Purpose It is unclear whether hypomagnesemia is an independent risk factor or innocent bystander for mortality in maintenance hemodialysis (MHD) patients. Thus, we studied associations between hypomagnesemia and all-cause as well as cardiovascular (CV) mortality in MHD patients. Methods Baseline clinical characteristics and coronary artery calcium score (CACS) of 353 Japanese MHD patients were reviewed. Three-year survival rate and mortality risk factors were assessed. Results Median (interquartile range) age, dialysis vintage, serum magnesium (Mg), serum albumin and CACS of the subjects were 68 (60–78) years, 75 (32–151) months, 2.4 (2.2–2.7) mg/dl, 3.6 (3.3–3.8) g/dl, and 1181 (278–3190), respectively. During the 3-year period, 91 patients died. Kaplan–Meier overall 3-year survival rates were 59.0% in in patients with Mg < 2.4 mg/dl ( n = 136) and 82.3% in patients with Mg ≥ 2.4 mg/dl ( n = 217), ( P < 0.0001). In Cox regression models not incorporating serum albumin, Mg < 2.4 mg/dl was significantly associated with 3-year all-cause death, independent of age, dialysis vintage, average ultrafiltration, Log (CACS + 1), warfarin use, serum potassium, high-sensitivity C-reactive protein (hsCRP), phosphate, uric acid, and intact parathyroid hormone [Hazard ratio (HR) 95% confidence interval (CI): 2.82 (1.31–6.29), P = 0.0078], and CV death, independent of age, dialysis vintage, Log (CACS + 1), warfarin use, serum hsCRP, and uric acid [HR (95% CI): 4.47 (1.45–16.76), P = 0.0086]. Nevertheless, associations of Mg < 2.4 mg/dl with all-cause and CV mortality were all absent in models that included serum albumin. Conclusions Hypomagnesemia is not an independent risk factor for mortality but is associated with malnutrition in MHD patients.

The role of transforming growth factor-beta 1 (TGF-beta 1) in human glomerulonephritis is still poorly understood. The relationship between expression of TGF-beta 1 protein or TGF-beta 1 mRNA and tissue damage was investigated using the enzyme-antibody and in situ hybridization method in frozen slices of renal tissue from 30 patients: 25 with glomerulonephritis (18 with immunoglobulin A nephropathy; two with focal glomerulosclerosis, one with membranous nephropathy, one with crescentic glomerulonephritis and three with lupus nephritis) and five control patients with minimal change disease. The expression of TGF-beta 1 mRNA was high in sclerotic and proliferative glomeruli, as well as in the tubular epithelial cells within tubulointerstitial lesions. There was significant correlation between the severity of tissue damage in immunoglobulin A nephropathy and the presence of TGF-beta 1 protein and TGF-beta 1 mRNA. These findings suggest that TGF-beta 1 is involved in glomerulosclerosis and the development of tubulointerstitial lesions, indicating its potential importance in the progression and aggravation of immunoglobulin A nephropathy.

Summary at a GlanceVascular calcification is a major contributor to morbidity and mortality in patients with CKD, although the optimal method and site for measurement of vascular calcification have not been determined. This study assesses and compares coronary artery calcification and common iliac artery calcification determined by CT in a cohort of non‐dialysis CKD patients and reports on associated variables and outcomes.

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Objective: This study evaluated associations of serum matrix Gla protein (MGP), plasma vitamin K1, and plasma vitamin K2 with coronary artery calcium score (CACS) and cardiovascular disease (CVD) in maintenance hemodialysis (MHD) patients. Methods: Subjects comprised 112 MHD patients aged 30-60 years and 40 age-matched healthy subjects. Total MGP, vitamin K1, vitamin K2, and lipid profile were examined in all subjects; other clinical data, medication use, and CACS were assessed only in MHD patients. Determinants of MGP in all subjects were identified by regression analysis. Factors associated with CACS and CVD in MHD patients were identified by regression analysis and logistic analysis, respectively. Results: Lower plasma levels of vitamin K1 corrected for triglycerides [0.39 (0.24-0.70) vs. 0.77 (0.48-1.34) ng/mg, p < 0.001], higher frequency of plasma vitamin K2 0.05 ng/ml (p ¼ 0.23), and higher serum total MGP (288.4 ± 44.2 vs. 159.7 ± 40.6 ng/ml, p < 0.0001) were observed in MHD patients than in healthy controls. Total MGP level was significantly associated with levels of vitamin K1 corrected for triglycerides (p <0 .001) and vitamin K2 0.05 ng/ml (p < 0.05) in all subjects. Total MGP level was significantly associated with presence of CVD (p <0 .05), but not CACS, in MHD patients. Conclusion: The end-stage renal disease on hemodialysis is a deficiency state of vitamin K. Total MGP was significantly higher in MHD patients compared to healthy subjects and total MGP was associated with the presence of CVD, but not CACS, in MHD patients.

Novel biomarkers might improve the prediction of mortality in hemodialysis (HD) patients. We simultaneously measured the levels of conventional and novel biomarkers [serum N-terminal pro-brain natriuretic peptide (NT-proBNP), intact fibroblast growth factor-23 (FGF23), β2-microglobulin (β2MG), cystatin C, and high-sensitivity C-reactive protein (hsCRP)] in 307 prevalent Japanese HD patients. There were 66 all-cause deaths, and 25 cardiovascular (CV) deaths during 2 years, which were assessed using Cox models and concordance (C)-statistics. The addition of NT-proBNP alone (P < 0.05) or NT-proBNP, hsCRP, and β2MG as a panel (C-statistics: 0.834 vs. 0.776, P < 0.01) to a conventional risk model composed of age, diabetes, and the serum albumin level significantly improved the prediction of 2-year all-cause mortality, and the addition of NT-proBNP and hsCRP as a panel to a conventional risk model composed of age significantly improved the prediction of 2-year CV mortality (P < 0.05) in Japanese prevalent HD patients. Neither FGF23 nor cystatin C improved mortality prediction.

AimIron deficiency stimulates fibroblast growth factor 23 (FGF23) transcription. This study aimed to determine whether oral ferrous iron (Fe2+) reduces the serum FGF23 levels of iron‐deficient maintenance haemodialysis (MHD) patients in the same way as oral ferric iron (Fe3+)MethodsThirty‐one MHD patients with iron deficiency were enrolled in this prospective study. Patients who had taken iron supplements during the 8 weeks before the study were excluded. The patients’ iron stores and their serum FGF23, phosphate, intact parathyroid hormone (iPTH), albumin, C‐reactive protein (CRP), and albumin‐adjusted calcium (Ca) levels were examined at the baseline and after 3 months’ treatment with sodium ferrous citrate (Fe2+).ResultsThe patients’ transferrin saturation values and serum iron and ferritin levels were significantly increased after 3 months’ treatment (P < 0.01), as were their serum albumin levels (P < 0.05). Conversely, their serum intact FGF23 (iFGF23) [1820 (342–4370) vs 1240 (214–2940) pg/mL, P < 0.05], C‐terminal FGF23 (cFGF23) [309 (120–1211) vs 259 (99–600) pg/mL, P < 0.05)], and CRP levels (P < 0.01) were significantly reduced after 3 months’ treatment. No changes were detected in the patients’ serum iFGF23:cFGF23 ratios or their serum phosphate, Ca, or iPTH levels. The changes in the patients’ serum iFGF23 and cFGF23 levels induced by sodium ferrous citrate supplementation were shown to be attributable to changes in their serum ferritin levels (P < 0.05).ConclusionShort‐term oral iron supplementation with sodium ferrous citrate replenished the iron stores and reduced the serum iFGF23 and cFGF23 levels of MHD patients with iron deficiency without affecting their serum phosphate, Ca, or iPTH levels.

Obstructed shunt vessels were studied immunohistochemically to clarify the mechanism of shunt obstruction in hemodialysis patients. The subjects were 12 hemodialysis patients with shunt obstruction, and 8 patients newly started on hemodialysis were used as the controls. Cryosections of shunt tissue were prepared and stained for thrombomodulin as well as transforming growth factor-β₁ using the enzyme antibody method. In the obstructed shunt group, the intima was significantly thicker than in the control group. In addition, staining of the intima for thrombomodulin was decreased in the obstructed shunt group when compared with the controls. Staining for transforming growth factor-β₁ was related to intimal thickening and cell proliferation. These results indicate that release of thrombomodulin occurs with vascular endothelial cell damage and that transforming growth factor-β₁ may be involved in intimal hypertrophic change and shunt obstruction.