti-inflammatory properties and its circulating levels are reduced in nonalcoholic steatohepatitis (NASH). METHODS: To assess the role of adiponectin in NASH, we measured expression of adiponectin gene (APM1) and receptors (AdipoR1/AdipoR2) in liver and subcutaneous and visceral fat in subjects with biopsy-proven NASH or pure steatosis (PS). In 103 subjects undergoing gastric bypass or elective abdominal surgery (17 with normal liver histology (C), 52 with PS, and 34 with NASH), RNA was extracted from tissue samples, and quantification of APM1, AdipoR1, and AdipoR2 was carried out by real-time polymerase chain reaction. RESULTS: In NASH vs C, circulating adiponectin levels (3.6[2.4] vs 5.3[4.3] mug/ml, median[interquartile range], p < 0.05) and adiponectin concentrations, APM1, AdipoR1, and AdipoR2 expression in visceral fat were all reduced (p 相似文献   

Soluble Fas: a novel marker of inflammation in uremia

BACKGROUND: Inflammation has been associated with atherosclerotic cardiovascular disease (CVD) and anemia in patients with end-stage renal disease (ESRD). Recent studies have shown that serum levels of soluble Fas (sFas), an antiapoptotic and proinflammatory molecule, are elevated in patients with cardiac disease and patients with ESRD. We therefore sought to investigate serum levels of sFas in uremic patients and its correlation with known markers of inflammation, anemia and CVD. METHODS: The study included 25 ESRD patients (14 on hemodialysis, 11 on CAPD), 27 patients with chronic kidney disease (CKD; creatinine clearance <50 ml/min/1.73 m2), and 14 normal control subjects. We measured serum levels of sFas, C-reactive protein (CRP), and albumin. We also investigated the association of serum sFas levels with the presence of CVD and with erythropoietin (EPO) dosage. RESULTS: Levels of sFas were elevated in CKD and ESRD patients compared to controls. sFas levels correlated negatively with creatinine clearance. In the dialysis patients, we observed that sFas levels were higher among those with CVD. Serum levels of sFas correlated with serum levels of CRP (r=0.31; P=0.03), serum levels of albumin (r=-0.35, P=0.02), and EPO dosage (r=0.51; P=0.009). CONCLUSION: These results suggest that sFas may be a marker of inflammation in CKD and ESRD patients.     

Visceral fat adipokine secretion is associated with systemic inflammation in obese humans

Although excess visceral fat is associated with noninfectious inflammation, it is not clear whether visceral fat is simply associated with or actually causes metabolic disease in humans. To evaluate the hypothesis that visceral fat promotes systemic inflammation by secreting inflammatory adipokines into the portal circulation that drains visceral fat, we determined adipokine arteriovenous concentration differences across visceral fat, by obtaining portal vein and radial artery blood samples, in 25 extremely obese subjects (mean +/- SD BMI 54.7 +/- 12.6 kg/m(2)) during gastric bypass surgery at Barnes-Jewish Hospital in St. Louis, Missouri. Mean plasma interleukin (IL)-6 concentration was approximately 50% greater in the portal vein than in the radial artery in obese subjects (P = 0.007). Portal vein IL-6 concentration correlated directly with systemic C-reactive protein concentrations (r = 0.544, P = 0.005). Mean plasma leptin concentration was approximately 20% lower in the portal vein than in the radial artery in obese subjects (P = 0.0002). Plasma tumor necrosis factor-alpha, resistin, macrophage chemoattractant protein-1, and adiponectin concentrations were similar in the portal vein and radial artery in obese subjects. These data suggest that visceral fat is an important site for IL-6 secretion and provide a potential mechanistic link between visceral fat and systemic inflammation in people with abdominal obesity.     

Adiponectin level is reduced and inversely correlated with the degree of proteinuria in type 2 diabetic patients

AIMS: Adiponectin seems to be an important modulator for metabolic and vascular diseases. We aimed to measure plasma adiponectin levels in type 2 diabetic patients and investigate any association with the severity of proteinuria. METHODS: 80 patients (mean age, 46.9 +/- 5.1 years; body mass index (BMI), 25.8 +/- 1.98 kg/m2) and 47 healthy volunteers (mean age, 46.1 +/- 5.5 years; BMI 26.74 +/- 2.23 kg/m2) were included. Plasma adiponectin concentration, insulin levels, homeostasis model assessment (HOMA) indices, calculated glomerular filtration rate (GFR), high sensitive C reactive protein (hsCRP) and biochemistry panel were determined in all subjects. The association between adiponectin concentration and proteinuria was evaluated. Additionally, the relationship between adiponectin and hsCRP and calculated GFR were also investigated. RESULTS: Adiponectin levels in patients were significantly lower than those of controls (n = 80; 8.76 +/- 4.50 microg/ml for patients, n = 47; 24.27 +/- 5.59 microg/ml for controls, p < 0.001). Plasma adiponectin levels in patients with proteinuria were significantly lower than those without proteinuria (n = 43; 6.81 +/- 2.82 microg/ml for proteinuria, n = 37; 11.98 +/- 3.32 microg/ml for no proteinuria, p < 0.001). There was a significant negative correlation between plasma adiponectin concentrations and the degree of proteinuria (r = -0.433, p < 0.001). There were also significant negative correlations between adiponectin concentrations and insulin levels as well as HOMA index in the patient group (r = -0.322, p = 0.004; r = -0.301, p = 0.032). Additionally there was a significant negative correlation between adiponectin and hsCRP levels in the patient group (r = -0.872, p < 0.001). CONCLUSION: The results show that adiponectin is lower in patients with type 2 diabetes and the levels are negatively correlated with the severity of proteinuria.     

Adiponectin as a novel determinant of bone mineral density and visceral fat

Growing evidence suggests that positive associations between fat mass (FM) and bone mineral density (BMD) are mediated by not only biomechanical but also biochemical factors. Adiponectin is a novel adipocyte-derived hormone that regulates energy homeostasis and has anti-inflammatory and anti-atherogenic effects. Unlike other adipokines such as leptin, adiponectin levels decrease in obesity and type 2 diabetes. The purpose of our study was to investigate associations of serum adiponectin with BMD (DXA and QCT), FM (DXA and QCT), and serum leptin and soluble leptin receptor levels in 38 women and 42 men (age 39-81, BMI 17-55, 86% with type 2 diabetes). After adjusting for age, gender, race, smoking, and diabetes status, serum adiponectin was inversely associated with areal BMD (r = -0.20 to -0.3, all P < 0.01), volumetric BMD (r = -0.35 to -0.44, all P < 0.01), and visceral fat volume (r = -0.30, P < 0.01). These associations remained significant after adjusting for whole body fat mass. The associations of adiponectin with subcutaneous fat volume, whole body FM, and serum leptin level were not significant (all P > 0.1). These data suggest that adiponectin may play a role in the protective effects of visceral fat on BMD.     

Peroxynitrite-induced oxidation of plasma lipids is enhanced in stable hemodialysis patients

BACKGROUND: The relationship between end-stage renal disease (ESRD), hemodialysis, and oxidative stress is controversial. To determine whether ESRD causes oxidative stress, we measured basal levels of plasma F2-isoprostanes as a marker of lipid peroxidation in vivo, and peroxynitrite-stimulated formation of F2-isoprostanes, as a marker of the oxidizibility of plasma lipids in vitro, before and after routine hemodialysis. METHODS: Total plasma F2-isoprostanes were measured by gas chromatography-mass spectrometry (GC-MS) before and after the oxidation of plasma lipids with the peroxynitrite-generating compound, 3-morpholino-sydnonimine (SIN-1), in 23 patients with ESRD patients undergoing regular hemodialysis, and 14 controls. Plasma vitamin E concentrations were measured by high-performance liquid chromatography (HPLC). RESULTS: There was no difference in basal plasma concentrations of F2-isoprostanes in the ESRD group prior to hemodialysis, 246 +/- 20 pg/mL, compared to controls, 252 +/- 28 pg/mL, or immediately on completion of hemodialysis, 236 +/- 14 pg/mL. Incubation of control plasma with SIN-1 caused the formation of F2-isoprostanes with plasma concentrations increasing to 987 +/- 54 pg/mL at 6 hours. The formation of F2-isoprostanes stimulated by SIN-1 was markedly enhanced in the plasma obtained from patients undergoing hemodialysis at 1861 +/- 174 pg/mL, P < 0.001, and SIN-1-induced formation of F2-isoprostanes was further increased in plasma obtained immediately after hemodialysis at 2437 +/- 168 pg/mL, P < 0.001. Incubation of plasma with SIN-1 resulted in the net consumption of vitamin E. CONCLUSION: Although basal plasma F2-isoprostanes were similar in patients with ESRD compared with controls, the presence of oxidative stress in patients with ESRD was unmasked when the plasma was stressed by peroxynitrite generated from SIN-1, and this was enhanced further by hemodialysis.