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...

Full description

Saved in:
Bibliographic Details
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
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2468024924000020
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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).
ISSN:2468-0249