Comparison between unattended automated office blood pressure and conventional office blood pressure under the environment of health checkup among Japanese general population.

Unattended automated office blood pressure (AOBP) measurement has been endorsed as the preferred in-office measurement modality in recent Canadian and American clinical practice guidelines. However, the difference between AOBP and conventional office blood pressure (CBP) under the environment of a health checkup remains unclear. We aimed to identify the clinical significance of AOBP as compared to CBP under the environment of a health checkup. There were 491 participants (333 females, mean age of 62.5 years) who were at least 20 years old, including 179 participants who were previously diagnosed with hypertension. Mean AOBPs were 131.8 ± 20.9/76.6 ± 11.7 mm Hg, and CBPs were 135.6 ± 21.6/77.3 ± 11.5 mm Hg. There was a difference of 3.9 mm Hg in systolic blood pressure (SBP) and 0.8 mm Hg in diastolic BP between AOBP and CBP. In all participants, SBP and pulse pressure, as well as the white coat effect (WCE), increased with age. The cutoff value used was 140/90 mm Hg for CBP and 135/85 mm Hg for AOBP, and the prevalence of WCE and masked hypertension effect (MHE) was 12.4% and 14.1%, respectively. Even in a health checkup environment of the general population, there was a difference between the AOBP and CBP, and the WCE was observed more strongly in the elderly with a history of hypertension, suggesting that a combination of AOBP with CBP may be useful in detecting WCE and MHE in all clinical scenarios including health checkups, and help solve the "hypertension paradox" not only in Japan but in all over the world.

Identification of pyridinoline, a collagen crosslink, as a novel intrinsic ligand for the receptor for advanced glycation end-products (RAGE).

Advanced glycation end-products (AGEs) elicit inflammatory responses via the receptor for AGEs (RAGE) and participate in the pathogenesis of diabetic complications. An earlier study showed that 3-hydroxypyridinium (3-HP), a common moiety of toxic AGEs such as glyceraldehyde-derived pyridinium (GLAP) and GA-pyridine, is essential for the interaction with RAGE. However, the physiological significance of 3-HP recognition by RAGE remains unclear. We hypothesized that pyridinoline (Pyr), a collagen crosslink containing the 3-HP moiety, could have agonist activity with RAGE. To test this hypothesis, we purified Pyr from bovine achilles tendons and examined its cytotoxicity to rat neuronal PC12 cells. Pyr elicited toxicity to PC12 cells in a concentration-dependent manner, and this effect was attenuated in the presence of either the anti-RAGE antibody or the soluble form of RAGE. Moreover, surface plasmon resonance-based analysis showed specific binding of Pyr to RAGE. These data indicate that Pyr is an intrinsic ligand for RAGE. ABBREVIATIONS: AGEs: advanced glycation end-products; RAGE: receptor for advanced glycation end-products; DAMPs: damage-associated molecular patterns; PRR: pattern recognition receptor; TLR: toll-like receptor; GLAP: glyceraldehyde-derived pyridinium; 3-HP: 3-hydroxypyridinium; Pyr: pyridinoline; HFBA: heptafluorobutyric acid; GST: glutathione S-transferase; SPR: surface plasmon resonance; ECM: extracellular matrix; EMT: epithelial to mesenchymal transition.

Receptor for advanced glycation end products (RAGE)-mediated cytotoxicity of 3-hydroxypyridinium derivatives.

Advanced glycation end products (AGEs) formed from glyceraldehyde (Gcer) and glycolaldehyde (Gcol) are involved in the pathogenesis of diabetic complications, via interactions with a receptor for AGEs (RAGE). In this study, we aimed to elucidate the RAGE-binding structure in Gcer and Gcol-derived AGEs and identify the minimal moiety recognized by RAGE. Among Gcer and Gcol-derived AGEs, GLAP (glyceraldehyde-derived pyridinium) and GA-pyridine elicited toxicity in PC12 neuronal cells. The toxic effects of GLAP and GA-pyridine were suppressed in the presence of anti-RAGE antibody or the soluble form of RAGE protein. Furthermore, the cytotoxicity test using GLAP analog compounds indicated that the 3-hydroxypyridinium (3-HP) structure is sufficient for RAGE-dependent toxicity. Surface plasmon resonance analysis showed that 3-HP derivatives directly interact with RAGE. These results indicate that GLAP and GA-pyridine are RAGE-binding epitopes, and that 3-HP, a common moiety of GLAP and GA-pyridine, is essential for the interaction with RAGE.

Hemocholecyst complicated in a hemodialysis patient with microscopic polyangiitis.

Microscopic polyangiitis (MPA) is a systemic vasculitis associated with antineutrophil cytoplasmic antibodies, and it involves multiple organs, including the kidneys and lungs. We report on the case of a 72-year-old woman with MPA who developed hemocholecyst in addition to alveolar hemorrhage and rapidly progressive glomerulonephritis. Although her renal function was not salvaged, the alveolar hemorrhage and hemocholecyst were treated conservatively. Clinicians should consider the possibility of hemocholecyst in patients with MPA complaining of abdominal pain.

Alteration of histone H3K4 methylation in glomerular podocytes associated with proteinuria in patients with membranous nephropathy.

BACKGROUND: Histone H3K4 trimethylation (H3K4 me3) is found in active euchromatic regions and plays an important role in podocyte function in which actin filaments are abundant in the foot processes. The pathogenesis of membranous nephropathy (MN), the most prevalent cause of primary nephrotic syndrome in the middle-aged and elderly, is podocyte dysfunction. METHODS: We investigated the role of H3K4 me3 in podocyte dysfunction in nephrotic syndrome using cultured podocytes and a mouse proteinuria model induced by LPS. We examined renal biopsy specimens from six patients with nephrotic syndrome caused by Phospholipase-A2-Receptor-positive primary MN. RESULTS: H3K4 me3 exhibited a pattern of nuclear expression in podocytes of the kidneys from patients with MN. The overlapping expression of H3K4 me3 and cathepsin L (a potent endoprotease causing the breakdown of actin-associated protein within lysosomal compartments in kidney podocytes) were higher in patients with MN compared with the controls. Histone H3K4 me3 in kidney podocytes was negatively correlated with synaptopodin, an actin-associated protein in podocytes, and the expression was positively correlated with the proteinuria levels in patients with MN. Histone H3K4 me3 levels were elevated in podocytes of LPS-treated mice, combined with an increase in podocyte swelling, an elevation of serum creatinine and urine albumin, increased cathepsin L, and decreased synaptopodin expression. Histone H3K4 me3 levels at the cathepsin L promoter were elevated in LPS-exposed mouse kidneys. The administration of shRNA against MLL3 (an H3K4 methyltransferase) to LPS-treated mice and cultured podocytes co-cultured with LPS-stimulated macrophages ameliorated podocyte swelling, an elevation in the serum creatinine and urine albumin levels and an increased expression of histone H3K4 me3 and cathepsin L, and a decreased expression of synaptopodin and increase in histone H3K4 me3 levels at the cathepsin L promoter. CONCLUSIONS: Histone H3K4 me3 upregulation may be involved in podocyte dysfunction and the pathophysiology of MN. Targeting this epigenetic signature of histone H3K4 me3 followed by modulating the actin dynamics may be an effective strategy to ameliorate the consequences of MN.

Insight into specific pro-arrhythmic triggers in Brugada and early repolarization syndromes: results of long-term follow-up.

The pro-arrhythmic triggers in Brugada and early repolarization syndromes (BrS, ERS) have not been analyzed systematically except for case reports. We clinically investigated the circumstances which precede/predispose to arrhythmic events in these syndromes during long-term follow-up. A detailed history from the patients/witnesses was taken to investigate the antecedent events in the last few hours that preceded syncope/ventricular fibrillation (VF); medical records, ECG and blood test from the emergency room (ER) were reviewed. 19 patients that fulfilled the investigation criteria were followed up for 71 ± 49 months (34-190 months). Prior to the event (syncope/VF), the patients were partaking different activities in the following decreasing order; drinking alcoholic beverage, having meal, and getting up from sleep, exercise. 3 patients reported mental/physical stress prior to the event and 2 patients developed VF several days after starting oral steroid for treatment of bronchial asthma. In the ER, elevated J-wave amplitude (0.27 ± 0.15 mV) was found with 58 % of the patients having hypokalemia. After electrolyte correction and cessation of steroids, the following day plasma K+ (4.2 ± 0.3 mEq/L, P < 0.001) was significantly increased and J-wave amplitude (0.13 ± 0.1 mV, P < 0.001) was remarkably reduced. Three patients were kept on oral spironolactone/potassium supplements. During follow-up for 71 ± 49 (34-190) months, among 4 patients with VF recurrence, one patient developed VF after taking oral steroid. In ERS and BrS, hypokalemia and corticosteroid therapy add substantial pro-arrhythmic effects, but potentially treatable. Stopping steroid therapy and avoiding hypokalemia had excellent long-term outcome.

Late Gadolinium Enhancement on Cardiac MRI Correlates with QT Dynamicity Represented by QT/RR Relationship in Patients with Ventricular Arrhythmias.

BACKGROUND: The distribution of late gadolinium enhancement (LGE) on the cardiac MRI (CMR) indicates myocardial fibrosis and provides information of possible reentry substrates. QT dynamicity reflecting repolarization abnormalities has gained attention as a potential prognostic predictive factor. OBJECTIVE: To clarify the correlation between the LGE distribution on CMR and QT dynamicity represented by the QT/RR relationship. METHODS: CMR and QT/RR analyses using Holter monitoring were performed in 34 patients (24 males, 60 ± 11 years) with ventricular tachycardia (VT) and/or ventricular fibrillation (VF). The LGE on CMR was scored using a 4-point score in 17 left ventricular segments. The sum of the LGE scores was calculated for each patient. The QT/RR slope and daytime/nighttime QT/RR ratio (day/night ratio) were calculated. The correlation between the slope or the day/night QT/RR ratio and late enhancement findings was analyzed. RESULTS: All patients were divided into 23 LGE positive (LGE(+)) and 11 LGE negative (LGE(-)) patients. The slopes of the QTe/RR and QTa /RR were significantly steeper in the LGE(+) than in LGE(-) patients (0.21 ± 0.03 vs 0.13 ± 0.02; P < 0.001, 0.19 ± 0.03 vs 0.13 ± 0.02; P < 0.001, respectively), and both slopes were significantly correlated with the total LGE scores (r = 0.83, P < 0.001; r = 0.71, P < 0.001, respectively). In the LGE(+) patients, the QTe day/night (1.37 ± 0.38 vs 0.91 ± 0.33; P = 0.002) and QTa day/night ratios (1.33 ± 0.26 vs 1.06 ± 0.30; P = 0.011) were significantly greater than those in the LGE(-) patients. CONCLUSION: The LGE distribution was closely related to the QT dynamicity, suggesting that a combination of these markers can be a powerful tool for understanding the background pathophysiology.

Minimal change nephrotic syndrome associated with gefitinib and a successful switch to erlotinib.

Minimal change nephrotic syndrome (MCNS) is a common form of nephrotic syndrome (NS). We herein present the case of a 57-year-old woman with advanced lung adenocarcinoma treated with the tyrosine kinase inhibitor (TKI) gefitinib who developed NS. A renal biopsy revealed minor glomerular abnormalities, and the patient's symptoms improved exclusively with the discontinuation of gefitinib. Therefore, we diagnosed her with MCNS associated with gefitinib treatment. A few months later, however, she developed recurrent lung tumors. Following the challenging initiation of the TKI erlotinib, she achieved remission without proteinuria. We thus conclude that erlotinib is a potential treatment option in patients with NS associated with gefitinib therapy.

Successful percutaneous transluminal angioplasty for the treatment of renovascular hypertension with an atrophic kidney.

Renovascular hypertension is an important cause of secondary hypertension. We present the case of a 61-year-old man with renovascular hypertension caused by chronic total occlusion of the left renal artery resulting in an atrophic kidney. Although renography indicated almost no residual function of the left kidney, renal vein sampling showed a significant increase of renin secretion in the left kidney. The endocrine function of the left kidney was believed to be preserved; thus, we performed percutaneous transluminal renal angioplasty with stent placement. After the procedure, the patient's blood pressure decreased gradually to within the normal range without adverse events. The laboratory data on endocrine function and the renography findings drastically improved. Percutaneous transluminal renal angioplasty is a promising therapeutic procedure for renovascular hypertension with an atrophic kidney.

Repolarization characteristics in early repolarization and brugada syndromes: insight into an overlapping mechanism of lethal arrhythmias.

INTRODUCTION: We reported impaired QT-rate dependence in early repolarization syndrome (ERS); however, contemporary data have shown peak incidence of sudden cardiac death (SCD) in ERS and Brugada syndrome (BrS) at mid-night and early morning. Taken together, we analyzed the nocturnal QT-rate dependence in both syndromes. METHODS AND RESULTS: A total of 172 subjects were enrolled: 11 ERS, 11 BrS patients, 50 subjects with an uneventful ER pattern (ERP), and 100 non-J-wave control subjects. Ambulatory ECG-derived parameters (QT, QTc, and QT/RR slope) and day-night QT difference were analyzed and compared. Among the groups, there was no significant difference in the average QT or QTc; however, the 24-hour QT/RR slope was significantly smaller in ERS and BrS patients (0.103 ± 0.01 and 0.106 ± 0.01, respectively) than in the control group (0.156 ± 0.03, P < 0.001). Detailed analysis showed a lower day-night QT difference in ERS and BrS patients (19 ±18.7 and 24 ±14 milliseconds, respectively) than in the controls (40 ± 22 milliseconds, P = 0.007) with the lowest QT/RR slopes seen in the ERS and BrS groups from 0 to 3:00 am (QT/RR; 0.076 ± 0.02 vs. 0.092 ± 0.04 vs. 0.117 ± 0.04, for the ERS, BrS, and controls, respectively, P = 0.004) and from 3 to 6 am (QT/RR 0.074 ± 0.03 vs. 0.079 ± 0.02 vs. 0.118 ± 0.04, P < 0.001). CONCLUSION: In a large population of age- and gender-matched groups, both ERS and BrS patients showed attenuated QT-rate dependence and impaired QT day-night modulation that may provide a baseline reentrant substrate. Importantly, QT/RR maladaptation was most evident at mid-night and early morning, which may explain the propensity of such patients to develop SCD during this critical period.

Surgical treatment of abdominal aortic aneurysm associated with horseshoe kidney: symphysiotomy using harmonic focus.

Coexistence of horseshoe kidney and abdominal aortic aneurysm (AAA) is a rare entity that presents a technical challenge to vascular surgeons. How to approach such an AAA with horseshoe kidney and whether to divide the renal isthmus remains a controversial issue. We report here the successful surgical repair of an AAA with horseshoe kidney via the transperitoneal approach with division of the renal isthmus by Harmonic Focus, which allowed easy division of the isthmus without bleeding. Harmonic Focus, a hand-held type of harmonic scalpel, was thus useful in symphysiotomy of the horseshoe kidney.

Epicardial adipose tissue is associated with prevalent atrial fibrillation in patients with hypertrophic cardiomyopathy.

Prevalent atrial fibrillation (AF) in patients with hypertrophic cardiomyopathy (HCM) represents an important issue with regard to stroke events caused by embolization and is associated with high mortality. Increased epicardial adipose tissue (EAT), which shows high metabolic activity, can locally influence the activity of the autonomic ganglia, enhancing autonomic dysregulation and increasing the likelihood of AF. We tested the hypothesis that EAT is associated with prevalent AF in HCM patients. Sixty-two patients with idiopathic HCM diagnosed on the basis of ultrasound cardiography findings and histopathological evaluation of myocardium obtained by right ventricular biopsy underwent cardiac magnetic resonance imaging to estimate the extent of EAT. EAT area was significantly higher in the group with AF episodes than in the group without. An increased incidence of AF was found to be significantly related to an increase in EAT, and this association persisted after adjustment for body mass index, sex, and age. Time domain measures of heart rate variability measured by Holter electrocardiography, standard deviation of normal to normal, and standard deviation of the average of normal to normal were negatively related to EAT area. EAT was positively correlated with intraventricular septal thickness and cystatin C level and negatively correlated with the 24-hour creatinine clearance rate. Increased EAT area in HCM patients is significantly related to the presence of AF, which is associated with changes in baseline autonomic nervous tone, left ventricular mass, and chronic kidney disease.

Silencing of p53 RNA through transarterial delivery ameliorates renal tubular injury and downregulates GSK-3ß expression after ischemia-reperfusion injury.

p53, a pivotal protein in the apoptotic pathway, has been identified as a mediator of transcriptional responses to ischemia-reperfusion (IR) injury. The characteristics and functional significance of the p53 response in vivo are largely unknown in IR-induced kidney injury. Therapeutic opportunities of delivering small interfering RNA (siRNA) via venous injection have gained recognition; however, systemic adverse effects of siRNA therapy should be considered. To prevent IR-induced kidney injury, we tested the efficacy of transarterial administration of siRNA targeting p53 (p53 siRNA). Female C57BL/6 mice underwent unilateral renal artery ischemia for 30 min, followed by reperfusion. siRNA experiments utilized short hairpin (sh) RNA plasmid-based approaches. Transfection of shRNA was performed using cationic polymer transfection reagent. Injection of synthetic p53 shRNA into the left renal artery just after ischemia improved tubular injury, apoptosis, and the swelling of mitochondria in cells of the thick ascending limb of Henle (mTALH) at the outer medullary regions. Staining of upregulated p53 was colocalized with the inducible expression of glycogen synthase kinase-3ß (GSK-3ß) at mTALH after IR injury. p53 shRNA inhibited GSK-3ß expression and restored ß-catenin expression at mTALH. For IR-induced kidney injury, transarterial delivery of p53 siRNA is an effective pharmacological intervention. Targeting siRNA to p53 leads to an attenuation of apoptosis and mitochondrial damage through the downregulation of GSK-3ß expression and upregulation of ß-catenin. Local delivery of vectors such as p53 siRNA through a transaortic catheter is clinically useful in reducing the adverse effect of siRNA-related therapy.

Mizoribine for crescentic glomerulonephritis with sarcoidosis: effectiveness not only for urinalysis abnormalities but also for hilar lymph node enlargement.

Sarcoidosis is a multisystem disease related to helper T cell responses. We recently experienced the case of a 57-year-old woman with sarcoidosis complicated by crescentic glomerulonephritis with low levels of myeloperoxidase-antineutrophil cytoplasmic antibody. We herein describe the details of her clinical course and discuss the effectiveness of mizoribine, which has an immunosuppressive effect equivalent to that of mycophenolate mofetil, not only for urinalysis abnormalities but also for hilar lymph node enlargement.

Retrospective comparison of the efficacy of tonsillectomy with and without steroid-pulse therapy in IgA nephropathy patients.

OBJECTIVE: Tonsillectomy and steroid-pulse (TSP) therapy have been proposed as a curative treatment for immunoglobulin A nephropathy (IgAN) in Japan. However, we sometimes encounter patients who reject steroid-pulse therapy because of concerns about the side effects of corticosteroids. Here, we examined the efficacy of TSP therapy and tonsillectomy alone for IgAN with urinary abnormalities. METHODS: Data on 40 IgAN patients diagnosed by renal biopsies, who presented glomerular hematuria and proteinuria at baseline and underwent bilateral palatine tonsillectomy, were analyzed retrospectively. Twenty of them underwent TSP therapy (TSP group), and 20 underwent tonsillectomy alone (T group). We examined associations between therapies, changes in urinary findings and renal function, and subsequent clinical remission (CR), defined as negative proteinuria and urinary erythrocytes of less than 5/high-power field. RESULTS: TSP group showed a significant decrease in proteinuria and hematuria earlier than T group. The rates of CR were significantly higher in TSP group compared with T group on the final observation period (75% vs. 45%, p<0.05). There was a significant difference between CR group and non-CR group only in the rate of receiving TSP therapy. CONCLUSION: TSP therapy significantly increased the probability of CR compared with tonsillectomy alone in IgAN patients with urinary abnormalities.

The intrinsic prostaglandin E2-EP4 system of the renal tubular epithelium limits the development of tubulointerstitial fibrosis in mice.

Inflammatory responses in the kidney lead to tubulointerstitial fibrosis, a common feature of chronic kidney diseases. Here we examined the role of prostaglandin E(2) (PGE(2)) in the development of tubulointerstitial fibrosis. In the kidneys of wild-type mice, unilateral ureteral obstruction leads to progressive tubulointerstitial fibrosis with macrophage infiltration and myofibroblast proliferation. This was accompanied by an upregulation of COX-2 and PGE(2) receptor subtype EP(4) mRNAs. In the kidneys of EP(4) gene knockout mice, however, obstruction-induced histological alterations were significantly augmented. In contrast, an EP(4)-specific agonist significantly attenuated these alterations in the kidneys of wild-type mice. The mRNAs for macrophage chemokines and profibrotic growth factors were upregulated in the kidneys of wild-type mice after ureteral obstruction. This was significantly augmented in the kidneys of EP(4)-knockout mice and suppressed by the EP(4) agonist but only in the kidneys of wild-type mice. Notably, COX-2 and MCP-1 proteins, as well as EP(4) mRNA, were localized in renal tubular epithelial cells after ureteral obstruction. In cultured renal fibroblasts, another EP(4)-specific agonist significantly inhibited PDGF-induced proliferation and profibrotic connective tissue growth factor production. Hence, an endogenous PGE(2)-EP(4) system in the tubular epithelium limits the development of tubulointerstitial fibrosis by suppressing inflammatory responses.

Angiotensin II receptor blocker and long-acting calcium channel blocker combination therapy decreases urinary albumin excretion while maintaining glomerular filtration rate.

Microalbuminuria is a recognized risk factor and predictor for cardiovascular events in patients with hypertension. We analyzed changes in hypotensive effect, urinary albumin excretion (UAE) and estimated glomerular filtration rate (eGFR) in subjects with hypertension and microalbuminuria as a subanalysis of the results of the Nifedipine and Candesartan Combination (NICE-Combi) Study. A total of 86 subjects with essential hypertension with microalbuminuria (UAE <300 mg g(-1) creatinine) were randomly assigned in a double-blind manner to a combination therapy group (standard-dose candesartan at 8 mg per day plus controlled-release (CR) nifedipine 20 mg per day) (n=42) or an up-titrated monotherapy group (candesartan 12 mg per day) (n=44) for 8 weeks of continuous treatment after initially receiving standard-dose candesartan (8 mg per day) monotherapy for 8 weeks (initial treatment). After 8weeks, blood pressure (BP) was significantly reduced in both groups compared with at the end of initial treatment. UAE also showed a significant decrease in the combination therapy group, while there was no significant change of eGFR in either group. A significant positive correlation was seen between BP reduction and UAE after 8 weeks of double-blind treatment in both groups, whereas no significant association was found between ΔUAE and ΔeGFR in either group. These findings show that combination therapy with standard-dose candesartan and nifedipine CR is more effective than up-titrated candesartan monotherapy for reducing BP and improving UAE while maintaining eGFR, and strongly suggest that the combination of an angiotensin II receptor blocker and long-acting calcium channel blocker is beneficial in patients with hypertension and microalbuminuria.

A case of idiopathic systemic capillary leak syndrome with high serum levels of G-CSF on exacerbation.

Systemic capillary leak syndrome (SCLS) is a life-threatening disorder which presents with periodic episodes of hypovolemic shock, due to plasma leakage to the extra-vascular space reflected by accompanying hypoalbuminemia, hemoconcentration and edema often with associated monoclonal gammopathy. We describe a 28-year-old woman with SCLS who required aggressive fluid resuscitation and was successfully treated with corticosteroid, terbutaline, and theophylline. At exacerbation, the levels of serum granulocyte colony-stimulating factor (G-CSF) were increased. Thus, G-CSF might play an important role and can be a useful biomarker for the severity of attacks in SCLS.

Potential impact of renin-angiotensin system inhibitors and calcium channel blockers on plasma high-molecular-weight adiponectin levels in hemodialysis patients.

Although metabolic syndrome confers an increased risk of cardiovascular disease in the general population, little is known about the alteration of abdominal adiposity and its association with adipocytokines in hemodialysis patients. We investigated the plasma high-molecular-weight (HMW) adiponectin level and its relationship to visceral fat area (VFA) and various markers of atherosclerosis in hemodialysis patients. In a cross-sectional study, conventional cardiovascular risk factors, plasma total and HMW adiponectin, the number of components of the metabolic syndrome and, using computed tomography, the distribution of abdominal adiposity were assessed in 144 hemodialysis patients (90 men and 54 women; mean age, 60.7 years) and 30 age- and sex-matched patients with chronic kidney disease (CKD). Plasma HMW adiponectin levels in hemodialysis patients were significantly higher than those in patients with CKD, negatively associated with VFA and serum triglycerides and positively associated with plasma total adiponectin, as well as the HMW-to-total adiponectin ratio in men and women (all P < 0.05) in a simple regression analysis. In a multiple regression analysis, VFA was a significant determinant of HMW adiponectin in hemodialysis patients. Furthermore, after adjustment for classical risk factors, HMW adiponectin levels were significantly higher in patients undergoing treatment with renin-angiotensin system inhibitors or calcium channel blockers compared with patients not undergoing such treatment. This study shows that plasma HMW adiponectin levels were negatively associated with VFA and positively associated with treatment with blockade of the renin-angiotensin system and of the calcium channel. Therefore, these drugs might be effective for improving adipocytokine-related metabolic abnormalities in hemodialysis patients.