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Shohei Nakanishi

Publications and source records attributed to Shohei Nakanishi.

16 recordsLinked to original sources
PubMed2007

[Therapeutic agents for disorders of bone and calcium metabolism. The calcimimetic cinacalcet HCl].

Calcimimetics drug such as cinacalcet suppress the secretion of parathyroid hormone by sensitizing parathyroid calcium receptors to extracellular ionized calcium. Standard treatment for secondary hyperparathyroidism is associated with the risk of hypercalcemia, but cinacalcet don't induce elevation of serum calcium. And some studies were reported the use of cinacalcet not only to manage primary hyperparathyroidism, but also secondary hyperparathyroidism in nondialyzed stage, renal transplant patients and parathyroid carcinoma.

Cinacalcet↗
PubMed2006

The kidney and bone metabolism: Nephrologists' point of view.

The kidney plays an important role in the regulatory system for bone and mineral metabolism. In chronic kidney disease (CKD), various abnormalities, recently named CKD-mineral and bone disorder (CKD-MBD), may develop in this system. The optimal management of CKD-MBD should be achieved without increasing the risk of metastatic calcification, including that of blood vessels. Thus, it is quite important to identify severe cases of hyperparathyroidism refractory to medical therapy. The size of the parathyroid glands, serum levels of fibroblast growth factor (FGF)23, and, possibly, the overproduction of a novel form of parathyroid hormone (PTH), serve as useful markers for this purpose. Adynamic bone disease with low buffering capacity for calcium is another major cause of hypercalcemia in dialysis patients. Our recent studies suggest that indoxyl sulfate accumulated in uremic serum is responsible for the suppression of osteoblastic function. In order to maintain the bone quality in patients with CKD, bone changes due to aging, menopause, and malnutrition need to be considered by nephrolgists and non-nephrologists in collaboration.

Animals↗
PubMed2006

Regulation of parathyroid function in chronic kidney disease (CKD).

In chronic kidney disease (CKD), several abnormalities in bone and mineral metabolism develop in the majority of patients. The parathyroid plays a very important role in regulating bone and mineral metabolism; thus, control of parathyroid function is one of the main targets of the management of CKD-mineral and bone disorder (CKD-MBD). In the development of secondary hyperparathyroidism, it has recently been suggested that fibroblast growth factor 23 (FGF23) plays a crucial role, both as a phosphaturic factor and as a suppressor of active vitamin D (1,25D) production in the kidney. FGF23 is originally secreted to prevent hyperphosphatemia in CKD, but this occurs at the expense of low 1,25D and hyperparathyroidism ("trade-off" hypothesis revisited). Furthermore, recent data suggest that FGF23 could be another useful marker for the prognosis of hyperparathyroidism, because a high serum level may reflect the cumulative dose of vitamin D analogues previously administered. We have also demonstrated that severe hyperparathyroidism was associated with the production and secretion of a new form of parathyroid hormone (PTH) molecule, which can be detected by third-generation assays for PTH, but not by the second-generation assays. For the regression of already established nodular hyperplasia, the more advanced type of parathyroid hyperplasia, it is certainly necessary, in the near future, to develop new agents that specifically induce apoptosis in parathyroid cells. Until such agents are developed, prevention and early recognition of nodular hyperplasia is mandatory for the effective and safe management of hyperparathyroidism in CKD.

Animals↗
PubMed2005

Intravenous calcitriol therapy increases serum concentrations of fibroblast growth factor-23 in dialysis patients with secondary hyperparathyroidism.

BACKGROUND/AIMS: Fibroblast growth factor-23 (FGF-23) is a recently discovered phosphaturic factor. Although increased levels of serum FGF-23 have been reported in dialysis patients, the role of high FGF-23 levels remains unclear. Since FGF-23 is associated also with vitamin D metabolism, we examined the changes of serum FGF-23 levels in chronic dialysis patients treated with intravenous calcitriol therapy. METHODS: Thirty patients with severe secondary hyperparathyroidism were treated with intravenous calcitriol (0.5-1.0 microg) two or three times per week for 6 months. The changes of serum levels of calcium, phosphate, intact PTH, and FGF-23 were evaluated. RESULTS: Baseline serum FGF-23 levels were markedly high. By intravenous calcitriol therapy, intact PTH levels decreased effectively in the first month (p < 0.001). In contrast, FGF-23 levels increased gradually during the study period (p = 0.027). The Delta serum FGF-23 level was significantly correlated with the total doses of calcitriol injected intravenously in 6 months in patients with refractory secondary hyperparathyroidism (R2 = 0.147; p = 0.036). CONCLUSIONS: Intravenous calcitriol decreased serum intact PTH level and increased serum FGF-23 levels significantly. Extremely high levels of serum FGF-23 in these patients may be attributed, at least in part, to the cumulative dose of vitamin D.

Calcitriol↗
PubMed2005

Serum fibroblast growth factor-23 levels predict the future refractory hyperparathyroidism in dialysis patients.

BACKGROUND: Secondary hyperparathyroidism is a common complication among long-term dialysis patients. The method of predicting future parathyroid function has not yet been established. Fibroblast growth factor-23 (FGF-23) is a newly found humoral phosphaturic factor. METHODS: One hundred and three nondiabetic dialysis patients whose plasma intact parathyroid hormone (PTH) levels were below 300 pg/mL were included in the study. Blood samples were stored at -80 degrees C for 2 years. Meanwhile, each physician in charge decided upon the strategy of medical therapy for maintaining intact PTH levels between 150 and 300 pg/mL. Patients were judged 2 years after the sample collection with regard to whether the hyperparathyroidism responded to the medical therapy. The definition of refractory secondary hyperparathyroidism was either (1) retaining intact PTH levels greater than 300 pg/mL 2 years after sample collection, or (2) having received the parathyroid intervention therapy during the observation period. Serum FGF-23 levels were determined with a sandwich enzyme-linked immunosorbent assay system that detects biologically active human FGF-23. RESULTS: Seventeen patients with intact PTH levels greater than 300 pg/mL were judged as having secondary hyperparathyroidism refractory to medical therapy. A stepwise regression analysis revealed that only serum levels of FGF-23 were significantly related to the prognosis of parathyroid function. A receiver-operated characteristic analysis demonstrated that the area under the curves obtained from FGF-23 (7099.9) was significantly greater than that obtained from intact PTH (6306.4, P < .01) and Ca x Pi (5670.3, P <.0001). Although the plasma intact PTH levels at the beginning of the observation period were comparable to each other, the intact PTH levels at 2 years after the sample collection were significantly higher in the patients with FGF-23 >/=7500 ng/L than in those with FGF-23 <7500 ng/L (P < .0001). CONCLUSION: Serum FGF-23 level was found to be the most useful factor in predicting future development of refractory secondary hyperparathyroidism in long-term dialysis patients with mild secondary hyperparathyroidism. The measurement of serum FGF-23 levels is a promising laboratory examination that can be applied in the clinical practice of uremic secondary hyperparathyroidism.

Adult↗
PubMed2004

Total parathyroidectomy reduces elevated circulating fibroblast growth factor 23 in advanced secondary hyperparathyroidism.

BACKGROUND: Secondary hyperparathyroidism is a common complication in patients with stage 5 chronic kidney disease (CKD), accelerated by hyperphosphatemia. Fibroblast growth factor 23 (FGF-23), a phosphorus-regulating protein, has key roles in several phosphate-wasting disorders. The aim of this study is to examine the association of advanced secondary hyperparathyroidism with circulating FGF-23 levels. METHODS: Fifteen patients with marked secondary hyperparathyroidism (parathyroid hormone [PTH], 990 +/- 118 pg/mL [ng/L]) were enrolled. All underwent parathyroidectomy with forearm autotransplantation (PTX), and their FGF-23 levels were measured before and after PTX (days 1, 3, 7, and 10) by means of sandwich enzyme-linked immunosorbent assay. RESULTS: Preoperative FGF-23 levels correlated positively with phosphorus (P < 0.05), calcium-phosphorus product (Ca x P; P < 0.0005), and PTH values (P < 0.05). Serum FGF-23 levels decreased time dependently after PTX (P < 0.0005). Both serum phosphorus and Ca x P values decreased similarly after PTX ( P = 0.0001). Furthermore, FGF-23 levels days 1 and 3 correlated linearly with serum phosphorus (P < 0.05; P < 0.005, respectively) and Ca x P values (P < 0.01; P < 0.0001, respectively). CONCLUSION: FGF-23 levels correlate positively with serum phosphorus, Ca x P, and PTH values in patients with advanced secondary hyperparathyroidism. Complete ablation of progressive parathyroid glands reduces circulating FGF-23 levels, simultaneously decreasing serum phosphorus and Ca x P values. These findings suggest that hyperplastic parathyroid glands, together with hyperphosphatemia, affect abnormal FGF-23 metabolism in patients with stage 5 CKD with advanced secondary hyperparathyroidism.

Chronic Disease↗
PubMed2004

[Role of vitamin D in the pathogenesis of renal osteodystrophy].

Renal osteodystrophy was occurred in patients with chronic renal failure and the biopsied patients had various forms of bone disease. Active vitamin D has an important role of calcium regulation and bone metabolism. In patients with end-stage renal disease, decreased levels of active vitamin D, reduced number of vitamin D receptors and calcium sensing receptors in parathyroid gland pay a major role in the development of hyperparathyroidism. It was invited osteitis fibrosa, high bone turnover. The parathyroid function is suppressed by active vitamin D, it was considered that lower parathyroid hormone levels was one of the cause of low bone turnover, adynamic bone disease.

Bone and Bones↗
PubMed2003

Role of parathyroid intervention in the management of secondary hyperparathyroidism.

Measurement of the size of the parathyroid glands is mandatory for the selection of the optimal therapy for secondary hyperparathyroidism. Surgical parathyroidectomy or parathyroid intervention is indicated for patients with nodular hyperplasia as this form is seldom responsive to medical therapy. Selection of the intervention should be determined by the number, size and location of the parathyroid glands with nodular hyperplasia, including ectopic glands.

Calcitriol↗
PubMed2003

Efficacy of direct injection of calcitriol into the parathyroid glands in uraemic patients with moderate to severe secondary hyperparathyroidism.

INTRODUCTION: Secondary hyperparathyroidism (2HPT) is a common complication in uraemic patients. When medical therapy, including high doses of intravenous calcitriol, fails to suppress the pathological secretion of parathyroid hormone (PTH), one of the newly developed interventional techniques, such as percutaneous ethanol injection therapy (PEIT), is an option before taking the surgical solution. A protocol for direct calcitriol injection therapy and a discussion of its effectiveness and limitations for an enlarged parathyroid gland(s) are presented. METHODS: Nine patients were selected according to the Japanese Guideline for Selective PEIT. Using the same technique as PEIT, a dose of calcitriol that was approximately 200-300% of the calculated volume of the selected parathyroid gland was injected directly into the gland under ultrasonographic guidance. RESULTS: In six cases, the intact PTH concentration decreased to <360 pg/ml. The total volume of the enlarged parathyroid gland(s) also decreased to 54.7% of the initial volume. The blood supply to the treated glands, as evaluated by colour Doppler imaging, appeared to diminish transiently after injection, probably from the volume effect of this procedure. The number of enlarged parathyroid glands was not a limiting factor for this therapy; however, a grossly enlarged parathyroid gland (>2000 mm(3)) appeared to be resistant to this intervention and an intrathoracic parathyroid gland was found in a non-responsive case. None of the patients had any severe complications, such as nerve palsy or massive haemorrhage. CONCLUSION: This new approach to the control of 2HPT is recommended as an alternative pharmacological parathyroidectomy to surgical therapy.

Calcitriol↗
PubMed2003

[Calcium and vitamin D metabolism in the kidney-parathyroid system].

Calcium level is maintained by parathyroid hormone, 1alpha, 25 (OH)(2)D(3) and calcitonin in cooperation with bone, kidney and intestine. In the kidney activation of vitamin D and transcellular calcium transport in distal tubule regulate calcium concentlation. In the parathyroid glands calcium-sensing receptor sense extracellular calcium and secretes parathyroid hormone. It is received negative feedback from 1alpha, 25 (OH)(2)D(3) and phosphate.

English Abstract↗
PubMed2002

[Mechanism of secondary hyperparathyroidism].

Renal osteodystrophy is an important concomitant disease in chronic renal failure. Secondary hyperparathyroidism cause high turnover bone. Hypocalcemia and phosphate retention stimulate the parathyroid and to proliferation of the parathyroid cells. In these days vitamin D deficiency, resistance to vitamin D, abnormality of sensitivity to calcium, direct effect of phosphorus , more severe form of parathyroid hyperplasia, abnormality of gene and increased skeletal resistance to PTH are pointed as cause of parathyroid hyperfunction.

English Abstract↗