Masaaki Inaba

Prospective study of reactivation of hepatitis B virus in patients with rheumatoid arthritis who received immunosuppressive therapy: evaluation of both HBsAg-positive and HBsAg-negative cohorts

BackgroundScreening and prophylactic treatment for hepatitis B virus (HBV) reactivation is recommended for patients who receive immunosuppressive or cytotoxic therapy. The aim of this study was to clarify the prevalence of HBV reactivation in rheumatoid arthritis (RA) patients who had received more than 1xa0year of immunosuppressive therapy. This study also evaluated guidelines for determining HBV reactivation in patients with RA.MethodsThis was a prospective non-randomized, non-controlled study. We enrolled 50 patients with RA who had antibodies against hepatitis B core antigen (anti-HBc) and who had started treatment with disease-modifying anti-rheumatic drugs, including those who had additionally received anti-tumor necrosis factor-α (anti-TNF-α). HBV DNA levels were measured every 2–3xa0months by a real-time, polymerase chain reaction-based method. Entecavir was administered to patients with HBV DNA levels >2.1 log/ml.ResultsThe mean observation period was 23xa0months (range 12–32xa0months). HBV reactivation occurred in 2 of 5 patients with HBV surface antigen (HBsAg) and in 1 of 45 patients without HBsAg. In patients who received anti-TNF-α therapy, antibodies against HBsAg decreased significantly. Entecavir therapy inhibited HBV amplification and prevented HBV-associated flares of hepatitis.ConclusionsThe incidence of HBV reactivation was low in RA patients in whom HBV infection had been resolved. Screening for HBV reactivation and prophylactic therapy with entecavir were effective means of preventing HBV-associated hepatic failure in patients with HBsAg, as well as in those with only anti-HBc who received immunosuppressive therapy for RA.

Geriatric Nutritional Risk Index, a simplified nutritional screening index, is a significant predictor of mortality in chronic dialysis patients

BACKGROUNDnMalnutrition is a common complication in haemodialysis patients. Recently, the Geriatric Nutritional Risk Index (GNRI) has been reported as a simple and accurate tool to assess nutritional status of haemodialysis patients. Our objective was to examine the association between GNRI and mortality in chronic haemodialysis patients.nnnMETHODSnWe examined the GNRI of 490 maintenance haemodialysis patients (60 ± 12 years, 293 males and 197 females) and followed up these patients for 60 months. Predictors for all-cause death were examined using Kaplan-Meier analysis and Cox proportional analyses.nnnRESULTSnThe GNRI was 98.0 ± 6.0, and was significantly and negatively correlated with age and haemodialysis duration. During the 60-month follow-up period, 129 patients died. According to the highest positive likelihood and risk ratios, the cutoff value of GNRI for mortality was set at 90. Kaplan-Meier analysis revealed that patients with a GNRI <90 (n = 50) had a significantly lower survival rate, compared to those with GNRI ≥90 (n = 440) (log-rank test, P < 0.0001). Multivariate Cox proportional hazards analyses demonstrated that GNRI was a significant predictor for mortality [hazard ratio (HR) 0.962, 95% confidence interval (CI) 0.931-0.995, P < 0.05], after adjustment for age, gender, C-reactive protein, presence of diabetes and haemodialysis duration.nnnCONCLUSIONSnThese results demonstrated that GNRI is a significant predictor for mortality in haemodialysis patients. The simple method of GNRI is considered to be a clinically useful marker for the assessment of nutritional status in haemodialysis patients.

Serum Levels of TRAP5b, a New Bone Resorption Marker Unaffected by Renal Dysfunction, as a Useful Marker of Cortical Bone Loss in Hemodialysis Patients

Tartrate-resistant acid phosphatase (TRAP) 5b is a new marker of bone resorption that is unaffected by renal dysfunction. The significance of TRAP5b was assessed in hemodialysis (HD) patients. Serum concentrations of TRAP5b and cross-linked N-telopeptide of type I collagen (NTX) were determined as bone resorption markers, and those of bone alkaline phosphatase (BAP) and intact osteocalcin (OC) were measured as bone formation markers in 58 HD patients. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry twice in the distal third of the radius, with a 2-year interval between measurements. Serum TRAP5b correlated significantly with BAP, intact OC, intact parathyroid hormone (PTH), and especially serum NTX. TRAP5b, NTX, BAP, and intact OC all correlated significantly with BMD at the time of the second measurement; and TRAP5b, NTX, and intact OC, but not BAP and intact PTH, correlated significantly with the annual change in BMD during the 2-year period. Among the bone markers, patients in the highest tertile for serum TRAP5b and intact OC showed the fastest rate of cortical bone loss. The sensitivity and specificity for detection of rapid bone loss were 57.9% and 76.9%, respectively, for serum TRAP5b. Measurement of serum TRAP5b, as well as intact OC, may be a clinically relevant assay for estimation of bone metabolic status in HD patients, although serum intact OC accumulates in uremic serum.

Utility of serum tartrate‐resistant acid phosphatase (TRACP5b) as a bone resorption marker in patients with chronic kidney disease: independence from renal dysfunction

Backgroundu2002 Serum tartrate‐resistant acid phosphatase (TRACP) 5b levels were assessed in predialysis patients with chronic kidney disease (CKD). The aim of the study was to establish the usefulness of a new assay for TRACP5b in assessing bone turnover in these patients.

Fatigue Is a Predictor for Cardiovascular Outcomes in Patients Undergoing Hemodialysis

BACKGROUND AND OBJECTIVESnDespite potential significance of fatigue and its underlying components in the occurrence of cardiovascular diseases, epidemiologic data showing the link are virtually limited. This study was designed to examine whether fatigue symptoms or fatigues underlying components are a predictor for cardiovascular diseases in high-risk subjects with ESRD.nnnDESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSn788 volunteer patients under hemodialysis therapy (506 male, 282 female) completed the survey between October and November 2005, with the follow-up period up to 26 months to monitor occurrence of fatal or nonfatal cardiovascular events. The questionnaire consisted of 64 questions, and promax rotation analysis of the principal component method conceptualized eight fatigue-related factors: fatigue itself, anxiety and depression, loss of attention and memory, pain, overwork, autonomic imbalance, sleep problems, and infection.nnnRESULTSn14.7% of the patients showed fatigue scores higher than twice the SD of the mean for healthy volunteers. These highly fatigued patients exhibited a significantly higher risk for cardiovascular events (hazard ratio: 2.17; P < 0.01), with the relationship independent of the well-known risk factors, including age, diabetes, cardiovascular disease history, and inflammation and malnutrition markers. Moreover, comparisons of the risk in key subgroups showed that the risk of high fatigue score for cardiovascular events was more prominent in well-nourished patients, including lower age, absence of past cardiovascular diseases, higher serum albumin, and high non-HDL cholesterol.nnnCONCLUSIONSnFatigue can be an important predictor for cardiovascular events in patients with ESRD, with the relationship independent of the nutritional or inflammatory status.

Effects of pioglitazone on serum fetuin-A levels in patients with type 2 diabetes mellitus

Fetuin-A (alpha2-Heremans-Schmid glycoprotein), a circulating glycoprotein, can inhibit insulin signaling both in vivo and in vitro. Recently, we and another independent group have shown that fetuin-A is positively associated with insulin resistance in humans. Furthermore, it has been reported that higher fetuin-A levels are associated with metabolic syndrome and atherogenic lipid profiles. These data suggest that fetuin-A might be a regulator of insulin resistance and/or metabolic syndrome. However, it is not clear how fetuin-A levels are regulated. To address this, we investigated the effects of representative insulin-sensitizing therapies such as pioglitazone, metformin, and aerobic exercise on fetuin-A levels. Twenty-seven patients with type 2 diabetes mellitus were divided into pioglitazone-treated (Pio), metformin-treated (Met), and exercise-treated (Ex) groups. Ten patients in the Pio group and 9 patients in the Met group took 15 or 30 mg/d pioglitazone or 500 or 750 mg/d metformin, respectively, for 6 months. Eight patients in the Ex group underwent a 3-month aerobic exercise program. Serum fetuin-A levels were measured before and after each intervention. Intervention significantly decreased hemoglobin A(1c) in all groups. After treatment, serum fetuin-A levels significantly decreased in the Pio group (291.2 +/- 57.7 to 253.1 +/- 43.9 microg/mL, P = .006), whereas there were no changes in serum fetuin-A after intervention in either the Met or the Ex groups. We hypothesize that pioglitazone could partially ameliorate insulin resistance via modulating fetuin-A levels.

Different Impacts of Neck Circumference and Visceral Obesity on the Severity of Obstructive Sleep Apnea Syndrome

Our aim was to investigate the significance of neck circumference (NC) on the presence and severity of obstructive sleep apnea (OSA) syndrome independent of visceral fat (VF) obesity. A total of 219 subjects with suspected OSA underwent a complete polysomnography (PSG) study, along with the measurement of NC, and total body fat (TF) and VF levels (VFLs) measured by bioelectrical impedance analysis. We proposed NC divided by height (NC/H) as the simple index for height‐corrected NC in Japanese subjects. NC/H exhibited a significantly stronger correlation than NC per se with BMI (r = 0.781 vs. 0.675, P = 0.0178), TF (r = 0.531 vs. 0.156, P < 0.0001), and VF (r = 0.819 vs. 0.731, P = 0.0203), indicating that NC/H is a better indicator of visceral obesity than NC per se. Interestingly, despite the strong correlation between NC/H and VFL, VFL was significantly associated with the apnea‐hypopnea index (AHI) ≥5, ≥15, and ≥30, but not with ≥40 or ≥50, whereas NC/H was significantly associated with higher AHI values, i.e., AHI ≥50 but not with lower AHI value. Furthermore, multiple regression analyses revealed that VFL and NC/H were independently associated with the square root of AHI (AHI0.5) levels in obese and nonobese patients, respectively. In conclusion, NC is associated with the severity of OSA independently of visceral obesity, especially in nonobese patients.

Arterial stiffness predicts cardiovascular death independent of arterial thickness in a cohort of hemodialysis patients

OBJECTIVEnBoth arterial thickness and stiffness are predictors of cardiovascular disease (CVD). Although these arterial changes develop in parallel, no study has ever tested a hypothesis that arterial stiffness can predict mortality from CVD independent of arterial thickness. This study tested this possibility.nnnMETHODSnThis was an observational cohort study in 423 hemodialysis patients (CKD stage 5D). We simultaneously measured intima-media thickness (CA-IMT) and stiffness parameter beta (CA-beta) by carotid ultrasonography at baseline, and the cohort was followed-up for a mean period of 70 months.nnnRESULTSnDuring the follow-up, 216 all-cause deaths occurred including 124 deaths from CVD. Univariate analyses indicated both CA-IMT and CA-beta were significant predictors for CVD death. Kaplan-Meier analysis, in which the total subjects were divided into four groups by the medians of CA-IMT and CA-beta, showed that the hazards ratio (95% confidence interval) was 5.87 (3.43-10.05) for the group with higher CA-IMT/higher CA-beta as compared to the group with lower CA-IMT/lower CA-beta. The hazards ratios for the group with lower CA-IMT/higher CA-beta (2.22, 1.16-4.25) and the group with higher CA-IMT/lower CA-beta (2.85, 1.52-5.33) were comparable. Multivariate Cox analysis revealed that both CA-IMT and CA-beta were independently predictive of CVD mortality even after adjustment for other relevant covariates.nnnCONCLUSIONnIncreased arterial stiffness predicted cardiovascular mortality independent of arterial thickness in this cohort, implicating the distinct roles of stiffness and thickness of arterial wall in the pathogenesis of CVD.

Significant correlation of glycated albumin, but not glycated haemoglobin, with arterial stiffening in haemodialysis patients with type 2 diabetes

Objectiveu2002 We recently reported that glycated albumin (GA) is a better indicator of glycaemic control compared with glycated haemoglobin (HbA1c) in haemodialysis (HD) patients with type 2 diabetes. As poor glycaemic control is considered an independent risk factor for atherosclerosis in diabetes, the relationship between GA, HbA1c and arterial stiffening was examined in HD patients with type 2 diabetes.

Fetuin-A is associated with calcified coronary artery disease.

ObjectiveFetuin-A is a circulating glycoprotein that is involved in various stages of atherosclerosis. Despite the fact that emerging evidence suggests fetuin-A acts as a calcification inhibitor that protects against advanced calcified atherosclerosis in dialyzed patients, the role of fetuin-A in cardiovascular disease is still controversial. As diabetes and uremia make the role of fetuin-A in cardiovascular disease uncertain, we investigated the association between fetuin-A and calcified coronary artery disease in participants without diabetes and renal dysfunction. MethodsSerum fetuin-A levels were measured in 92 participants who underwent coronary angiography. The number of diseased vessels and the presence of calcification were evaluated. ResultsFetuin-A levels significantly decreased in patients with advanced three-vessel disease compared with those without stenosis (245.5±50.9, 289.0±71.8u2009μg/ml, respectively; P<0.05). Likewise, fetuin-A levels were significantly lower in patients with coronary artery calcification compared with those without coronary artery calcification (257.1±49.7, 288.0±63.1u2009μg/ml, respectively; Pu2009=u20090.010). Multivariate logistic regression analysis revealed that fetuin-A levels inversely correlated with the presence of coronary artery calcification (odds ratio: 0.54; 95% confidence interval: 0.31–0.92; Pu2009=u20090.025). ConclusionSerum fetuin-A levels inversely correlated with advanced calcified coronary artery disease.