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Effects of phosphate binder therapy on vascular stiffness in early-stage chronic kidney disease.

ABSTRACT: Cardiovascular disease (CVD) is increased in chronic kidney disease (CKD), and contributed to by the CKD-mineral bone disorder (CKD-MBD). CKD-MBD begins in early CKD and its vascular manifestations begin with vascular stiffness proceeding to increased carotid artery intima-media thickness (cIMT) and vascular calcification (VC). Phosphorus is associated with this progression and is considered a CVD risk factor in CKD. We hypothesized that modifying phosphorus balance with lanthanum carbonate (LaCO3) in early CKD would not produce hypophosphatemia and may affect vascular manifestations of CKD-MBD.We randomized 38 subjects with normophosphatemic stage 3 CKD to a fixed dose of LaCO3 or matching placebo without adjusting dietary phosphorus in a 12-month randomized, double-blind, pilot and feasibility study. The primary outcome was the change in serum phosphorus. Secondary outcomes were changes in measures of phosphate homeostasis and vascular stiffness assessed by carotid-femoral pulse wave velocity (PWV), cIMT and VC over 12 months.There were no statistically significant differences between LaCO3 and placebo with respect to the change in serum phosphorus, urinary phosphorus, tubular reabsorption of phosphorus, PWV, cIMT, or VC. Biomarkers of the early CKD-MBD such as plasma fibroblast growth factor-23, Dickkopf-related protein 1 (DKK1), and sclerostin were increased 2- to 3-fold at baseline, but were not affected by LaCO3.Twelve months of LaCO3 had no effect on serum phosphorus and did not alter phosphate homeostasis, PWV, cIMT, VC, or biomarkers of CKD-MBD.

SUBMITTER: Seifert ME

PROVIDER: S-EPMC3874122 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Effects of phosphate binder therapy on vascular stiffness in early-stage chronic kidney disease.

Seifert Michael E ME de las Fuentes Lisa L Rothstein Marcos M Dietzen Dennis J DJ Bierhals Andrew J AJ Cheng Steven C SC Ross Will W Windus David D Dávila-Román Víctor G VG Hruska Keith A KA

American journal of nephrology 20130807 2

<h4>Background/aims</h4>Cardiovascular disease (CVD) is increased in chronic kidney disease (CKD), and contributed to by the CKD-mineral bone disorder (CKD-MBD). CKD-MBD begins in early CKD and its vascular manifestations begin with vascular stiffness proceeding to increased carotid artery intima-media thickness (cIMT) and vascular calcification (VC). Phosphorus is associated with this progression and is considered a CVD risk factor in CKD. We hypothesized that modifying phosphorus balance with ...[more]

PMID: 23941761

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Project description:ImportanceThe global burden of chronic kidney disease (CKD) is substantial and potentially leads to higher health care resource use.ObjectiveTo examine the association between early-stage CKD and health care spending and its changes over time in the general population.Design, setting, and participantsCohort study using nationwide health checkup and medical claims data in Japan. Participants included individuals aged 30 to 70 years with estimated glomerular filtration rates (eGFR) of 30 mL/min/1.73 m2 or greater at the baseline screening in 2014. Data analyses were conducted from April 2021 to October 2023.ExposureThe CKD stages at baseline, defined by the eGFR and proteinuria, were as follows: eGFR of 60 mL/min/1.73 m2 or greater without proteinuria, eGFR of 60 mL/min/1.73 m2 or greater with proteinuria, eGFR of 30 to 59 mL/min/1.73 m2 without proteinuria, and eGFR of 30 to 59 mL/min/1.73 m2 with proteinuria.Main outcome and measuresThe primary outcome was excess health care spending, defined as the absolute difference in health care spending according to the baseline CKD stages (reference group: eGFR ≥60 mL/min/1.73 m2 without proteinuria) in the baseline year (2014) and in the following 5 years (2015 to 2019).ResultsOf the 79 988 participants who underwent a health checkup (mean [SD] age, 47.0 [9.4] years; 22 027 [27.5%] female), 2899 (3.6%) had an eGFR of 60 mL/min/1.73 m2 or greater with proteinuria, 1116 (1.4%) had an eGFR of 30 to 59 mL/min/1.73 m2 without proteinuria, and 253 (0.3%) had an eGFR of 30 to 59 mL/min/1.73 m2 with proteinuria. At baseline, the presence of proteinuria and an eGFR less than 60 mL/min/1.73 m2 were associated with greater excess health care spending (adjusted difference, $178; 99% CI, $6-$350 for proteinuria; $608; 99% CI, $233-$983 for an eGFR of 30-59 mL/min/1.73 m2; and $1254; 99% CI, $134-$2373 for their combination). The study consistently found excess health care spending over the following 5 examined years.Conclusions and relevanceIn this cohort study of nationwide health checkup and medical claims data in Japan, early-stage CKD was associated with excess health care spending over the 5 examined years, and the association was more pronounced with a more advanced disease stage.

Project description:BackgroundCardiovascular disease is the leading cause of death in end-stage renal disease and is strongly associated with vascular calcification. Both kidney transplantation and phosphate binders may lower the risk of vascular calcification. Vascular calcification is actively inhibited by vitamin-K-dependent matrix ?-carboxyglutamic acid protein (MGP). Whether kidney transplantation or phosphate binders affect vitamin K status is unknown. Therefore, we studied the influence of kidney transplantation and phosphate binder use on vitamin K status.MethodsWe measured plasma desphospho-uncarboxylated MGP (dp-ucMGP), a marker reflecting low vitamin K status, in a cross-sectional study of patients on hemodialysis (n = 82), peritoneal dialysis (n = 31) or who recently received a kidney transplantation (n = 36). By medication inventory, we assessed phosphate binder use. With linear regression, we assessed the influence of kidney transplantation and phosphate binder use on natural-log-transformed dp-ucMGP, adjusting for potential confounders.ResultsMean age of patients was 52±13 years; 102 (68%) were male. Dp-ucMGP levels were significantly lower in kidney transplant recipients (median 689 pmol/L) compared to patients on dialysis (median 1537 pmol/L, p<0.001). Eighty-nine patients on dialysis used phosphate binders. Using any phosphate binder was not associated with dp-ucMGP levels (median 1637 pmol/L, p = 0.09) compared to no phosphate binders (median 1142 pmol/L). Twenty-six patients used sevelamer monotherapy, which was associated with higher dp-ucMGP levels (median 1740 pmol/L, p = 0.04) after adjusting for age, sex and vitamin K antagonist use.ConclusionsRecent kidney transplantation is associated with lower dp-ucMGP levels suggesting improved vitamin K status after transplantation. Sevelamer monotherapy is associated with higher dp-ucMGP levels suggesting worsening of vitamin K status. Both findings warrant more attention to vitamin K status in patients on dialysis, as vitamin K is necessary for protection against vascular calcification.

Dataset Information

Effects of phosphate binder therapy on vascular stiffness in early-stage chronic kidney disease.

Publications

Effects of phosphate binder therapy on vascular stiffness in early-stage chronic kidney disease.

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