Significant Association of Diabetes With Mortality of Chronic Hemodialysis Patients, Independent of the Presence of Obesity, Sarcopenia, and Sarcopenic Obesity.

OBJECTIVES: This retrospective cohort study investigated the association of diabetes with mortality in hemodialysis patients with regard to obesity, sarcopenia, and sarcopenic obesity, along with examining the prevalence of each group and diabetes. METHODS: Muscle strength, muscle mass, and fat mass were evaluated using a hand dynamometer and dual-energy X-ray absorptiometry, respectively, in 308 chronic hemodialysis patients (age 58.0 ± 11.9 years, hemodialysis duration 6.5 ± 6.0 years, males 60.1%, diabetes 32.8%). Sarcopenia was defined according to the new criteria established by the Asian Working Group on Sarcopenia 2019. Obesity was defined by percent body fat mass (males ≥25%, females ≥35%). RESULTS: The enrolled patients were divided into the normal (38.7%), obesity (18.8%), sarcopenia (26.9%), and sarcopenic obesity (15.6%) groups. The prevalence of diabetes was significantly skewed among the 4 groups (χ2 test, P = .0057), being higher in the sarcopenic obesity group (54.2%) compared to the others (25.9-33.7%). Multivariate regression analysis revealed that diabetes was significantly and independently associated with sarcopenic obesity (odds ratio 3.495, 95% confidence interval 1.683-7.255, P = .0008) after adjustments for several cofounders, but not significantly associated with sarcopenia. During the follow-up period of 76 ± 35 months, 100 patients died. Those in the sarcopenia and sarcopenic obesity groups had significantly higher rates of all-cause mortality compared to patients in the normal and obesity groups (P = .0004, log-rank test). Furthermore, multivariate Cox proportional hazards analysis revealed that presence of diabetes was significantly associated with higher all-cause mortality in all 308 patients, after adjustments for several factors, including the presence of each group in 4 models. CONCLUSION: Sarcopenic obesity is highly prevalent in chronic hemodialysis patients. Diabetes was found to be a significant and independent contributor to the presence of sarcopenic obesity. Diabetes was shown to be a significant predictor of all-cause mortality, independent of the present normal, obesity, sarcopenia, and sarcopenic obesity groups.

Comparative Effects of Etelcalcetide and Maxacalcitol on Serum Calcification Propensity in Secondary Hyperparathyroidism: A Randomized Clinical Trial.

BACKGROUND AND OBJECTIVES: Vitamin D receptor activators and calcimimetics (calcium-sensing receptor agonists) are two major options for medical treatment of secondary hyperparathyroidism. A higher serum calcification propensity (a shorter T50 value) is a novel surrogate marker of calcification stress and mortality in patients with CKD. We tested a hypothesis that a calcimimetic agent etelcalcetide is more effective in increasing T50 value than a vitamin D receptor activator maxacalcitol. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A randomized, multicenter, open-label, blinded end point trial with active control was conducted in patients with secondary hyperparathyroidism undergoing hemodialysis in Japan. Patients were randomly assigned to receive intravenous etelcalcetide 5 mg thrice weekly (etelcalcetide group) or intravenous maxacalcitol 5 or 10 µg thrice weekly (maxacalcitol group). The primary, secondary, and tertiary outcomes were changes in T50 value, handgrip strength, and score of the Dementia Assessment Sheet for Community-Based Integrated Care System from baseline to 12 months, respectively. RESULTS: In total, 425 patients from 23 dialysis centers were screened for eligibility, 326 patients were randomized (etelcalcetide, n=167; control, n=159), and 321 were included in the intention-to-treat analysis (median age, 66 years; 113 women [35%]). The median (interquartile range) of T50 value was changed from 116 minutes (interquartile range, 90-151) to 131 minutes (interquartile range, 102-176) in the maxacalcitol group, whereas it was changed from 123 minutes (interquartile range, 98-174) to 166 minutes (interquartile range, 127-218) in the etelcalcetide group. The increase in T50 value was significantly greater in the etelcalcetide group (difference in change, 20 minutes; 95% confidence interval, 7 to 34 minutes; P=0.004). No significant between-group difference was found in the change in handgrip strength or in the Dementia Assessment Sheet for Community-Based Integrated Care System score. CONCLUSIONS: Etelcalcetide was more effective in increasing T50 value than maxacalcitol among patients on hemodialysis with secondary hyperparathyroidism. There was no difference in handgrip strength or cognition between the two drugs. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: VICTORY; UMIN000030636 and jRCTs051180156.

Significant association between bone-specific alkaline phosphatase and vascular calcification of the hand arteries in male hemodialysis patients.

BACKGROUND/AIMS: Bone-specific alkaline phosphatase (BAP) hydrolyzes pyrophosphate, which inhibits vascular calcification. We examined association between serum BAP and vascular calcification of male hemodialysis patients. METHODS: Hand roentgenography of 167 male maintenance hemodialysis patients was conducted, and visible vascular calcification of the hand arteries was evaluated. Serum levels of 3 bone formation markers (BAP, osteocalcin, and N-terminal propeptide of type I collagen) and 2 bone resorption markers (C-terminal telopeptide of type I collagen, and cross-linked N-telopeptide of type I collagen) were measured, along with serum intact parathyroid hormone (PTH). RESULTS: Of 167 patients, visible vascular calcification was seen in 37 patients. Among the bone formation and resorption markers, serum BAP was significantly higher in patients with vascular calcification than in those without (p<0.05); although the other 5 serum bone markers were not significantly different between them. Multivariate logistic regression analyses revealed that log [BAP] was significantly associated with vascular calcification after adjustment for age, hemodialysis duration, presence of diabetes, log [intact PTH] and each of the other 5 bone markers (p<0.0001). CONCLUSIONS: Higher serum BAP, but not other bone markers, is significantly associated with the presence of vascular calcification in male hemodialysis patients.

Tumor necrosis factor-related apoptosis-inducing ligand as an independent predictor of mortality in hemodialysis patents.

BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was originally isolated as an inducer of apoptosis in transformed cells. In addition to tumor surveillance, recent findings suggest that TRAIL and its receptor system have a protective role against infection and cardiovascular disease (CVD). Patients undergoing hemodialysis have a high mortality rate with a unique risk factor profile. Considering that the leading causes of death in these patients are infection and CVD, TRAIL represents an attractive candidate for predicting mortality in this population. We therefore investigated whether TRAIL predicted mortality in hemodialysis patients. METHODS: The study was a retrospective observational cohort design of 45-month duration in 149 male hemodialysis patients. The subjects were divided into two groups according to their baseline TRAIL level measured by ELISA (low or high TRAIL group). The main outcome was all-cause mortality. RESULTS: During the follow-up period, 33 patients died, mostly because of CVD (n=11) or infection (n=9). Crude survival analyses showed that a low TRAIL level was a powerful predictor of all-cause (p=0.011) and infectious mortality (p=0.048). The predictive power of TRAIL remained after adjustment for various confounding factors. CONCLUSIONS: The serum TRAIL level may be a novel biomarker for predicting prognosis in hemodialysis patients.

Significant positive association between parathyroid hormone and fat mass and lean mass in chronic hemodialysis patients.

BACKGROUND: It has been reported that there is a significant positive relationship between PTH and body weight or body mass index in the general population. However, little is known about this relationship in dialysis patients in whom PTH levels are higher. It is also not known whether fat mass or lean mass is associated with serum PTH among these patients. In the present study, we examined the association of intact PTH with fat mass and lean mass in hemodialysis patients. METHODS: Serum intact PTH, calcium, and phosphate were measured in 590 hemodialysis patients (age, 60.2 ± 12.2 y; median hemodialysis duration, 59.6 mo; 343 males and 247 females; diabetics, 27.7%). Fat mass and lean mass were measured by dual-energy x-ray absorptiometry. RESULTS: Intact PTH correlated significantly and positively with body weight and body mass index in all patients. Intact PTH correlated significantly and positively with fat mass and lean mass in males (P < .01), and tended to correlate positively with fat mass and lean mass in females (P < .1). In multiple regression analyses after adjustment for age, gender, hemodialysis duration, calcium, phosphate, vitamin D use, and phosphate binder use, intact PTH was associated significantly with body weight (ß = .190; P < .0001), body mass index (ß = .177; P < .0001), fat mass (ß = .142; P < .0005), and lean mass (ß = .192; P < .01). Furthermore, intact PTH was associated significantly and independently with both fat mass and lean mass after adjustment (R(2) = .206; P < .0001). CONCLUSION: Serum intact PTH in chronic hemodialysis patients is associated significantly and positively with body composition of fat mass and lean mass.

Significant positive relationship between serum magnesium and muscle quality in maintenance hemodialysis patients.

BACKGROUND/AIMS: Serum magnesium (Mg) levels have been associated with muscle performance in the general population. We hypothesized that serum Mg would be associated with muscle quality in hemodialysis patients. METHODS: A total of 310 patients were examined (age: 58 ± 12 years, hemodialysis duration: 6.4 ± 6.0 years, 60.6% men, and 36.1% diabetics). Arm lean mass was measured by dual energy X-ray absorptiometry (DXA) on the dominant side. Arm muscle quality was defined as the ratio of the handgrip strength to the arm lean mass of the same side (kg/kg). RESULTS: Serum Mg was 1.15 ± 0.16 mmol/L (2.8 ± 0.4 mg/dL), being higher than the reference range of normal subjects. There was a significant negative correlation between muscle quality and age (r = -0.326, p<0.0001) and duration of hemodialysis (r = -0.253, p<0.0001). The muscle quality of the diabetics was significantly lower than that of the non-diabetics (p<0.001). There was a significant, positive correlation between muscle quality and serum Mg (r = 0.118, p<0.05), but not serum calcium or phosphate. In multiple regression analysis, age, gender, hemodialysis duration, diabetes, and serum Mg (ß = 0.129, p<0.05) were significantly and independently associated with muscle quality (R(2) = 0.298, p<0.0001). CONCLUSION: These results demonstrated that a lower serum Mg concentration was significantly associated with poor muscle quality in hemodialysis patients. Further studies are needed to explore the mechanism by which lower serum Mg affects muscle quality.