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Biomedical subjects

Takashi Shigematsu

Publications and source records attributed to Takashi Shigematsu.

At least 19 recordsLinked to original sources
PubMed2005

Fibroblast growth factor-23 in patients with Graves' disease before and after antithyroid therapy: its important role in serum phosphate regulation.

OBJECTIVE: Hyperthyroidism is a well-described cause of hyperphosphatemia. We aimed to clarify the physiological role of fibroblast growth factor (FGF)-23 in serum phosphate homeostasis in patients with Graves' disease during the course of treatment for hyperthyroidism. CONTEXT: The study group comprised 56 patients (45 for a cross-sectional study and 11 for a longitudinal study) with Graves' disease. For the cross-sectional study, patients were assigned, on the basis of their serum phosphate level, to a hypophosphatemia group (n = 14), a normophosphatemia group (n = 16), or a hyperphosphatemia group (n = 15). Serum FGF-23, calcium, phosphate, PTH, and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] levels were compared between the three groups. For the longitudinal study, we assessed changes in these biochemical indices before and after antithyroid treatment. RESULTS: In the cross-sectional study, the serum FGF-23 level was significantly higher (P < 0.05) in the hyperphosphatemia group than in the other groups (61 +/- 36 ng/liter vs. 31 +/- 22 ng/liter and 30 +/- 9 ng/liter). In the longitudinal study, serum levels of FGF-23 decreased significantly (P < 0.05) from a high of 54 +/- 12 ng/liter before treatment to 29 +/- 14 ng/liter after treatment. In contrast, the serum 1,25(OH)(2)D level increased significantly (P < 0.005) from 55 +/- 22 pmol/liter before treatment to 185 +/- 76 pmol/liter 3 months after treatment. Serum FGF-23 levels were positively correlated with serum phosphate levels (P < 0.0001) and negatively correlated with serum 1,25(OH)(2)D levels (P < 0.0001). CONCLUSIONS: The significant positive correlation between serum levels of phosphate and FGF-23 indicates that FGF-23 may play an important role in serum phosphate homeostasis by its up-regulation in the hyperphosphatemic condition.

Adult↗
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↗
PubMed2005

Role of circulating fibroblast growth factor 23 in the development of secondary hyperparathyroidism.

It would be useful to predict the future development of hyperparathyroidism before treatment with active vitamin D agents. Fibroblast growth factor 23 (FGF23) is a newly identified humoral phosphaturic factor. Positive correlation was found between parathyroid function and serum FGF23 levels in dialysis patients. Interestingly, FGF23 levels showed even better correlation with intact parathyroid hormone (iPTH) levels 2 years after the sample collection for the FGF23 measurement. In long-term dialysis patients with mild secondary hyperparathyroidism, serum FGF23 level was the best screening test to discriminate patients with future advanced secondary hyperparathyroidism within 2 years. In dialysis patients with advanced secondary hyperparathyroidism, the pretreatment FGF23 levels, as well as iPTH levels, significantly affected the outcome of calcitriol therapy. Thus, the measurement of serum FGF23 level is a promising laboratory examination to predict the future development of secondary hyperparathyroidism. The mechanism of this phenomenon, however, remains to be revealed.

Clinical Trials as Topic↗
PubMed2005

Sevelamer hydrochloride and calcium bicarbonate reduce serum fibroblast growth factor 23 levels in dialysis 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.

Bicarbonates↗
PubMed2005

Prospective randomized multicenter trial of sevelamer hydrochloride and calcium carbonate for the treatment of hyperphosphatemia in hemodialysis patients in Japan.

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.

Analysis of Variance↗
PubMed2005

Efficacy of combined sevelamer and calcium carbonate therapy for hyperphosphatemia in Japanese hemodialysis patients.

In Japan, calcimimetics and other phosphate binders such as lantanum carbonate are not available for patients on long-term hemodialysis (HD), so we prospectively evaluated the clinical efficacy of the combination of sevelamer hydrochloride and calcium carbonate (CaCO3) for hyperphosphatemia. The study group comprised 65 HD patients who had been administered CaCO3 (>or=1500 mg/day) for hyperphosphatemia [>or=6.0 mg/dL (>or=1.94 mmol/L)]. At the beginning of the study the dose of CaCO3 was reduced by 1500 mg/day and the patients divided into two groups according to the dose of additional sevelamer hydrochloride: group A 2250 mg/day; group B 3000 mg/day. Oral active vitamin D therapy was unchanged. Fourteen patients (21.5%) dropped out because of adverse effects and of the 51 remaining patients 35 (53.8%) suffered from gastrointestinal problems. Serum phosphate concentration decreased significantly [from 7.5+/-0.8 mg/dL (2.42+/-0.26 mmol/L) to 6.6+/-1.3 mg/dL (2.13+/-0.42 mmol/L), P<0.01] in group B only after the 8 weeks of combination therapy. The calcium-phosphate product (CaxPi) also decreased in group B only [from 74.4+/-13.4 mg2/dL2 (5.99+/-1.07 mmol2/l2) to 63.7+/-15.8 mg2/dL2 (5.13+/-1.27 mmol2/l2), P<0.001]. The combination of sevelamer hydrochloride and CaCO3 is a suitable regimen for hyperphosphatemia treatment in HD patients because it avoids both the hypercalcemia of CaCO3 and the adverse effects of sevelamer hydrochloride when each is used as single-drug therapy. The ability of sevelamer hydrochloride to decrease the serum phosphate concentration is 2/3 (2250/1500 mg) that of CaCO3.

Calcium Carbonate↗
PubMed2005

Direct comparison between two 1-84PTH assays in dialysis patients.

BACKGROUND/AIM: Today, two kinds of 1-84PTH assays are available in clinical practice. Few studies have directly compared the results of these assays in the same plasma. METHODS: Plasma samples were collected from 235 dialysis patients and analyzed by the 1-84PTH-IRMA, intact PTH-IRMA, 1-84PTH-CLIA, and intact PTH-CLIA assays simultaneously. RESULTS: The results obtained by the 1-84PTH-IRMA and 1-84PTH-CLIA were highly correlated to each other (r(2) = 0.971, p < 0.0001). In 90.2-92.3% of patients, the assays agreed when classifying them into three categories based on the K/DOQI guidelines. However, the 1-84PTH assays agreed in only 41.3-83.4% of patients when classifying them into two categories by calculating 1-84PTH/(intact PTH - 1-84PTH). CONCLUSION: The results obtained by the two assays could be regarded as comparable in clinical practice. However, the 1-84PTH/(intact PTH-1-84PTH) ratio has to be carefully applied since it amplified the error of these assays.

Adolescent↗
PubMed2005

[The role of phosphatonin in phosphate metabolism].

PTH and active vitamin D are well known as classical phosphate regulating hormones. However, presence of some phosphaturic factors is assumed from investigations about TIO, XLH, ADHR. Those diseases cause hypophsophatemia, hyperphosphaturia, low vitamin D and rickets/ostepmalacia. FGF-23, which has been detected from TIO tumors, can induce hypophosphatemia by direct inhibition on phosphate reabsorption and by suppressing 1,25 (OH)(2)D(3) production through the inhibition of 25-hydroxyvitaminD 1alpha-hydroxylase, in the kidney. We have still other phosphatonin candidates such as MEPE, FRP4, etc. The role of these substances are not clear yet. Future investigations are required to clarify their roles in phosphate metabolism.

Fibroblast Growth Factor-23↗
PubMed2005

[Fibroblast growth factor (FGF)-23 in patients with hypoparathyroidism].

Hypoparathyroidism is a well-described cause of hyperphosphatemia. We aimed to clarify the physiological role of FGF-23 in serum phosphate homeostasis in hypoparathyroidism after thyroidectomy. Increased serum FGF-23 levels were found in patients with hyperphosphatemia and hypocalcemia, caused by hypoparathyroidism after thyroidectomy. After the recovery of parathyroid function, the serum level of calcium, phosphate, and FGF-23 was normalized. Serum FGF-23 levels were significantly higher in patients with permanent hypoparathyroidism than in healthy controls. These results indicate that FGF-23 may play an important role in serum phosphate homeostasis by its up-regulation in the hyperphosphatemic condition.

Female↗
PubMed2005

[Clinical investigation of the effect of blood sampling day on serum phosphorus concentration].

Whether the presence or absence of notification about the blood sampling date affects the serum phosphate concentration was examined. After periodical sampling at the beginning of the week with 2-day interval for regular dialysis, the blood was sampled on the midweek day with 1-day interval for dialysis upon the patient's consent right before sampling without an advance notification. In the next month subsequently periodical sampling at the beginning of the week and the sampling on the midweek day were performed after notification of the twice blood sampling before 1 week in advance. Then both serum phosphorus data were comparably investigated. In case the sampling was not notified, there is no difference in the serum concentration between the beginning of the week and the midweek day. On the other hand, in case the sampling was notified, the serum concentration significantly decreased on the weekday compared to that at the beginning of the week. It therefore was risky that the serum phosphorus concentration at the beginning of the week with 2-day interval for dialysis was presumed to be higher value than that on the midweek day with 1-day interval for dialysis. We need to consider the possibility that the presence or absence of notification about the blood sampling date affects the level of serum phosphorus concentration.

Blood Specimen Collection↗
PubMed2004

Possible involvement of circulating fibroblast growth factor 23 in the development of secondary hyperparathyroidism associated with renal insufficiency.

BACKGROUND: Fibroblast growth factor 23 (FGF-23) is a recently identified polypeptide that promotes renal phosphate excretion and decreases serum 1,25-dihydroxyvitamin D3 (1,25D) levels. Serum FGF-23 levels are extraordinarily elevated in patients with end-stage renal failure. METHODS: Blood and urine samples were obtained from 62 predialysis patients (age, 51.3 +/- 14.0 years; range, approximately 18 to 76 years; 32 men, 30 women). Serum FGF-23 levels were determined by means of a sandwich enzyme-linked immunosorbent assay system using 2 kinds of monoclonal antibodies that does not detect biologically inactive N-terminal and C-terminal fragments derived from an identified internal cleavage site to date. RESULTS: Serum FGF-23 levels increased with the decrease in creatinine clearance (Ccr). Both intact parathyroid hormone (PTH) and 1-84 PTH levels correlated closely with FGF-23 levels (r2 = 0.857; r2 = 0.860). A negative correlation between serum concentrations of FGF-23 and 1,25D (r2 = 0.255) was found. The maximum tubular reabsorptive rate of phosphate correlated negatively with serum FGF-23 concentrations (r2 = 0.460). However, the amount of daily urinary phosphate excretion was significantly less in patients with a Ccr less than 30 mL/min (<0.50 mL/s; P < 0.01), whereas their circulating FGF-23 levels were significantly greater (P < 0.001). CONCLUSION: Circulating FGF-23 levels increase with the decrease in renal function. FGF-23 is a likely candidate to lead the reduction in serum 1,25D levels. FGF-23 becomes a potential uremic toxin to decrease 1,25D levels when it loses its hypophosphatemic action because of a decreased number of viable nephrons in patients with advanced renal failure. As such, FGF-23 may be an important determinant in the regulation of mineral metabolism with renal insufficiency.

Adolescent↗
PubMed2004

Inhibitory effects of etidronate on the progression of vascular calcification in hemodialysis patients.

The present study was designed to determine if etidronate inhibits the development of aortic calcification in hemodialysis (HD) patients. Eighteen Japanese HD patients were divided randomly into etidronate-treated or control groups. Etidronate was given orally at the dose of 200 mg just before sleep on the day of dialysis, which was performed three times per week. In the control group, the aortic calcification area (ACA) increased after 6 months. In the patients who received etidronate, however, when compared to the control group, increases in ACA were significantly suppressed. Serum Ca, P, and the Ca x P product did not change during etidronate treatment. These results suggest that etidronate inhibits the progression of vascular calcification without changes in serum Ca and P levels.

Aged↗