Sarcopenia has become a serious disorder in modern society. Chronic kidney disease requiring dialysis and diabetes are some of the disorders that accelerate the onset and progression of sarcopenia. We, therefore, investigated the prevalence of sarcopenia in patients undergoing hemodialysis (HD) and confirmed the impact of diabetes mellitus (DM) on this population. This study included 308 patients whose muscle strength and mass had been evaluated using handgrip strength and dual-energy X-ray absorptiometry, respectively. Sarcopenia was defined according to the criteria established by the Asian Working Group on Sarcopenia. In addition, this cohort had been followed up for 9 years. The prevalence of sarcopenia was 40% (37% in males and 45% in females) with gender differences being insignificant (p = 0.237). The DM morbidity rate was significantly higher in those with sarcopenia than in those without sarcopenia (41% vs. 27%, p = 0.015). Multivariate regression analyses showed that the presence of DM was an independent contributor to sarcopenia in patients undergoing HD (odds ratio 3.11; 95% confidence interval 1.63–5.93; p < 0.001). During the follow-up of 76 ± 35 months, 100 patients died. Patients with sarcopenia demonstrated significantly higher rates of all-cause mortality than those without sarcopenia (p < 0.001 using the log-rank test). Multivariate Cox proportional hazards analyses revealed that the presence of DM was significantly associated with higher all-cause mortality (adjusted hazard ratio: 2.39; 95% confidence interval 1.51–3.81; p < 0.001). The prevalence of sarcopenia among this cohort of patients undergoing HD was determined to be 40%. Moreover, the presence of DM was an independent contributor to sarcopenia and an independent predictor of all-cause mortality in this population.

Deficiency of the micronutrient zinc is common in patients with chronic kidney disease (CKD). The aim of this review is to summarize evidence presented in literature for consolidation of current knowledge regarding zinc status in CKD patients, including those undergoing hemodialysis. Zinc deficiency is known to be associated with various risk factors for cardiovascular disease (CVD), such as increased blood pressure, dyslipidemia, type 2 diabetes mellitus, inflammation, and oxidative stress. Zinc may protect against phosphate-induced arterial calcification by suppressing activation of nuclear factor kappa light chain enhancer of activated B. Serum zinc levels have been shown to be positively correlated with T₅₀ (shorter T₅₀ indicates higher calcification propensity) in patients with type 2 diabetes mellitus as well as those with CKD. Additionally, higher intake of dietary zinc was associated with a lower risk of severe abdominal aortic calcification. In hemodialysis patients, the beneficial effects of zinc supplementation in relation to serum zinc and oxidative stress levels was demonstrated in a meta-analysis of 15 randomized controlled trials. Thus, evidence presented supports important roles of zinc regarding antioxidative stress and suppression of calcification and indicates that zinc intake/supplementation may help to ameliorate CVD risk factors in CKD patients.

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

Background/Aims: Megalin mediates the uptake of glomerular-filtered iron in the proximal tubules. Urinary full length megalin (C-megalin) excretion has been found to be increased in association with megalin-mediated metabolic load to the endo-lysosomal system in proximal tubular epithelial cells (PTECs) of residual nephrons. In the present study, we investigated the association between urinary iron and C-megalin in chronic kidney disease (CKD) patients, and the possible harmful effect of iron in renal tubules. Methods: Urinary levels of iron and C-megalin were measured in 63 CKD patients using automatic absorption spectrometry and a recently-established sandwich ELISA, respectively. Results: Although both urinary C-megalin and urinary total protein levels were correlated with urinary iron (C-megalin: ρ = 0.574, p <0.001; total protein: ρ = 0.500, p <0.001, respectively), urinary C-megalin alone emerged as an independent factor positively associated with urinary iron (β = 0.520, p <0.001) (R² = 0.75, p <0.001). Furthermore, urinary iron was significantly and positively associated with urinary 8-hydroxydeoxyguanosine, an oxidative stress marker, while no association with other markers of renal tubular injury, i.e., β₂-microglobulin and N-acetyl-β-D-glucosaminidase, was noted. Conclusions: Our findings suggest that renal iron handling may be associated with megalin-mediated endo-lysosomal metabolic load in PTECs of residual nephrons and oxidative stress in renal tubules.

Zinc inhibits vascular calcification in vivo and in vitro. Patients with type 2 diabetes mellitus show hypozincemia and are at an elevated risk of cardiovascular events. Recently, an in vitro test (T₅₀-test) was developed for determination of serum calcification propensity and a shorter T₅₀ means a higher calcification propensity. This cross-sectional study investigated the association between serum zinc and T₅₀ in 132 type 2 diabetes mellitus patients with various kidney functions. Furthermore, the effect of exogenous zinc on T₅₀ was also investigated in vitro using separately pooled serum samples obtained from healthy volunteers and patients with hemodialysis. We measured T₅₀ levels using the established nephelometric method. The median (interquartile range) levels of T₅₀ and serum zinc were 306 (269 to 332) min, and 80.0 (70.1 to 89.8) µg/dL, respectively. Serum zinc level showed a weak, but positive correlation with T₅₀ (r_s = 0.219, p = 0.012). This association remained significant in multivariable-adjusted analysis, and was independent of known factors including phosphate, calcium, and magnesium. Kidney function and glycemic control were not significantly associated with T₅₀. Finally, in vitro experiments showed that addition of a physiological concentration of exogenous zinc chloride significantly increased serum T₅₀. Our results indicate that serum zinc is an independent factor with a potential role in suppressing calcification propensity in serum.