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Background: Hemodialysis patients with mineral and bone disorders (MBDs) have an abnormally high relative risk of death, but their absolute risk of death is unknown. Further, previous studies have not accounted for possible time-dependent confounding of the association between MBD markers and death due to the effect of markers of MBD on treatments, which subsequently may affect MBD markers., Study Design: Multicenter, 3-year, prospective, case-cohort study., Setting & Participants: 8,229 hemodialysis patients with secondary hyperparathyroidism (parathyroid hormone level ≥180 pg/mL and/or receiving vitamin D receptor activators) at 86 facilities in Japan., Predictors: Serum phosphorus, calcium, and parathyroid hormone levels., Outcome: All-cause mortality., Measurements: Marginal structural models were used to compute absolute differences in all-cause mortality associated with different levels of predictors while accounting for time-dependent confounding., Results: The association between phosphorus level and mortality appeared U-shaped, although only higher phosphorus level categories reached statistical significance: compared to those with phosphorus levels of 5.0-5.9 mg/dL (1.61-1.93 mmol/L), patients with the highest (≥9.0 mg/dL [≥2.90 mmol/L]) phosphorus levels had 9.4 excess deaths/100 person-years (rate ratio, 2.79 [95% CI, 1.26-6.15]), whereas no association was found for the lowest phosphorus category (<3.0 mg/dL [<0.97 mmol/L]; rate ratio, 1.54 [95% CI, 0.87-2.71]). Similarly, hypercalcemia (≥10.0 mg/dL [≥2.50 mmol/L]) was associated with excess deaths, and the highest level of hypercalcemia (≥11.0 mg/dL [≥2.75 mmol/L]) was associated with 5.8 excess deaths/100 person-years (rate ratio, 2.38 [95% CI, 1.77-3.21]) compared to those with levels of 9.0-9.4 mg/dL (2.25-2.37 mmol/L). Abnormally high parathyroid hormone levels were not associated with excess deaths., Limitations: Possible residual confounding., Conclusions: These results reinforce the idea that serum calcium (in addition to phosphorus) level is an important predictor of the absolute risk of death in hemodialysis patients with secondary hyperparathyroidism., (Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Mineral and bone disorders (MBD), including hypercalcemia and hypophosphatemia, are common complications after renal transplantation; however, the natural course of these disorders has not been well documented, and the pathogenesis of persistent post-transplant MBD still remains elusive. This study was carried out to show the natural history of mineral metabolism in recipients after living-donor kidney transplantation and also to clarify post-transplant risk factors of persistent hypercalcemia and/or hypophosphatemia at 12months after transplantation. Living-donor kidney transplant recipients (N=34) at Tokyo Women's Medical University were prospectively and consecutively recruited. Parameters of MBD, including intact parathyroid hormone and full-length fibroblast growth factor23, were followed. Serum calcium levels increased until the fourth week post-transplantation, after which it reached a plateau; and serum phosphate decreased substantially at one week post-kidney transplantation, but recovered to the reference level at two months. Fibroblast growth factor23 gradually decreased to comparable levels for renal function, while hyperparathyroidism persisted for 12months after transplantation. Multivariate linear regression analysis revealed that intact parathyroid hormone was the best correlating factor with both hypercalcemia and persistent hypophosphatemia at 12months. This study suggests the need for testing of other interventions used for treatment of hyperparathyroidism which may help to offer better management of MBD after kidney transplantation., (© 2011 The Authors. Therapeutic Apheresis and Dialysis © 2011 International Society for Apheresis.)

Background and Objectives: Control of serum concentrations of calcium (Ca), phosphorus (P), and parathyroid hormone (PTH) is essential for management of secondary hyperparathyroidism (SHPT)., Design, Setting, Participants, & Measurements: This is a planned interim analysis of a longitudinal cohort study. The settings are dialysis facilities in Japan. Eligible patients comprise all those who were receiving hemodialysis at one of 86 participating facilities and who have SHPT. Using data from a random sample (n = 3276) of the participants from January 2008 through June 2009, we measured changes in the percentages of patients who were within the national guideline-specified target ranges of Ca (8.4 to 10 mg/dl), P (3.5 to 6.0 mg/dl), and intact PTH (iPTH) (60 to 180 pg/ml), and changes in prescriptions of drugs targeting SHPT. We used regression models to identify factors affecting the achievement of the guideline-specified targets., Results: There were no notable changes in the percentage of patients who were within the guideline for Ca, P, or both. The percentage who were within the iPTH guideline increased from 14.5% to 43.3% (P < 0.001). There were no remarkable changes in the percentage of patients receiving vitamin D or phosphate binders. The percentage who received cinacalcet increased from 0% to 29%. Prescription of cinacalcet was associated with improvement or target-achievement for iPTH and for Ca by 16.8 percentage points (95% CI: 8.1 to 17.0) and by 12.6 percentage points (13.7 to 19.9), respectively., Conclusions: In the routine care of hemodialysis patients, increasing use of cinacalcet was associated with better control of SHPT.

Background: Kidney transplantation (KTx) restores many of the disorders accompanying end-stage renal failure. However, hypercalcemia and hypophosphatemia are both common complications after renal transplantation. Prospective observation of these complications has not been well described and pre-transplant predictors also remain unknown. This prospective observational cohort study was carried out to clarify pre-transplant risk factors of persistent hypophosphatemia and/or hypercalcemia at 12 months after transplantation., Methods: Consecutive living donor KTx recipients (n = 39) at Tokyo Women's Medical University were prospectively recruited. Parameters of bone and mineral metabolism including intact parathyroid hormone (iPTH) and full-length fibroblast growth factor (FGF) 23 were followed., Results: FGF23 decreased to comparable levels for renal function while hyperparathyroidism persisted at 12 months after transplantation. Multivariate linear regression analysis revealed that pre-transplant iPTH correlated with hypercalcemia at 12 months and pre-transplant FGF23 was the best pre-transplant predictor of persistent hypophosphatemia at 12 months., Conclusions: It is intriguing that although FGF23 is not a causal factor for hypophosphatemia at 12 months post-transplantation, it is a significant predictor of this common complication.