Presence of abdominal aortic calcification is significantly associated with all-cause and cardiovascular mortality in maintenance hemodialysis patients.

BACKGROUND: Although abdominal aortic calcification (AAC) is reported as a predictor for cardiovascular mortality in the general population, it is unknown whether this is also true in hemodialysis patients in whom vascular calcification and cardiovascular diseases are highly prevalent. STUDY DESIGN: Cohort study. SETTINGS & PARTICIPANTS: 515 patients on maintenance hemodialysis therapy at a single center. PREDICTOR: AAC evaluated in a plain roentgenograph of the lateral abdomen at baseline. OUTCOMES & MEASUREMENTS: All-cause and cardiovascular death. RESULTS: Mean age was 60 +/- 12 (SD) years. AAC was present in 291 patients (56.5%). During a mean follow-up period of 51 +/- 17 months, there were 103 all-cause deaths, of which 41 were from cardiovascular diseases. Of patients with and without AAC, 27.8% and 9.8% died, respectively (11.6% and 3.1% of cardiovascular diseases, respectively). Kaplan-Meier analysis showed that all-cause mortality was significantly greater in patients with AAC compared to those without (P < 0.0001, log-rank test). Similarly, cardiovascular mortality was significantly greater in the former than in the latter group (P = 0.0001, log-rank test). Multivariate Cox proportional hazards analysis found that the presence of AAC was significantly associated with increased all-cause mortality (hazard ratio, 2.07; 95% confidence interval, 1.21 to 3.56; P < 0.01) and increased cardiovascular mortality (hazard ratio, 2.39; 95% confidence interval, 1.01 to 5.66; P < 0.05) after adjustment for age, hemodialysis duration, presence of diabetes, serum albumin level, and C-reactive protein level. LIMITATIONS: Nonquantitative assessment of AAC and the lack of information for medication and history of cardiovascular diseases. CONCLUSION: The presence of AAC is significantly associated with both all-cause and cardiovascular mortality in hemodialysis patients, suggesting that careful attention should be given to the presence of AAC in a simple radiograph of the lateral abdomen as a prognostic indicator.

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.

[Calcium and vitamin D intake after menopause].

It is thought that the decrease in bone mass after menopause is attributable to the changes with increasing age physiologically caused by rapid decrease in female hormone, decline in calcium absorption, and acceleration of bone resorption. But it is possible to prevent it from occurring by improving the living habits including daily dietary intake and physical exercise. In the 6th Revised Nutrient Intake Requirements for the Japanese People that was drawn up in 1999, the intake criteria for vitamin D were also newly established. In the process of considering the prevention of osteoporosis in the future, the intake amounts of calcium and vitamin D will become extremely important contributing factors.

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.

Relationship between parathyroid gland size and responsiveness to maxacalcitol therapy in patients with secondary hyperparathyroidism.

BACKGROUND: Although vitamin D has been reported to be useful in the treatment of patients with secondary hyperparathyroidism, it is not effective in some of them. The goal of this study was to see whether a relationship could be found between maxacalcitol responsiveness and parathyroid gland size. METHODS: Parathyroid gland size was measured by ultrasonography in 25 patients with secondary hyperparathyroidism [serum intact parathyroid hormone (PTH) >300 pg/ml, 58.1 +/- 2.8 years old, 15 males and 10 females], who were treated with maxacalcitol. Patients were divided into two groups according to the mean value of the maximum diameter of the glands: group S with a diameter <11.0 mm and group L with a diameter >or =11.0 mm. Between the two groups there were no significant differences in serum intact PTH, calcium or phosphate level or duration of haemodialysis. RESULTS: Mean (+/- SE) maximal diameter of detectable parathyroid glands was 11.0 +/- 0.7 mm before treatment. At 4-24 weeks after administration of maxacalcitol, intact PTH concentrations decreased significantly in group S (from 546 +/- 39 to 266 +/- 34 pg/ml at 24 weeks; P < 0.01), but did not significantly change in group L (from 481 +/- 39 to 403 +/- 49 pg/ml at 24 weeks). At 24 weeks after maxacalcitol administration, the number of detectable parathyroid glands was significantly decreased in group S (from 2.2 +/- 0.3 to 1.8 +/- 0.4; P < 0.05), but not in group L. Serum calcium increased significantly in group L (from 9.6 +/- 0.2 to 10.2 +/- 0.3 mg/dl; P < 0.05), but not in group S. There was a significant correlation between reduction in PTH and parathyroid gland size (r = -0.42, P < 0.05). CONCLUSIONS: These results indicate that the responsiveness to maxacalcitol therapy of secondary hyperparathyroidism is dependent on parathyroid gland size and that the simple measurement of maximum parathyroid gland diameter by ultrasonography may be useful for predicting responsiveness to maxacalcitol treatment.

Clinical usefulness of measurements of urinary deoxypyridinoline (DPD) in patients with postmenopausal osteoporosis receiving intermittent cyclical etidronate: advantage of free form of DPD over total DPD in predicting treatment efficacy.

Deoxypyridinoline (DPD) in urine, which reflects systemic bone resorption, is considered useful for assessing the effects of osteoporosis treatment. However, there are various methods of measuring DPD in urine but have been few comparative studies of the effectiveness of these methods. In this study, we investigated 94 postmenopausal women (63 patients administered with intermittent cyclical etidronate (ICE), and 31 control patients) focusing on total DPD and free DPD, measured by high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA), respectively. For other metabolic bone markers, i.e., tartrate-resistant acid phosphatase (TRAP), bone-specific alkaline phosphatase (BAP), and osteocalcin (OC), we also investigated the ability of these markers to predict increases in bone mineral density (BMD), by employing receiver operating characteristic (ROC) analysis in relation to increasing BMD following ICE therapy, and we determined the usefulness of the different metabolic bone markers, using the signal-noise ratio derived from the mean significant change (MSC), which is double the day-to-day coefficient of variation in healthy volunteers. In the same way, we defined a significant change in BMD as double the mean change in BMD for 6 months after the initiation of observation in the control group, and we used this value as the cutoff value for ROC analysis. It was found that the assessment of urinary DPD was useful for assessing the treatment efficacy of ICE, and the assessment of changes at week 12 of therapy was most effective. In order to recognize changes in metabolic bone markers when the MSC is considered as the cutoff value, it is useful to assess the change in total DPD by HPLC. However, in order to predict increases in BMD 6 months or more after the initiation of ICE, it seems more effective to measure free DPD by ELISA. We conclude, therefore, that the measurement of free DPD by ELISA is more useful, especially when treatment efficacy of ICE is clinically predicted in individual patients with osteoporosis.

Vitamin K(2) (menaquinone 4) reduces serum undercarboxylated osteocalcin level as early as 2 weeks in elderly women with established osteoporosis.

Twenty elderly osteoporotic women with vertebral fracture(s) were randomly allocated to two groups; women in the MK(4) group received calcium with menaquinone 4 (MK(4)) at a dose of 45 mg/day for 2 weeks, and women in the control group received calcium alone for the same period. Serum intact osteocalcin (OC) and undercarboxylated osteocalcin (uc-OC) levels were measured by immunoradiometric assay and enzyme immunoassay, respectively, at baseline and on the 7th and 14th days following the start of the treatment. There were no differences in the baseline data including age, weight, phylloquinone, menaquinone 4, menaquinone 7, OC, and uc-OC levels between the MK(4) group and the control group. Administration of MK(4) significantly raised the MK(4) level from 0.20 +/- 0.10 (mean +/- SE) pg/ml to 15.09 +/- 5.62 pg/ml ( P < 0.04), and reduced serum uc-OC levels from 2.80 +/- 0.93 ng/ml to 1.76 +/- 0.56 ng/ml ( P < 0.05) at the end of the study, respectively. No significant changes in these levels were observed in the control group. Serum OC levels were stable during the period in both groups. In this randomized prospective study, the MK(4) group shows a reduction in the serum uc-OC level within 2 weeks without any significant change in OC, suggesting that the uc-OC is changed to carboxylated OC. This early effect of MK(4) on bone metabolism may be estimated by the measurement of serum uc-OC in elderly osteoporotic women with vertebral fractures.

Clinical usefulness of the serum N-terminal propeptide of type I collagen as a marker of bone formation in hemodialysis patients.

BACKGROUND: An intact collagen I amino-terminal propeptide (PINP) assay has been developed as a useful assay for bone formation. The present study was performed to investigate the clinical usefulness of serum PINP as a bone-formation marker in hemodialysis (HD) patients. METHODS: PINP and other bone-formation markers, ie, bone alkaline phosphatase (BAP) and intact osteocalcin (OC), were determined in serum samples collected from 209 HD patients. RESULTS: Serum PINP levels, in contrast to serum BAP and OC levels, did not change significantly during a single HD session (P = 0.069; n = 14). There were significant positive correlations between serum PINP and BAP (r = 0.723; P < 0.001) and OC values (r = 0.739; P < 0.001), as well as intact parathyroid hormone (r = 0.652; P < 0.001) and bone-resorption marker values: deoxypyridinoline (DPD; r = 0.823; P < 0.001), pyridinoline (PYD; r = 0.735; P < 0.001), and beta-crosslaps (r = 0.705; P < 0.001). Serum PINP values correlated significantly more strongly than serum BAP values with all bone-resorption markers. Serum PINP values significantly correlated negatively with annual changes in bone mineral density (BMD) in the distal third of the radius (r = -0.286; P < 0.001). When subjects were divided into tertiles according to degree of bone loss, subjects with greater bone loss had significantly greater serum PINP, BAP, and OC levels, although PINP and OC provided greater discrimination than BAP. PINP-PYD and PINP-DPD ratios, indices of osteoblast function not confounded by enhanced bone resorption, significantly positively correlated with annual BMD changes in the distal third of the radius (PINP-PYD ratio, P = 0.008; PINP-DPD, P = 0.015). CONCLUSION: Serum PINP may provide a better marker of osteoblast function in HD patients and thus be clinically useful for predicting radius bone loss.

[Effect of alfacalcidol on bone and calcium metabolism in elderly women].

Oral administration of active vitamin D3 can reduce the loss of bone mass and the incidence of fractures in patients with osteoporosis in Japan. We conducted a prospective study to confirm the effects of 1 alpha(OH)D3 (Alfacalcidol, Alfarol Chugai Tokyo) on bone and calcium metabolism in elderly women with osteoporosis. Enrolled in the present study were 16 elderly osteoporosis women aged 72.6 +/- 4.5 years to whom 1 microgram of 1 alpha(OH)D3 was administered daily. Fasting blood and urine were obtained at baseline, 1 week, 4 weeks, 12 weeks and 24 weeks after the treatment. Monitored parameters were vitamin D metabolites, intact-PTH, bone alkaline phosphatase (BAP), osteocalcin (OC), deoxypyridinoline (DPD) and pyridiuium crosslinked type I collagen telopeptides (CTx). Serum 1 alpha, 25(OH)2D and PTH levels were significantly increased (p < 0.01) and decreased (p < 0.05), respectively at 1 week after commencing administration. There was a significant decrease of DPD (p < 0.05) at 12 weeks after commencing administration compared to the baseline levels. Serum levels of BAP and OC were found elevated at 1 week, and decreased at 12 weeks. In conclusion, the present study clinically confirmed that 1 alpha(OH)D3 stimulates bone formation in vitro. Long-term administration of 1 alpha(OH)D3 indirectly suppressed bone resorption through the suppression of parathyroid function in the elderly.