Background/Objectives: Zinc is an essential microelement, and its deficiency is common in patients undergoing hemodialysis. However, the association between serum zinc and mortality in these patients remains unclear. The aim of this study was to explore the possible association between serum zinc levels and all-cause mortality in prevalent patients with kidney failure on maintenance hemodialysis. Methods: This was a prospective cohort study of maintenance hemodialysis patients followed up for 5 years. The key exposure was serum zinc level measured at baseline, and the outcome was all-cause mortality. Their association was analyzed using Cox proportional hazard models. Results: Among 1662 eligible patients selected for this analysis, 468 (28%) died. Lower serum zinc levels were associated with a higher risk for mortality, independent of the major demographic factors and factors including mineral and bone disorder and renal anemia. However, this association was no longer significant when adjusted for serum albumin. Because there was a close correlation between serum zinc and albumin levels, we performed further analyses in which participants were categorized into four groups by median serum zinc (68 µg/dL) and albumin (3.7 g/dL) levels. In the lower serum albumin groups, risk of death was significantly higher in those with lower zinc than those with higher zinc levels, whereas such a difference was not significant in the high serum albumin groups. Conclusions: In patients undergoing maintenance hemodialysis with lower serum albumin levels, a lower serum zinc level was associated with a higher risk of mortality.

Cognitive impairment and dementia are common in patients with chronic kidney disease, including those undergoing hemodialysis. Since magnesium and phosphate play important roles in brain function and aging, alterations in these and other factors related to bone mineral disorder (MBD) may contribute to low cognitive performance in patients on hemodialysis. This cross-sectional study examined the associations between cognitive function and MBD-related factors among 1207 patients on maintenance hemodialysis. Cognitive function was assessed by the Modified Mini-Mental State examination (3MS). The exposure variables of interest were serum magnesium, phosphate, calcium, calcium–phosphate product, intact parathyroid hormone, fetuin-A, T50 calciprotein crystallization test, use of phosphate binders, use of cinacalcet, and use of vitamin D receptor activators. Multivariable-adjusted linear regression models were used to examine the associations between 3MS and each of the exposure variables independent of 13 potential non-mineral confounders. We found that lower 3MS was associated with lower serum magnesium, lower phosphate, lower calcium–phosphate product, and nonuse of phosphate binders. These results suggest that magnesium and phosphate play potentially protective roles against cognitive impairment in this population.

In primary aldosteronism (PA), aldosterone could affect glomerular hemodynamics by elevating renal vascular resistance and glomerular capillary pressure. However, the relationship between plasma aldosterone concentrations (PAC) and glomerular hemodynamics including efferent arteriolar resistance (R_e), afferent arteriolar resistance (R_a) in humans is still unclear. The aim of this study was to investigate the relationships of PAC with intraglomerular hemodynamic parameters in patients with PA. An observational study of glomerular hemodynamics was performed using simultaneous measurements of plasma clearance of para-aminohippurate and inulin (C_in; glomerular filtration rate (GFR)) in 17 patients with PA. Kidney function was evaluated by C_in, estimated GFR based on serum creatine (eGFR_cre) and serum cystatin C (eGFR_cys) and creatine clearance (Ccr). Intraglomerular hemodynamic parameters, including R_e, R_a, and intraglomerular hydrostatic pressure (P_glo) were calculated using Gomez's formulae. In the 17 PA cases, PAC was significantly correlated with C_in (rho=0.752, p=0.001) and eGFR_cys (rho=0.567, p=0.018), but was not correlated witheGFR_creand Ccr_. PAC was also significantly correlated with P_glo, R_e, and urinary protein/day (rho=0.775, p=0.0004, rho=0.625, p=0.009, and rho=0.625, p=0.007, respectively). Multivariable regression analysis showed that PAC was significantly associated with C_in and R_e. In comparing aldosterone producing adenoma (APA) and non-APA cases, C_in was significantly elevated in APA (p=0.037), whereas eGFR_cre, eGFR_cys, and Ccr were not. R_e tended to be higher in APA (p=0.064). These results suggest high aldosterone cause glomerular hyperfiltration by constricting R_e. C_in, but not eGFR_cre and Ccr, may be useful for evaluating kidney function in PA.

Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors continually stabilize hypoxia-inducible factor-1α (HIF-1α). These inhibitors are effective in the clinical treatment of renal anemia. However, the effects of continued HIF-1α stabilization on skeletal muscle differentiation remain unclear. This study aimed to investigate the effects of continued HIF-1α stabilization on skeletal muscle differentiation using a HIF-PH inhibitor in both in vitro and in vivo models. We cultured mouse C2C12 myoblasts to differentiate into myotubes with or without FG-4592, a HIF-PH inhibitor. Additionally, we treated nine-week-old male C57BL/6 mice with either FG-4592 or vehicle via intraperitoneal injections three times a week for four weeks. In vitro, FG-4592 treatment stabilized HIF-1α continually. Morphological analysis revealed that 72 h FG-4592 treatment suppressed differentiation of C2C12 myoblasts into myotubes. This treatment decreased the gene and protein expression of MyoD and myogenin, reduced the protein expression of myosin heavy chain (MHC), and increased the gene and protein expression of myostatin. HIF-1α knockdown mitigated the decrease in MHC protein expression induced by FG-4592. In vivo, FG-4592 treatment increased HIF-1α protein expression and decreased MyoD, myogenin, and MHC protein expression in gastrocnemius muscle. These findings suggest that pharmacological HIF-PH inhibition suppresses myoblast differentiation through continued HIF-1α stabilization.