Alkaline Phosphatase and Parathyroid Hormone Levels: International Variation and Associations With Clinical Outcomes in the DOPPS

Introduction: Secondary hyperparathyroidism (SHPT) increases the risk of fractures and cardiovascular (CV) disease in patients on hemodialysis (HD). The relationship between parathyroid hormone (PTH) and outcomes has been inconsistent, possibly due to variable bone responsiveness to PTH. The KDIGO g...

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Main Authors: Suguru Yamamoto, Hanne Skou Jørgensen, Junhui Zhao, Angelo Karaboyas, Hirotaka Komaba, Marc Vervloet, Sandro Mazzaferro, Etienne Cavalier, Brian Bieber, Bruce Robinson, Pieter Evenepoel, Masafumi Fukagawa
Format: Article
Language:English
Published: Elsevier 2024-04-01
Series:Kidney International Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2468024924000020
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author Suguru Yamamoto
Hanne Skou Jørgensen
Junhui Zhao
Angelo Karaboyas
Hirotaka Komaba
Marc Vervloet
Sandro Mazzaferro
Etienne Cavalier
Brian Bieber
Bruce Robinson
Pieter Evenepoel
Masafumi Fukagawa
author_facet Suguru Yamamoto
Hanne Skou Jørgensen
Junhui Zhao
Angelo Karaboyas
Hirotaka Komaba
Marc Vervloet
Sandro Mazzaferro
Etienne Cavalier
Brian Bieber
Bruce Robinson
Pieter Evenepoel
Masafumi Fukagawa
author_sort Suguru Yamamoto
collection DOAJ
description Introduction: Secondary hyperparathyroidism (SHPT) increases the risk of fractures and cardiovascular (CV) disease in patients on hemodialysis (HD). The relationship between parathyroid hormone (PTH) and outcomes has been inconsistent, possibly due to variable bone responsiveness to PTH. The KDIGO guideline suggests monitoring total alkaline phosphatase (ALP), but the role of ALP versus PTH in the management of mineral and bone disorder (MBD) is not clear. Methods: The analysis included 28,888 patients on HD in 9 countries in Dialysis Outcomes and Practice Patterns Study (DOPPS) phase 3 to 7 (2005–2021). The primary exposures of interest were normalized ALP and PTH, which are raw values divided by facility upper normal limit, measured at study enrollment. Cox models were used to estimate hazard ratios of all-cause or CV mortality and any or hip fracture adjusted for potential confounders. Linear mixed models, adjusted for potential confounders, were employed to investigate the relationship between normalized ALP levels and patient characteristics. Results: Normalized PTH showed a J-shaped association with all-cause or CV mortality, and a weak linear association with fracture. In contrast, normalized ALP showed a strong association with all outcomes. Factors associated with higher ALP levels after controlling for PTH included Black race, longer dialysis vintage, diabetes mellitus, hypocalcemia, hypophosphatemia, elevated C-reactive protein (CRP), and the use of cinacalcet. Conclusion: Total ALP is a more robust exposure of adverse outcomes than PTH in patients on HD. PTH responsiveness is affected by race, primary renal disease, comorbidities, and mineral metabolism and therapy. Our results indicate that it may be useful to evaluate target organ response, rather than PTH alone when considering the consequences of (SHPT).
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spelling doaj-art-475ba3d6fc53463497c6f7a0e018c49c2025-08-20T03:45:02ZengElsevierKidney International Reports2468-02492024-04-019486387610.1016/j.ekir.2024.01.002Alkaline Phosphatase and Parathyroid Hormone Levels: International Variation and Associations With Clinical Outcomes in the DOPPSSuguru Yamamoto0Hanne Skou Jørgensen1Junhui Zhao2Angelo Karaboyas3Hirotaka Komaba4Marc Vervloet5Sandro Mazzaferro6Etienne Cavalier7Brian Bieber8Bruce Robinson9Pieter Evenepoel10Masafumi Fukagawa11Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Correspondence: Suguru Yamamoto, Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Niigata 951-8510, Japan.Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, KU Leuven, Belgium; Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark; Department of Nephrology, Aalborg University Hospital, Aalborg, DenmarkArbor Research Collaborative for Health, Ann Arbor, Michigan, USAArbor Research Collaborative for Health, Ann Arbor, Michigan, USADivision of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, JapanDepartment of Nephrology, Amsterdam University Medical Center, Amsterdam, the NetherlandsDepartment of Translational and Precision Medicine, Sapienza University of Rome, ItalyDepartment of Clinical Chemistry, University of Liège, CHU de Liège, Sart Tilman, Liège, BelgiumArbor Research Collaborative for Health, Ann Arbor, Michigan, USADivision of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USADepartment of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, KU Leuven, Belgium; Department of Nephrology and Renal Transplantation, University Hospitals Leuven, BelgiumDivision of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, JapanIntroduction: Secondary hyperparathyroidism (SHPT) increases the risk of fractures and cardiovascular (CV) disease in patients on hemodialysis (HD). The relationship between parathyroid hormone (PTH) and outcomes has been inconsistent, possibly due to variable bone responsiveness to PTH. The KDIGO guideline suggests monitoring total alkaline phosphatase (ALP), but the role of ALP versus PTH in the management of mineral and bone disorder (MBD) is not clear. Methods: The analysis included 28,888 patients on HD in 9 countries in Dialysis Outcomes and Practice Patterns Study (DOPPS) phase 3 to 7 (2005–2021). The primary exposures of interest were normalized ALP and PTH, which are raw values divided by facility upper normal limit, measured at study enrollment. Cox models were used to estimate hazard ratios of all-cause or CV mortality and any or hip fracture adjusted for potential confounders. Linear mixed models, adjusted for potential confounders, were employed to investigate the relationship between normalized ALP levels and patient characteristics. Results: Normalized PTH showed a J-shaped association with all-cause or CV mortality, and a weak linear association with fracture. In contrast, normalized ALP showed a strong association with all outcomes. Factors associated with higher ALP levels after controlling for PTH included Black race, longer dialysis vintage, diabetes mellitus, hypocalcemia, hypophosphatemia, elevated C-reactive protein (CRP), and the use of cinacalcet. Conclusion: Total ALP is a more robust exposure of adverse outcomes than PTH in patients on HD. PTH responsiveness is affected by race, primary renal disease, comorbidities, and mineral metabolism and therapy. Our results indicate that it may be useful to evaluate target organ response, rather than PTH alone when considering the consequences of (SHPT).http://www.sciencedirect.com/science/article/pii/S2468024924000020alkaline phosphatasefractureshemodialysismortalityparathyroid hormone
spellingShingle Suguru Yamamoto
Hanne Skou Jørgensen
Junhui Zhao
Angelo Karaboyas
Hirotaka Komaba
Marc Vervloet
Sandro Mazzaferro
Etienne Cavalier
Brian Bieber
Bruce Robinson
Pieter Evenepoel
Masafumi Fukagawa
Alkaline Phosphatase and Parathyroid Hormone Levels: International Variation and Associations With Clinical Outcomes in the DOPPS
Kidney International Reports
alkaline phosphatase
fractures
hemodialysis
mortality
parathyroid hormone
title Alkaline Phosphatase and Parathyroid Hormone Levels: International Variation and Associations With Clinical Outcomes in the DOPPS
title_full Alkaline Phosphatase and Parathyroid Hormone Levels: International Variation and Associations With Clinical Outcomes in the DOPPS
title_fullStr Alkaline Phosphatase and Parathyroid Hormone Levels: International Variation and Associations With Clinical Outcomes in the DOPPS
title_full_unstemmed Alkaline Phosphatase and Parathyroid Hormone Levels: International Variation and Associations With Clinical Outcomes in the DOPPS
title_short Alkaline Phosphatase and Parathyroid Hormone Levels: International Variation and Associations With Clinical Outcomes in the DOPPS
title_sort alkaline phosphatase and parathyroid hormone levels international variation and associations with clinical outcomes in the dopps
topic alkaline phosphatase
fractures
hemodialysis
mortality
parathyroid hormone
url http://www.sciencedirect.com/science/article/pii/S2468024924000020
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