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Serum Mg levels are elevated in patients with renal insufficiency: harmful effects of hypomagnesemia have been reported in patients receiving hemodialysis (HD). In this cross-sectional study, which included 86 HD patients (male : female = 56:30, age 68 ± 12 years), we examined the clinical factors associated with serum Mg levels, with a focus on sevelamer, a phosphate binder widely used to control the hyperphosphatemia of HD patients. The mean serum Mg concentration among our patients was 2.48 ± 0.37 mg/dL (1.02 ± 0.15 mmol/L). Sevelamer was administered to 67 patients (77.9%) at a mean dose of 1.98 ± 1.64 g/day. Sex, diabetes mellitus, cardiovascular disease, anuria, and drugs other than sevelamer were not associated with serum Mg levels. HD duration, serum calcium, albumin, high-density lipoprotein cholesterol, normalized protein catabolic rate (nPCR), creatinine generation rate, and sevelamer dose correlated positively with serum Mg levels, whereas a negative correlation was observed for age and high-sensitivity C-reactive protein. A stepwise multiple regression analysis revealed that age, nPCR, and the dose of sevelamer were independently associated with serum Mg levels. Sevelamer and Mg have been reported to exhibit similar effects, such as an anti-inflammatory effect, inhibition of cardiovascular calcification, and decreased mortality. Therefore, the pleiotropic effects of sevelamer may be partly attributable to the increase in serum Mg levels caused by the drug itself.

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Eldecalcitol (ELD), a new active vitamin D3 analog developed in Japan, has attracted attention as an effective osteoporotic therapeutic drug. However, because ELD leads to greater calcium absorption than does conventional active vitamin D3, it has yet to be used in patients with renal insufficiency. Therefore, we evaluated the efficacy and safety of ELD treatment in 27 postmenopausal women receiving maintenance dialysis in our institution and underwent ELD treatment (starting at 0.5 µg/day) for 6 months. The mean serum albumin-corrected calcium (Caalb) level was significantly increased following treatment (9.01 ± 0.60 before versus 9.56 ± 0.55 after treatment, mean ± SD). Severe hypercalcemia was prevented through cessation or adjustment of the dosage of calcium-containing phosphate binders or existing active vitamin D. The mean serum phosphorus and intact parathyroid hormone levels were well-controlled throughout. The median levels of bone turnover markers, bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase-5b were significantly decreased. The mean lumbar spine bone mineral density (BMD) was increased, a significant difference being observed in age-matched Z-scores (-0.60 ± 1.6 versus -0.36 ± 1.5, p = 0.018). The average change in lumbar spine BMD after ELD treatment was 3.10%, and in patients with a T-score of <-4.0, it was 5.63%. There was no effect on forearm BMD. Although this study is based on short-term observation in a single institution, our results suggest that ELD could be used to increase bone density in dialysis patients.

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Sevelamer, a non-absorbable anion exchange resin, is used to control hyperphosphatemia in chronic kidney disease (CKD) by binding to dietary phosphate in the gastrointestinal tract. Lipid-lowering effect is a widely recognized pleiotropic effect of sevelamer. In addition, many studies have reported that sevelamer leads to reduced vascular calcification compared with calcium-containing phosphate binders, which is attributed to the improved lipid profiles and decreased calcium load. In addition, recent studies have suggested novel pleiotropic effects on bone structure, inflammation, oxidative stress, anemia, fetuin-A, and trace element metabolism in CKD patients. All of these effects have the potential to suppress the development/progression of cardiovascular lesions and reduce mortality. This review summarizes novel findings from recent studies and discusses the potential pleiotropic effects of sevelamer on non-traditional cardiovascular risk factors in CKD patients.

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OBJECTIVE: Copper is an essential mineral nutrient for humans. Serum copper levels of hemodialysis patients are higher than those of healthy subjects, but it remains to be elucidated whether increased serum copper may have harmful effects. In addition, a recent in vitro study has shown that sevelamer can adsorb copper. In the present study, we searched for clinical factors associated with serum copper levels in hemodialysis patients. METHODS: This cross-sectional study included patients undergoing hemodialysis for more than 6 months. In these patients, we statistically tested associations between serum copper levels and other parameters, including nutritional markers, lipid profiles, oxidative stress, inflammation, and sevelamer administration. RESULTS: Among 48 patients (male/female = 28:20, age 71 ± 10 years, hemodialysis duration 84 ± 72 months), sevelamer hydrochloride was administered in 39 patients (81.3 %). In univariate analysis, serum copper levels showed significant positive correlations with serum levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, high-sensitivity C-reactive protein (hs-CRP), and malondialdehyde modified-LDL and negative correlations with plasma total homocysteine levels and the administered dose of sevelamer. In multivariate analysis, serum levels of LDL-cholesterol and hs-CRP were found to be independent determinants of serum copper levels. CONCLUSION: We found that serum copper levels were independently associated with dyslipidemia and inflammation in hemodialysis patients, but the pathogenic roles of copper remain to be elucidated. In addition, potential effect of sevelamer on serum copper levels should be examined in appropriately designed studies.

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AIM: Vitamin D analogues, cinacalcet, and sevelamer play pivotal roles in the management of chronic kidney disease-mineral bone disorder, and are noted to have pleiotropic effects. We examined whether these agents might be associated with the responsiveness to erythropoiesis-stimulating agents (ESA). METHODS: In this cross-sectional study including haemodialysis patients treated with ESA, we searched for clinical parameters associated with the ESA resistance index, which was calculated as the weekly ESA dose divided by the patient's haemoglobin value. RESULTS: Among 45 patients (male: female = 28 : 17, age 68 ± 10 years, haemodialysis duration 84 ± 60 months), vitamin D analogue, cinacalcet, and sevelamer were used in 95.6%, 26.7%, and 84.4% of the patients, respectively. Univariate analysis showed significant association of the ESA resistance index with transferrin saturation rate (TSAT), vitamin D analogue dose, and sevelamer dose. In multivariate analysis, the sevelamer dose and TSAT were found to be independent determinants of the ESA resistance index. CONCLUSION: Our preliminary data showed an independent association between sevelamer dose and the responsiveness to ESA in haemodialysis patients. Further studies are required to investigate the causal relationship between sevelamer and ESA responsiveness.

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