Serum oxalate concentration is associated with coronary artery calcification and cardiovascular events in Japanese dialysis patients.

Coronary artery calcification (CAC) is associated with cardiovascular disease (CVD). CAC might contain calcium oxalate, and a high serum oxalate (S) concentration is associated with cardiovascular mortality in dialysis patients. We assessed the associations between S and CAC or CVD events in Japanese hemodialysis patients.

Impact of phosphate binders on medication dosing frequency, timing, and number of prescribed pills in hemodialysis patients.

Introduction: Phosphate binders (PBs) account for a large proportion of the daily pill burden in hemodialysis patients. However, patients do not take them all at once but at several dosing timings.

Methods: We analyzed the dosing timings of all 322 types of oral drugs prescribed to 533 hemodialysis patients.

Phosphate Binders Derived from Natural Ores Contain Many Kinds of Metallic Elements Besides Their Active Ingredient Metals.

Most patients undergoing dialysis are required to take many phosphate binder pills to control hyperphosphatemia. Phosphate binders prescribed in Japan are classified into two types: metal-based binders (Ca carbonate, lanthanum carbonate, ferric citrate hydrate, and sucroferric oxyhydroxide) and chemically synthesized polymers (sevelamer hydrochloride and bixalomer). The raw materials of metal-based phosphate binders are natural ores; thus, such binders may contain several other metallic elements.

Fibroblast growth factor 23 is upregulated in the kidney in a chronic kidney disease rat model.

The hormone fibroblast growth factor 23 (FGF23) is secreted from bone and is involved in phosphorus (P) metabolism. FGF23 mainly binds the FGF receptor, which interacts with αKlotho in the kidney or parathyroid and regulates Na-dependent phosphate co-transporter type IIa (NaPi-IIa) and type IIc (NaPi-IIc) expression, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) activity, and parathyroid hormone (PTH) secretion. In this study, we utilized hemi-nephrectomized rats fed a high-P diet (HP Nx), rats subjected to a partial nephrectomy (PN) and rats with doxorubicin-induced renal failure (DXR) as chronic kidney disease (CKD) animal models and analyzed the P metabolism and FGF23 expression in the kidneys in each CKD model.

Impact of the Visceral Fat Area Measured by Dual Impedance Method on the Diagnostic Components of Metabolic Diseases in a Middle-aged Japanese Population.

Objective The aim of this study was to examine the associations between the visceral fat area (VFA) and the subcutaneous fat area (SFA) as estimated by the dual impedance method with a body composition monitor (BCM) and the diagnostic components of metabolic syndrome in a middle-aged Japanese population. Methods The subjects included 303 men (average age 51.3±9.

[Pharmacological characteristics of drugs targeted on calcium-sensing receptor.-properties of cinacalcet hydrochloride as allosteric modulator].

Calcimimetics act as positive allosteric modulators of the calcium-sensing receptor (CaSR), thereby decreasing parathyroid hormone (PTH) secretion from the parathyroid glands. On the other hand, negative allosteric modulators of the CaSR with stimulatory effect on PTH secretion are termed calcilytics. The calcimimetic cinacalcet hydrochloride (cinacalcet) is the world's first allosteric modulator of G protein-coupled receptor to enter the clinical market.

Effect of Polydextrose Intake on Constipation in Japanese Dialysis Patients: A Triple-Blind, Randomized, Controlled Trial.

The objective of the present study was to evaluate bowel habits induced by ingestion of 10 g polydextrose (PDX) fed to Japanese hemodialysis (HD) patients. This was a randomized, placebo-controlled, triple-blind, parallel-group controlled, 8-wk study. A total of 50 HD outpatients capable of self-management (51-79 y of age) were recruited at H Clinic, Japan.

Klotho/FGF23 Axis in CKD.

The sequential bone disorders, serum parameter abnormalities and vascular calcification that are associated with chronic kidney disease (CKD) have come to be generally known as CKD-mineral bone disorder (MBD). Klotho, a causative protein of aging, and fibroblast growth factor 23 (FGF23), a bone-derived phosphaturic factor, have been reported to be involved in CKD-MBD, and their relationship to the pathophysiology of this disease is gradually being elucidated. Klotho functions as a cofactor of FGF receptors and has been reported to cause FGF23 action and specificity in the kidney.

Fibroblast growth factor 23/klotho axis in chronic kidney disease.

Fibroblast growth factor-23 (FGF23) is a bone-derived hormone that regulates phosphate and 1,25-hydroxyvitamin D [1,25(OH)2D] metabolism. FGF23 binds to FGF receptor 1 with its coreceptor Klotho and maintains serum phosphate levels within the normal range by increasing renal phosphate excretion. In addition, FGF23 reduces the synthesis and accelerates the degradation of 1,25(OH)2D to reduce intestinal phosphate absorption.

[Cinacalcet hydrochloride and phosphate metabolism].

The inhibitory effect of cinacalcet hydrochloride (cinacalcet) on blood phosphorus (P) levels is widely-accepted. However, this effect is only observed in patients on dialysis. Reduction in parathyroid hormone (PTH) induced by cinacalcet increases blood P levels with decreased urinary P excretion in pre-dialysis patients with chronic kidney disease (CKD).

Cinacalcet HCl suppresses Cyclin D1 oncogene-derived parathyroid cell proliferation in a murine model for primary hyperparathyroidism.

Cinacalcet HCl (cinacalcet) is a calcimimetic compound, which suppresses parathyroid (PTH) hormone secretion from parathyroid glands in both primary hyperparathyroidism (PHPT) and secondary hyperparathyroidism (SHPT). We previously reported the suppressive effect of cinacalcet on PTH secretion in vivo in a PHPT model mouse, in which parathyroid-targeted overexpression of the cyclin D1 oncogene caused chronic biochemical hyperparathyroidism and parathyroid cell hyperplasia. Although cinacalcet suppressed parathyroid cell proliferation in SHPT in 5/6-nephrectomized uremic rats, its effect on PHPT has not yet been determined.

Direct evidence for a causative role of FGF23 in the abnormal renal phosphate handling and vitamin D metabolism in rats with early-stage chronic kidney disease.

Circulating levels of fibroblast growth factor 23 (FGF23) are elevated in patients with early chronic kidney disease (CKD) and are postulated to cause low blood levels of 1,25-dihydroxyvitamin D, as well as normal phosphate levels. In order to provide more direct evidence for the pathophysiological role of FGF23 in the settings of mineral ion homeostasis typically seen in early CKD, we studied rats with progressive CKD treated with anti-FGF23 neutralizing antibody. Without antibody treatment, rats with CKD exhibited high circulating levels of FGF23 and parathyroid hormone, low 1,25-dihydroxyvitamin D, and normal serum phosphate levels, accompanied by increased fractional excretion of phosphate.

Cinacalcet suppresses calcification of the aorta and heart in uremic rats.

High serum parathyroid hormone levels are associated with vascular calcification. Cinacalcet is a calcimimetic agent that inhibits parathyroid hormone secretion and is used to treat patients with secondary hyperparathyroidism. Here we measured the effects of oral cinacalcet on calcification of the aorta and heart in rats with a remnant kidney (5/6 nephrectomy) model of uremia that were fed a high-phosphate diet containing lactose to accelerate the process of aortic calcification.

[Basic and clinical aspects of calcimimetics. Discovery and development of calcimimetics].

Parathyroid cells can sense small fluctuations in plasma calcium ion (Ca(2 + )) levels by virtue of a cell surface calcium receptor (CaR) that belongs to superfamily of G-protein-coupled receptors. Dr. Nemeth and his colleagues discovered that certain phenylalkylamine compounds stereo-selectively increased intracellular Ca(2 + ) concentration and inhibited parathyroid hormone (PTH) secretion in cultured bovine parathyroid cells.

Direct in vitro evidence of the suppressive effect of cinacalcet HCl on parathyroid hormone secretion in human parathyroid cells with pathologically reduced calcium-sensing receptor levels.

Clinical studies have been performed to determine the effect of cinacalcet HCl (cinacalcet), an allosteric modulator of the calcium-sensing receptor (CaR), on primary hyperparathyroidism (PHPT) and secondary hyperparathyroidism of uremia (SHPT). However, no in vitro studies on human parathyroid cells have been reported to date. In this study, the inhibitory effect of cinacalcet on PTH secretion was analyzed in primary cultured parathyroid cells obtained from patients.