[en] [en] 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).
Disciplines :
Urology & nephrology Laboratory medicine & medical technology
Author, co-author :
Yamamoto, Suguru; Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
Jørgensen, Hanne Skou; 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, Denmark
Zhao, Junhui; Arbor Research Collaborative for Health, Ann Arbor, Michigan, USA
Karaboyas, Angelo; Arbor Research Collaborative for Health, Ann Arbor, Michigan, USA
Komaba, Hirotaka; Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, Japan
Vervloet, Marc; Department of Nephrology, Amsterdam University Medical Center, Amsterdam, the Netherlands
Mazzaferro, Sandro; Department of Translational and Precision Medicine, Sapienza University of Rome, Italy
Cavalier, Etienne ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Bieber, Brian; Arbor Research Collaborative for Health, Ann Arbor, Michigan, USA
Robinson, Bruce; Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
Evenepoel, Pieter; Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, KU Leuven, Belgium ; Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Belgium
Fukagawa, Masafumi; Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, Japan
Language :
English
Title :
Alkaline Phosphatase and Parathyroid Hormone Levels: International Variation and Associations With Clinical Outcomes in the DOPPS.
This manuscript was directly supported by Kyowa Kirin. Global support for ongoing DOPPS Programs is provided without restriction on publications by a variety of funders (details inhttps://www.dopps.org/AboutUs/Support.aspx). This manuscript was directly supported by Kyowa Kirin Co. Global support for the ongoing DOPPS Programs is provided without restriction on publications by a variety of funders. For details seehttps://www.dopps.org/AboutUs/Support.aspx. All grants were made to Arbor Research Collaborative for Health and not to co-authors directly. None of the funders had any role in study design; collection, analysis, and interpretation of data; writing the report; or the decision to submit this report for publication. Restrictions apply to the availability of the data analyzed in this study to preserve patient confidentiality. Data will be shared on request to the corresponding author with permission from the DOPPS investigators. All authors contributed study conception, design, analysis, and interpretation of data. Research idea and study design was by SY, HSJ, JZ, AK HK, MV, SM, EC, BB, BR, PE, and MF; data acquisition by BB and BR; data analysis/interpretation by SY, HSJ, JZ, AK HK, PE, and MF; statistical analysis by JZ and AK; drafting of the article: SY, HSJ, JZ, AK, and PE; and supervision or mentorship by BR and MF. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved.
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