These results suggest that warfarin may not prevent ischemic stroke in Japanese hemodialysis patients with chronic sustained AF. Adequately powered studies are needed to determine the risks and benefits of anticoagulation therapy in these patients.

Fibroblast growth factor 23 (FGF23) is a member of the fibroblast growth factor superfamily which displays a strong phosphaturic action and an inhibition of vitamin D 1-alpha hydroxylase activity. Fourty-six patients undergoing maintenance hemodialysis therapy participated in the study. They were randomly divided into 2 groups, and treated with either 3 g sevelamer hydrochloride+3 g of calcium bicarbonate (CaCO3), or 3 g of CaCO3 alone. Serum FGF23 levels were determined by a sandwich enzyme-linked immunosorbent assay (ELISA) system that detects the intact form of FGF23 molecules. Although the serum inorganic phosphate (Pi) levels were comparable before treatment, the levels were significantly lower in the patients treated with sevelamer hydrochloride+CaCO3 than those with CaCO3 alone after 4 weeks of treatment (P<0.05). Serum FGF23 levels significantly decreased after 4 weeks of the treatment with sevelamer hydrochloride+CaCO3 from the pretreatment levels (P<0.05), while no changes were found in the patients treated with CaCO3 alone. Thus, the use of sevelamer hydrochloride and CaCO3 reduced serum FGF23 levels in dialysis patients presumably through inhibiting phosphate load into the intestine.

A prospective, randomized open-label trial of sevelamer hydrochloride with or without calcium carbonate (CC) involved 86 hemodialysis patients in Japan. The dosage of CC was fixed at 3.0 g/day for the 12-week study. After the first 4 weeks all subjects were changed from CC to sevelamer 3.0 g/day for another 4 weeks, then allocated randomly to three groups for the final 4 weeks: group A, sevelamer 6.0 g/day; group B, sevelamer 3.0 g/day and CC 3.0 g/day; group C, CC 3.0 g/day. The target serum phosphorous concentration (P)=5.5 mg/dL and the corrected calcium concentration (Ca) was 9.0-10.0 mg/dL. Of the 86 patients, 62 finished the study without a change of dosage and their data were analyzed (group A, N=16; group B, N=26; group C, N=20). At week 8 compared with week 4, the concentration of P increased from 5.7+/-1.4 to 6.4+/-1.7 mg/dL in group A, and decreased significantly in groups B and C, and in group B compared with groups A and C; groups A and C had similar concentrations at week 8. The Ca concentration decreased significantly from 9.7+/-1.0 to 9.1+/-0.7 mg/dL after the change to sevelamer. At week 8 Ca was not significantly changed in group A, whereas a significant increase occurred in groups B and C. Side-effects with sevelamer administration occurred in 34 of the 86 patients and 24 dropped out of the study, with a high frequency in group A (13/29; 44.8%). In conclusion, there was an additive effect of sevelamer for the treatment of hyperphosphatemia with CC. The combination therapy was better tolerated and showed higher patient compliance than CC or sevelamer monotherapy.

Background and objectives: A new assessment system for bone histology, termed the turnover-mineralization-volume system, is advocated for patients with chronic kidney disease-related mineral and bone disorder. The system measures cancellous bone volume (BV/TV) as a third major evaluation axis; however, the physiologic significance of BV/TV remains unclear.Design, setting, participants, & measurements: Conventional bone histomorphometry was performed in 75 iliac bone samples obtained from dialysis patients. In 47 of the 75 samples, the remaining samples were subjected to direct microfocus x-ray computed tomographic observation. Quantitative morphologic examinations, including micro-bone mineral densitometry, and marrow space star volume, Euler number, and node-strut analyses, were performed in the virtual three-dimensional space reconstructed from the microfocus x-ray computed tomographic images.Results: The levels of BV/TV were comparable in each of the conventional bone histomorphometric criteria. No significant correlations were found between BV/TV and other parameters. Two-and three-dimensional BV/TVs were significantly correlated with cancellous bone mass but not with cortical bone thickness or cortical bone mass. Two-and three-dimensional BV/TVs were significantly correlated with trabecular bone connectivity as determined by marrow space star volume, Euler number, and node-strut analyses.Conclusions: In dialysis patients, BV/TV is not dependent on bone turnover or bone mineralization. BV/TV is unlikely to indicate the balance between bone formation and bone resorption. Instead, it reflects trabecular bone connectivity, and improved trabecular bone connectivity is physiologically beneficial in terms of bone quality. The turnover-mineralizationvolume system offers an advantage over the conventional system for the assessment of bone quality.

Lanthanum carbonate (LC), a newly developed non-calcium-containing phosphate binder, has been shown to possess high phosphate-binding capacity and safety when used for hyperphosphatemia in patients with chronic kidney disease undergoing dialysis. The effects of LC on bone metabolism in Japanese dialysis patients have not been investigated; therefore, we performed histomorphometric analysis on bone from dialysis patients with hyperphosphatemia. This was a prospective, open-label study in Japanese chronic kidney disease patients on dialysis, with a flexible daily dosage of 750-4500 mg to achieve target phosphorus levels of 3.5-5.5 mg/dL (1.10-1.78 mmol/L). Bone biopsy samples for histomorphometric analysis were obtained at baseline and after treatment with LC. The median bone lanthanum level increased during the LC treatment from 54.1 µg/kg at baseline to 4270.9 µg/kg at three years. After one year of treatment with LC, two cases with an initial classification of osteitis fibrosa improved toward normal bone turnover. The diagnosis of normal remained the same for up to three years. We also noted that two cases with a baseline classification of adynamic bone disease improved after one year, and was maintained for three years. Our data suggest that LC is effective not only for treating hyperphosphatemia, but also for improving renal osteodystrophy in Japanese dialysis patients.