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Biomedical subjects

Senji Okuno

Publications and source records attributed to Senji Okuno.

At least 19 recordsLinked to original sources
PubMed2006

Annual fat mass change is a significant predictor of mortality in female hemodialysis patients.

BACKGROUND: Although obesity confers an increased risk of mortality in the general population, it has been reported to be associated with improved survival in dialysis patients. However, the influence of fat mass change over time on mortality in dialysis patients has not been determined. METHODS: This relationship was examined in 190 female maintenance hemodialysis patients. Fat mass was measured twice with a 12-month interval, using dual energy X-ray absorptiometry (DEXA). The patients were followed up for 5 years, and predictors for all-cause death were examined using Kaplan-Meier analysis and Cox proportional hazards analyses. RESULTS: During the 5-year follow-up period, 65 patients died. Annual fat mass changes in the expired group tended to be greater than in the surviving group (-1.0 +/- 2.5 vs. -0.3 +/- 2.6 kg; P = 0.0776), although initial body fat mass was not significantly different. Kaplan-Meier analysis revealed that patients with decreased fat mass (N = 110) had a significantly lower survival rate, compared with those with increased fat mass (N = 80; P = 0.021). Multivariate Cox proportional hazards analyses demonstrated that annual fat mass change was a significant predictor of all-cause mortality after adjustments for confounding factors, such as age, serum albumin, serum creatinine, and the presence of diabetes. An increase in annual fat mass of 1 kg reduced mortality by 14.5%. CONCLUSIONS: These results demonstrate that the decrease in annual fat mass is a significant predictor for mortality in female hemodialysis patients. Fat mass change is also a useful parameter for measurement of nutritional status in hemodialysis patients.

Absorptiometry, Photon↗
PubMed2006

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. The investigation involved three PHPT and three SHPT patients subjected to therapeutic parathyroidectomy. Notably, all SHPT patients were resistant to intravenous vitamin D analogue therapy. Removed parathyroid tumors were used for immunohistochemistry and parathyroid cell primary culture. Immunohistochemical analyses revealed diminished expression of CaR and vitamin D receptor (VDR) in all parathyroid tumors. PTH secretion from cultured parathyroid cells of PHPT and SHPT patients was suppressed by extracellular Ca2+ and cinacalcet in a dose-dependent manner. Rates of suppression of PTH secretion in PHPT and SHPT by cinacalcet (1000 nmol/l) were 61% +/- 21% and 61% +/- 19%, respectively. Cinacalcet demonstrates significant potency in the suppression of PTH secretion in primary cultured human parathyroid cells in vitro, despite reduced levels of the target protein, CaR. Data from this in vitro analysis support the clinical application of cinacalcet in PHPT and SHPT therapy.

Cinacalcet↗
PubMed2006

[Bone abnormalities in diabetic hemodialysis patients].

In patients with end stage renal disease, metabolic bone abnormalities are frequently seen. Diabetes may affect bone metabolism through various mechanisms, including hyperglycemia, insulin deficiency, and accumulation of advanced glycation end-products. Bone disease in hemodialysis patients with diabetes mellitus is characterized by low bone turnover, resulting from either impaired secretion of parathyroid hormone or osteoblast dysfunction. The prevalence rate of vertebral fractures in diabetic hemodialysis patients was 32%, which was greater than that of non-diabetic hemodialysis patients (13%). In non-diabetic hemodialysis patients, those with vertebral fracture showed significantly lower bone mineral density in either lumbar spine or distal one third of radius than the respective value in those without fracture. However, in diabetic hemodialysis patients, neither bone mineral density in lumbar spine nor distal one third of radius was significantly lower in those with vertebral fracture than in those without.

Aged↗
PubMed2005

Positive correlation of serum bio-intact PTH(1-84) but not intact PTH with parathyroid gland size in hemodialysis patients.

To evaluate the usefulness of newly-developed bio-intact parathyroid hormone (Bio-PTH) assay, which measures exclusively intact PTH(1-84) molecule, serum PTH level determined by Bio-PTH assay, in comparison with second-generation intact PTH (I-PTH) assay, was examined for its correlation with parathyroid gland size. Serum PTH was determined in 46 male HD patients, together with bone formation markers bone alkaline phosphatase, intact osteocalcin, N-terminal propeptide of type I collagen, and bone resorption markers deoxypyridinoline, pyridinoline, beta-crossLaps. Maximal diameter of parathyroid gland was determined with ultrasonography as the parathyroid gland size. Serum Ca and Pi correlated significantly with parathyroid gland size rationalizing our method to define parathyroid gland size. Serum Bio-PTH was correlated significantly in a positive manner with parathyroid gland size (R = 0.308, P = 0.0474), whereas serum I-PTH did not. Furthermore, parathyroid gland size did not exhibit a significant correlation with any of bone formation markers or bone resorption markers. The lack of correlation between bone markers and parathyroid gland size in HD patients may be explained by the occurrence of refractoriness of bone to PTH. In conclusion, serum Bio-PTH assay could provide a better assay than I-PTH assay to estimate parathyroid function in HD patients, due mainly to its exclusive correlation with parathyroid gland size.

Alkaline Phosphatase↗
PubMed2005

Serum concentrations of cross-linked N-telopeptides of type I collagen: new marker for bone resorption in hemodialysis patients.

BACKGROUND: Urinary cross-linked N-telopeptide of type I collagen (NTX) is a reliable bone resorption marker in patients with metabolic bone disease. We assessed a clinically available serum NTX assay suitable for anuric patients on hemodialysis (HD). METHODS: Serum concentrations of NTX, C-terminal telopeptide of type I collagen (beta-CTX), pyridinoline (PYD), and deoxypyridinoline (DPD) were determined as bone resorption markers, and those of bone alkaline phosphatase (BAP) and intact osteocalcin (OC) as bone formation markers, in 113 male HD patients (mean age, 59.3 years; mean HD duration, 67.7 months). Each patient's bone mineral density (BMD) in the distal third of the radius was measured twice, with a 2-year interval between measurements, by dual-energy x-ray absorptiometry. RESULTS: Serum NTX correlated significantly with beta-CTX, PYD, DPD, BAP, and intact OC. NTX, as well as beta-CTX, PYD, DPD, BAP, and intact OC, correlated significantly with BMD at the time of measurement. NTX, beta-CTX, and DPD correlated significantly with the annual change in BMD during the 2-year period thereafter, in contrast to PYD, BAP, and intact OC. Patients in the highest quartile of serum NTX concentrations showed the fastest rate of bone loss. The sensitivity and specificity for detecting rapid bone loss were 48% and 83%, respectively, for serum NTX. CONCLUSION: Serum NTX may provide a clinically relevant serum assay to estimate bone turnover in HD patients.

Adult↗
PubMed2005

Direct in vitro evidence of extracellular Ca2+-induced amino-terminal truncation of human parathyroid hormone (1-84) by human parathyroid cells.

CONTEXT: Although serum calcium (Ca2+) concentration regulates the generation of amino-terminally (N-terminally) truncated forms of human PTH (hPTH) degraded from (1-84)hPTH, no studies have yet reported whether the parathyroid gland itself is responsible for this process. OBJECTIVE: Our objective was to determine the site of N-terminal truncation and its roles in PTH metabolism in parathyroid cells in vitro. METHODS: The effect of extracellular Ca2+ concentration was examined on N-terminal truncation in primary cultured parathyroid cells. The parathyroid glands were obtained from the patients with primary and uremia-associated secondary hyperparathyroidisms who underwent therapeutic parathyroidectomies. RESULTS: The N-terminally truncated fragments were detectable with commercially available intact PTH (I-PTH) assays, but not with the bio-intact PTH (Bio-PTH) assay, which detected only the (1-84)hPTH. HPLC revealed that generation of N-terminally truncated fragments detectable by I-PTH increased with extracellular Ca2+ concentration. Suppression of PTH secretion by increasing the extracellular Ca2+ concentration was more evident with the Bio-PTH assay than with the I-PTH assay for both cultured parathyroid cells prepared from parathyroid adenomas and uremia-associated secondary hyperparathyroidism. The Bio-PTH/I-PTH ratio, which is the ratio of (1-84)hPTH to the sum of (1-84)hPTH and N-terminally truncated fragments, decreased in response to increases in extracellular Ca2+. CONCLUSIONS: These findings suggest that the N-terminal truncation is regulated by extracellular Ca2+ concentration and works to suppress the generation of (1-84)hPTH in parathyroid cells.

Calcium↗
PubMed2005

Serum BAP as the clinically useful marker for predicting BMD reduction in diabetic hemodialysis patients with low PTH.

With decrease of serum PTH in hemodialysis (HD) patients, other factors besides parathyroid hormone (PTH) become important in regulating bone metabolism. We investigated which serum bone metabolic marker is the best to predict the bone mineral density (BMD) reduction in HD patients with serum PTH<180 pg/ml. The bone formation markers, bone alkaline phosphatase (BAP), intact osteocalcin (OC), and N-terminal propeptide of type I collagen (PINP), and the bone resorption markers, deoxypyridinoline (DPD), pyridinoline (PYD), and beta-crossLaps (beta-CTx) were measured in serum from 137 HD patients. BMD of all patients was measured twice, approximately 1.5 years before and 1.5 years after measurement of their markers of bone metabolism. In all 137 HD patients, serum BAP was the only marker significantly higher in those with BMD reduction than in those without. In 42 diabetes mellitus (DM) HD patients with serum PTH<180 pg/ml, hypothetically low bone turnover state, serum BAP was again the only marker to discriminate those with BMD reduction from those without. At serum PTH<60 pg/ml, serum BAP retained tendency toward higher value. These findings suggest that serum BAP might be the most sensitive to identify small changes of bone metabolism in low bone turnover state. Retrospective study confirmed the usefulness of serum BAP in clinical practice by significantly higher values in those with bone loss at PTH<180 pg/ml even in under routine sample handling. In conclusion, serum BAP is a clinically useful bone formation marker to predict the BMD reduction in DM HD patients with low level of PTH.

Absorptiometry, Photon↗
PubMed2005

C-reactive protein is a significant predictor of decrease in fat mass in hemodialysis patients.

Malnutrition and inflammation are common in hemodialysis patients, and are usually closely associated. We examined annual body fat mass changes, a possible nutritional parameter, in maintenance hemodialysis patients, and investigated the factors affecting such changes. Body fat mass of 454 hemodialysis patients (61+/-11 years, 269 males and 185 females) was measured twice by dual energy X-ray absorptiometry (DEXA), with a 12-month interval between measurements. In a total of 65 patients with hemodialysis duration of less than 1 year at the first measurement, fat mass at the second measurement had increased significantly over the course of a year (P<0.0001). In contrast, in a total of 389 patients with hemodialysis duration of more than 1 year at the first measurement, fat mass at the second measurement significantly decreased (P<0.005). In the 389 patients, significant negative correlations were seen between fat mass changes and CRP (r=-0.165, P<0.005). In a multiple regression analysis, CRP was a significant factor (beta=-0.163, P<0.005) affecting fat mass changes, independent of other confounding clinical factors (R(2)=0.127, P<0.001). These results show that body fat mass of long-term hemodialysis patients decreases after an initial increase in the first to second years of hemodialysis. In hemodialysis patients, fat mass change appears to be a parameter indicative of nutritional changes. Chronic inflammation, represented by higher CRP levels, is a significant factor affecting decrease in fat mass, and is related to poorer nutritional status.

Absorptiometry, Photon↗
PubMed2005

[Correlation of serum Bio-intact PTH (1-84) and parathyroid gland size in hemodialysed patients].

Bio-intact parathyroid hormone (Bio-PTH) assay, which measures exclusively intact PTH (1-84) molecule, provides a better assay for estimating parathyroid function in hemodialysis (HD) patients, whereas intact PTH (I-PTH) assay cross-react with PTH (7-84) as well as PTH (1-84). We have found that PTH (7-84) accumulated into serum of hemodialysis patients due probably to its impaired excretion into urine. We have reported that parathyroid gland size is one of major predictor for vitamin D responsiveness in secondary hyperparathyroidism. Therefore, we investigated whether serum Bio-PTH, in comparison with serum I-PTH, may provide a relevant assay to estimate parathyroid function as evidence by its correlation with parathyroid gland size on ultrasound examination.

Biomarkers↗
PubMed2005

[Effect of calcium on N-terminal truncation of PTH in human parathyroid cells].

Serum PTH (7-84) is accumulated in patients with secondary hyperparathyroidism. It is also known that serum calcium (Ca) increases the generation of N-terminally truncated forms of parathyroid hormone (PTH). In this study, we examined whether accumulation of PTH (7-84) fraction is a parathyroid glandular origin or not by using primary cultured parathyroid cells from patients with primary and secondary hyperparathyroidism. The Bio-PTH/I-PTH ratio, indicating the ratio of PTH (1-84) to the sum of (1-84) PTH and N-terminally truncated fragment, was suppressed by increase in extracellular Ca2+ concentration for both cultured parathyroid cells prepared from parathyroid adenomas and uremia-associated secondary hyperparathyroidism. There is no difference between the ratios in primary and secondary hyperparathyroidism. These findings suggest that N-terminal truncation is regulated by extracellular Ca2+ concentration in parathyroid cells, but accumulation of PTH (7-84) fragments in patients with secondary hyperparathyroidism is mainly caused by uremia.

Calcium↗
PubMed2005

[Significance of serum PTH (7-84) as a reliable nutritional marker in hemodialysis patients].

To evaluate the significance of serum PTH (7-84) in hemodialysis patients, correlation of the serum PTH (7-84) level with various nutritional markers was investigated in HD patients. Serum PTH was determined in 170 male HD patients by either a Bio intact PTH assay or a second-generation intact PTH assay. The level of bone formation markers and bone resorption markers were also measured. Lean body mass in trunk region was measured by dual X-ray absorptiometry. The serum PTH (7-84) level was obtained for the difference between serum I-PTH and Bio-PTH. Serum PTH (1-84) was directly obtained from the serum Bio-PTH value. Serum PTH (7-84) correlated significantly with nutritional markers such as body weight, albumin, PCR, TAC BUN, BUN, phosphate and lean body mass in trunk, whereas PTH (1-84) only correlated with phosphate. The correlation of serum PTH (7-84) with bone metabolic markers was no less significant than that for PTH (1-84). The results suggest that serum level of PTH (7-84) may provide clinically useful information, not only of the bone metabolic state but also of the nutritional state in HD patients, in sharp contrast to the exclusive correlation of PTH (1-84) with bone metabolic state.

Biomarkers↗
PubMed2004

Significance of Bio-intact PTH(1-84) assay in hemodialysis patients.

The aim of the present study was to examine whether the newly developed bio-intact parathyroid hormone (Bio-PTH) assay, which exclusively measures the intact PTH(1-84) molecule, provides a better assay for estimating parathyroid function in hemodialysis (HD) patients, and to evaluate the factors associated with serum PTH levels measured by Bio-PTH assay and by second-generation intact PTH (I-PTH) assay. The study also examined whether Bio-PTH/I-PTH ratio, an index of the active fraction of PTH, could provide information not obtainable from simple PTH results. Serum levels of PTH were measured in 177 male HD patients, together with the bone formation markers bone alkaline phosphatase (BAP), intact osteocalcin (iOC), N-midfragment osteocalcin (N-Mid OC), and N-terminal propeptide of type I collagen (PINP), and the bone resorption markers deoxypyridinoline (DPD), pyridinoline (PYD), and beta-CrossLaps (beta-CTx). Bone mineral density (BMD) was determined twice at distal radius one-third by dual-energy X-ray absorptiometry. Serum Bio-PTH was significantly elevated in HD patients compared to normal controls. Serum Bio-PTH and I-PTH correlated significantly in a positive manner with serum bone formation markers (BAP, iOC, N-Mid OC, PINP), and resorption markers (DPD, PYD, beta-CTx), and in a negative manner with BMD and annual change therein at distal radius one-third. The degree of correlation of Bio-PTH was not significantly different from that of I-PTH. The Bio-PTH/I-PTH ratio was significantly lower in HD patients than in normal individuals, due probably to accumulation of N-truncated PTH fragments in the former. The Bio-PTH/I-PTH ratio correlated significantly in a negative manner with serum calcium (Ca) (r=-0.251, P<0.001) and nutritional marker serum urea nitrogen, protein catabolic rate and serum creatinine. Multiple regression analysis further revealed that serum I-PTH, but not Bio-PTH, was significantly associated with each of these nutritional markers, and that the Bio-PTH/I-PTH ratio was negatively associated with serum Ca. It was also found that I-PTH, but not Bio-PTH, was influenced by nutritional state. It is concluded that serum Bio-PTH assay could be of similar value to I-PTH assay in evaluating parathyroid function in HD patients and that their combined use in the form of the Bio-PTH/I-PTH ratio could provide information not obtainable from simple PTH results.

Adult↗
PubMed2004

Serum levels of C-terminal telopeptide of type I collagen: a useful new marker of cortical bone loss in hemodialysis patients.

Renal osteodystrophy is a major complication in hemodialysis patients. Measurement of serum peptide derived from the degradation of bone collagen could potentially provide an indirect estimate of bone resorption. The present study estimated the significance of the C-terminal telopeptide of type I collagen (beta-CTx) as a serum bone resorption marker in male hemodialysis patients. The mean age and hemodialysis duration of the 160 patients were 59.7 years (26-86 years) and 67.2 months (17-142 months), respectively. Bone mineral density (BMD) in the distal third of the radius was measured using dual-energy X-ray absorptiometry twice with a 2-year interval. A blood sample was collected immediately before the hemodialysis session at the time of the second BMD measurement. Other serum bone markers determined were bone-specific alkaline phosphatase (BAP) and intact and N-terminal midfragment (N-Mid) osteocalcin (OC) as bone-formation markers and serum pyridinoline (PYD) and deoxypyridinoline (DPD) as bone resorption markers. Serum beta-CTx correlated significantly in a positive manner with serum PYD, DPD, BAP, intact OC, and N-Mid OC. Serum beta-CTx, as well as PYD, DPD, BAP, intact OC, and N-Mid OC, correlated significantly with BMD in the distal third of the radius at the second measurement and with the rate of BMD reduction during the preceding 2 years. The highest quartile of serum beta-CTx was positively associated with rapid bone loss, defined as a change in the value for BMD in the distal third of the radius falling within the upper tertile of patients, in 55% of cases, and each quartile progress in serum beta-CTx increased the odds ratio of rapid bone loss by a factor of 1.73. Since the Youden index was twice as accurate for beta-CTx, BAP and N-Mid OC as for intact PTH, these bone-remodeling markers may be better risk markers of cortical bone loss than intact PTH. Inclusion in the highest quartile of PTH (above 288 pg/ml) predicted rapid bone loss with a sensitivity of only 26%. This means that the upper limit for serum PTH level recommended by K/DOQI may be too high, since 74% of cases with rapid bone loss showed serum PTH levels of below 288 pg/ml. In conclusion, serum measurement of beta-CTx may provide a new commercially viable and relevant serum assay to reflect cortical bone resorption in hemodialysis patients.

Adult↗
PubMed2004

C-reactive protein is a significant predictor of vascular calcification of both aorta and hand arteries.

Although evidence has accumulated indicating a close relationship between inflammation and atherosclerosis, the relationship between inflammation and vascular calcification in patients with chronic renal failure is unclear. In the present study, the relationship between C-reactive protein (CRP) and vascular calcification in dialysis patients was examined. Vascular calcification of the aorta and hand arteries of 512 hemodialysis patients without significant infection (age 58.8 +/- 10.1 y; 305 men, 207 women) were examined by roentgenography of the lateral abdomen and hands, respectively. Patients with a mean CRP level greater than 1.0 mg/L (n = 254) were older than those with a CRP level less than or equal to 1.0 mg/L (n = 258) and had a longer duration of dialysis, lower serum albumin level, and higher phosphate level ( P < .01, P < .05, P < .001, and P < .01, respectively). Prevalence of vascular calcification of aorta and hand arteries in the former group was significantly higher than in the latter (65.0% versus 43.8% for aorta, P < .0001; and 25.0% versus 14.7% for hand arteries, P < .01). In a multivariate logistic regression analysis adjusted for age, hemodialysis duration, sex, levels of calcium and phosphate, and presence of diabetes, CRP level was a significant predictor for the presence of aortic calcification (odds ratio for highest versus lowest quartile, 2.669; 95% confidence interval, 1.539-5.421, P = .0010) and of calcification of hand arteries (odds ratio, 2.243; 95% confidence interval, 1.039-4.841; P = .0395). In conclusion, the present study shows that increased levels of CRP are significantly associated with the presence of vascular calcification in both aorta and hand arteries (ie, with both atheromatous and medial forms of calcification), indicating evidence for a relationship between inflammation and vascular calcification in hemodialysis patients.

Aortic Diseases↗
PubMed2004

FGF-23 in patients with end-stage renal disease on hemodialysis.

BACKGROUND: Fibroblast growth factor (FGF)-23 is a recently identified circulating factor which causes renal phosphate wasting disorders. Although the mechanism of regulation of FGF-23 secretion is unknown, plasma FGF-23 level may be regulated or affected by serum phosphate levels because of its hypophosphatemic effect. METHODS: We tested the hypothesis that plasma FGF-23 levels may be increased in hyperphosphatemia in patients with end-stage renal disease (ESRD) on maintenance hemodialysis. We measured plasma FGF-23 levels in 158 male uremic patients on maintenance hemodialysis. Plasma samples were obtained before starting dialysis sessions to determine FGF-23 levels by enzyme-linked immunosorbent assay (ELISA). RESULTS: Plasma FGF-23 level exhibited significant and positive correlations with inorganic phosphate, intact parathyroid hormone (PTH), corrected calcium, and duration of hemodialysis on simple regression analyses. All these associations remained significant in multiple regression analyses. CONCLUSION: Serum phosphate, calcium, and intact PTH could be regulators of FGF-23 levels in uremic patients on maintenance hemodialysis. Our results may provide new insights into the pathophysiologic effects of FGF-23 on calcium-phosphate homeostasis.

Case-Control Studies↗
PubMed2004

[Extraskeletal actions of parathyroid hormone in hemodialysis patients].

In uremic patients, secondary hyperparathyroidism is caused by disturbances of calcium and phosphorus metabolism such as elevated plasma phosphate and reduced production of active vitamin D metabolites. Although the etiologies for complications in renal failure are multiple, there is evidence suggesting that increased circulating parathyroid hormone associated with secondary hyperparathyroidism may play important roles in uremic syndrome.

Humans↗
PubMed2003

Intima-media thickness of carotid artery predicts cardiovascular mortality in hemodialysis patients.

BACKGROUND: Cardiovascular disease is the leading cause of death in patients with end-stage renal disease (ESRD). Previous studies showed that patients with ESRD had increased intima-media thickness of the carotid artery (CA-IMT). In the present study, we examined whether CA-IMT would predict cardiovascular mortality in patients with ESRD. METHODS: The cohort consisted of 438 patients with ESRD treated with hemodialysis. CA-IMT was measured by high-resolution B-mode ultrasonography. RESULTS: During the follow-up period of 30 months, 82 deaths, including 44 cardiovascular fatal events, occurred. Compared with those with CA-IMT less than 1.0 mm, those with moderately increased CA-IMT (1.0 to 2.0 mm) and those with severely increased CA-IMT (>or=2.0 mm) showed a significantly greater risk for death from cardiovascular causes; odds ratios were 3.17 (95% confidence interval [CI], 1.41 to 7.17; P = 0.005) and 10.20 (95% CI, 3.67 to 28.3; P < 0.0001), respectively, in a multivariate Cox analysis including age, sex, duration of hemodialysis therapy, presence of diabetes mellitus, blood pressure, body mass index, and high-density lipoprotein and non-high-density lipoprotein cholesterol levels as covariates. Conversely, CA-IMT was not significantly associated with noncardiovascular mortality. CONCLUSION: These results indicate that increased CA-IMT is an independent predictor of cardiovascular mortality in the hemodialysis population.

Adult↗