Decreases in parathyroid gland volume after cinacalcet treatment in hemodialysis patients with secondary hyperparathyroidism.

BACKGROUND/AIM: Cinacalcet, an allosteric modulator of the calcium-sensing receptor, effectively reduces serum parathyroid hormone (PTH). It was examined whether a regression of parathyroid glands in hemodialysis patients with secondary hyperparathyroidism was induced by cinacalcet treatment. METHODS: Ultrasonography of the parathyroid glands was performed to examine the changes in the parathyroid gland volumes after cinacalcet treatment in 58 patients. RESULTS: After cinacalcet treatment, serum calcium, phosphate, alkaline phosphatase, and intact PTH significantly decreased (p < 0.0001). The total volumes of the parathyroid glands were significantly decreased 6 months after cinacalcet treatment (942 +/- 747 vs. 708 +/- 550 mm(3), p < 0.0005). There was a significant positive correlation between the parathyroid gland volumes at the start of cinacalcet treatment and the volume reduction in parathyroid glands (r = 0.716, p < 0.0001). Of the 58 patients, the total parathyroid gland volume was decreased in 42 patients and increased in 16 although the doses of cinacalcet, phosphate binders or vitamin D were not significantly different. In both groups, the intact PTH serum levels were significantly decreased after cinacalcet treatment. CONCLUSION: Cinacalcet treatment in patients with secondary hyperparathyroidism significantly reduced the total parathyroid gland volume in a short 6-month period. This study suggests that cinacalcet treatment may postpone parathyroidectomy and/or reduce cases.

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.

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.

Impaired secretion of parathyroid hormone, but not refractoriness of osteoblast, is a major mechanism of low bone turnover in hemodialyzed patients with diabetes mellitus.

Diabetic bone disease is characterized by low bone turnover resulting from either impaired secretion of parathyroid hormone (PTH) or refractoriness of osteoblasts to PTH. The present study was performed to elucidate which factor contributes more to the reduction in bone turnover by comparison between 64 hemodialyzed patients with diabetes mellitus and 106 hemodialyzed patients without diabetes mellitus. Only men were enrolled to avoid the influence of the menstrual cycle on bone metabolism. Serum intact PTH (iPTH) levels were significantly lower in hemodialyzed patients with diabetes than those without diabetes, although no significant difference existed in age, duration of hemodialysis therapy, or serum calcium or phosphate levels. Of the biochemical markers measured, serum intact osteocalcin (iOC) and deoxypyridinoline levels were significantly lower in patients with diabetes, although serum bone-specific alkaline phosphatase (BAP) and pyridinoline levels did not differ significantly between the two groups of patients. When patients were restricted to those with serum iPTH levels greater than 180 pg/mL, this parameter correlated significantly in a positive manner with both serum iOC and BAP levels and negatively with bone mineral density at distal radius 1/3. Regression slopes between iPTH levels and these parameters were not significantly different between the two groups of patients, indicating the absence of refractoriness of bone to PTH in patients with diabetes. In conclusion, our findings suggest that impaired PTH secretion, but not refractoriness of osteoblasts to PTH, may be responsible for the low bone turnover in hemodialyzed patients with diabetes.

The role of peritoneal lavage and the prognostic significance of mesothelial cell area in preventing encapsulating peritoneal sclerosis.

BACKGROUND: Severe peritoneal injury and encapsulating peritoneal sclerosis (EPS) as complications of long-term peritoneal dialysis (PD) are issues of concern. The usefulness of peritoneal lavage after withdrawal of PD and the risk factors for EPS have not been addressed until now. Little is known about mesothelial cell area (MCA) in the effluent as a marker of peritoneal injury. In the present study, we investigated the clinical significance of peritoneal lavage after PD withdrawal and tried to clarify the risk factors related to MCA, with the aim of preventing EPS. We also developed an algorithm for the clinical management of long-term PD patients. METHODS: We assigned 247 PD patients to one of two cohorts after PD withdrawal: a non-lavage group (73 patients) and a lavage group (174 patients). To clarify the risk factors, we studied these potential predictors: PD duration, dialysate-to-plasma ratio of creatinine (D/P Cr) at the time of PD withdrawal, frequency of peritoneal lavage, type of PD or lavage solution, MCA at the time of PD withdrawal ("PD area"), and MCA at the time of peritoneal lavage withdrawal or censoring ("LA area"). Recurrent intestinal obstruction was defined as the main manifestation of EPS. Diagnostic performance and cut-off values were then calculated for the selected risk factors. RESULTS: The overall incidence of EPS was significantly lower in the lavage group, at 6.9% (5.2% during lavage and 2.5% after lavage), than in the non-lavage group, at 15.1%. The risk factors and cut-off values were PD area (350 µm(2)) and PD duration (78 months) for the non-lavage group; and PD area (350 µm(2)) and LA area (320 µm(2)) for the lavage group. Patients with a PD duration of 78 months or more and a PD area of 350 µm(2) or more were defined as high-risk patients in the non-lavage group (risk ratio: 11.14), and patients with a PD area of 350 µm(2) or more and an LA area of 320 µm(2) or more were defined as high-risk patients in the lavage group (risk ratio: 10.43). CONCLUSIONS: Peritoneal lavage is effective in reducing the incidence of EPS after PD withdrawal. The PD duration and MCA are significant risk factors, and these markers are useful for classifying patients into low- and high-risk groups for the development of EPS.

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.

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.